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Biomedical subjects

S Merk

Publications and source records attributed to S Merk.

11 recordsLinked to original sources
PubMed2006

Gene expression signature of primary imatinib-resistant chronic myeloid leukemia patients.

Although the selective tyrosine kinase inhibitor imatinib is successfully used in the treatment of chronic myeloid leukemia (CML), inherent mechanisms confer primary resistance to leukemic patients. In order to search for potentially useful genes in predicting cytogenetic response, a retrospective gene expression study was performed. Leukocyte RNA isolated before imatinib from interferon-alpha-pretreated chronic phase CML patients (n=34) with or without major cytogenetic remission (< or =35% Philadelphia (Ph)+ metaphases) during the first year of treatment was comparatively analyzed using Affymetrix U133A chips. Using support vector machines for gene classification, an outcome-specific gene expression signature consisting of 128 genes was identified. Comparative expression data of specific genes point to changes in apoptosis (e.g. casp9, tumor necrosis factor receptor-associated protein 1, hras), DNA repair (msh3, ddb2), oxidative stress protection (glutathione synthetase, paraoxonase 2, vanin 1) and centrosomes (inhibitor of differentiation-1) within primary resistant patients. Independent statistical approaches and quantitative real-time reverse transcriptase-polymerase chain reaction studies support the clinical relevance of gene profiling. In conclusion, this study establishes a candidate predictor of imatinib resistance in interferon-alpha-pretreated CML patients to be subjected to future investigation in a larger independent patient cohort. The resulting expression signature point to involvement of BCR-ABL-independent mechanisms of resistance.

Antineoplastic Agents↗
PubMed2006

Detection of Burkholderia cepacia DNA from artificially infected EDTA-blood and lung tissue comparing different DNA isolation methods.

Bacterial DNA (Burkholderia cepacia) was prepared from artificially infected equine ethylenediaminetetraacetic acid (EDTA)-blood and lung tissue by using four standard methods (lysis buffer containing proteinase K, phenol/chloroform/isoamylalcohol-extraction, microwave-treatment, heat treatment) and six commercially available kits (Puregene, High Pure PCR Template Preparation Kit, InstaGene, QiaAmp Tissue Kit, DNAzol and Elu-Quik). After a subsequent polymerase chain reaction (PCR), their efficacy and sensitivity were compared. Concerning the detection limits, the simple lysis with a proteinase K-containing buffer led to the best results for EDTA-blood as well as for artificially infected lung tissue.

Animals↗
PubMed2006

A generic concept for large-scale microarray analysis dedicated to medical diagnostics.

BACKGROUND: The development of diagnostic procedures based on microarray analysis confronts the bioinformatician and the biomedical researcher with a variety of challenges. Microarrays generate a huge amount of data. There are many, not yet clearly defined, data processing steps and many clinical response variables which may not match gene expression patterns. OBJECTIVES: To design a generic concept for largescale microarray experiments dedicated to medical diagnostics; to create a system capable of handling several 1000 microarrays per analysis and more than 100 clinical response variables; to design a standardized workflow for quality control, data calibration, identification of differentially expressed genes and estimation of classification accuracy; and to provide a user-friendly interface for clinical researchers with respect to biomedical interpretation. METHODS: We designed a database structure suitable for the storage of microarray data and analysis results. We applied statistical procedures to identify differential genes and developed a technique to estimate classification accuracy of gene patterns with confidence intervals. RESULTS: We implemented a Gene Analysis Management System (GAMS) based on this concept, using MySQL for data storage, R/Bioconductor for analysis and PHP for a web-based front-end for the exploration of microarray data and analysis results. This system was utilized with large data sets from several medical disciplines, mainly from oncology (approximately 2000 microarrays). CONCLUSIONS: A systematic approach is necessary for the analysis of microarray experiments in a medical diagnostics setting to get comprehensible results. Due to the complexity of the analysis, data processing (by bioinformaticians) and interactive exploration of results (by biomedical experts) should be separated.

Adult↗
PubMed2004

mdclust--exploratory microarray analysis by multidimensional clustering.

MOTIVATION: Unsupervised clustering of microarray data may detect potentially important, but not obvious characteristics of samples, for instance subgroups of diagnoses with distinct gene profiles or systematic errors in experimentation. RESULTS: Multidimensional clustering (mdclust) is a method, which identifies sets of sample clusters and associated genes. It applies iteratively two-means clustering and score-based gene selection. For any phenotype variable best matching sets of clusters can be selected. This provides a method to identify gene-phenotype associations, suited even for settings with a large number of phenotype variables. An optional model based discriminant step may reduce further the number of selected genes.

Cluster Analysis↗
PubMed2003

Bioinformatics for medical diagnostics: assessment of microarray data in the context of clinical databases.

MOTIVATION: To identify genes suitable for medical diagnostics microarray data is assessed in the context of clinical databases, which store complex information about the patient phenotype. The wealth of data and lacking standards make it difficult to analyse this kind of data. RESULTS: We present a workflow for exploratory analysis of microarray data together with clinical data consisting of four steps: definition of clinically meaningful research questions in a masterfile, generation of analysis files, selection and characterization of differentially expressed genes, and estimation of classification accuracy. We applied this workflow to large data sets from the field of cardiology and oncology (n~500 patients). Systematic data management of microarray data and clinical data helps to make results more transparent and comparable.

Cardiology↗
PubMed2002

[Infected animal bite injuries of the extremities].

The appearance of animal bite injuries varies in regard to location and extent. Injuries with puncture wounds involving the extremities carry great risk of infection. Managing the complications often requires substantial medical treatment and increased costs. The aim of this study is the evaluation of the course of disease, medical care, and treatment costs in patients with infected bite injuries. In the year 2000, 16 patients were treated for infection after bite injuries of the extremities. Fourteen patients received substandard therapy because of incorrect assessment of the extent of the bite wound. Because of infection, the average time needed for treatment before returning to work was 3 months, including 12 days of hospitalization and 16 days of out-patient treatment. The average treatment costs exceeded 6,100 Euro for the health insurance companies. Because of its increasing prevalence and inadequate treatment, this type of injury has become a serious public health problem.

Absenteeism↗
PubMed2001

[Calculating the basal metabolic rate and severe and morbid obesity].

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the currently available predictive equations for basal metabolic rate (BMR) in subjects with obesity class II and III, and to assess the contribution by the components of a two-compartment model of body composition, namely the lean body mass (LBM) and the fat mass (FM) to the prediction. A second objective was to examine the reliability of the Harris Benedict equation in obese subjects, especially with a weight > or = 120 kg. PATIENTS AND METHODS: In 43 patients (age range 18 to 61 years, 5 men, 38 women) with obesity class II and III (body mass index, BMI, mean +/- SD 45.6 kg/m2 +/- 5.4 kg/m2, range 37.1-58.6 kg/m2) basal metabolic rate BMR was determined using indirect calorimetry (Deltatrac MBM, Datex, Instrumentarium Corp., Helsinki, Finnland) and the components of body composition were determined using the bioelectrical-impedance-analysis (BIA) method (BIA, Akern-Gerät, RJL Systems, Detroit). Calculated BMR was compared with measured BMR. RESULTS: The best fitting equations for predicting BMR in these 43 severe und morbidly obese subjects were the Harris-Benedict (ratio calculated BMR to measured, BMR mean +/- SD%; correlation coefficient r = 101 +/- 12.9; 0.69), the Jensen (101.5 +/- 12.3; 0.74), the Nelson (99.3 +/- 11.4; 0.76) and the Cunningham equation (98.9 +/- 11.7; 0.74). The predictive value of the original Harris-Benedict equation was slightly different from modified Harris-Benedict equation, which was recalculated by Roza et al. (101.1 +/- 12.9; 0.69 vs. 99.7 +/- 12.8; 0.69). In the group of the 22 subjects with a body weight > or = 120 kg ratio of estimated values for BMR using original Harris-Benedict equation to measured BMR was 102.2 +/- 15.4% (mean +/- SD%, r = 0.61), respectively 93.2 +/- 14.5% (r = 0.50) when weight was set at 120 kg due to current recommendations. The ratio calculated BMR/measured BMR according to the Nelson equation in this subgroup was 101.0 (12.1/0.74). CONCLUSION: In patients with obesity class II and III the equation of Harris-Benedict predicted the average BMR with acceptable precision for clinical use and was better fitting than most of the currently available predictive equations for basal metabolic rate (BMR). However, the recalculated version (by Roza et al.) was more accurate and should therefore be used instead of the original equation: BMR (men) = 88.362 + 4.799 x (length) + 13.397 x (weight) - 5.677 x (age); BMR (women) = 447.593 + 3.098 x (length) + 9.247 x (weight) - 4.330 x (age). The Nelson equation, including not only LBM but FM as additional predictor, was the best predicting equation ([108 LBM + 16.9 FM]0.239). Harris-Benedict equation had sufficient precision also in extreme obese subjects with a body weight > or = 120 kg, so there is no need for adaptation.

Adolescent↗
PubMed2001

[Dorsal V-ligament reconstruction in scapholunate instability].

In dynamic and static scapholunate instability after trauma, the repair of the scapholunate ligament is important to avoid scapholunate advanced collapse of the wrist. Direct suture even of fresh-torn ligaments can be technically demanding and occasionally unreliable, thus reconstruction may require additional tissue beside the ligament. Eighteen patients suffering from dynamic (n = 10) and static (n = 8) scapholunate instability were treated by a dorsal ligament reconstruction six months after trauma. A clinical wrist score according to Cooney showed an average of 86 points (maximum 100) within a follow-up of nineteen months after surgery. X-ray films documented no significant loss of scapholunate reduction. Using local tissue only, this method is always possible, very reliable and easy to perform.

Adolescent↗
PubMed2001

Comparison of different methods for the isolation of Burkholderia cepacia DNA from pure cultures and waste water.

DNA from Burkholderia cepacia was prepared from suspensions of pure cultures and artificially contaminated waste water. The efficacy of four standard methods (lysis buffer containing proteinase K, phenol/chloroform/isoamylalcohol extraction, microwave treatment, heat treatment) and six commercially available kits (Puregene, High Pure PCR Template Preparation Kit, InstaGene, QIAamp Tissue Kit, DNAzol, Elu-Quik) was compared in terms of sensitivity in a subsequent PCR. The results showed that a simple and inexpensive procedure using a lysis buffer containing proteinase K was superior to all other methods tested.

Burkholderia cepacia↗