Biomedical subjects

G Fischer

Publications and source records attributed to G Fischer.

At least 19 recordsLinked to original sources

PubMed2025

Magnesium protects against anaphylactic shock and cardiac myolysis in guinea-pigs.

The pathophysiological responses to immune stress (IS) include activation of several processes which are dependent on cytosolic Ca2+ elevation. Magnesium frequently acts as a natural Ca2+ antagonist. In this study we have observed that Mg2+ can protect guinea-pigs against IS. Antigen-sensitized guinea-pigs, which had been fed a magnesium-deficient diet, were given a single dose (15 mg) of MgCl2 intraperitoneally 1 h before antigen challenge. The development of anaphylactic shock (AS) was observed during the next 2 h, and the hearts were subsequently examined histologically for signs of cardiac myolysis (CM). Magnesium (i) reduced the incidence of CM from 40% to 10% (p < 0.05); (ii) reduced the incidence of AS from 61% to 35% (p < 0.05); (iii) attenuated the severity of the AS; and (iv) lowered mortality from 39% in the control to 19% in the Mg(2+)-treated group (p = 0.1). Serum and tissue total [Mg2+] were not affected by the administration of MgCl2. Also, the serum and heart Mg2+ levels were the same whether or not the guinea-pigs developed AS or CM. In cell culture we demonstrated that by elevating the [Mg2+] in the medium bathing sensitized rat basophilic leukemia (RBL) cells, the increase in cytosolic [Ca2+] subsequent to antigen challenge was reduced from 174 +/- 23.28% (1 mM) to 82.74 +/- 13.22% (3 mM). We conclude that a single treatment with Mg2+ can considerably diminish damage induced by immune stress, probably by its altering the Ca2+: Mg2+ ratio. Since the physiological reaction to different types of stress is similar, Mg2+ could prove beneficial in preventing stress-induced shock in general. Studies examining the mechanisms by which Mg2+ exerts its effects thus provide a scientific basis for the current clinical use of Mg2+ in acute myocardial infarction (AMI) and asthma.

Anaphylaxis↗

PubMed2007

AAM-based segmentation for imaging cardiac electrophysiology.

OBJECTIVES: Activation time (AT) imaging from electrocardiographic (ECG) mapping data has been developing for several years. By coupling 4-dimensional volume data (3D + time) the electrical sequence can be computed non-invasively. In this paper an approach for extracting the ventricular and atrial blood masses for structurally normal hearts by using cine-gated short-axis data obtained via magnetic resonance imaging (MRI) is introduced. METHODS: The blood masses are extracted by employing Active Appearance Models (AAMs). The ventricular blood masses are segmented, applying the AAMs after providing apex cordis and base of the heart in the volume data, whereas the more complex geometry of the atria requires a more specific attempt. On account of this the atrium was divided into three divisions of appearance, where the images of the volume data in the related divisions have a maximum affinity. The first division reaches from the base of the heart to initial visibility of the upper and left lower pulmonary vein. The second division up from there to the last occurrence and the third division from there to the end of the visibility of the right upper and lower pulmonary vein. After extracting the cardiac blood masses the result gets triangulated and remeshed for activation time imaging. RESULTS: With this method the cardiac models of eight patients were extracted and the AT imaging approach was applied to single-beat ECG data of atrial and ventricular depolarization. CONCLUSION: The advantage of the proposed AAM approach is that only a few initial parameters have to be set. Therefore, the approach can be integrated into a processing pipeline that works semi-automatically. The extracted models can be used for further investigations.

Atrial Function↗

PubMed2006

Predisposition for de novo gene aberrations in the offspring of mothers with a duplicated CYP21A2 gene.

CONTEXT: Although CYP21A2 de novo mutations are assumed to account for 1 to 2% of congenital adrenal hyperplasia (CAH) alleles and CYP21 genotyping has been done worldwide, there are only a few well-documented cases of CYP21A2 de novo mutations. The majority of these are deletions resulting from unequal crossings over owing to misalignment of homologous chromosomes during meiosis. Whereas so far, only heterozygous deletions of the CYP21A1P pseudogene were seen as premutations for de novo aberrations, the present report addresses such a predisposing role for parental duplicated CYP21A2 genes. SUBJECTS AND METHODS: As part of routine diagnostic procedures, CYP21 genotyping has been performed in two unrelated female CAH index patients and in their clinically asymptomatic parents and siblings. RESULTS: Both patients have inherited the paternal Intron2splice mutation and have harbored a de novo gene aberration (large deletion and I271N/exon 4) on their maternal haplotype. Surprisingly, both mothers were carriers of rare duplicated CYP21A2 haplotypes carrying CAH alleles, which were not detected in the daughters. Among 133 CAH alleles that were detected in patients and that could be traced to the respective family members by genotyping, these two de novo aberrations (representing 1.5% of 133 traced CAH alleles) were the only ones identified. CONCLUSION: Because both de novo CYP21A2 gene aberrations so far identified in our laboratory occurred in the gametes of mothers carrying rare duplicated CYP21A2 haplotypes, we hypothesize that duplicated CYP21A2 genes could predispose for de novo mutations in the offspring, which is of relevance for prenatal CYP21 genotyping and genetic counseling.

Adrenal Hyperplasia, Congenital↗

PubMed2006

Diagnostic reference levels and effective dose in paediatric cardiac catheterization.

European states within the EEC are required to establish and use diagnostic reference levels (DRLs) in X-ray examinations. However, up to now there have been no DRLs for cardiac catheterization in children, nor as a rule is the effective dose estimated. We have evaluated the dose-area products (DAPs) for three different types of angiocardiography systems over a time span of 8 years. For each system DAP increased in proportion to the body weight (BW) over two orders of magnitude. The proportionality constant decreased over the years. To reduce the broad distribution of DAP the doses for cine acquisition (DAPA) and fluoroscopy (DAPF) were indexed with respect to the total numbers of acquired images (AN) and the total times of fluoroscopy (FT). DAPA/AN is directly proportional to BW with a high correlation (r = 0.896, n = 1346). Likewise, DAPF/FT is proportional to BW from 0.1 kg to 100 kg (r = 0.84, n = 2138). Therefore, by normalizing DAP to BW the growth dependent variation of DAP can be eliminated. There are numerous short examinations with very small total DAPs, which were separated from the group of diagnostic examinations. The mean DAP/BW of this group is 0.41 Gycm2 kg(-1) (90th percentile: 0.81 Gycm2 kg(-1), n = 1106). For interventional procedures in congenital heart diseases DAP/BW is significantly higher (p<0.001) (mean: 0.56 Gycm2 kg(-1), 90th percentile: 1.16 Gycm2 kg(-1), n = 883). There are significant differences between different types of interventional procedures, the mean values being between 0.35 Gycm2 kg(-1) (occlusion of patent ductus botalli, n = 165) and 1.30 Gycm2 kg(-1) (occlusion of ventricular septal defect, n = 32). For patients who are catheterized several times over the years, the cumulative effective dose (E) may reach high values, being especially high for patients with hypoplastic left heart syndrome (typically 11 mSv). E is derived from DAP/BW by use of a constant DAP/BW to E conversion factor, independent of the age of the patient. DAP/BW is appropriate to describe paediatric DRLs and is recommended instead of using mean DAP values for age groups.

Adolescent↗

PubMed2006

[The viewpoints of doctor and patient].

Patient-related end points are generally used to open up opinions and perspectives to the patient, which he/she may not previously have had or not been aware of. Such end points can only be reached if, first, the patient's priorities are taken into account when assessing cost-effectiveness of a medical measure and, second, if the doctor acts to mediate between the individual patient's preferences and medical needs. This requires a doctor's effort to communicate: this cannot be left to chance but has in part to be freshly conceived and systematically employed.

Attitude of Health Personnel↗

PubMed2006

Determination of the enantiomeric composition of a new insulin sensitizer in plasma samples from non-clinical and clinical investigations using chiral HPLC with electrospray tandem mass spectrometric detection.

Two drug assays were developed and applied to assess the enantiomeric composition of an insulin sensitizer drug in plasma after administration of its racemate to man, and in human and animal plasma and serum samples generated after in vitro experiments. The sample preparation for the assays consisted either of protein precipitation and column-switching, or liquid-liquid extraction and direct injection. Subsequently, both assays employed chiral HPLC coupled to atmospheric pressure ionization mass spectrometry. An interconversion of the racemate to a mixture enriched with the (+)-enantiomer could be confirmed for all species and biological matrices. The individual enantiomers could be quantified in the concentration range 0.5-500 ng/ml, starting with a 100-microl plasma aliquot. Inter- and intra-assay precision and accuracy were in the range 0.1-7.9 and 88.8-106.0%, respectively. Run times of 5 min for a single sample allows the analysis of more than 200 samples overnight.

Animals↗

PubMed2006

Raf1, Aurora-A/STK15 and E-cadherin biomarkers expression in patients with pTa/pT1 urothelial bladder carcinoma; a retrospective TMA study of 246 patients with long-term follow-up.

AIMS: The study was designed to evaluate Raf1, Aurora-A/STK15 and E-cadherin (E-CD) protein expression and their prognostic value in patients with pTa/pT1 tumours. MATERIALS AND METHODS: A tissue microarray of 105 pTa, and 141 pT1 tumours was constructed and sections were immunostained with these three antibodies. RESULTS: There were significant associations between Raf1 overexpression and tumour grade (p = 0.03), between Aurora-A overexpression/alterations of E-CD and tumour grade and stage (p < 0.001 and p < 0.001). In multiple Cox regression analysis, moderate/strong expression of E-CD seemed to be an independent factor in predicting slower tumour progression (p = 0.003) and Aurora-A overexpression (p = 0.022) displays an independent value in predicting tumour recurrences. CONCLUSION: Evaluation of E-CD and Aurora-A expressions in tissue of patients with pTa/pT1 UC have been proven to be useful in predicting tumours behavior and Raf1 protein expression seemed to have no potential use in this regard.

Adult↗

PubMed2006

FGFR3 and p53 protein expressions in patients with pTa and pT1 urothelial bladder cancer.

AIMS: This study is designed to evaluate the expression and prognostic value of FGFR3 protein expression in patients with pTa/pT1 tumours and to determine the significance of the combinations of FGFR3 and p53 protein expressions in bladder pathogenesis. MATERIALS AND METHODS: A tissue microarray (TMA) of 107 pTa, and 147 pT1 tumours was constructed. The TMA sections were immunostained with FGFR3 and p53 monoclonal antibodies. RESULTS: There were significant associations between loss of FGFR3 and tumour stage (p<0.001) and grade (p<0.001) and between p53 overexpression and tumour stage and grade (p<0.001 and p<0.001, respectively). There was no association between FGFR3 and p53 proteins (p=0.107). In addition, tumours with FGFR3+/p53- phenotype have slower recurrence rate than other (FGFR3+/p53+, FGFR3-/p53- and FGFR3-/p53+). CONCLUSION: 1-FGFR3 expression is significantly associated with two important prognostic factors; stage and grade. 2-FGFR3 protein expression is not an independent predictive factor for pTa/pT1 tumour recurrence and progression. 3-Tumours with FGFR3+/p53- phenotype seem to have a distinctive pathway in bladder tumorigenesis.

Adult↗

PubMed2006

Pharmacological targeting of catalyzed protein folding: the example of peptide bond cis/trans isomerases.

Peptide bond isomerases are involved in important physiological processes that can be targeted in order to treat neurodegenerative disease, cancer, diseases of the immune system, allergies, and many others. The folding helper enzyme class of Peptidyl-Prolyl-cis/trans Isomerases (PPIases) contains the three enzyme families of cyclophilins (Cyps), FK506 binding proteins (FKBPs), and parvulins (Pars). Although they are structurally unrelated, all PPIases catalyze the cis/trans isomerization of the peptide bond preceding the proline in a polypeptide chain. This process not only plays an important role in de novo protein folding, but also in isomerization of native proteins. The native state isomerization plays a role in physiological processes by influencing receptor ligand recognition or isomer-specific enzyme reaction or by regulating protein function by catalyzing the switch between native isomers differing in their activity, e.g., ion channel regulation. Therefore elucidating PPIase involvement in physiological processes and development of specific inhibitors will be a suitable attempt to design therapies for fatal and deadly diseases.

Animals↗

PubMed2006

Atrial and ventricular myocardium extraction using model-based techniques.

OBJECTIVES: This paper presents an efficient approach for extracting myocardial structures from given atrial and ventricular blood masses to enable non-invasive estimation of electrical excitation in human atria and ventricles. METHODS: Based on given segmented atrial and ventricular blood masses, the approach constructs the myocardial structure directly, in the case that the myocardium can be detected in the volume data, or by using mean model information, in the case that the myocardium cannot be seen in the volume data due to image modalities or artefacts. The approach employs mathematical and gray-value morphology operations. Regulated by the spatial visibility of the myocardial structure in the medical image data especially the atrial myocardium needs to be estimated repeatedly using the a-priori knowledge given by the anatomy. RESULTS: The approach was tested using eight patient data sets. The reconstruction process yielded satisfying results with respect to an efficient generation of a volume conductor model which is essential when trying to implement the estimation of electrical excitation in clinical application. CONCLUSION: The approach yields ventricular and atrial models that qualify for cardiac source imaging in a clinical setting.

Algorithms↗

PubMed2005

Photoswitchable elements within a peptide backbone-ultrafast spectroscopy of thioxylated amides.

A series of thioxo compounds, thioacetamide, N-methylthioacetamide, a cyclic thioxoamide [(S)-5-thioxopyrrolidine-2-carboxylic acid ethyl ester], two thioxylated dipeptides (Ala-Psi[CS-NH]-Ala and Phe-Psi[CS-NH]-Ala) and a thioxylated dodecapeptide (Lys-Glu-Thr-Ala-Ala-Ala-Lys-Phe-Glu-Arg-Gln-His-Psi[CS-NH]-Nle-Asp-Ser-Ser-Thr-Ser-Ala-Ala, or [thioxo-His(12)]-S-peptide; Nle = norleucine) are investigated by ultrafast spectroscopy in the visible and near UV. The different molecules show very similar absorption dynamics featuring a rise of a strong visible absorption band on the subpicosecond and picosecond time scale. The decay of the visible absorption occurs within 150-600 ps. The observations are interpreted by the ultrafast formation of triplet states and their decay on the subnanosecond time scale. Comparison with published IR experiments on N-methylthioacetamide indicates that the cis-trans isomerization around the thioxopeptide bond is terminated within less than 1 ns.

Amides↗

PubMed2005

[Quality assurance in the diagnosis of indoor fungi].

In co-ordination with the Umweltbundesamt Berlin, the Landesgesundheitsamt Baden-Wurttemberg (LGA) initiated external quality assurance in the diagnosis of indoor fungi in autumn 2001. Four of six fungal strains commonly found indoors have to be fully identified (on the genus and species level). There are two distributions per year; the six distributions hitherto carried out resulted in correct identification by 46-89% of laboratories (40-71 participants, total 148). It is clear from the results that repeat participants were more successful. In addition to the pure cultures sent out we offered actual samples (two air samples, one wood material, one sample of house dust, hitherto); 43- 69% of participating laboratories also took part in this facultative investigation of actual samples and 29-62% were successful. Results that differed considerably revealed problems while treating and evaluating actual samples. Therefore, activities in this field should be enhanced. In conclusion, external quality assurance in the diagnosis of indoor fungi is a useful management aid in the maintenance and improvement of laboratory performance.

Air Pollution, Indoor↗

PubMed2005

[Comparison of methods for quantification of MVOC in indoor environments].

For several years now, MVOC have been regarded as indicators for microbial growth in indoor environments. Until now, a direct correlation between the occurrence of microfungi and MVOC could not be shown in scientific investigations. One reason may be that different analytical methods were applied, and moreover they were not validated sufficiently. The present investigation aimed to test the comparability of both methods (Tenax adsorption/thermal desorption; charcoal adsorption/elution). It turned out that with both methods comparable results can be achieved if the technical handling of the calibration is standardized to a wide extent. Thus, highest demands have to be made on quality assurance. Therefore, it is necessary to formulate technical regulations for the quantification of MVOC.

Air Pollutants, Occupational↗

PubMed2005

Lead field computation for the electrocardiographic inverse problem--finite elements versus boundary elements.

In order to be able to solve the inverse problem of electrocardiography, the lead field matrix (transfer matrix) has to be calculated. The two methods applied for computing this matrix, which are compared in this study, are the boundary element method (BEM) and the finite element method (FEM). The performance of both methods using a spherical model was investigated. For a comparable discretization level, the BEM yields smaller relative errors compared to analytical solutions. The BEM needs less computation time, but a larger amount of memory. Inversely calculated myocardial activation times using either the FEM or BEM computed lead field matrices give similar activation time patterns. The FEM, however, is also capable of considering anisotropic conductivities. This property might have an impact for future development, when also individual myocardial fiber architecture can be considered in the inverse formulation.

Anisotropy↗

PubMed2005

[How about the uncertainty in the haplotypes in the population-based KORA studies?].

In the KORA surveys, numerous candidate genes in the context of type 2 diabetes, myocardial infarction, atherosclerosis or obesity are under investigation. Current focus is on genotyping single nucleotide polymorphism (SNPs). Haplotypes are also of increasing interest: haplotypes are combinations of alleles within a certain section of one chromosome. Analysing haplotypes in genetic association studies is often more efficient than studying the SNPs separately. A statistical problem in this context is the reconstruction of the phase: genotyping the SNPs determines the alleles of an individual at one particular locus of the DNA, but does not reveal which allele is located on which one of the two chromosomes. This information is required when talking about haplotypes. There are statistical approaches to identify the most likely two haplotypes of an individual given the genotypes. However, a certain error in prognosis is unavoidable. There are also errors in the genotypes. These errors are assumed to be small for one SNP but can accumulate over the SNPs involved in one haplotype and thus can induce further uncertainty in the haplotype. It is therefore the aim of our project to quantify the uncertainties in the haplotypes particularly for genes investigated in the KORA surveys. We conduct computer simulations based on the haplotypes and their frequencies observed in the KORA individuals and compare the results with simulations based on mathematical modelling of the evolutionary process ("coalescent models"). The uncertainties in the haplotypes have an impact on the search for association between genes and disease: an association may not be detected as the haplotype uncertainty obscures the haplotype frequency differences between cases and controls. It is a further aim of our project to elucidate the extent of this problem and to develop strategies for reducing it.

Adult↗

PubMed2005

Association study of mast cell chymase polymorphisms with atopy.

BACKGROUND: Atopic disorders are the result of complex interactions between genetic and environmental factors. Associations analyses between the promoter polymorphism rs1800875 in the mast cell chymase gene (CMA1) and atopy-related phenotypes have yielded inconsistent results. METHODS: We sequenced the CMA1 locus in 24 unrelated healthy individuals with serum IgE levels <50% percentile and 24 individuals with atopic eczema and serum IgE levels >90% percentile. Seven CMA1 single nucleotide polymorphisms (SNPs) were evaluated for evidence of associations with atopic phenotypes within a large population of German adults (n = 1875). Subjects were phenotyped by standardized questionnaires and interviews, skin prick testing and serum IgE measurements. Genotyping was performed using MALDI-TOF MS (Matrix-Assisted Laser Desorption Ionization-Time of Flight mass spectrometry). RESULTS: Promoter polymorphism rs1800875 was significantly associated with atopic eczema. No associations between any other single SNP and atopic phenotypes could be detected. Haplotype reconstruction revealed four of 128 possible haplotypes reaching estimated frequencies of 3% or more. Two of these haplotypes showed a borderline-significant association with atopic eczema, which did not remain significant after correction for multiple testing. CONCLUSIONS: Results confirm previous observations of a significant association between the CMA1 promoter polymorphism rs1800875 and atopic eczema, but not with serum IgE levels, and support the hypothesis that CMA1 serves as candidate gene for atopic eczema.

Chymases↗

PubMed2005

A signal processing pipeline for noninvasive imaging of ventricular preexcitation.

OBJECTIVES: Noninvasive imaging of the cardiac activation sequence in humans could guide interventional curative treatment of cardiac arrhythmias by catheter ablation. Highly automated signal processing tools are desirable for clinical acceptance. The developed signal processing pipeline reduces user interactions to a minimum, which eases the operation by the staff in the catheter laboratory and increases the reproducibility of the results. METHODS: A previously described R-peak detector was modified for automatic detection of all possible targets (beats) using the information of all leads in the ECG map. A direct method was applied for signal classification. The algorithm was tuned for distinguishing beats with an adenosine induced AV-nodal block from baseline morphology in Wolff-Parkinson-White (WPW) patients. Furthermore, an automatic identification of the QRS-interval borders was implemented. RESULTS: The software was tested with data from eight patients having overt ventricular preexcitation. The R-peak detector captured all QRS-complexes with no false positive detection. The automatic classification was verified by demonstrating adenosine-induced prolongation of ventricular activation with statistical significance (p <0.001) in all patients. This also demonstrates the performance of the automatic detection of QRS-interval borders. Furthermore, all ectopic or paced beats were automatically separated from sinus rhythm. Computed activation maps are shown for one patient localizing the accessory pathway with an accuracy of 1 cm. CONCLUSIONS: The implemented signal processing pipeline is a powerful tool for selecting target beats for noninvasive activation imaging in WPW patients. It robustly identifies and classifies beats. The small beat to beat variations in the automatic QRS-interval detection indicate accurate identification of the time window of interest.

Action Potentials↗

PubMed2005

Computationally efficient noninvasive cardiac activation time imaging.

OBJECTIVE: The computer model-based computation of the cardiac activation sequence in humans has been recently subject of successful clinical validation. This method is of potential interest for guiding ablation therapy of arrhythmogenic substrates. However, computation times of almost an hour are unattractive in a clinical setting. Thus, the objective is the development of a method which performs the computation in a few minutes run time. METHODS: The computationally most expensive part is the product of the lead field matrix with a matrix containing the source pattern on the cardiac surface. The particular biophysical properties of both matrices are used for speeding up this operation by more than an order of magnitude. A conjugate gradient optimizer was developed using C++ for computing the activation map. RESULTS: The software was tested on synthetic and clinical data. The increase in speed with respect to the previously used Fortran 77 implementation was a factor of 30 at a comparable quality of the results. As an additional finding the coupled regularization strategy, originally introduced for saving computation time, also reduced the sensitivity of the method to the choice of the regularization parameter. CONCLUSIONS: As it was shown for data from a WPWpatient the developed software can deliver diagnostically valuable information at a much shorter span of time than current clinical routine methods. Its main application could be the localization of focal arrhythmogenic substrates.

Arrhythmias, Cardiac↗