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Biomedical subjects

N Wilke

Publications and source records attributed to N Wilke.

At least 19 recordsLinked to original sources
PubMed2007

Postmortem determination of concentrations of stress hormones in various body fluids--is there a dependency between adrenaline/noradrenaline quotient, cause of death and agony time?

To find out whether a certain cause of death or a certain length of an agonal period shows specific adrenaline or noradrenaline profiles, heart blood, femoral vein blood, liquor, urine and vitreous humour were taken from corpses (n = 98) at the Medical School Hannover, and noradrenaline and adrenaline were determined using high-performance liquid chromatography (HPLC). Corpses were classified according to the following five categories: short agony, long agony, state after hanging, state after asphyxiation and state after CPR with documented administration of epinephrine. Once results were collected the adrenaline/noradrenaline quotient was determined. It became clear that there were no significant differences regarding the concentration of adrenaline and noradrenaline in the various body fluids in relation to the above-mentioned categories. The means adrenaline/noradrenaline quotients in femoral vein blood were 0.21 +/- 0.29 for hanged persons, 0.38 +/- 0.47 for asphyxiated persons, 0.17 +/- 0.19 for those with short agony and 0.42 +/- 0.43 for those with long agony, significantly below 1 (p < 0.001; p = 0.001; p = 0.003). For condition after CPR we found an adrenaline/noradrenaline quotient of 2.81 +/- 5.8. In liquor the adrenaline/noradrenaline quotients for short agony was 0.17 +/- 0.17, for hanged persons 0.18 +/- 0.19 and for asphyxiated ones 0.30 +/- 0.38, significantly lower than 1 (p < 0.001). In urine the adrenaline/noradrenaline quotients for all categories are lower than 1 (p < 0.001); short agony (0.13 +/- 0.09), long agony (0.21 +/- 0.16), hanged (0.15 +/- 0.16), asphyxiated (0.14 +/- 0.08) and CPR (0.14 +/- 0.06). In vitreous humour the quotients for short agony (0.14 +/- 0.28), long agony (0.13 +/- 0.12), hanged (0.07 +/- 0.09) and asphyxiated (0.09 +/- 0.11) are lower than 1 (p < 0.001). The spread of data for the adrenaline/noradrenaline quotient did not allow for any conclusions about cause of death and length of agony in individual cases.

Asphyxia↗
PubMed2006

Externally applied electric fields on immiscible lipid monolayers: repulsion between condensed domains precludes domain migration.

Lipid and protein molecules anisotropically oriented at a hydrocarbon-aqueous interface configure a dynamic array of self-organized molecular dipoles. Electrostatic fields applied to lipid monolayers have been shown to induce in-plane migration of domains or phase separation in a homogeneous system. In this work, we have investigated the effect of externally applied electrostatic fields on different lipid monolayers exhibiting surface immiscibility. In the monolayers studied, lipids in the condensed state segregate in discontinuous round-shaped domains, with the lipid in the liquid-expanded state forming the continuous phase. The use of fluorescent probes with selective phase partitioning allows analyzing by epifluorescence microscopy the migrations of the domains under the influence of inhomogeneous electric fields applied to the surface. Our observations indicate that a positive potential applied to an electrode placed over the monolayer promotes a repulsion of the domains until a steady state is reached, indicating the presence of a force opposed to the externally applied electric force. The experimental results were modeled by considering that the opposing force is generated by the dipole-dipole repulsion between the domains.

Animals↗
PubMed2006

Biophysics of sphingolipids II. Glycosphingolipids: an assortment of multiple structural information transducers at the membrane surface.

Glycosphingolipids are ubiquitous components of animal cell membranes. They are constituted by the basic structure of ceramide with its hydroxyl group linked to single carbohydrates or oligosaccharide chains of different complexity. The combination of the properties of their hydrocarbon moiety with those derived from the variety and complexity of their hydrophilic polar head groups confers to these lipids an extraordinary capacity for molecular-to-supramolecular transduction across the lateral/transverse planes in biomembranes and beyond. In our opinion, most of the advances made over the last decade on the biophysical behavior of glycosphingolipids can be organized into three related aspects of increasing structural complexity: (1) intrinsic codes: local molecular interactions of glycosphingolipids translated into structural self-organization. (2) Surface topography: projection of molecular shape and miscibility of glycosphingolipids into formation of coexisting membrane domains. (3) Beyond the membrane interface: glycosphingolipid as modulators of structural topology, bilayer recombination and surface biocatalysis.

Biophysical Phenomena↗
PubMed2005

Properties of galactocerebroside layers transferred to glassy carbon electrodes: effect of an applied electric field.

Galactocerebroside films deposited onto glassy carbon electrodes have been previously studied through the electrochemical response of a redox couple present in solution. Those experiments indicated that the film is inhomogeneous and that there are lipid-free places. In this work, we present experimental results indicating that those bare regions are formed when the electrode is introduced in an aqueous solution, and that the size and/or amount of uncovered domains increase when negative potentials are applied to the film. The experimental techniques employed for these findings are epifluorescence microscopy and ellipsometry.

Carbon↗
PubMed2004

[Cricothyroidotomy training on cadavers - experiences in the education of medical students, anaesthetists, and emergency physicians].

OBJECTIVE: Should the technique of surgical cricothyroidotomy be practiced on cadavers and should it be a compulsory part of the teaching curriculum? Is it wise to use a speculum for the insertion of the endotracheal tube? What is the optimum size of the tube? METHODS: A surgical cricothyroidotomy with a speculum was carried out on 30 cadavers from the Institute of Legal Medicine, Medical School Hannover. This took place as part of a official and voluntary course for students of advanced semesters, anaesthetists and emergency doctors with the subjects "cricothyroidotomy, chest drainage and venous cut-down". The surgical cricothyroidotomy without the use of a speculum was carried out on 5 cadavers by two clinicians well practiced in this technique. The elapsed time between skin incision and the insertion of the endotracheal tube was measured on all five subjects. After the course the participants were asked if they were able to carry out a cricothyroidotomy in an emergency. They were also asked whether this course should be a compulsory part of their curriculum and whether practical sessions should take place. During autopsies at the Institute of Legal Medicine the length of the ligamentum conicum was measured on 40 corpses with reclined and non-reclined heads. RESULTS: The average time of storage of the cadavers was 4.2 days +/- 1.9 days. The cricothyroidotomy was possible on all 35 cadavers. In one case (3,3 %) the result was a complete rupture of the cricoid cartilage. In 5 cases (16.7 %) the horizontal incision was torn due to prising with the speculum. Difficult situations always occured when the skin incision was not exactly in the midline. The average time to place the endotracheal tube into the trachea by the surgical procedure of cricothyroidotomy was 22.4 seconds +/- 3.1 seconds (minimum 18 seconds, maximum 26 seconds). 10 % of the medical students and 50 % of the anaesthetists and emergency doctors felt they would be prepared to carry out a cricothyroidotomy in an emergency. 90 % of the students and respectively 80 % of the anaesthetists and emergency doctors stated that they would like to practice the technique on a cadaver again. Almost all participants were of the opinion that the course should be integrated as a compulsory course in a future educational curriculum. The average distance between the thyroid cartilage and the cricoid cartilage was 9.5 mm +/- 1.9 mm with non-reclined head (minimum 6 mm, maximum 14 mm) and 11.9 mm +/- 2.5 mm with reclined head (minimum 7 mm, maximum 18 mm). The average difference of distances was 2.4 mm +/- 1.2 mm (minimum 1 mm, maximum 6 mm) in reclined and non-reclined heads. CONCLUSIONS: In our opinion it is highly recommended that the technique of cricothyroidotomy should be practiced on cadavers and that the course should become a compulsory part in a future educational curriculum. In addition the incision of the ligamentum conicum using dilators or a speculum is not to be recommended from the point of view of this study. The tracheal tube used in this study (reinforced wire tube, ID 6.0) was best suited for surgical cricothyroidotomy.

Anesthesia↗
PubMed2001

Echo-planar magnetic resonance myocardial perfusion imaging: parametric map analysis and comparison with thallium SPECT.

Magnetic resonance (MR) perfusion FLASH imaging has been used for assessing coronary artery disease (CAD). Echo-planar MR techniques have advantages in speed and in making MR perfusion imaging results more clinically accessible through parametric maps, but have not been previously assessed. We implemented a spin-echo, echo-planar MR technique and applied it at rest and during adenosine stress in 26 patients with CAD and abnormal thallium single-photon-emission computed tomography (SPECT), and analyzed the results by using a newly developed parametric map analysis of time to peak, peak intensity, and slope of contrast washin. The results were compared with the results of conventional visual analysis of the perfusion cine series. For detecting abnormal coronary territories, MR and SPECT were comparable for sensitivity, specificity, and accuracy (thallium, 70%, 78%, and 73%; MR, 79% 83%, and 80%; P = NS). There was good agreement between thallium and MR during stress (kappa = 0.49), but defects were larger by MR (2.4 vs. 3.1 segments for slope; P < 0.01). Additional segments were detected at rest by MR (58 for slope vs. 25 for thallium), which correlated with areas that became abnormal with stress in the thallium (sensitivity, 100%; specificity, 63%). The parametric maps were easier and faster to interpret than review of the original first-pass series of images (chi2 = 10.8; P < 0.04). The diagnostic performance of echo-planar perfusion MR and SPECT was similar, and combining the results with parametric mapping was useful for interpretation and considerably improved data display for clinical interpretation. MR, however, was faster and yielded images of higher resolution with no radiation burden. In multislice mode, these new MR techniques may have clinical value.

Aged↗
PubMed2001

Amplification of growth regulatory genes in intraductal breast cancer is associated with higher nuclear grade but not with the progression to invasiveness.

Ductal carcinoma in situ (DCIS), as an identifiable progenitor lesion of invasive breast cancer, represents a morphologically, biologically, and prognostically heterogeneous disease. It is not clear which molecular mechanisms are involved in progression to infiltrative growth. In this study, 83 DCIS classified according to the Van Nuys grading scheme were examined for amplification of growth regulatory genes that have been found to be amplified in invasive breast cancer (c-erbB2, topoisomerase IIalpha, c-myc, and cyclinD1 genes). Exact quantification of gene amplification was enabled by a combination of laser microdissection of paraffin-embedded tissue with real-time PCR. In DCIS, gene amplifications of all tested genes were found. The most frequently amplified gene was c-erbB2 found in 21 of 83 (25%) cases. Amplification of the other genes under investigation was observed in 4% to 6% of cases, high-grade DCIS being predominantly affected. High-grade DCIS differed significantly from low- and intermediate-grade DCIS in frequency and level of c-erbB2 amplification. In addition, high-grade DCIS revealed an accumulation of genetic aberrations. Amplification status in pure in situ lesions did not differ from intraductal carcinoma with an infiltrative component, indicating that although associated with a higher nuclear grade gene amplification might not represent an independent prognostic marker of disease progression.

Breast Neoplasms↗
PubMed2000

Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression.

Adaptive changes in gene expression are thought to contribute to dependence, addiction and other behavioral responses to chronic ethanol abuse. DNA array studies provide a nonbiased detection of networks of gene expression changes, allowing insight into functional consequences and mechanisms of such molecular responses. We used oligonucleotide arrays to study nearly 6000 genes in human SH-SY5Y neuroblastoma cells exposed to chronic ethanol. A set of 42 genes had consistently increased or decreased mRNA abundance after 3 days of ethanol treatment. Groups of genes related to norepinephrine production, glutathione metabolism, and protection against apoptosis were identified. Genes involved in catecholamine metabolism are of special interest because of the role of this pathway in mediating ethanol withdrawal symptoms (physical dependence). Ethanol treatment elevated dopamine beta-hydroxylase (DBH, EC 1.14.17.1) mRNA and protein levels and increased releasable norepinephrine in SH-SY5Y cultures. Acute ethanol also increased DBH mRNA levels in mouse adrenal gland, suggesting in vivo functional consequences for ethanol regulation of DBH. In SH-SY5Y cells, ethanol also decreased mRNA and secreted protein levels for monocyte chemotactic protein 1, an effect that could contribute to the protective role of moderate ethanol consumption in atherosclerotic vascular disease. Finally, we identified a subset of genes similarly regulated by both ethanol and dibutyryl-cAMP treatment in SH-SY5Y cells. This suggests that ethanol and cAMP signaling share mechanistic features in regulating a subset of ethanol-responsive genes. Our findings offer new insights regarding possible molecular mechanisms underlying behavioral responses or medical consequences of ethanol consumption and alcoholism.

Animals↗
PubMed2000

Detection of gene amplification in intraductal and infiltrating breast cancer by laser-assisted microdissection and quantitative real-time PCR.

Gene amplification is one essential mechanism leading to oncogene activation which is supposed to play a major role in the pathogenesis of invasive breast cancer. However, using standard methodologies the detection of gene amplifications has been limited especially in small-sized lesions, like pre-invasive precursor lesions. The combination of two novel technologies, laser-based microdissection and quantitative real-time PCR, facilitates the detection of low-level amplifications in morphologically defined lesions. As a model system we investigated in situ breast cancer (ductal carcinoma in situ, DCIS) classified according to the morphology-based Van Nuys grading system for amplification of growth-regulatory genes. In this study 83 formalin-fixed, paraffin-embedded archival DCIS specimens were examined after laser-based microdissection by quantitative real-time PCR using the TaqMan detection system for amplification of the c-erbB2, topoisomerase IIalpha, c-myc and cyclinD1 gene. In a subset of 17 DCIS with adjacent infiltrating tumour components we compared intraductal and invasive tumour components in parallel for differences in amplification status. The combination of these new techniques represents an excellent tool to gain new insights into carcinogenesis by analyzing genetic alterations in morphologically identified heterogeneous lesions in breast cancer progression within the very same specimen or even tissue slide.

Antigens, Neoplasm↗
PubMed2000

Magnetic resonance imaging of myocardial perfusion in single-vessel coronary artery disease: implications for transmural assessment of myocardial perfusion.

The purpose of the study was to investigate the potential of magnetic resonance imaging (MRI) to assess transmural differences in myocardial perfusion. Contrast-enhanced MRI was performed at rest and during hyperemia in a dog model and in 22 patients with single-vessel coronary artery disease. From MR signal intensity-versus-time curves, three perfusion parameters were derived: maximum myocardial contrast enhancement (MCE), slope, and inverse mean transit time (1/MTT). In dogs, MCE correlated well (r = 0.87, p < 0.00001) with microsphere-assessed myocardial blood flow. In the patients, the subendocardial MCE decreased during hyperemia (0.89 +/- 0.18 vs. 0.74 +/- 0.15, p < 0.003) and was lower in subendocardium than in subepicardium (0.74 +/- 0.15 vs. 0.84 +/- 0.21, p < 0.02). Parameters slope and 1/MTT paralleled MCE. Contrast-enhanced MRI reflects the transmural redistribution of myocardial perfusion during hyperemia. Perfusion abnormalities can be identified most distinctly in subendocardial myocardium.

Adult↗
PubMed2000

Characterization of promoter elements mediating ethanol regulation of hsc70 gene transcription.

Chronic exposure to ethanol increases transcription of the molecular chaperone Hsc70 in NG108-15 neuroblastoma X glioma cells. This and other ethanol-induced changes in gene expression may contribute to central nervous system tolerance and dependence in alcoholics. Here, we characterized sequences in the hsc70 promoter that are required for ethanol-induced transcriptional regulation. Deletion analysis of the hsc70 promoter showed that the 74-base pair region proximal to the transcription start site was sufficient for ethanol responsiveness. Point mutation or deletion of a consensus Spl-binding site at -67/-61 base pairs greatly reduced the induction by ethanol. Hsc70 promoter constructs with diminished ethanol responsiveness in NG108-15 cells similarly had decreased transcriptional activation by exogenous Sp1 in Drosophila SL2 cells. Some artificial promoter constructs containing multiple Sp1 sites were highly responsive to ethanol, but others were not, suggesting that the organization of the proximal promoter region was an additional factor that affected the ethanol response. Gel mobility shift analysis confirmed that an Sp1-like protein bound to the -67/-61 consensus Sp1 site. However ethanol exposure did not alter Sp1 DNA-binding activity. Together, our findings show that ethanol induction of Hsc70 requires a functional Sp1-binding site. Additional proximal promoter elements may also play a role in determining whether an Sp1-containing promoter will respond to ethanol.

Animals↗
PubMed1999

Myocardial oxygenation during high work states in hearts with postinfarction remodeling.

BACKGROUND: Postinfarction left ventricular remodeling (LVR) is associated with reductions in myocardial high-energy phosphate (HEP) levels, which are more severe in animals that develop overt congestive heart failure (CHF). During high work states, further HEP loss occurs, which suggests demand-induced ischemia. This study tested the hypothesis that inadequate myocyte oxygen availability is the basis for these HEP abnormalities. METHODS AND RESULTS: Myocardial infarction was produced by left circumflex coronary artery ligation in swine. Studies were performed in 20 normal animals, 14 animals with compensated LVR, and 9 animals with CHF. Phosphocreatine (PCr)/ATP was determined with 31P NMR and deoxymyoglobin (Mb-delta) with 1H NMR in myocardium remote from the infarct. Basal PCr/ATP tended to be decreased in postinfarct hearts, and this was significant in animals with CHF. Infusion of dobutamine (20 microg x kg-1 x min-1 IV) caused doubling of the rate-pressure product in both normal and LVR hearts and resulted in comparable significant decreases of PCr/ATP in both groups. This decrease in PCr/ATP was not associated with detectable Mb-delta. In CHF hearts, rate-pressure product increased only 40% in response to dobutamine; this attenuated response also was not associated with detectable Mb-delta. CONCLUSIONS: Thus, the decrease of PCr/ATP during dobutamine infusion is not the result of insufficient myocardial oxygen availability. Furthermore, in CHF hearts, the low basal PCr/ATP and the attenuated response to dobutamine occurred in the absence of myocardial hypoxia, indicating that the HEP and contractile abnormalities were not the result of insufficient oxygen availability.

Adenosine Triphosphate↗
PubMed1999

Myocardial viability.

This article reviews various means to assess myocardial viability by imaging, and provides recommendations for current clinical practice. This article also discusses future directions in assessing myocardial viability.

Contrast Media↗
PubMed1999

The seismocardiogram as magnetic-field-compatible alternative to the electrocardiogram for cardiac stress monitoring.

Seismocardiography (SCG) is a methodology derived from the field of seismology to measure non-invasively compression waves generated by myocardial motion. The use of SCG is proposed here as method to monitor cardiac function during stress testing and magnetic resonance imaging (MRI). It is shown that recording of the seismocardiogram in subjects undergoing an MRI study is not compromised by flow-induced electrical voltages that can severely distort the electrocardiogram. Electromagnetic compatibility of the seismocardiograph device with the MRI scanner hardware was tested. Experiments in an animal model proved that changes in the SCG waveform during different levels of LAD stenosis correlate with the changes seen in LV function with cine MRI. The changes in the SCG waveform characteristic for the onset of ischemia were observed almost immediately after the creation of a flow-limiting stenosis. This novel application of SCG to monitor changes in peak acceleration from cardiac blood flow and wall motion may represent a solution to the long-standing and important problem of monitoring patients for signs of myocardial ischemia during MRI.

Coronary Circulation↗
PubMed1999

Direct comparison of an intravascular and an extracellular contrast agent for quantification of myocardial perfusion. Cardiac MRI Group.

A direct comparison of extracellular and intravascular contrast agents for the assessment of myocardial perfusion was carried out in a porcine model (N = 5) with a flow-limiting occluder on the left anterior descending coronary artery. Rapid imaging during the first pass of an extracellular or intravascular contrast agent with a saturation-recovery-prepared TurboFLASH sequence showed comparable peak contrast-to-noise enhancements in myocardial tissue regions with flows averaging 1.1 +/- 0.2 at baseline to 4.8 +/- 0.6 ml/min/g during hyperemia. The coefficient of variation between the MR estimates of blood flow with Gadomer-17 and the microsphere blood flow measurements was 11 +/- 11%, while the corresponding co-efficient of variation for blood flow estimates with the extracellular CA was 23 +/- 11%. Blood volume differences between rest and hyperemia observed with the intravascular tracer were significant (Vvasc(rest) = 0.078 +/- 0.013 ml/g, versus Vvasc(hyperemia) = 0.102 +/- 0.019 ml/g; p < 0.05). The effects of water exchange were minimized through the choice of pulse sequence parameters to provide blood volume estimates consistent with the changes expected between rest and hyperemia. This study represents the first application of multiple indicators in first pass imaging studies for the assessment of myocardial perfusion. The use of an intravascular instead of an extracellular contrast agent allows a reduction of the degrees of freedom for modeling tissue residue curves and results in improved accuracy of blood flow estimates.

Animals↗
PubMed1998

Assessing myocardial perfusion in coronary artery disease with magnetic resonance first-pass imaging.

MRFP perfusion imaging can now be used clinically on most MR scanner systems (1.0 to 1.5 T). The current experimental data demonstrate that MRFP imaging allows the quantitative assessment of myocardial blood flow changes and accurate measurements of collateral flow, including changes in the collateral dependent zones. Certain protocols, however, as outlined here have to be followed to obtain all the possible diagnostic information. Based on the current data on MRFP imaging, it is realistic to anticipate that MRFP imaging in combination with cine or tagging MR imaging will provide clinicians with better methods to distinguish stunned and hibernating, from nonviable myocardium and obtain better outcome data. Dedicated MR scanners are now being designed to meet the needs for MR imaging of patients with coronary artery disease. These scanners, small in size and with better patient access, make placement near the coronary care unit or catheterization laboratory feasible. This is a major step toward enhancing the utility of this new technique by providing the necessary infrastructure for scanning large numbers of patients. The main obstacle to wider use of these new diagnostic tools to assess perfusion is the lack of a large clinical database because there have not yet been major multicenter trials. With the development of novel intravascular contrast agents, however, larger trials are planned that should provide the clinical data mandatory for full integration of MRFP imaging into clinical practice. In particular, the development of dedicated and user-friendly perfusion analysis software will create the means to evaluate MR perfusion data accurately in large patient populations. These studies need to be conducted in a collaborative fashion by cardiologists, heart surgeons, and radiologists to be fully accepted by health care providers in an increasingly cost-averse and competitive health care environment.

Coronary Disease↗