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Biomedical subjects

H Seidel

Publications and source records attributed to H Seidel.

At least 19 recordsLinked to original sources

High leucovorin doses during high-dose methotrexate treatment may reduce the cure rate in childhood acute lymphoblastic leukemia.

We explored the relationship between time to relapse and different exposure variables (serum methotrexate (S-MTX) 23, 36 and 42 h after start of administration, MTX elimination time and leucovorin (LV) dose) during high-dose MTX (HDM) treatment of 445 children with acute lymphoblastic leukemia. MTX was infused at 5 g/m2 (non-high risk) or 8 g/m2 (high risk) over 24 h, 2-9 times per patient. LV rescue dose was adjusted according to the S-MTX concentration. Time from end of the last HDM to relapse was analyzed by Cox regression analysis with the logarithms of S-MTX and LV dose as exposures. The combined results from all risk groups suggest that high LV dose is related to higher risk for relapse. Doubling of the LV dose increased the relapse risk by 22% (95% confidence interval 1-49%, P = 0.037). High LV doses correlated with high MTX levels at 23, 36 and 42 h and longer elimination time. The results suggest that high doses of LV increase the risk for relapse despite the fact that they were correlated with high MTX levels and longer MTX elimination time. The choice of MTX and LV doses may be regarded as an intricate balance between effect and counter-effect.

Antimetabolites, Antineoplastic↗

Bioremediation process for sediments contaminated by heavy metals: feasibility study on a pilot scale.

The core stages of a sediment remediation process--the conditioning of dredged sludge by plants and the solid-bed leaching of heavy metals using microbially produced sulfuric acid--were tested on a pilot scale using a highly polluted river sediment. Conditioning was performed in 50 m3 basins at sludge depths of 1.8 m. During one vegetation period the anoxic sludge turned into a soil-like oxic material and became very permeable to water. Reed canary grass (Phalaris arundinacea) was found to be best suited for conditioning. Bioleaching was carried out in an aerated solid-bed reactor of 2000 L working volume using oxic soil-like sediment supplemented with 2% sulfur. When applying conditioned sediment, the oxidation of easily degradable organic matter by heterotrophic microbes increased the temperature up to 50 degrees C in the early leaching phase, which in turn temporarily inhibited the sulfur-oxidizing bacteria. Nevertheless, most of the metal contaminants were leached within 21 days. Zn, Cd, Mn, Co, and Ni were removed by 61-81%, Cu was reduced by 21%, while Cr and Pb were nearly immobile. A cost-effectiveness assessment of the remediation process indicates it to be a suitable treatment for restoring polluted sediments for beneficial use.

Biodegradation, Environmental↗

Fusarial toxins and their role in animal diseases.

Fusarial toxins are toxic metabolites produced mostly by toxigenic micromycetes of genus Fusarium. Dominant mycotoxins of this group include trichothecenes, moniliformin, zearalenone, and fumonisins. Recently, special attention has been paid to these toxins because of their harmful effects on both animals and humans. On the basis of the available literature, we review here the characteristics of major fusarial mycotoxins with an emphasis on their toxic effects on animals. The most important fusarial mycotoxins, their sources, and their pathology including clinical signs, necropsy findings, as well as changes in haematological, biochemical, and immunological indices, are addressed.

Animal Diseases↗

The effect of zearalenone on some enzymatic parameters in rabbits.

The effects of low (10 microg/kg b.w.) and high (100 microg/kg b.w.) doses of mycotoxin-zearalenone on selected blood serum enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), and total lactatedehydrogenase (LD) of rabbits were studied. The toxin was administered orally for 14 days. In the experimental group E(1) (10 microg/kg b.w.), a significant increase in ALP activity was observed at 168 and 336 h during the experiment. In the 100 microg zearalenone sera (group E(2)), significant increases in activities of AST, ALT, ALP, GGT, and LD were observed at 168 and 336 h, indicating possible liver toxicity due to chronic effects of the toxin.

Alanine Transaminase↗

Modelling the response of the spinal system to whole-body vibration and repeated shock.

Back problems are very common and contribute to discomfort and days off work. Some back disorders are attributed to inappropriate loading of the spine that can be combined with other influential factors such a body posture, whole-body vibration and shock. Many models have been developed to predict the forces in the spine associated with vibration and shock. However, the problem is complex due to the incompletely understood dynamic responses of the body, the influence of many variables and the effect of muscle forces. This paper summarises the current state of knowledge relevant to the prediction of forces in the spine associated with whole-body vibration and shock. The paper also introduces presentations at a workshop on the modelling of spinal loads associated with vibration and shock held in Berlin in October 1999. RelevanceBiodynamic models may be used to estimate risks of injury or disease and optimise environments so as to minimise risks. However, the development of useful models requires an understanding of the complex interaction between mechanical forces and the living body. The application of models requires knowledge of their accuracy and limitations.

Humans↗

Examination of the myoelectric activity of back muscles during random vibration--methodical approach and first results.

OBJECTIVE: To elaborate methods for an elimination of artefacts and the analysis of the relationship between random whole-body vibration and electromyographic responses of back muscles. DESIGN: A procedure involving wavelets and digital filtering has been used for the removal of artefacts from the electromyogram during whole-body vibration. BACKGROUND: Back muscle forces contribute essentially to the whole-body vibration-induced spinal load. The electromyogram can help to estimate these forces during whole-body vibration. METHODS: 38 subjects were exposed to identical random low-frequency whole-body vibration. Artefacts caused by the electrocardiogram in the electromyogram were identified by appropriate wavelets and eliminated in the time-domain. After averaging the individual high-pass filtered and rectified undistorted electromyograms across subjects, the transfer function from seat acceleration to the average electromyogram was determined and used for the prediction of the electromyogram. RESULTS: A sufficient procedure involving wavelets and digital filtering has been elaborated for the removal of artefacts from the electromyogram of back muscles during whole-body vibration. A systematic relationship between random vibration and back muscle-response was obtained and described. The transfer function suggests two different reflex-mechanisms - one elicited below, the other above 4 Hz. CONCLUSIONS: The approach of analysing and predicting the muscle-response to random vibration by using the transfer function seems to be promising and could be a valuable tool for the future calculation of muscle forces as an input to active models. RELEVANCE: The knowledge of the extent and timing of the back muscle-response to random whole-body vibration is relevant for an improved evaluation of whole-body vibration with respect to health.

Adult↗

Intradiscal pressure together with anthropometric data--a data set for the validation of models.

OBJECTIVE: To provide a database of intradiscal pressure measurements together with anthropometric data as basis for the validation of models that predict spinal loads. DESIGN: Intradiscal pressure was measured in a non-degenerated L4-5 disc of a volunteer. The anthropometric characteristics of this subject were extensively determined. BACKGROUND: Since it is usually impossible to quantify the load in the spine directly, it is predicted by various biomechanical models. However, they often cannot be validated because of the few in vivo data and missing anthropometric characteristics pertaining to them. METHODS: A pressure transducer (diameter 1.5 mm) was implanted in the nucleus pulposus of a non-degenerated L4-5 disc of a volunteer. Pressure was determined during exercises while standing, lifting activities, sitting unsupported on a stool or an ergonomic sitting ball, sitting in different postures and others. The anthropometric characteristics were determined using different tools. RESULTS: Pressure values: relaxed standing 0.5 MPa; standing flexed forward 1.1 MPa; standing extended backward 0.6 MPa; sitting unsupported 0.46 MPa; maximum values during lateral bending 0.6 MPa, during axial rotation 0.7 MPa, lifting a 20 kg weight with a round flexed back 2.3 MPa, with flexed knees 1.7 MPa, close to the body 1.1 MPa; sitting unsupported relaxed 0.45 MPa, actively straightening the back 0.55 MPa, with flexion 0.9 MPa; non-chalant sitting 0.3 MPa and others. Anthropometric characteristics with emphasis on data for the trunk are provided in tables.Conclusions. Intradiscal pressure depends on the kind of preceding activity, posture, external loads and muscle activity. RELEVANCE: The data set can be used to verify a biomechanical model adjusted to the individual characteristics by a comparison of measured and predicted intradiscal pressures.

Anthropometry↗

Application of finite-element models to predict forces acting on the lumbar spine during whole-body vibration.

OBJECTIVE: To predict forces acting on the spine during whole-body vibration for a variety of boundary conditions - body mass, height and posture.Design. Representative anthropometric data and models for an upright, relaxed and bent forward sitting posture were used to derive model families with 30 variants of a finite-element model. BACKGROUND: A given exposure to whole-body vibration can cause a variable health risk depending on the concomitant conditions. The latter could contribute to the considerable uncertainty of the current evaluation of whole-body vibration. METHODS: Plane symmetric linear finite-element models were used for the prediction of static and dynamic compression and shear forces acting on the lumbar discs during whole-body vibration. Transfer functions from seat acceleration to forces were determined. RESULTS: A bent forward posture augments essentially the compressive and shear stress, predicted for erect and relaxed sitting postures. The normal variation of body mass and height causes a considerable variation of static internal shear stress, but a minor variation of compressive pressure. The dynamic internal stress varies nearly proportionally to the body mass. The transfer functions from seat acceleration to compressive force depend significantly on the posture. CONCLUSIONS: The variability of the spinal loads for a given whole-body vibration and associated with a normal range of several biological factors suggests a ratio between the minimum and maximum internal loads of about 1:2. RELEVANCE: Finite-element models can be used to compare the health risk arising from different whole-body vibration exposures and individual conditions. These results help to prevent work-related disorders of the lumbar spine.

Adult↗

Transfer functions as a basis for the verification of models--variability and restraints.

OBJECTIVE: The seat-to-head transfer function of the human body reflects the biodynamic response. Based on measured data, biodynamic models have been proposed to reflect this response. They must satisfy usually the international published mean values of the seat-to-head transfer function. The question arises to what extent mean values reflect individual pattern of biodynamics. METHODS: An experimental study was performed with 39 male subjects sitting on a hard seat without back rest and with supported feet. They were exposed to random whole-body vibration at three intensities with a relaxed and an erect posture. The accelerations in the z-direction were measured at the seat and head. The seat-to-head transfer functions with the associated coherence functions were calculated. RESULTS: The biodynamic response characterised by the maximum of the seat-to-head transmissibility and the frequency of its occurrence is influenced by the posture of the subjects in a dominant way and shows an individual variability of considerable extent. The mean responses suggest a missing effect of vibration intensity, but individually different effects of the intensity were found. Repeated measurements confirmed this result. CONCLUSIONS: The application of a model validated by the comparison with mean values of the transmissibility could cause misleading conclusions, if it is used for the prediction of individual spinal loads. Models prepared for the calculation of individual loads should be validated by a mean individual transmissibility derived from repeated measurements. RELEVANCE: The results illustrate the loss of information by averaging individual transfer functions and the consequence of a limited validity and applicability in occupational health, ergonomics, and design.

Acceleration↗

Automated image analysis for array hybridization experiments.

MOTIVATION: Image analysis is a major part of data evaluation for array hybridization experiments in molecular biology. The program presented here is designed to analyze automatically images from hybridization experiments with various arrangements: different kinds of probes (oligonucleotides or complex probes), different supports (nylon filters or glass slides), different labeling of probes (radioactively or fluorescently). The program is currently applied to oligonucleotide fingerprinting projects and complex hybridizations. The only precondition for the use of the program is that the targets are arrayed in a grid, which can be approximately transformed to an orthogonal equidistant grid by a projective mapping. RESULTS: We demonstrate that our program can cope with the following problems: global distortion of the grid, missing of grid nodes, local deviation of the spot from its specified grid position. This is checked by different quality measures. The image analysis of oligonucleotide fingerprint experiments on an entire genetic library is used, in clustering procedures, to group related clones together. The results show that the program yields automatically generated high quality input data for follow up analysis such as clustering procedures. AVAILABILITY: The executable files will be available upon request for academics.

Algorithms↗

Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans.

Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.

Adrenergic beta-Antagonists↗

The effect of arterial blood sampling sites on blood gases and acid-base balance parameters in calves.

In 21 healthy calves, 1-6 months old, the interrelationship and comparability of acid-base balance variables (pH, HCO3-, BE) and blood gases (pCO2, pO2, and sat-O2) were evaluated in arterial blood collected from a larger, centrally localised (the a. axillaris) and a smaller peripheral artery (the a. auricularis caudalis). Sampling was done by direct puncture of the vessels without local anaesthesia. Except for blood pH, significant differences were observed in the average values of pCO2, pO2, HCO3-, sat-O2 (P < 0.001), and BE (P < 0.05). Analyses of blood from the a. axillaris showed higher pH, pO2, and sat-O2 values, and lower pCO2, HCO3-, and BE values compared with that from the a. auricularis caudalis. Despite statistically significant differences between some variables, in all indices high and significant correlation relationships were recorded (R = 0.928-0.961; P < 0.001). Therefore, from the biological and clinical point of view, these differences are unimportant and the presented method of peripheral arterial blood sampling can be considered suitable for evaluating blood gases and acid-base status.

Acid-Base Equilibrium↗

Influence of intoxication with organophosphates on rumen bacteria and rumen protozoa and protective effect of clinoptilolite-rich zeolite on bacterial and protozoan concentration in rumen.

The effect of O-ethyl-S-(2-diisopropylaminoethyl) methylthiophosphonate on rumen bacteria and rumen protozoa was investigated in sheep (after premedication with clinoptilolite-rich zeolite and without that premedication). In control animals a decrease in the total concentration of rumen protozoa was observed 3-7 d after intoxication (particularly in small and large ones). In clinoptilolite-rich-zeolite-treated animals only a slight decrease in protozoan numbers occurred during the first hours after the intoxication. Similarly, in every category of rumen bacteria marked differences between the groups were recorded, particularly in concentration of lipolytic bacteria. The results suggest some protective effect of clinoptilolite-rich zeolite for rumen microbiota against the organophosphate poison.

Animals↗

Bioleaching of heavy metal-contaminated sediments by indigenous Thiobacillus spp: metal solubilization and sulfur oxidation in the presence of surfactants.

The efficiency of surfactant application to improve or inhibit metal solubilization and sulfur oxidation kinetics during the bioleaching of heavy metal-contaminated sediments was studied in suspension-leaching experiments. The river sediment used contained large amounts of fine particles and organic matter. Three types of surfactants were tested: sodium dodecylsulfate (SDS), a C(12/14)-alkanolethoxylate (Präwozell F1214/5N), and a wettable sulfur (Netzschwefel 80 WP). Adding 10 mmol SDS/l led to transient inhibition of acidification, metal solubilization and sulfur oxidation. Inhibiting bioleaching for just 14 days required about ten times more SDS than the amount used for mine waste mitigation. The use of Präwozell resulted in poor inhibition; and using of wettable sulfur did not improve leaching efficiency. The bulk of these surfactants was sorbed onto the solid particles immediately on application, while the remainder in the aqueous phase disappeared within a few days.

Environmental Pollutants↗

Variability in methotrexate serum and cerebrospinal fluid pharmacokinetics in children with acute lymphocytic leukemia: relation to assay methodology and physiological variables.

Methotrexate (MTX) steady state concentrations were evaluated in 42 children who had received high-dose infusions (6-8 g/m2) for acute lymphocytic leukemia. Concentrations in serum and cerebrospinal fluid (CSF) measured by immunoassay were found to be highly variable. Reanalysis by a reference high-pressure liquid chromatography method ruled out analytical factors as a source of this variability. The correlation coefficient between the analytical methods was 0.77 for the serum data and 0.88 for the CSF data. The variability of serum and CSF concentrations was higher in younger patients (serum; P = 0.05 and CSF; P = 0.18), and the CSF concentration decreased with decreasing age and in later courses. Body surface area, body mass index, weight, and gender were not significantly related to MTX variability. We conclude that the pronounced pharmacokinetic variability seen during MTX infusions remains largely unexplained.

Antimetabolites, Antineoplastic↗