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Biomedical subjects

G Rau

Publications and source records attributed to G Rau.

At least 19 recordsLinked to original sources

[Cardiac involvement in the hypereosinophilia syndrome. the importance of echocardiography in the follow-up].

A 51-year-old man and a 39-year-old woman with the hypereosinophilic syndrome developed a restrictive cardiomyopathy in the course of cardiac involvement. Echocardiography demonstrated typical thrombotic obliteration at the apex of both ventricles. Doppler ultrasound showed changes of impaired filling in both ventricles. Glucocorticoid treatment (prednisone, 85 mg daily) had to be drastically reduced (to 10 mg daily) in case 1, because of the development of a Cushing syndrome. The man died 18 months later of advanced heart failure. In the woman the eosinophil count fell after prednisone administration (1 mg/kg daily) and there was no recurrence. But heart failure due to impaired diastolic filling has persisted so that orthotopic cardiac transplantation has been planned.

Adult

Knowledge-based decision support for patient monitoring in cardioanesthesia.

An approach to generating 'intelligent alarms' is presented that aggregates many information items, i.e. measured vital signs, recent medications, etc., into state variables that more directly reflect the patient's physiological state. Based on these state variables the described decision support system AES-2 also provides therapy recommendations. The assessment of the state variables and the generation of therapeutic advice follow a knowledge-based approach. Aspects of uncertainty, e.g. a gradual transition between 'normal' and 'below normal', are considered applying a fuzzy set approach. Special emphasis is laid on the ergonomic design of the user interface, which is based on color graphics and finger touch input on the screen. Certain simulation techniques considerably support the design process of AES-2 as is demonstrated with a typical example from cardioanesthesia.

Anesthesia

CAD-design, stress analysis and in vitro evaluation of three leaflet blood-pump valves.

The computer-supported development of valves for cardiac-assist devices or artificial hearts is shown in relation to plastic technology. A CAD-system is used for the design development, whereas the dimensioning of the critical and highly stressed membranes is examined by FEM-analyses. Economic manufacture is permitted by the combined thermoforming-dip moulding technique; the blood-side components are made from biocompatible polyurethane to minimize blood damage. The first long-term results in the test set-up are compared to the FEM results.

Equipment Design

[Cryopreservation of human erythrocytes with hydroxyethyl starch (HES)--Part 1: The procedure].

Although the efficacy of hydroxyethyl starch (HES) as a cryoprotectant for human red blood cells (HRBC) was demonstrated in 1967, no clinical application has evolved so far. In contrast to glycerol, which has been widely used for this purpose, HES offers the advantage of being nontoxic if administered intravenously. Being also a plasma substitute, HES in combination with HRBC can normalize blood volume as well as oxygen transport in the case of extended blood loss. This may be of importance for autologous blood supply for elective surgery and for disaster treatment plans. For a volume of 40 ml, the optimal combination of important parameters [e.g. cooling rate 200-250 K/min, warming rate 400 K/min, hematocrit 40%, HES concentration 12% (w/w)] has led to a survival after thawing in terms of saline stability of 93 +/- 1% (n = 10). Additionally, the age prior to cryopreservation (0-3 days) had an influence on postthaw survival, but at least 90% survival can be obtained if the samples are washed 3-5 times before freezing.

Adult

[Cryopreservation of human erythrocytes with hydroxyethyl starch (HES)--Part 2: Analysis of survival].

Red blood cells (RBC) were obtained from 5 whole blood units by centrifugation and were purified using a simple washing procedure. Hematocrit and HES concentration in the 108-ml samples to be frozen were adjusted to 40% (v/v) and 12% (w/w), respectively. Cooling was performed by submerging into liquid nitrogen using containers to generate a flat sample geometry (3 mm thickness). After thawing in a shaking water bath, HES and free hemoglobin were removed in a simple washing step. To investigate the influence of the resuspension medium, the RBC were transferred into freshly drawn autologous plasma and into Locke's solution. Survival after thawing in terms of saline stability reached 86.3 +/- 2.3%. The cryopreservation procedure caused no major changes with regard to osmotic fragility, 2,3-DPG or intracellular Na+ and K+. ATP was reduced by 16%, but this had completely recovered after 3 h resuspension in autologous plasma. Some morphological changes present after thawing (e.g. stomatocytes, echinocytes) also recovered after 1.5 h. In conclusion, those RBC which survived the preservation process can be considered to be fully viable with regard to the parameters investigated.

Adult

[Cryopreservation of erythrocytes with hydroxyethyl starch. In vitro results leading to an autologous retransfusion model in the dog].

Although the effectiveness of hydroxyethyl starch (HES) as a cryoprotectant for human red blood cells (HRBC) is well known, no clinical application has evolved so far. In contrast to glycerol HES has the advantage of causing no hemolysis per se. This offers the opportunity of a one-step procedure without a time consuming postthaw washing procedure prior to transfusion. In this study the in vitro results obtained with red blood cells from 8 dogs (DRBC) are reported and compared to HRBC (n = 5). It turned out that DRBC had a similar 2,3-DPG and a lower ATP content. Postthaw survival in terms of saline stability differed markedly (67 +/- 6 and 86 +/- 2%, respectively). DRBC were more susceptible to hypotonic stress than HRBC. Nevertheless, after cryopreservation 91% (HRBC) and 92% (DRBC) of the original 2,3-DPG were found in the thawed RBC concentrates.

2,3-Diphosphoglycerate

Cavitation of mechanical heart valves under physiologic conditions.

Cavitation has recently entered the discussion of factors leading to blood and material damage after implantation of mechanical heart valves. Since direct evidence for this phenomenon cannot yet be demonstrated in vivo, an in vitro method had to be developed to permit the investigation whether cavitation actually occurs under (simulated) physiologic conditions and to clarify its clinical relevance. Previous studies have shown that different types of commercially available mechanical valves exhibit different tendencies to generate cavitation in vitro. The present study presents a test protocol for the assessment of cavitation generated by different replacement valves under simulated physiologic conditions. Comparative investigations were performed in order to transfer the in vitro results in vivo conditions. Although mechanical valves with an overlapping closing body/valve ring configuration tend to create cavitation earlier, cavitation could not be demonstrated for any investigated mechanical valve type under simulated resting conditions. The danger of continuous cavitation damage is therefore low. Certain valve types exhibit cavitation only at higher heart rates (more than 120-140 beats/min). Some valve types do not show cavitation even during heavy exercise. Based on mathematical models and experimental investigations, it is very likely that if cavitation does occur, blood and material damage may be expected.

Blood

Electromechanical artificial heart with a new gear type and angled pump chambers.

The intrathoracic anatomical situation after explantation of the natural heart defines the maximum available space for the design of the housing as well as of the inlet- and outlet connectors of a fully implantable electromechanical artificial heart. Based on computer-assisted anatomical studies, a total artificial heart housing is designed which facilitates an oblique orientation of the pumping chambers for a better fluidmechanical and anatomical arrangement of the in- and outlet connectors. The pumping chamber geometry is based on modifications of an existing cardiac assist-system. Subsequently a mechanical gear which conforms to this anatomically adapted housing is developed.

Heart, Artificial

Compact mock loops of the systemic and pulmonary circulation for blood pump testing.

Mock loops are an important tool for in vitro investigations of artificial blood pumps. The simple windkessel, throttle, and atrium principle was used for the mock loop design presented. The components of the systemic and the pulmonary mock loop were designed according to calculated numerical simulation parameters. The loops offer a compact design and simple handling. For simulating biventricular assist or total artificial heart (TAH), both loops can be coupled correspondingly. The numerical simulation and the first results with the loops show very good similarity to physiological data of systemic and pulmonary circulation. The measurements of pump characteristics are significant for quantitative comparison of different pump sizes and types, or driving systems.

Blood Circulation

An interactive computer simulator of the circulation for knowledge acquisition in cardio-anesthesia.

Knowledge-based decision support systems for use in cardio-anesthesia can provide online support to the anesthesiologist by generating intelligent alarms. However, the acquisition and validation of a consistent knowledge base for this application bears problems related to the transfer of clinical experiences into a rule system. An interactive simulator of the human circulation is presented that supports the process of knowledge acquisition and testing. The simulator can be controlled in realtime by an anesthesiologist during the simulation run thus providing a basis for interdisciplinary discussion of routine as well as critical situations. The output data can be transferred to a knowledge-based system for test purposes. The simulator is currently being used for the development of the Anesthesia Expert Assist System AES-2. With regard to the special application a model of the heart-function was integrated which enables the simulation of heart insufficiency. Simulation runs under various conditions are presented and discussed. The simulator was implemented on an ATARI ST personal computer.

Anesthesiology

Where should the cooling rate be determined in an extended freezing sample?

Computer simulations have been performed to calculate the transient cooling and solidification process at different locations in a flat plate-shaped freezing container filled with isotonic solution (0.9 wt% NaCl in water). The one-dimensional model accounts for the influences of the external cooling conditions, the container wall, the freezing bag, and the nonplanar solidification of an aqueous solution. The cooling rate was found to increase within the sample from the portions adjacent to the inner surface of the bag toward the center. An important result for cryobiological experiments was the fact that the geometrical center of the sample, a commonly used location for the determination of cooling rate, is not representative for the entire volume of the sample. Even worse, the calculations have shown that the center is often the least representative place. As an alternative, the most suitable location for cooling rate measurements has been determined. With the assumed surface cooling and geometry conditions an optimum location at x/(d/2) approximately 2/3 (x is the space coordinate, originating at the inner surface of the freezing bag; d is the sample thickness) has been calculated, i.e., a distance of one-third away from the center and two-thirds from the inside surface of the sample container. Admitting a 50% range of variation, the cooling rate measured at this point represents at least 80% of the entire sample volume. The survival signature, i.e., the functional dependence of cell survival from cooling rate (determined at a single location), for a fictitious cell kind is also influenced by the location of temperature determination: the "optimum" cooling rate seems to be shifted, and the shape of the signature is changed depending on the location where the cooling rate is determined.

Computer Simulation

[Testing vision in children].

Measurement of visual acuity in children is more difficult than in adults. Children tend to riet when the threshold is reached and become inattentive. However the exact determination of visual acuity in children is important in some situations (Screening, Amblyopia). In this paper we examined whether an automated procedure is more exact than measurement by an examiner. Three series of experiments were done. In n = 173 we measured visual acuity first by an examiner using an optotype projector and second by an automated procedure (computer, keyboard, television screen). Both, the examiner and the computer used the same test-procedure and threshold criterion (DIN-Norm). The correlation coefficient was 0.84. In n = 53 children (age 4 to 7) visual acuity was measured by an examiner without a special strategy. Afterwards visual acuity was measured by the automated procedure. The correlation coefficient was 0.1. In n = 63 children (age 5-7) visual acuity was measured by an examiner using a strategy and a threshold criterion. Afterwards the automated procedure was used. The correlation coefficient was 0.69. The results show, that without a strategy and defined threshold criterion it is not possible to compare the measurements of visual acuity in different times. An automated procedure presented in this paper guaranties constant test conditions in an optimal way.

Adult

Influence of tissue inhomogeneities on noninvasive muscle fiber conduction velocity measurements--investigated by physical and numerical modeling.

The determination of conduction velocity in the muscle fibers of single motor units from noninvasive recordings of single motor unit action potentials can be improved by the method of spatially filtering multielectrode EMG. The use of this conduction velocity as a diagnostic tool requires a high reliability of the detected values. However, experiments did reveal that the measured conduction velocity values showed remarkably high fluctuations depending on the recording site along the muscle fibers which could not be attributed to the influence of the endplate and tendon region. The present work examines the hypothesis that the observed fluctuations in propagation velocity were caused by electrically inhomogeneous tissue, regions of different electrical conductivity which are located between the excited muscle fibers and the recording electrodes and which cause a deformation of the extracellular electric current field. The investigation was performed by means of a physical model as well as by finite element model calculations. In both models single, simple shaped (cylindrical) inhomogeneity regions with a conductivity of 0.1 to 10 times that of the surrounding medium and diameters ranging between 1.6 and 2.7 mm were placed between excitation sources and recording site. The results indicate that the observed conduction velocity fluctuations of up to some 10% can be well attributed to inhomogeneity effects of the tissue conductivity. Based on these results, one may look for signal processing methods to cut down such fluctuations in conduction velocity measurements.

Computer Simulation

Intracellular ice formation: cryomicroscopical observation and calorimetric measurement.

The formation of ice crystals within biological cells is generally deleterious and results in a severe loss of cellular viability and function. With the aim of circumventing this lethal event, the mechanisms of nucleation and their dependence on governing parameters such as temperature, cooling rate and solute and/or additive concentration, and the correlation with the osmotically induced water transport across the cell membrane were investigated. Quantitative low-temperature light microscopy was used for this purpose as it offers the major advantage of studying the dynamics of the involved processes. To substantiate further the visual observations of the morphological changes associated with intracellular ice formation, supplementary studies by differential scanning calorimetry (DSC) were performed under comparable conditions to measure the quantity of water actually transformed into the crystalline state due to the evolution of latent heat. Human lymphocytes were used as a biological model cell. In particular it could be shown that the twitching type of intracellular ice formation which is evident but difficult to observe under the cryomicroscope can be attributed to a liquid-solid phase change within the cells as determined by DSC. Good agreement was obtained between the results measured by both techniques with respect to the following dependencies of governing parameters: the fraction of cells exhibiting intracellular ice determined as a function of the cooling rate shows a sharp demarcation zone with an increase from 0 to 100% at about the same threshold cooling rate. On the other hand, the temperatures at which intracellular ice forms were found to be only weakly dependent on the cooling rate. With respect to the effect of cryo-additive concentration at a fixed value of the cooling rate, the crystallization temperatures were seen to decrease with concentration. The DSC results may hence be regarded as a validation of the microscopic observations.

Calorimetry, Differential Scanning

New J-3 flexible-leaflet polyurethane heart valve prosthesis with improved hydrodynamic performance.

The aim of this new three-leaflet valve development was to design a leaflet with minimum membrane stresses during performance. This is achieved by manufacturing the valve leaflets shaped almost flat in a medium opening position. Thus, the leaflets have two stable positions, one with maximum opening area and the other with favorable stress distribution in the closed position. The transition between the two end positions is achieved through a two-dimensional rolling motion without buckling and with minimum membrane stresses (bulge forces). The manufacturing technique is dip-coating in polyurethane. Hydrodynamic evaluation of the J-3 valve in steady and pulsatile flow showed minimum pressure drop compared to other commercially available valves. Laser-Doppler-anemometry studies indicated very low shear stresses in the flow field downstream of the valve. In durability tests prototypes have reached lifetimes of up to 17 years. In conclusion, the J-3 valve shows superior hydrodynamic performance thereby reducing potential thrombus formation. Minimization of stresses within the valve leaflets through design could reduce calcification.

Biomechanical Phenomena

Shear stress related blood damage along the cusp of a tri-leaflet prosthetic valve.

Blood flowing through a prosthetic heart valve can be damaged by flow-induced shear forces. Fluid dynamics variables and geometric factors play an important role in the evaluation of shear-stress-related blood damage. Central-flow prosthetic valves have been considered as an optimal replacement for mechanical and biological valves. Recently it was shown that shear stress distribution along the surface of a polyurethane cusp reaches values that can damage the blood elements. A mathematical model correlating the effects of shear stresses on blood corpuscles with clinical findings was employed in vitro. The model can be applied to the effects of blood-surface interaction and is of clinical relevance.

Blood Cells

High-resolution, real-space imaging of conformational structures of poly-L-proline helixes.

In 1954, Edsall postulated that the imino-acid proline, which is a frequently found constituent of protein molecules, is a key determinant to the three-dimensional architecture of proteins. It not only should play a fundamental role in stabilizing helical structures of polypeptides, it should allow for sharp bends and even for a complete reversal of the direction of a helix looping back on itself. No direct evidence has yet been published to prove this prediction. Using scanning tunneling microscopy, we have presented high-resolution, real-space images of two conformations of poly-L-proline, where one structure clearly exhibits the predicted 180 degrees back-folding behavior. The measured length, 1.89 nm, of the repeating unit cells agrees with available X-ray data for poly-L-proline I with cis-peptide bonds. We further observe aggregated poly-L-proline II, consisting of highly-ordered, periodically and parallel-linked trans-peptide chains which are 2.4 nm apart from each other. Stacking of these aggregates with their orientation rotated by 90 degrees is also observed.

Microscopy, Scanning Tunneling

Cavitation potential of mechanical heart valve prostheses.

Just like technical check valves, the function of mechanical heart valve prostheses may presumably also lead to cavitation effects during valve closure. Due to the waterhammer effect, cavitation may primarily occur in the mitral position leading to high mechanical loading of the valve itself and of corpuscular blood elements. Ten different types of commercial mechanical heart valves were investigated in the mitral position of a pulsatile mock loop, to detect cavitation thresholds under physiologically similar conditions by cinematographic techniques. Almost all these valve prostheses show cavitation up to a ventricular pressure gradient of 5000 mmHg/s. The threshold depends on valve type and size and is sometimes within the physiological range below 2000 mmHg/s. Visible cavitation bubbles with a diameter of up to 1.8 mm and a collapse time of less than 0.1 ms suggest that vapour cavitation may play an important role for material and blood damage in mechanical heart valve prostheses.

Coronary Circulation