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Biomedical subjects

P Niederer

Publications and source records attributed to P Niederer.

At least 55 records · Page 3Linked to original sources

Determination of displacement, stress- and strain-distribution in the human heart: a FE-model on the basis of MR imaging.

The determination of characteristic cardiac parameters, such as displacement, stress and strain distribution are essential for an understanding of the mechanics of the heart. The calculation of these parameters has been limited until recently by the use of idealised mathematical representations of biventricular geometries and by applying simple material laws. On the basis of 20 short axis heart slices and in consideration of linear and nonlinear material behaviour we have developed a FE model with about 100,000 degrees of freedom. Marching Cubes and Phong's incremental shading technique were used to visualise the three dimensional geometry. In a quasistatic FE analysis continuous distribution of regional stress and strain corresponding to the endsystolic state were calculated. Substantial regional variation of the Von Mises stress and the total strain energy were observed at all levels of the heart model. The results of both the linear elastic model and the model with a nonlinear material description (Mooney-Rivlin) were compared. While the stress distribution and peak stress values were found to be comparable, the displacement vectors obtained with the nonlinear model were generally higher in comparison with the linear elastic case indicating the need to include nonlinear effects.

Algorithms↗

Time-resolved flow cytometry for the measurement of lanthanide chelate fluorescence: I. Concept and theoretical evaluation.

The concept of a flow cytometer suited for the time-resolved measurement of lanthanide chelate luminescence with a decay time on the order of 10 microseconds to 2 ms is presented and evaluated. The instrument proposed encompasses a continuous-wave laser for fluorescence excitation and an optical switch for the elimination of cellular autofluorescence decaying within 1 ns to 1 microseconds during the luminescence detection period. The slowly decaying fluorescence is to be quantified by a photon-counting system, whereas light scatter and prompt fluorescence parameters are acquired by a conventional detection system. The detection limit of the method, in terms of the smallest detectable number of fluorescing chelates per cell, is examined. It was found to be nearly 30,000 complexes of a europium chelate with a decay time of 1.6 ms and a quantum efficiency of 17%, independent of fast decaying cellular autofluorescence or prompt dye emission intensity. The probability of cells passing through the instrument without being detected while the laser beam is turned off was estimated, and the implications for cell throughput and sorting performance of the instrument were assessed. At typical fluorescence detection intervals of 500 microseconds to 1 ms, cell flow rates of 100-200 particles per second lead to detection probabilities of more than 90% and sorting purities comparable to those found in conventional fluorescence-activated cell sorting.

Chelating Agents↗

Time-resolved flow cytometry for the measurement of lanthanide chelate fluorescence: II. Instrument design and experimental results.

A time-resolved flow cytometer capable of measuring a luminescence with a decay time in the range of 10 microseconds to 2 ms, typical for some lanthanide chelates, is presented. The instrument permits acquisition of conventional light scatter and prompt fluorescence signals as well as detection of slowly decaying luminescence by a photon counting unit for a selectable time period of 1 microsecond to 1 ms. During photon counting, the laser beam is turned off by an acoustooptic deflector. The design of a flow chamber with an average geometrical light collection efficiency of 35% over a distance of 1.7 mm is presented and analyzed by ray tracing. A pulse processing system featuring digital integration of the conventional signals and a transputer system for the acquisition and the transfer of the measured parameter values to a host computer is described. Instrument function is verified with lyophilized human lymphocytes stained for the CD8 antigen with dye-loaded liposomes. Quantitation of cell-associated europium chelate fluorescence, displaying a decay time of 1.6 ms, is demonstrated. Elimination of fast decaying background emission generated by DNA-associated ethidium bromide is shown. The background generated by instrument components in the time-gated measurement channel is characterized, and measures for its complete elimination are discussed.

Chelating Agents↗

[GRIN-endoscopy for laser treatment in ophthalmology].

Endoscopes for use in ophthalmology can be manufactured with diameters smaller than 0.89 mm. Because gradient-index (GRIN) lenses yield a higher resolution than ordered fiber bundles having the same diameter, GRIN lenses with a diameter of either 0.35 mm or 0.50 mm were utilized to manufacture thin high resolution endoscopes. Whatever the working distance, the resolution obtained with a GRIN lens having a diameter of 0.50 mm was higher than that obtained with a GRIN lens of 0.35 mm. Thanks to the miniaturization, an additional working channel could also be integrated within the endoscope. This allowed new combinations of various surgical instruments. This channel can be used as a guide for an optical fiber for laser therapy or as an irrigation/aspiration channel. The use of such an instrument where the observation path is parallel to the surgical instrument was compared to the application of the endoscope as a separate monitoring system. The advantages and inconveniences of both systems are discussed. Preference is given to a system where the diameter of the observation channel is maximum and the optical fiber for laser delivery is integrated but adjustable along its length within the endoscope.

Endoscopes↗

[Surgery with the laser scalpel. Physical principles and clinical effectiveness].

BACKGROUND: The conventional surgical method for cutting vascularized tissue with scalpel and scissors may now be improved by use of the laser scalpel. In particular, the frequent interruption necessitated and the poor visibility caused by bleeding may be mitigated owing to the haemostatic properties of laser light. This instrument may be of particular value for tasks involving extrabulbar structures, such as extraocular muscles and lacrimal tissue, as well as for facial surgery. MATERIALS AND METHODS: The mode of action and physical properties of a new laser scalpel are described and its characteristics compared with those of other instruments on the market. The probe consists of a clad, sculptured silica fibre with a core diameter of 0.6 mm and a conical 0.15 mm-diameter cutting tip. Radiation generated by a low cw-Nd:YAG laser module is fed into the probe, at the exit point of which a maximal power density of 57 kW/cm2 is attained. Radiated laser energy penetrates the tissue as an incision is made, thereby inducing an efficient blood flow stasis which is amplified by thermal energy diffusing from the immediate surroundings of the scalpel tip. RESULTS: In this report, the laser scalpel is implemented for the excision of a vascularized, amelanotic, facial naevus. Both the cutting and haemostatic effects were found to be excellent, occurrence of the latter phenomenon being supported by ultrastructural findings. The healing response was comparable to that observed after conventional surgery. CONCLUSION: The new laser scalpel represents an inexpensive and effective cutting and haemostatic tool powered by a standard cw Nd:YAG laser module, with a wide spectrum of potential applications.

Aged↗

Monte Carlo docking of oligopeptides to proteins.

A new two-step procedure has been developed for the docking of flexible oligopeptide chains of unknown conformation to static proteins of known structure. In the first step positions and conformations are sampled and the association energy minimized starting from an approximate preselected docking position. The resulting conformations are further optimized in the second step by a Metropolis Monte Carlo minimization, which optimizes each of these structures. The method has been tested on the HIV-1 aspartic proteinase complex with an inhibitor, whose crystallographic structure is known at 2.3 A resolution. Furthermore, the application of this method to the docking of the hendecapeptide 58-68 of the influenza A virus matrix protein to the HLA-A2 molecule produced results which are in agreement with experimental observations in identifying side chains critical for T cell recognition and residues responsible of MHC protein binding.

Algorithms↗

Monte Carlo minimization with thermalization for global optimization of polypeptide conformations in cartesian coordinate space.

A new minimization procedure for the global optimization in cartesian coordinate space of the conformational energy of a polypeptide chain is presented. The Metropolis Monte Carlo minimization is thereby supplemented by a thermalization process, which is initiated whenever a structure becomes trapped in an area containing closely located local minima in the conformational space. The method has been applied to the endogenous opioid pentapeptide methionine enkephalin. Five among 13 different starting conformations led to the same apparent global minimum of an in-house developed energy function, a type II' reverse turn, the central residues of which are Gly-3-Phe-4. A comparison between the ECEPP/2 global minimum conformation of methionine enkephalin and the apparent one achieved by the present method shows that minimum-energy conformations having a certain similarity can be generated by relatively different force fields.

Amino Acid Sequence↗

Fluorescence spectroscopy for identification of atherosclerotic tissue.

OBJECTIVE: Vessel perforation and limited steerability of the laser light are the major limitations of laser angioplasty. To improve steerability fluorescence spectroscopy has been proposed for identification of atherosclerotic plaques. The aim was to investigate this. METHODS: Fluorescence spectroscopy with three different excitation wavelengths (325 nm, 380 nm, 450 nm) was tested in an emission range of 400 nm to 600 nm. Intensity ratios at 480/420 nm were determined in different types of blood vessels. Necropsy material from 40 patients (punch biopsies of 4 mm diameter from the coronary and carotid artery as well as from the ascending and descending aorta) was studied spectroscopically. Histological alterations of the vessel wall were assessed by a semiquantitative score (0 to 10 points): (a) normal tissue, 0 to 2 points (mean = 0.25; n = 38); (b) mild atherosclerotic lesions, 3 to 5 points (mean = 3.35; n = 39); (c) severe atherosclerotic lesions, greater than or equal to 6 points (mean = 6.75; n = 43). RESULTS: Best spectroscopic results were obtained with an excitation wavelength of 325 nm. In samples with severe atherosclerotic lesions the fluorescence spectra showed a significant reduction of the emitted wavelength intensities when compared to normal tissue. There was a clear separation of the fluorescence spectra between normal and mild as well as between normal and severe atherosclerotic lesions; normal tissue showed an increased intensity in the range from 420 nm to 540 nm, whereas atherosclerotic lesions had no or only a small peak at 480 nm. There was a significant correlation between the semiquantitative score (n = 120) and the fluorescence ratio at 480/420 nm (excitation wavelength 325 nm) with a correlation coefficient of 0.87. The spectroscopic results showed no differences between the samples taken from different types of vessels. CONCLUSIONS: Fluorescence spectroscopy allows a reliable identification of normal and atherosclerotic lesions. The close correlation between the emitted light intensity ratio at 480/420 nm and the histological alterations of the vessel wall suggests a relationship between vessel wall fluorescence and the atherosclerotic alterations of the wall.

Adolescent↗

Devices for the control of laser transmission across the sclera during transscleral photocoagulation.

Improving the reproducibility of transscleral photocoagulation necessitates controlling the transmission of the laser beam through the sclera. Two factors make such control problematic: the locally increased transparency of the sclera resulting from the contact procedure and the occurrence of time-related relaxation phenomena. Two instruments have been devised to help control these factors. The first is a mechanical compensation unit comprised of magnets and a spring that allows the force exerted on the sclera to be adjusted to between 0.1 and 0.4 N, the pressure being determined by the outer diameter of the contact tip. The second instrument monitors the portion of the aiming beam reflected by the sclera as a means of determining the exact level of power actually transmitted through it. This information theoretically could be fed back to the treatment laser, allowing the level of power being delivered to be adjusted accordingly.

Ciliary Body↗

Validation of a new automatic system for biplane quantitative coronary arteriography.

In a collaboration between the University of Texas (software) and the University of Zürich (hardware) a compact, automatic system for biplane quantitative coronary arteriography was developed. The system is based on a 35 mm film projector, a slow-scan CCD-camera (image digitizing) and a computer workstation (Apollo DN 3000, image storage and processing). A new calibration procedure based on two fixed reference points in the center of the image intensifier was used (isocenter technique). Contour detection of coronary arteries was carried out in biplane projection using a geometric-densitometric edge-detection algorithm. The proximal and distal luminal areas, as well as the minimal luminal area of the stenotic vessel segment were determined. Accuracy and precision were determined from precision drilled holes in a plexiglas cube which were filled with 50%, 75% and 100% contrast medium. The diameter of the holes ranged from 0.5 to 5.0 mm. The mean difference and the standard deviation of the differences between the true and the measured diameters were 0.12 +/- 0.14 mm for plane A and 0.26 +/- 0.17 mm for plane B, respectively. After a second order correction the mean difference amounted to 0.02 +/- 0.09 mm for plane A and 0.02 +/- 0.12 mm for plane B, respectively. Intra- and interobserver variability were evaluated in 5 patients (age 60 +/- 10 years) with coronary artery disease using 16 normal and 5 stenotic vessel segments (cross-sectional area ranging from 0.8 to 8.7 mm2). Two independent observers analyzed the same vessel segment twice. Intraobserver variability expressed as the standard error of estimate in percent of the mean angiographic vessel area (SEE) amounted to 2.1% for observer 1 and 4.4% for observer 2, respectively. Interobserver variability expressed as SEE was 4.1% for measurement 1 and 3.6% for measurement 2, respectively.

Aged↗

Potential role of coronary vasoconstriction in ischaemic heart disease: effect of exercise.

Coronary vasomotion plays an important role in the regulation of coronary perfusion at rest and during exercise. Normal coronary arteries show coronary vasodilation of the proximal (+20%) and distal (+40%) vessel segments during supine bicycle exercise. However, patients with coronary artery disease show exercise-induced vasoconstriction of the stenotic vessel segments. The exact mechanism of exercise-induced stenosis narrowing is not clear but might be related to a passive collapse of the disease-free vessel wall (Venturi mechanism), elevated plasma levels of circulating catecholamines, an insufficient production of the endothelium-derived vasorelaxing factor or increased platelet aggregation due to turbulent blood flow with release of thromboxane A2 and serotonin. Various vasoactive drugs, such as nitroglycerin and calcium antagonists, prevent exercise-induced stenosis vasoconstriction. An additive effect on coronary vasodilation of the stenotic vessel segment was observed after combination of nitroglycerin with diltiazem. Thus, exercise-induced stenosis narrowing plays an important role in the pathophysiology of myocardial ischaemia during dynamic exercise. The antianginal effect of vasoactive substances can be explained--besides the effect on pre- and afterload--by a direct action on coronary stenosis vasomotion.

Angiography↗

[High-frequency artificial respiration. II. Intratracheal high-frequency pressure changes with a rotation-valve catheter].

From the history of ventilatory support, the early studies of Auer und Meltzer only now seem to find a functional explanation. A rotating valve mounted on the tip of an endotracheal tube delivers a widespread gas bolus. The turbulent flow acts as a stirring device on the intrapulmonary gas volume. The method reduces the directional selectivity that typically limits the efficiency of jet ventilation. Systematically changing the rotational frequency between 10 and 80 Hz allows sequential stimulation, compartment by compartment, of the entire lung, which also gives rise to frequency-dependent local air-trapping that sequentially inflates different compartments. Jet ventilation and high-frequency oscillation were compared in dogs with the rotating valve tube by taking blood gas samples from 4-6 intrapulmonary veins: jet ventilation is characterized by preponderant ventilation of lung compartments opposite the lower aperture of the endotracheal tube. High-frequency oscillation induces a frequency dependent repartition of alveolar ventilation. The rotating valve tube definitely contributes to the homogenisation of alveolar ventilation in a manner that is less dependant upon segmental compliance than conventional ventilation.

Animals↗

[High-frequency ventilation. I. Distribution of alveolar pressure amplitudes during high frequency oscillation in the lung model].

The pattern of intrapulmonary pressure distribution was studied during high-frequency ventilation in order to explain the inconsistent results reported in the literature. Methods. Pressure and flow velocity (hot-wire anemometry) were measured in different lung compartments: 1. In transalveolar chambers sealed to the perforated pleural surfaces of dried pig lungs; 2. In emphysema-simulating airbags sealed to the isolated bronchial trees of dried pig lungs; and 3. In transalveolar chambers sealed to the perforated pleural surfaces of freshly excised pig lungs. Results. 1. The pressure amplitudes change from one area to another and depending on the exciting frequency. 2. High-frequency oscillation is associated with an increase in pressure amplitude when the exciting frequency rises, whereas with conventional high-frequency jet ventilation the pressure amplitude is more likely to decrease with frequency. 3. During high-frequency jet ventilation the local pressure amplitude changes with the position of the tube in the trachea rather than with the exciting frequency. 4. When the volume of the measuring chamber is doubled the resulting pressure amplitude falls to half the control value. 5. The pressure amplitude and mean pressure measured in the transalveolar chamber vary more or less independently from the peak flow velocity. High-frequency ventilation is thus seen to be a frequency-dependant, inhomogeneous mode of ventilation that can essentially be homogenized by systematically changing the exciting frequency. The frequency-dependant response to different lung areas to excitation is likely to result from an intrabronchially-localized aerodynamic effect rather than the mechanical properties of the lung parenchyma.

Animals↗

Comparison of intravenous digital subtraction cineangiocardiography with conventional contrast ventriculography for the determination of the left ventricular volume at rest and during exercise.

Left ventricular volumes were determined by means of digital subtraction cineangiocardiography (DSA) which was performed in the right anterior oblique projection after contrast agent injection into the superior vena cava. Monoplane end-diastolic (EDV), end-systolic volumes (ESV), and ejection fraction (EF) were calculated using the 'area-length' method and were compared with the same parameters obtained by conventional left ventricular cineangiocardiography. A first group of 20 patients was studied at rest and a second group of 10 patients during bicycle exercise at a work load of 64 watts during 2 min, by DSA and conventional cineangiocardiography. Three different subtraction modes were evaluated: (1) mask mode subtraction (MMS), (2) time interval difference (TID) method and (3) a combination of MMS and TID called MMS + TID method. With the MMS method good correlations were obtained for EDV, ESV and EF at rest (r greater than 0.91) and during exercise (r greater than 0.91). The TID method showed only moderate correlations for patients at rest (r greater than 0.86) and during exercise (r greater than 0.79). Similar results as with MMS were achieved by the combined method (MMS + TID) at rest (r greater than 0.91) and during exercise (r greater than 0.91). Interobserver variability indicated a high reproducibility for all methods except for TID during exercise. It is concluded that DSA is an accurate technique for left ventricular volume determination not only at rest but also during exercise. The best results are obtained with MMS or MMS + TID methods, while left ventricular contour detection is easier and more convenient with MMS + TID.

Adult↗