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Feasibility of using intracardiac impedance measurements for capture detection.

Energy consumption and longevity of modern pacemakers are determined by the controlling electronic circuitry and by the stimulation energy. While with technological progress the electronics' energy consumption has been reduced significantly, clinical practice shows that many cardiac pacemakers are programmed to suboptimal settings with regard to minimization of pacing energy consumption. Several methods for optimizing pacemaker output settings have been proposed in the past. The most promising concept is an output parameter optimizing pacemaker with automatic capture detection. We examined whether it is possible to distinguish between effective and ineffective pacemaker stimulus capture by analyzing high pass filtered intracardiac impedance signals that are derived from standard bipolar pacing leads. In one series of 11 patients undergoing replacement or implantation of chronic bipolar pacemakers, four patients during electrophysiology studies, and eight volunteers undergoing invasive electrophysiology trials, we examined intracardiac impedance signals obtained with various stimulation rates and output parameter settings. Additionally we analyzed a series of five patients with implanted pacemakers that can measure and telemeter intracardiac impedance signals. Several evaluation concepts have been analyzed regarding their ability to discriminate between effective and ineffective stimuli. We developed an adequate algorithm that detects capture or loss of capture at different output parameter settings based on intracardiac impedance analysis. The sensitivity is 98.5% and specificity is 91% to loss of capture for the currently investigated algorithm and this can be used to determine the optimal setting of pulse width and amplitude with regard to energy consumption. This concept is currently under realization in the external programmer and in the future an implementation of these algorithms within the pacemaker itself is intended.

Algorithms↗

Wall compliance and violin cavity modes.

Violin corpus wall compliance, which has a substantial effect on cavity mode frequencies, was added to Shaw's two-degree-of-freedom (2DOF) network model for A0 ("main air") and A1 (lowest length mode included in "main wood") cavity modes. The 2DOF model predicts a V(-0.25) volume dependence for A0 for rigid violin-shaped cavities, to which a semiempirical compliance correction term, V(-x(c)) (optimization parameter x(c)) consistent with cavity acoustical compliance and violin-based scaling was added. Optimizing x(c) over A0 and A1 frequencies measured for a Hutchins-Schelleng violin octet yielded x(c) approximately 0.08. This markedly improved A0 and A1 frequency predictions to within approximately +/- 10% of experiment over a range of about 4.5:1 in length, 10:1 in f-hole area, 3:1 in top plate thickness, and 128:1 in volume. Compliance is a plausible explanation for A1 falling close to the "main wood" resonance, not increasingly higher for the larger instruments, which were scaled successively shorter compared to the violin for ergonomic and practical reasons. Similarly incorporating compliance for A2 and A4 (lowest lower-/upper-bout modes, respectively) improves frequency predictions within +/-20% over the octet.

Journal Article↗

[Electrostimulation of the phrenic nerve in dogs].

Respiratory parameters have been studied by electrical stimulation of phrenic nerves (EPN) in 12 dogs. The optimal parameters of an electrical stimulus were found for long-term EPN. EPN increased minute respiratory volume, when respiratory rate raised to 18 per min, and decreased, when respiratory rate diminished to 6 per min. Another parameter--oxygen utilization index--diminished at high respiratory rate and increased at low one, which reflected hyper- or hypoventilation status, respectively. The data obtained indicate that controlled lung ventilation may maintain living status of dogs for a long time without alteration of general respiratory parameters.

Animals↗

Measurement of ultrasound biomicroscopy images: intraobserver and interobserver reliability.

PURPOSE: To evaluate intraobserver and interobserver reproducibility of measurement of images obtained during ultrasound biomicroscopy. METHODS: Four anterior segment images of four normal patients were obtained by a single examiner. The measurements of three independent observers were compared to assess interobserver reproducibility in quantifying the images. Thirteen different anterior segment parameters were measured by each observer on each image. Intraobserver and interobserver reproducibility of measurement were assessed by calculating the coefficient of variation for each individual observer and by using the F test to detect a difference among observers. RESULTS: Intraobserver reproducibility was high. Interobserver reproducibility for the measured parameters varied considerably and was affected by subjective interpretation of visualized anatomic landmarks. CONCLUSIONS: The optimal parameters for quantitative ultrasound biomicroscopy require refinement. Measurements of alterable parameters are best measured presently by a single observer. Ultrasound biomicroscopy has the potential to elucidate anatomic relationships underlying much anterior segment disease, but caution in interpreting quantitative differences is warranted.

Anterior Eye Segment↗

Systematic studies on parameters influencing the performance of the polymerase chain reaction.

To obtain a detailed understanding of the various factors influencing the polymerase chain reaction, we optimized parameters such as ion concentration, pH, primer sequence and concentration, hybridization stringency, cycle numbers, etc. Using 3 different plasmids (2 HIV2 clones and pUC18) and several genomic DNA samples from HIV-positive patients as templates, together with 6 sets of primers, the following optimal conditions were found: the DNA should be linearized, the primer concentration should be 0.1-0.2 mumol/l, and the magnesium ion concentration should be less than 2 mmol/l. The pH of the reaction mixture should be 8.5-9.0. Twenty five cycles are sufficient. For fragments greater than 10(3) bases the elongation time should be 5 min. The elongation temperature is not critical and can vary between 50 and 70 degrees C. The hybridization temperature can be used to control the specificity of the polymerase chain reaction and, finally, mismatches at the 3' end of the primer can totally inhibit the amplification.

Base Sequence↗

Electrical stimulation of the hypothalamus: new observations on the parameters necessary for ovulation in rats anaesthetised with pentobarbitone during the pro-oestrous "critical period".

The experiments were designed to specifiy optimal parameters of hypothalamic electrical stimulation to induce ovulation in rats anaesthetised with pentobarbitone during the "critical period" on the afternoon of pro-oestrous. We have established that duration of stimulation in the arcuate region of the hypothalamus is of greater importance than total number of pulses delivered. The minimum period of stimulation to ensure that all rats ovulated was 45 min. However, stimulation in the arcuate region did not have to be continuous throughout this period. Indeed, three 5-min bursts at 100 Hz distributed equally through 45 min always caused ovulation whereas a continuous 15-min stimulation at the same frequency was without effect. With 30 min of continuous stimulation in the arcuate region, at frequencies ranging from 10 to 100 Hz, approximately half of the rats ovulated.

Anesthesia, General↗

[Early treatment of acute myocardial infarct: implementation of therapy guidelines in routine clinical practice, MITRA pilot phase].

The prognostic value of thrombolytics, aspirin, beta-blockers and ACE-inhibitors has been well documented in large clinical trials, but the application of these drugs in clinical practice is not known. MITRA is a multicenter study of 54 hospitals in a defined region in southwest Germany. The aim is to document actual clinical practice (pilot phase) and to establish an individually optimised prognostic therapy for acute myocardial infarction, considering only the absolute contraindications for each drug. In the pilot phase, 1303 consecutive patients with acute transmural myocardial infarction were enrolled. The median age was 66 years, the prehospital time was 2.7 hours. 47% had an anterior infarction. In the subgroup of patients without absolute contraindications, only 53.4% were treated with thrombolytics, 87.6% with aspirin, 37.1% with beta-blocker, and 17.4% with ACE-inhibitor. Out of these, patients were classified as "optimally treated" if they received thrombolysis, aspirin as well as beta-blocker. Patients were also included if any of these medications was withheld in the presence of absolute contraindications. Treatment was defined suboptimal, if the patients did not receive any of these three medications despite the absence of absolute contraindications. Only 29% (n = 383) received an optimal post-infarction therapy and 71% (n = 775) a suboptimal treatment. The univariate analysis revealed 10 variables influencing optimal therapy. In this subgroup patients were younger, they more often had clear ECG-findings or left bundle branch block, an anterior infarction, acute cardiac failure, AV-block, bradycardia, recent trauma or surgery (less then 2 weeks) and a severe chronic obstructive lung disease. The prehospital time was more often available. Early mortality after 2 days was 5.0% versus 9.3% in the suboptimal treated patients (OR: 0.5, CI: 0.30-0.86) the total inhospital mortality was 10.9% in the optimal versus 17.7% in the suboptimal group (OR: 0.6, CI: 0.38-0.84). In a multivariate analysis the parameter "optimal treatment" was found to be an independent predictor of the early (OR = 0.4; CI: 0.20-0.69) and the inhospital mortality (OR = 0.4; CI: 0.25-0.64). The following in-hospital events occurred: stroke 2.8%, reinfarction 12.9%, cardiac failure 21.5%, cardiogenic shock 10.4% and in-hospital mortality 18.1% (2-days mortality 9.5%). Pharmacological therapy for acute myocardial infarction is inconsistent with the recommendations suggested in recent clinical trials and needs to be individually optimised. Optimal treatment is an independent predictor of early and inhospital mortality.

Adrenergic beta-Antagonists↗

C2 domains from different Ca2+ signaling pathways display functional and mechanistic diversity.

The ubiquitous C2 domain is a conserved Ca2+ triggered membrane-docking module that targets numerous signaling proteins to membrane surfaces where they regulate diverse processes critical for cell signaling. In this study, we quantitatively compared the equilibrium and kinetic parameters of C2 domains isolated from three functionally distinct signaling proteins: cytosolic phospholipase A2-alpha (cPLA2-alpha), protein kinase C-beta (PKC-beta), and synaptotagmin-IA (Syt-IA). The results show that equilibrium C2 domain docking to mixed phosphatidylcholine and phosphatidylserine membranes occurs at micromolar Ca2+ concentrations for the cPLA2-alpha C2 domain, but requires 3- and 10-fold higher Ca2+ concentrations for the PKC-beta and Syt-IA C2 domains ([Ca2+](1/2) = 4.7, 16, 48 microM, respectively). The Ca2+ triggered membrane docking reaction proceeds in at least two steps: rapid Ca2+ binding followed by slow membrane association. The greater Ca2+ sensitivity of the cPLA2-alpha domain results from its higher intrinsic Ca2+ affinity in the first step compared to the other domains. Assembly and disassembly of the ternary complex in response to rapid Ca2+ addition and removal, respectively, require greater than 400 ms for the cPLA2-alpha domain, compared to 13 ms for the PKC-beta domain and only 6 ms for the Syt-IA domain. Docking of the cPLA2-alpha domain to zwitterionic lipids is triggered by the binding of two Ca2+ ions and is stabilized via hydrophobic interactions, whereas docking of either the PKC-beta or the Syt-IA domain to anionic lipids is triggered by at least three Ca2+ ions and is maintained by electrostatic interactions. Thus, despite their sequence and architectural similarity, C2 domains are functionally specialized modules exhibiting equilibrium and kinetic parameters optimized for distinct Ca2+ signaling applications. This specialization is provided by the carefully tuned structural and electrostatic parameters of their Ca2+ and membrane-binding loops, which yield distinct patterns of Ca2+ coordination and contrasting mechanisms of membrane docking.

Binding Sites↗

Characterization of embryonic aortic impedance with lumped parameter models.

We systematically constructed and analyzed 18 analog circuit models to characterize embryonic arterial impedance. We measured simultaneous dorsal aortic pressure and flow, and we calculated experimental impedance in stage 24 chick embryos (n = 15). Cycle length was altered with thermal probes to improve frequency resolution of the impedance spectrum. Models were categorized according to the framework and the location of inductance and resistance terms. Models were excluded if they failed to reproduce the fundamental characteristics of the experimental impedance spectrum. We used weighted least-square parameter optimization to fit the model impedance curves to the experimental impedance data. Models that failed to converge parameters or revealed overparameterization were also excluded. We assessed goodness of fit in the frequency domain with the F-test, Akaike information criterion, and Schwarz criterion to determine the best-fit model. The addition of a serial inductance term to the traditional three-element windkessel model improved fit by reproducing modulus fluctuation and phase zero crossing (P < 0.001). Thus, despite dramatic differences in scale and geometry, the embryonic and mature vascular systems can be described using lumped parameter circuit models.

Animals↗

[Force-based local navigation in robot-assisted implantation bed anlage in the lateral skull base. An experimental study].

Excellent precision, miss of retiring, reproducibility are main characteristics of robots in the operating theatre. Because of these facts their use for surgery in the lateral scull base is of great interest. In recent experiments we determined process parameters for robot assisted reaming of a cochlea implant bed and for a mastoidectomy. These results suggested that optimizing parameters for thrilling with the robot is needed. Therefore we implemented a suitable reaming curve from the geometrical data of the implant and a force controlled process control for robot assisted reaming at the lateral scull base. Experiments were performed with an industrial robot on animal and human scull base specimen. Because of online force detection and feedback of sensory data the reaming with the robot was controlled. With increasing force values above a defined limit feed rates were automatically regulated. Furthermore we were able to detect contact of the thrill to dura mater by analyzing the force values. With the new computer program the desired implant bed was exactly prepared. Our examinations showed a successful reaming of an implant bed in the lateral scull base with a robot. Because of a force controlled reaming process locale navigation is possible and enables careful thrilling with a robot.

Biomechanical Phenomena↗

Fatigue life improvement of nitrogen-ion-implanted pedicle screws.

An experimental study of the fatigue life of pedicle screws and their nitrogen-ion-implanted counterparts was conducted. Nitrogen-ion implantation parameters were varied in the first part of the study to obtain the best implantation characteristics. Using this optimal parameter for N(+)-implantation, the performance of two matched groups were compared at two bending moments near the "knee" of the S-N curves. At 3.96 N-m and 5.09 N-m of applied bending moments, the increase in the mean fatigue life for the former was 98% and for the latter 20%. The 98% prolongation was statistically significant at P less than 0.005; however, the 20% increase was statistically insignificant (P less than 0.1). The implantation depth is about 0.1 mu in the near surface of the screw. This appears to be thick enough to inhibit crack initiation at 3.96 N-m, but only marginally at 5.09 N-m. Increasing the implantation depth has the potential of increasing the fatigue life at the higher bending moments.

Bone Screws↗

[Multislice CT angiography: optimization of scan parameters in a vascular phantom].

PURPOSE: The aim of this study is to determine the optimal scan parameters for the evaluation of experimental vascular stenoses with a multislice-helical CT. MATERIAL AND METHODS: A vascular phantom consisting of four tubes with an inner diameter of 8 mm and with experimental stenoses of 50%, 75% and 90% was scanned in different tube orientations using a multislice-CT scanner (LightSpeed QX/i, GE, Milwaukee, USA). Examinations were performed with increasing collimations (1.25-5 mm), tube currents (100-300 mA) and two different table speeds (0.75 HQ mode and 1.5 HS mode). RESULTS: The most exact measurements were obtained in tubes angulated parallel to the scan direction with a collimation of 2.5 mm in the HQ mode (7.5 mm/rot.). An almost equivalent accuracy was obtained in the HS mode (15 mm/rot.) with a collimation of 2.5 mm when higher tube currents (300 mA) were employed. The degree of stenoses was overestimated when the tube was angulated perpendicular to the z-axis. CONCLUSION: Multislice-CT provides a good detection rate of vascular stenoses especially at 0 degree and also at 45 degrees angulation in the HQ mode. The use of the HS mode with higher tube currents allows scanning of longer distances with almost identical accuracy.

Angiography↗

An optimal reference plane to detect glaucomatous nerve fiber layer abnormalities with computerized image analysis.

Nerve fiber layer height measured with respect to a standardized retinal reference plane is diminished by glaucoma. The definition of the reference plane influences the nerve fiber layer measurements. We empirically determined the best reference plane for measurement of nerve fiber layer height. Optimal parameters for measurement reproducibility were determined for a group of 6 normal and 6 glaucomatous eyes each imaged nine times. Optimal ability to distinguish normal from glaucomatous eyes was determined for a group of 33 normal eyes and 36 glaucomatous eyes each imaged once. Measurements with the smallest variability (root mean square error = 32 microns) and the highest sensitivity (83%) and specificity (88%) were achieved when the reference plane is defined by portions of the image from a peripheral temporal area 32 degrees wide, and for two peripheral nasal areas of 55 degrees width centered 30 degrees above and below horizontal. These parameters for the definition of the reference plane should provide measurements of nerve fiber layer height with the least variability and the greatest ability to discriminate between eyes with early glaucomatous damage and normal eyes.

Glaucoma↗

Measurement-based evaluation of optical pathlength distributions reconstructed from simulated differential interference contrast images.

Recently a method was presented for reconstructing optical pathlength distributions (OPDs) from images of weak phase objects obtained by a conventional differential interference contrast (DIC) microscope. A potential application of this technique is the determination of the mass of biological objects: by integrating the optical pathlength over the projected surface of the image of an object, a measure of the dry mass, i.e. the total mass of all solid constituents present in the object, is obtained. To assess the possibilities of DIC microscopy for this application, simulations were performed on computer-generated DIC images of objects of various sizes, shapes and orientation angles. After reconstructing the OPDs from these images, the integrated optical pathlength of each of the test objects was determined, and compared with the expected results. The parameter settings used in the reconstruction algorithm were found to be very important in obtaining a reliable measurement. Using optimal parameter settings, errors in the integrated OPD could be limited to a few per cent for circular objects within the investigated size range. For non-circular objects, however, the orientation angle of the object relative to the lateral shift was found to influence the measured values. Ellipses with their long axes perpendicular to the shift direction had a significantly higher integrated OPD than ellipses orientated parallel to the shift. By adjusting the reconstruction parameters the effect could be limited, but complete elimination of the artefact was not possible within the parameter range investigated.

Journal Article↗

Improving the in vivo X-ray fluorescence (XRF) measurement of renal mercury.

In vivo polarised X-ray fluorescence (XRF) measurements of renal mercury have previously been reported (Börjesson J, Barregård L, Sällsten G, Schütz A, Jonson R, Alpsten M, Mattsson S, 1995. In vivo XRF analysis of mercury: the relation between concentrations in the kidney and the urine. Phys. Med. Biol. 40, 413-426). However, with the detection limit reported therein, this system is limited to measurements in cases of significant mercury exposure. An improvement in detection limit is desirable to produce a tool capable of occupational monitoring in cases of mild to moderate exposure. Therefore, design changes have been investigated to improve system performance. Through Monte Carlo simulation and experiment, optimal parameters were determined with respect to polarisation and filtration, as well as the ideal X-ray tube voltage. The optimal configuration will be discussed. A preliminary comparison in terms of minimum detectable limit (MDL) will be made with the preceding polarised XRF renal mercury system.

Filtration↗

Quantitative structure-activity relationships of antitumor guanidinothiazolecarboxamides with survival enhancement for therapy in the 3LL Lewis lung carcinoma model.

Guanidinothiazolecarboxamides (GTCs) are a novel class of antitumor agents found to be systemically active against experimental pulmonary metastases of 3LL Lewis lung carcinoma. A series of substituted benzothiazole GTCs were found to produce enhancement of survival in this model by using 8 days of intraperitoneal dosing initiated 2 days after intravenous tumor challenge. Quantitative structure-activity relationships have been discovered in the GTC series with survival enhancement correlated to substituent parameters. Optimal correlations were found between the probit transform of the drug-induced increased lifespan (ILS) and field and pi parameters. Among the most effective analogues in this series was N-(5-fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxam ide.

Adenocarcinoma↗

The mechanism of reaction of fully reduced membrane-bound cytochrome oxidase with oxygen at 176K.

1. The results of non-linear optimization studies on the mechanism of reaction of fully reduced cytochrome oxidase with O2 at 176K are presented. The analysis is carried out on data obtained by means of dual-wavelength multi-channel spectroscopy at three wavelength pairs (604-630, 608-630 and 830-940 nm) and at three O2 concentrations (60, 200 and 1180 micron). The only model that satisfies the triple requirement of a standard deviation within the standard error of the experimental data, good determination of the optimized parameters and a random distribution of residuals is a three-species sequential mechanism. 2. On the basis of the optimized values of the relative absorption coefficients of the intermediates at each wavelength obtained from the present paper together with data from low-temperature trapping, e.p.r. and magnetic-susceptibility studies, the possible valence states of the metal centres in each of the intermediates are discussed.

Chemical Phenomena↗