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PubMed2003

Spectral EEG effects of electroconvulsive shock stimulus parameters: the development of a rationale for the optimization of the ECT stimulus.

BACKGROUND: Electroconvulsive therapy (ECT) stimulus parameters, such as pulse amplitude, pulse width, pulse frequency, and stimulus duration, differently influence seizure threshold and, possibly, other neurobiological effects of ECT. We examined the influence of these parameters on the EEG power spectrum in an animal model. METHODS: Adult, male, Wistar rats (n=54) were randomized to receive one of five differently constituted (approximately) 30-mC electroconvulsive shock (ECS) stimuli administered once on alternate days for a total of three ECS. A single-lead, unipolar EEG recording was obtained before, during, and immediately after each ECS seizure. EEG power was computed in eight frequency bands from 2 to 40 Hz. Greater ictal EEG power, greater postictal EEG suppression, and greater interictal EEG power, especially in lower frequency bands, were a priori defined as proxies of seizure efficacy. RESULTS: Motor and EEG seizure duration and a proxy for seizure generalization did not differ significantly across the five stimulus groups. Despite equivalent charge, the five stimuli varied widely in their effects on the EEG proxies of seizure efficacy. The narrow (0.6 milliseconds) pulse width, high (100 Hz) pulse frequency combination was best associated with EEG proxies of seizure efficacy; with this combination, a longer stimulus train duration appeared superior to a greater pulse amplitude. The wide (2 milliseconds) pulse and low (30 Hz) frequency combination was least associated with EEG proxies of efficacy. Stimulus "on" time, number of pulses delivered, and the rate of delivery of charge were not associated with the EEG proxies; the former finding questions the validity of dosing ECT in units of charge. CONCLUSIONS: These findings suggest a rationale for optimizing stimulus parameter choices during ECT and provide a framework for the evaluation of electrical aspects of the ECT stimulus.

Animals↗

PubMed2004

High-throughput morphometric analysis of individual neurons.

To facilitate high-throughput quantitative analysis of neuronal structure, this study optimized the diOlistic method of whole neuron labeling to examine multiple neurons in fixed brain, and optimized image acquisition parameters to preserve signal for subsequent photoconversion. Fluorescent dye-coated gold particles were successively delivered by helium-powered ejection to 250 microm thick brain slices with loading density and penetration depth optimized to maximize the yield of labeled neurons within the slice while avoiding overlapping labeled dendritic processes in the x-y plane and z-axis. Labeled neurons were imaged using confocal laser-scanning microscopy with pinhole aperture and scan speed enhanced to minimize capture time and fluorescence degradation. Optimized image acquisition parameters preserved fluorescence signal and facilitated subsequent oxygen-enriched photoconversion for higher magnification dendritic spine analysis. Sampling criteria limited analysis to neurons whose z-axis dendritic processes were fully contained within the tissue slice and in which dye transport extended to the most distal portions of the dendrites. The yield of completely labeled neurons was, on average, more than 20 cells per brain region per animal. With optimized spatio-temporal diOlistic loading parameters, along with image acquisition parameters optimized for subsequent photoconversion, the present protocol provides a high-throughput strategy for full-scale quantitative analysis of three-dimensional neuronal morphology.

Animals↗

PubMed1987

Implantable extra-aortic balloon assist powered by transformed fatigue-resistant skeletal muscle.

The hypothesis tested in this study was whether a skeletal muscle could be transformed to be fatigue resistant, to be used to power an implantable extra-aortic balloon assist device, and therefore to provide dynamically significant cardiac assistance. Eight dogs underwent implantation of an Itrel pacemaker to stimulate the thoracodorsal nerve over 8 to 18 weeks and transform the latissimus dorsi muscle. Biopsies of these muscles confirmed near complete (up to 98%) transformation into fatigue-resistance type I muscle fibers, identified by the adenosinetriphosphatase histochemical stains. Biochemical assays showed conversion of myosin isoforms to that of myocardial V3 phenotype, decreased activity of anaerobic glycolytic marker, and increased activity of aerobic enzyme marker, which indicated greater resemblance of such muscle to the myocardial fibers. In four dogs, the optimal stimulation parameters of such muscles in response to a burst stimulator, which synchronizes and summates the muscle contraction, were studied and compared with the contralateral, nontransformed muscle. Fatigue tests confirmed the marked fatigue resistance of the transformed muscle. In four dogs, a 100 ml balloon was placed beneath the transformed latissimus dorsi muscle and connected to the thoracic aorta with a Dacron graft. By means of the optimal burst-stimulating parameters identified above, the latissimus dorsi muscle was stimulated to contract during diastole, compressing the balloon to achieve diastolic augmentation while allowing the balloon to fill during systole. A 39% increase (p less than 0.001) in the "subendocardial viability index" (diastolic pressure-time index/tension-time index) was obtained as calculated from the left ventricular and ascending aortic pressure tracings. We conclude that the skeletal muscle can be transformed to resemble myocardium, which can generate sufficient force to provide hemodynamically significant and clinically relevant counterpulsation.

Animals↗

PubMed2005

Determination of carbamates and organophosphorus pesticides by SDME-GC in natural water.

Water contamination due to the wide variety of pesticides used in agriculture practices is a global environmental pollution problem. Analytical methods with low quantification limits are necessary. The application of a new extraction technique, solvent drop microextraction (SDME), followed by gas chromatography with a nitrogen-phosphorus detector, was assessed for determining carbamates and organophosphorus pesticides in natural water. Experimental parameters which control the performance of SDME such as selection of microextraction solvent, optimization of organic drop volume, effects of sample stirring, salt addition, and, finally, sorption time profiles were studied. Once SDME was optimized, analytical parameters such as linearity (r 2>0.99), precision (<13%), and detection limits (0.2 to 5 microg/L), plus matrix effects were evaluated (no matrix effects were found). SDME is a dynamic technique able to extract pesticides from water in 14 min; the use of organic solvents and water samples for SDME is negligible compared to other extraction techniques.

Carbamates↗

PubMed2005

Analysis of trace levels of pesticides in rainwater using SPME and GC-tandem mass spectrometry.

A multiresidue method using gas chromatography coupled to ion trap tandem mass spectrometry (GC-ITD-MS/MS) associated with solid phase microextraction (SPME) was developed for the analysis of 20 pesticides commonly used in the Alsace region in rainwater samples. Since the pesticides were expected to be present at very low concentrations and in complex matrices, the analytical method used was both highly selective and sensitive. Therefore, fibers coated with polyacrylate (PA), polydimethylsiloxane (PDMS) and polydimethylsiloxane-divinylbenzene (PDMS-DVB) were tested, and the parameters affecting the precision and accuracy of the SPME method were investigated and optimized. These parameters include the type of fiber, the adsorption time, the effect of salt, and the extraction temperature. The PDMS fiber was the most polyvalent for the extractions of the different pesticides studied. Detection limits of between 5 and 500 ng L(-1), depending on the compounds under study (except for those which could not be analyzed: captan and mevinphos), were obtained with this analytical procedure. This method was applied to the analysis of rainwater samples collected simultaneously on a weekly basis at one rural and one urban site between March 2002 and July 2003. While some of the 20 pesticides analyzed were constantly detected (such as lindane and atrazine), a strong temporal variability was observed for some of the others (including alachlor, metolachlor, atrazine).

Journal Article↗

PubMed2002

[Historical review and recent research trends of the antidepressant repetitive transcranial magnetic stimulation (rTMS)].

The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) has been studied intensively over the last years. Numerous studies worldwide yielded variable results ranging from ineffectivity to an efficacy rate of more than 50 % for the reduction of depressive symptoms. A comparison of the effectiveness of TMS across studies is difficult due to the variety of chosen stimulation parameters, different inclusion criteria, and different designs. The discrepancies in results could be partially in account to these factors. From a pathophysiological point of view, there are no empirically justified parameters published carrying out an antidepressant TMS. Further studies are required to find optimal stimulation parameters using complementary methods like functional imaging techniques or regarding other factors that could interfere with its efficacy. An overview of studies published in the last ten years, a critical analysis of stimulation procedures and protocols, and possible future perspectives of this method are reviewed in this article.

Brain↗

PubMed2005

Detection of hearing loss using 2f2-f1 and 2f1-f2 distortion-product otoacoustic emissions.

Although many distortion-product otoacoustic emissions (DPOAEs) may be measured in the ear canal in response to 2 pure tone stimuli, the majority of clinical studies have focused exclusively on the DPOAE at the frequency 2f1-f2. This study investigated another DPOAE, 2f2-f1, in an attempt to determine the following: (a) the optimal stimulus parameters for its clinical measurement and (b) its utility in differentiating between normal-hearing and hearing-impaired ears at low-to-mid frequencies (<or=2,000 Hz) when measured either alone or in conjunction with the 2f1-f2 DPOAE. Two experiments were conducted. In Experiment 1, the effects of primary level, level separation, and frequency separation (f2/f1) on 2f2-f1 DPOAE level were evaluated in normal-hearing ears for low-to-mid f2 frequencies (700-2,000 Hz). Moderately high-level primaries (60-70 dB SPL) presented at equal levels or with f2 slightly higher than f1 produced the highest 2f2-f1 DPOAE levels. When the f2/f1 ratio that produced the highest 2f2-f1 DPOAE levels was examined across participants, the mean optimal f2/f1 ratio across f2 frequencies and primary level separations was 1.08. In Experiment 2, the accuracy with which DPOAE level or signal-to-noise ratio identified hearing status at the f2 frequency as normal or impaired was evaluated using clinical decision analysis. The 2f2-f1 and 2f1-f2 DPOAEs were measured from both normal-hearing and hearing-impaired ears using 2 sets of stimulus parameters: (a) the traditional parameters for measuring the 2f1-f2 DPOAE (f2/f1 = 1.22; L1, L2 = 65, 55 dB SPL) and (b) the new parameters that were deemed optimal for the 2f2-f1 DPOAE in Experiment 1 (f2/f1 = 1.073, L1 and L2 = 65 dB SPL). Identification of hearing status using 2f2-f1 DPOAE level and signal-to-noise ratio was more accurate when the new stimulus parameters were used compared with the results achieved when the 2f2-f1 DPOAE was recorded using the traditional parameters. However, identification of hearing status was less accurate for the 2f2-f1 DPOAE measured using the new parameters than for the 2f1-f2 DPOAE measured using the traditional parameters. No statistically significant improvements in test performance were achieved when the information from the 2 DPOAEs was combined, either by summing the DPOAE levels or by using logistic regression analysis.

Adolescent↗

PubMed1996

Microencapsulation for cell implants into the central nervous system: the importance of alginate viscosity and related factors.

We have developed microcapsules using sodium alginate and poly-L-lysine with optimal combinations of experimental parameters and also used different autoclave times to evaluate the impact of sterilization on the property of capsules. We found that an autoclave time of 20 min was sufficient for sterilization of the alginate, and the optimal concentration of the alginate of low and high viscosity was 1.75 and 1.25% respectively. The capsules made with those optimal parameters remained intact for 6 months in an environment resembling that of the brain. Our results suggest that it is important to optimally combine experimental parameters in order to obtain reliable microcapsules, which may be used for many secretory cell implantats into the central nervous system in vivo.

Alginates↗

PubMed2000

Investigation of the chemical stability of an erythromycin-tretinoin lotion by the use of an optimization system.

A combination of 2% erythromycin and 0.05% tretinoin in an alcohol-isopropanol lotion was prepared. Two parameters were investigated for their influence on the stability of erythromycin and/or tretinoin, namely pH and the concentration of butylhydroxytoluene (BHT) as antioxidant. To investigate these two parameters, an optimization technique was used with two factors (pH and concentration of BHT) at two levels. Accelerated stability analysis was performed at 45 degrees C in the dark to exclude isomerization of tretinoin. To analyse erythromycin and tretinoin in the combination preparation, a TLC method, previously developed in the laboratory, was used. The degradation of erythromycin seemed to be much faster than the tretinoin degradation. Optimal stability is shown in the pH range of 8.2-8.6 for erythromycin and 7.2-8.2 for tretinoin while the concentration of BHT had no significant influence.

Anti-Bacterial Agents↗

PubMed2004

A modified TIP3P water potential for simulation with Ewald summation.

The charges and Lennard-Jones parameters of the TIP3P water potential have been modified to improve its performance under the common condition for molecular dynamics simulations of using Ewald summation in lieu of relatively short nonbonded truncation schemes. These parameters were optimized under the condition that the hydrogen atoms do not have Lennard-Jones parameters, thus making the model independent of the combining rules used for the calculation of nonbonded, heteroatomic interaction energies, and limiting the number of Lennard-Jones calculations required. Under these conditions, this model provides accurate density (rho = 0.997 g/ml) and heat of vaporization (DeltaH(vap) = 10.53 kcal/mol) at 25 degrees C and 1 atm, but also provides improved structure in the second peak of the O-O radial distribution function and improved values for the dielectric constant (epsilon(0) = 89) and the diffusion coefficient (D = 4.0 x 10(-5) cm(2)/s) relative to the original parametrization. Like the original parameterization, however, this model does not show a temperature density maximum. Several similar models are considered with the additional constraint of trying to match the performance of the optimized potentials for liquid simulation atom force field to that obtained when using the simulation conditions under which it was originally designed, but no model was entirely satisfactory in reproducing the relative difference in free energies of hydration between the model compounds, phenol and benzene. Finally, a model that incorporates a long-range correction for truncated Lennard-Jones interactions is presented, which provides a very accurate dielectric constant (epsilon(0) = 76), however, the improvement in this estimate is on the same order as the uncertainty in the calculation.

Computer Simulation↗

PubMed2004

Single-drop microextraction and gas chromatography/mass spectrometric determination of anisaldehyde isomers in human urine and blood serum.

The application of single-drop microextraction (SDME) followed by gas chromatography/chemical ionization mass spectrometry (GC/CI-MS) was investigated for the determination of anisaldehyde isomers in human urine and blood serum. The effects of extraction solvent, sample agitation rate, salt addition, sampling time and temperature on the extraction efficiency were examined and optimized. Analytical parameters such as linearity, reproducibility, detection limit and relative recovery were evaluated under the optimized experimental conditions. Good reproducibilities of replicate extractions (n = 5) were obtained, with relative standard deviation (RSD) values below 6%. The limits of detection (LOD) using an extraction time of 5 min were found to be in the range 2-5 ng/mL under the selected ion monitoring (SIM) mode of GC/MS. Recoveries of 82-98% were achieved after 5 min extraction.

Benzaldehydes↗

PubMed2006

A simplified type-2 fuzzy logic controller for real-time control.

Increasingly, genetic algorithms (GAs) are used to optimize the parameters of fuzzy logic controllers (FLCs). Although GAs provide a systematic design approach, the optimization process is generally performed off-line using a plant model. Differences between the model and physical plant may result in unsatisfactory control performance when the FLCs are deployed in practice. Type-2 FLCs are an attractive alternative because they can better cope with modeling uncertainties. Unfortunately, type-2 FLCs are computationally intensive. This paper presents a simplified type-2 FLC that is suitable for real-time applications. The key idea is to only replace some critical type-1 fuzzy sets by type-2 sets. Experimental results indicate that the proposed simplified type-2 FLC is as robust as a conventional type-2 FLC, while lowering the computational cost.

Journal Article↗

PubMed1999

Intensity-modulated tangential beam irradiation of the intact breast.

PURPOSE: To evaluate the potential benefits of intensity modulated tangential beams in the irradiation of the intact breast. METHODS AND MATERIALS: Three-dimensional treatment planning was performed on five left and five right breasts using standard wedged and intensity modulated (IM) tangential beams. Optimal beam parameters were chosen using beams-eye-view display. For the standard plans, the optimal wedge angles were chosen based on dose distributions in the central plane calculated without inhomogeneity corrections, according to our standard protocol. Intensity-modulated plans were generated using an inverse planning algorithm and a standard set of target and critical structure optimization criteria. Plans were compared using multiple dose distributions and dose volume histograms for the planning target volume (PTV), ipsilateral lung, coronary arteries, and contralateral breast. RESULTS: Significant improvements in the doses to critical structures were achieved using intensity modulation. Compared with a standard-wedged plan prescribed to 46 Gy, the dose from the IM plan encompassing 20% of the coronary artery region decreased by 25% (from 36 to 27 Gy) for patients treated to the left breast; the mean dose to the contralateral breast decreased by 42% (from 1.2 to 0.7 Gy); the ipsilateral lung volume receiving more than 46 Gy decreased by 30% (from 10% to 7%); the volume of surrounding soft tissue receiving more than 46 Gy decreased by 31% (from 48% to 33%). Dose homogeneity within the target volume improved greatest in the superior and inferior regions of the breast (approximately 8%), although some decrease in the medial and lateral high-dose regions (approximately 4%) was also observed. CONCLUSION: Intensity modulation with a standard tangential beam arrangement significantly reduces the dose to the coronary arteries, ipsilateral lung, contralateral breast, and surrounding soft tissues. Improvements in dose homogeneity throughout the target volume can also be achieved, particularly in the superior and inferior regions of the breast. It remains to be seen whether the dosimetric improvements achievable with IMRT will lead to significant clinical outcome improvements.

Breast↗

PubMed1982

A candidate reference method for uric acid in serum. I. Optimization and evaluation.

We describe our optimization and evaluation of a candidate Reference Method for uric acid in serum. Reaction parameters were optimized for a manual, enzymic method for uric acid in which highly purified microbial uricase is used to quantitate uric acid by a differential ultraviolet procedure. We evaluated the method in terms of freedom from interferences, analytical recovery, precision, and comparison with five other uric acid methods. We conclude that (a) the candidate uric acid Reference Method exhibits the least interference; (b) all six methods exhibit satisfactory analytical recoveries and precision; and (c) results by all six methods agree well. As a result of this evaluation study, the manual ultraviolet uricase method for uric acid, with Tris as buffer, was chosen as the candidate Reference Method for uric acid.

Adult↗

PubMed1995

Optimal truncation of defibrillation pulses.

The statement that the optimal pulse for defibrillation has not yet been discovered implies that an ideal pulse exists, but that it is different in shape, duration, and energy as compared to pulses of today. The optimum pulse is that which can defibrillate with lowest energy. Reduction of energy can be reached twofold: by looking for a pulse duration with lowest energy threshold, and by finding the optimal truncation with lowest refibrillating effect. Assuming that there is also a rheobase in defibrillation below which no defibrillating but probably a refibrillating effect exists, the exponential pulse should be truncated if it intersects with the rheobase. Combining the fundamental law of electrostimulation with this boundary condition allows for the mathematical solution of the above problem of optimal energy. Defibrillation can be optimized with respect to pulse duration or tilt and to energy efficiency. The most important parameter in determining other optimized parameters such as output capacitor is the chronaxie. The calculations reveal that the "concept of constant energy" does not accurately describe defibrillation, that today's implantable cardioverter defibrillator devices possess refibrillating tilts, that pulse durations should be programmed to values between 4 and 10 msec, and that smaller output capacitors around 30 microF would minimize the energy requirements. Whether optimized monophasic pulses are inferior or equal to biphasic pulses needs further experimental studies.

Defibrillators, Implantable↗

PubMed1995

Optimal truncation of defibrillation pulses.

Animals↗

PubMed2002

Combined ab initio/empirical approach for optimization of Lennard-Jones parameters for polar-neutral compounds.

The study of small functionalized organic molecules in aqueous solution is a useful step toward gaining a basic understanding of the behavior of biomolecular systems in their native aqueous environment. Interest in studying amines and fluorine-substituted compounds has risen from their intrinsic physicochemical properties and their prevalence in biological and pharmaceutical compounds. In the present study, a previously developed approach which optimizes Lennard-Jones (LJ) parameters via the use of rare gas atoms combined with the reproduction of experimental condensed phase properties was extended to polar-neutral compounds. Compounds studied included four amines (ammonia, methylamine, dimethylamine, and trimethylamine) and three fluoroethanes (1-fluoroethane, 1,1-difluoroethane, and 1,1,1-trifluoroethane). The resulting force field yielded heats of vaporization and molecular volumes in excellent agreement with the experiment, with average differences less than 1%. The current amine CHARMM parameters successfully reproduced experimental aqueous solvation data where methylamine is more hydrophilic than ammonia, with hydrophobicity increasing with additional methylation on the nitrogen. For both the amines and fluoroethanes the parabolic relationship of the extent of methylation or fluorination, respectively, to the heats of vaporization were reproduced by the new parameters. The present results are also discussed with respect to the impact of parameterization approach to molecular details obtained from computer simulations and to the unique biological properties of fluorine in pharmaceutical compounds.

Amines↗

PubMed1999

[Modification of vision by change in rheologic parameters in senile macular degeneration through membrane differential filtration--initial results of a randomized study].

BACKGROUND: Membrane differential filtration (MDF) is known to optimize rheological parameters by eliminating high molecular weight proteins und lipoproteins from the blood and was shown to influence ocular perfusion parameters. Following the hypothesis that these changes may influence the natural course of age-related macular degeneration (AMD) we tested their efficacy in improving visual function in these patients in a randomized trial. PATIENTS AND METHODS: 20 patients (36 eyes) were randomized into two groups. Ten patients (18 eyes) were treated with MDF and ten (18 eyes) served as controls. The first group was treated five times over a period of 21 weeks. In both groups 8/18 of the eyes showed subfoveolar subretinal neovascularisations. Main parameter of the study was visual acuity. Macular visual evoked potentials were also recorded. Plasmaviscosity, whole blood viscosity and erythrocyte aggregation were measured. RESULTS: The ten patients, treated repeatedly over a period of 21 weeks, showed a mean improvement 1.1 (SD 1.9) lines after 21 weeks, while the control group showed a deterioration of visual acuity (0.6 lines, SD 1.7). The macular visual evoked potentials showed an increase of 0.28 microV (SD 1.12) for the therapy group and a deterioration of 0.57 microV (SD 1.31) in the control group. The rheological parameters were lowered in all patients. CONCLUSIONS: We conclude that repetitive treatment with MDF is able to improve visual function in patients with AMD. Further research is necessary to show how to optimize the selection of patients and how to create an individual treatment strategy.

Aged↗