[Use of a hybrid analog laboratory computer with small computation capacity for control of feedback signal donors by electromyogram amplitude].
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Computers↗
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Results for “COMPUTERS, ANALOG”
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Bromide pharmocokinetics: a model for residue accumulation in animals.
Using data obtained from pharmacokinetic experiments with bromide, illustrations are given of the application of pharmacokinetics to toxicological studies. Analog computers may be helpful, though not indispensable. The significance of ancillary pharmacokinetic investigations in the evaluation of toxicity studies is discussed.
Animals↗
Pharmacokinetics of beta-methyldigoxin in healthy humans I: intravenous studies.
The pharmacokinetics of intravenously administered solutions of 0.30-and 0.60-mg bolus doses of 3H-beta-methyldigoxin, labeled in the 12alpha-position, were dose independent. Individual radioactivities assignable to the parent drug and specifically identified metabolites after TLC separation were followed in the plasma, urine, and feces. A sum of four exponentials described the plasma beta-methyldigoxin data with apparent half-lives of 0.04, 0.33, 3.5, and 41 hr. beta-Methyldigoxin was 10% plasma protein bound and had a red blood cell-plasma water partition coefficient of 0.9. The only significant metabolite observed in plasma was digoxin, although glucuronides and sulfates of beta-methyldigoxin, digoxin and digoxigenin also were observed in urine. As much as 92 +/- 3% of the dose was excreted by all processes by 144 hr. Of this amount, renal excretion accounted for fractions that were 0.47 unchanged, 0.35 digoxin, and 0.058 water-soluble metabolites. The fraction in the feces was 0.13. The urine flow independent renal clearances of beta-methyldigoxin and derived digoxin were 59 and 206 ml/min, respectively. The metabolism was a relatively fast process. The terminal pseudo-steady-state elimination of beta-methyldigoxin with a half-life of 41 hr was reached 27 hr after drug administration and was primarily dependent on the slow release of sequestered or distributed drug drom the tissues into the central compartment. The drug and metabolite levels in plasma and urine were consistent with analog computer fitting to the proposed pharmacokinetic multicompartmental model.
Adult↗
Pharmacokinetics of beta-methyldigoxin in healthy humans II: Oral studies and bioavailability.
The pharmacokinetics of orally administered aqueous 3H-beta-methyldigoxin solutions were studied at two dose levels, 0.3 and 0.6 mg, in healthy human subjects. The drug and its metabolites were specifically assayed in biological fluids and compared with results after intravenous doses to the same subjects. No significant dose dependency was observed. The apparent half-life of absorption was 16+/-6 min (SEM). Digoxin was the only metabolite observed in the plasma and comprised 28.6+/-3.7% of the dose in the urine. 3H-beta-Methyldigoxin, renally excreted unchanged, comprised 25.7+/-1.7% (SEM). Water-soluble metabolites in the urine comprised 9.0+/-1.8%. Fecal and urinary excretion accounted for 85% of the dose at 144 hr. The oral absorption of unchanged 3H-beta-methyldigoxin from solution was 59+/-6% by area under the curve methods and 60+/-4% by renal excretion. A total of 73% of the dose in the solution was absorbed as beta-methyldigoxin and digoxin. First-pass metabolism prior to absorption was largely prehepatic and assignable to GI degradation; 21.9+/-2.8% was degraded with 12.8+/-4.0% to digoxin and 9.1+/-4.0% to water-soluble metabolites. From 14 to 18% of the administered oral dose did not reach the systemic circulation. Analog computer fitting of plasma and urine levels of drug and digoxin was consistent with the first-pass premise with a delayed absorption of GI-generated digoxin and other metabolites. There were no significant differences between the oral absorption of a tablet formulation and the solution. Orally administered beta-methyldigoxin solution delivered 97% cardioactivity as itself and digoxin with respect to an equivalent amount of intravenously administered digoxin. This value contrasts to the 140% delivered by intravenously administered beta-methyldigoxin on the premise of pharmacodynamic equivalence of systemically appearing digoxin and beta-methyl-digoxin. Literature reports on the oral bioavailability of solutions and solid dosage forms of digoxin were critically reviewed, but no reliable comparison of the extent and reproducibility of oral absorption of cardioactive agents from administered digoxin or beta-methyldigoxin could be made from the widely variable digoxin studies with nonspecific assays.
Administration, Oral↗
A model of Alexander's law of vestibular nystagmus.
The observation that the amplitude of vestibular nystagmus grows as gaze is increased in the direction of the nystagmus fast phase and diminished with gaze in the opposite direction is known as "Alexander's law". We have developed an analog computer model to simulate Alexander's law in nystagmus secondary to dysfunction of a semicircular canal. The model utilizes relevant brainstem anatomy and physiology and includes gaze modulation of vestibular signals and push-pull integration to create eye position commands. When simulating normally functioning semicircular canals, the model produced no nystagmus. When simulating total impairment of the canal on one side with gaze directed maximally in the opposite direction, the model produced a large amplitude nystagmus with linear slow phases directed toward the affected side. As gaze was changed from far contralateral to ipsilateral, the nystagmus gradually diminished to zero. When simulating partial impairment of one canal, the nystagmus was smaller in amplitude and absent in ipsilateral gaze.
Brain Stem↗
[Model for describing tremor (authors transl)].
Acceleration measurements of lower arm, hand and finger tremor principally contain several reproducible peaks in thier power spectral density function. The transfer function of the system was determined by application of a sinusiodal force with an amplitude of less than 1 p.c. of the maximum isometric strength. For description of the lower arm tremor a closed loop system was proposed combining the vibration of a mechanical resonant system with stochastic forcing and the oscillation of the neuromuscular reflex arc, The elements of this system were analyzed by cros-correlation of elctrical of electrical activity and tremor vibration and by analog computer simulation.
Computers, Analog↗
The role of action reflexes in the damping of mechanical oscillations.
Reflex responses measured during voluntary contraction of the muscle being stretched are known to differ markedly from reflex responses elicited from passive muscle. The term 'action tonic stretch reflex' or 'action TSR' has been used previously to describe a reflex response to continuous stretch, separated from voluntary activity by means of a cross-correlational and spectrographic analysis. In this paper it is proposed that the action TSR play a functional role during voluntary movement by damping the transient oscillations associated with the natural resonant frequencies of the limbs. It is suggested that oscillations excite an action TSR force response with phase lead ahead of muscle stretch. This force response can be resolved into two force components, one of which has a 90 degree phase lead ahead of muscle stretch and behaves like a viscous friction reaction force causing damping of oscillations. Three experiments which support this proposition are described. (1) Analog computer model stimulation studies of a muscle supporting a mass-spring load reveal that damping only occurs when the force response has a phase lead ahead of muscle stretch. When the force response has a phage lag behind muscle stretch, the system is unstable and the amplitude of oscillation increases with time. (2) It is demonstrated that when a mass-spring load is supported as rigidly as possible by the human arm, reaction forces from the arm damp and mass-spring oscillations more rapidly than when the mass-spring is rigidly supported. Electromyogram (EMG) recordings reveal that mass-spring oscillations excite action TSR responses with phase lead ahead of muscle stretch. (3) Recordings of elbow angle and biceps EMG during rapid forearm flexion or extension movements followed by sudden stops reveal critically damped oscillations in the elbow angle signal (i.e. no more than one or two small overshoots), which are accompanied by EMG action TSR responses with phase lead ahead of muscle stretch.
Arm↗
The use of dynamic models to study the role of calcium in the oxytocin-induced contractions of the uterus.
The question as to whether calcium can be considered to be a mediator of oxytocin-induced myometrial contraction has been investigated. Assuming that the contraction is linearly proportional to the myoplasmic calcium concentration, several possible molecular mechanisms leading to its increase (calcium release from the cell membrane, acceleration of calcium transport from extracellular space by a 'gate' mechanism, release from intracellular organelles, blockade of calcium pumps) were modelled on an analog computer. The oxytocin intervention in the calcium distribution was mimicked by a discontinuous change of the appropriate rate constants. The computed transient simulating the myoplasmic calcium concentration was then compared with an experimental time profile of uterine tension. The result of screening the models shows that oxytocin must act predominantly via release of calcium bound to the cell membrane. A quantitative comparison, however, requires that the kinetics of oxytocin distribution in myometrium also be considered in the model. The problem treated in this paper demonstrates the possibilities and limitations of a screening procedure based upon direct comparison of time profiles of experimental processes with several computed model alternatives.
Animals↗
Intraoperative application of intraaortic balloon counterpulsation determined by clinical monitoring of the endocardial viability ratio.
Persistent unrecognized subendocardial ischemia with development of subendocardial necrosis is a major cause of patient death following cardiopulmonary bypass. The lesion is caused by a discrepancy between the oxygen needs of subendocardial muscle and the available blood supply. If sole reliance is placed upon monitoring conventional vital signs, the more subtle factors contributing to decreased blood flow may go unrecognized. Reported studies have confirmed that the adequacy of subendocardial perfusion can be predicted by calculating the supply/demand ratio, defined as the ratio of the diastolic pressure-time index (DPTI) divided by the systolic pressure-time index (TTI). An analog computer was designed and built that measures the area under the systolic and diastolic component, calculates the DPTI/TTI ratio, and digitally displays the result as the endocardial viability ratio (evr). The EVR was used to determine the adequacy of left ventricular subendocardial blood flow in 64 consecutive patients undergoing cardiac operations. Unidirectional intraaortic balloon counterpulsation (IABC) was utilized in 14 patients with 9 long-term survivors. The difference in mean EVR between survivors and nonsurvivors at the initiation of balloon support was statistically significant. Early application of unidirectional IABC when subendocardial ischemia persists following open cardiac procedures may prevent deterioration to subendocardial necrosis with subsequent morbidity or mortality.
Assisted Circulation↗
Kinetic evidence for the obligatory formation of a 30S initiation complex in polyphenylalanine synthesis initiated with N-acetylphenylalanyl-5RNA.
The problem of whether the initiation of bacterial protein synthesis involves the obligatory formation of a 30S initiation complex intermediate was examined in a model system with N-acetylphenylalanyl-tRNA as initiator 5RNA nad poly(uridylic acid) as mRNA. The time courses of the formation of the 30S and 70S initiation complex with Escherichia coli ribosomes were measured simultaneously by stopping the reaction with dextran sulfate and differentiating the N-acetylphenylalanyl-tRNA bound to 30S ribosomal subunits from that bound to 70S ribosomes with RNase I, which hydrolyzes N-acetylphenylalanyl-tRNA bound to 30S subunits but not that bound to 70S ribosomes. A maximum in the 30S complex concentration was observed within the first 10-15 sec of the reaction, whereas 70S complex formed formed more slowly with a slight initial time lag. When an analog computer was programmed with rate constants determined separately for the formation of the 30S initiation complex from preformed 30S complex, kinetic curves very similar to the empirical curves were obtained for the entire time course of the reaction. The results show clearly that formation of the 70S complex obeys the kinetic laws for consecutive reactions, and the 30S complex is, therefore, an obligatory intermediate in the initiation of polyphenylalanine synthesis in the model system.
Binding Sites↗
Influence of an aggregated multienzyme system on transient time: kinetic evidence for compartmentation by an aromatic-amino-acid synthesizing complex of Neurospora crassa.
The aromatic complex of Neurospora crassa is an aggregated multienzyme system which catalyzes five consecutive reactions in the central pathway leading to the biosynthesis of the aromatic amino acids. In an attempt to understand the physiological importance of this complex in particular, as well as the importance of cellular organization of enzyme systems in general, we have isolated the complex and have begun to characterize its catalytic properties. Optimum conditions for the assay of the overall 5-step reaction catalyzed by the partially purified complex have been determined. An analog computer was programmed to represent an unaggregated system of five enzymes with rate constants identical to those found for the constituent enzymes of the complex. By direct comparison, it was shown that the lags (transient times) obtained for the overall reaction were 10-15 times longer for the hypothetical unaggregated system than for the complex. We conclude from these data that the aggregated multienzyme system compartmentalizes intermediate substrates during the course of the overall reaction. We suggest that, in addition to "channeling" intermediates of competing pathways, reduction of the transient time may be an important consequence of the containment of intermediates within a physically associated enzyme sequence. The fact that the aromatic complex exhibits a second catalytic property unique to aggregated enzyme systems, "coordinate activation" [Welch, G.R. & Gaertner, F.H. (1975) Arch. Biochem. Biophys., in press] indicates that the physical association of these enzymes may have more than one physiological function.
Amino Acids↗
Enhancement of photosynthesis by alternated light beams and a kinetic model.
Using the alga Chlorella and 2 light beams of defined wavelength, we have found that short period (1 sec) alternation gives all characteristics of enhancement of net oxygen evolution observed when the beams are superimposed. With increasing period of alternation (1-20 see) decay in enhancement is more rapid at higher intensities. We have developed a kinetic model for the current hypothesis of 2 photoacts operating in series and separated by electron transport reactions. The model is applicable at low light intensity such that rate is governed only by intensities and the fractions of reaction centers open for each photoact. Potentials and pool sizes of intermediates were taken from current estimates. Wavelength dependency of the 2 photoacts was taken from enhancement spectra for superimposed light beams. Analog computer treatment of the kinetic equations gave predictions of chromatic transients and alternated enhancement which are in reasonable but not complete agreement with experimental observations.
Chemical Phenomena↗
Validation of an automated determination of pulmonary resistance by electrical subtraction.
An analog computer to determine dynamic pulmonary compliance (C) and pulmonary resistance (R) on a breath-by-breath basis was tested in guinea pigs and dogs. C was determined by dividing volume by transpulmonary pressure at instants of zero flow. R was determined by the method of electrical subtraction at predetermined flows. In both species the computer outputs and the results of direct analysis were in close agreement. In guinea pigs, the device reliably followed the rapid three- to fourfold changes in C and R resulting from histamine infusion. In unanesthetized dogs, the dispersion and mean values of C and R were similar by the two methods.
Airway Resistance↗
[Analytical and analogical study of a model of the adrenal-postpituitary function (author's transl)].
After an analyitical study of mathematical models connected with osmotic or volemic regulations, and the mention of its contribution to the therapeutic act, the authors approach the stimulation, by the mean of an analogical computer, of the complete and non-linear model which associates both types of regulation. So it is possible to attempt to determine the level of adrenal and vasopressin actions according to: 1 degree the sum of the agonistic effects and the difference of their antagonistic effects; 2 degrees the perturbations brought to the system; 3 degrees the parametric values of the model. Theoretical and empirical curves seem to be in favour of such a formulation.
Adrenal Cortex↗
A sampling method for mean alveolar gas in normal subjects and patients with respiratory disease.
The paper describes an alveolar gas sampling method based on the criterion of equality of mean alveolar (RA) and expired (RE) respiratory quotients. Expired gas is sampled at an expired volume equal to VT/2 + VD by means of a mechanical sampler controlled by an analog computer. Eleven normal subjects and 50 patients with cardiopulmonary disease have been tested. When the difference between mean alveolar and expired respiratory quotients did not exceed 0.05, the result was considered to be satisfactory. Such results have been obtained in 40 patients and all of the normal subjects. For the remaining 10 patients, either experimental error and/or particular non-homogeneities in ventilation seemed to be the cause of the unsatisfactory results. Arterial to alveolar PCO2 differences have been calculated. The mean difference in normal subjects was never negative (1.86 +/- 1.58 torr).
Analysis of Variance↗
[Technical and experimental study of two electronic spirometers (author's transl)].
Two electronic spirometers which use standard pneumotachographs were evaluated for their static and dynamic response, and clinically compared in 20 subjects to a reference flow channel. In the Pneumoscreen the data are digitalized and stored, permitting to play back the flow-volume curves at low or high speed. The instrument provides a direct read-out of forced vital capacity and of five indexes of forced expiration. It was found perfectly adequate with respect to linearity and frequency response. However, due to some systematic error in digital processing, maximum flow at low lung volumes appeared substantially over-estimated. Besides forced vital capacity and a number of indexes of forced expiration, the Medistor type M 010 may be used to measure ventilation, tidal volume, frequency and maximum breathing capacity. The data are processed by an analog computer. The transducer was found poorly linear with inadequate frequency response. However, no systematic bias in the measurements was found, except for peak flow and maximum breathing capacity.
Airway Obstruction↗
[The theory of thermoluminescence].
The interaction of stimulating radiation with matter produces defects which can be divided into two groups: 1. electronic defects, 2. ionic defects. The formation of defects is essentially determined by electronic processes and elastic impacts. The supply of energy in the form of heat makes possible a thermal stimulation the probability of which is characterized by a Boltzmann factor. Whereas the classical explications are based on thermodynamic or statistical considerations, the quantum mechanical calculation relates to non-radiative transitions from traps. For the radiating recombination a selective rule is valid which guarantees the conservation of energy and impulse. The phenomenological description of thermoluminescence makes use of the kinetic processes in the non-stationary case and allows in simple models the determination of trap parameters, such as activation energy or pre-exponential factor. The simple models can be extended by introducing thermally separated trap levels. If the kinetic balance equations are solved exactly with the aid of an analogic computer, the simulated Glow curves show a good correspondence with experimental curves.
Computers, Analog↗
Nystagmus computation by analog technics. SAM-TR-70-7.
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Computers, Analog↗