The objective of the research was to develop a transducer to measure arterial blood pressure. It was required that the transducer provide a continuous measure of blood pressure, that it not encumber the subject and that it not require cannulation. Two basic techniques were investigated both analytically and experimentally. First, an indirect measurement of blood pressure based on arterial deflection was attempted. Difficulties of calibration; and sensitivity to physiological changes of skin and tissue around the artery led to the decision to attempt a more direct measurement of arterial blood pressure. In this second approach, arterial deflection is restrained by the transducer and the resultant restraining force is measured. A mathematical model of the transducer artery system was developed and was used as a guide for the design of the experimental prototype transducers. Tests performed on these experimental transducers gave results consistent with the predictions of the model. These transducers have been used to measure blood pressure at large superficial arteries, with results comparable to sphygmomanometer determinations.
A simple and versatile microspectrofluorometer is described together with suitable electronic circuits for single-differential-or double-aperture operation. The apparatus is suitable for measuring oxidation-reduction states of mitochondrial and cytoplasmic pyridine nucleotide in various organs with apertures ranging from 15 microns up to a few millimeters. Suitable optical and electronic components are briefly described together with some of their limitations. The application of the method to the state of oxygenation of brain and liver together with the recording of hormonal responses in the heart is indicated. An outline of the limitations of the present apparatus and desirable future developments is included.
Automatic interpretation of electrocardiograms is a particular example of the application of digital computers to medical diagnosis; this paper describes our experience with a new approach involving pattern recognition techniques. The program employs a multiple adaptive matched filter system with a variety of normalization, weighting, comparison, decision, modification, and adapting operations. The flexibility of the method has permitted study of effects of experimental variations of these operations on the pattern classification process to simulate human interpretation of electrocardiograms more closely. These programs have been successfully applied to actual electrocardiograms from cardiac patients. These researches in application of computer pattern recognition techniques to the automatic interpretation of electrocardiograms have been undertaken because they join together three fields of great interest. First, an example of artificial intelligence or a self-organized system is represented by the adaptive filter memory, together with the related decision operations. Second, we consider our program to be a model of complex sensory discrimination and use our intuition of human psychology as a guide when selecting one of several possible program mechanisms to overcome temporary obstacles. Third, the automation of medical diagnosis is a rapidly developing and promising field contributing to medical progress. This paper pays particular attention to the third of these objectives. The present state of computer analysis of electrocardiograms is mainly one of orthogonalization of the spatial vector, point recognition to separate the various component waves, parameterization, in one case via Fourier techniques, and then statistical matrix analysis.
Experiments have been conducted which reveal the existence of a detectable magnetic field associated with cardiac electrical activity. The relationship between the magnetic record and the electrocardiogram has been explored and it is shown that under certain conditions of axis orientation the voltage induced into a toroidal sensing element around the heart has the form of the first time derivative of the electrocardiogram. A formula based on Maxwell's equations has been developed to relate these two phenomona.
Some important requirements are outlined for future research on the nervous system if more complex details are to be determined and effectively applied to engineering systems. In particular, these include the development of more precisely controlled and accurate complex stimulus-response experiments, the rapid analysis of characteristically noisy records for the detection of fine detail responses and the intensive correlation of such experiments with adequate theoretical modeling. An "on-line" remote computer station used in conjunction with a central data processing system is described which facilitates the above objectives. This biological control and data processing system is designed to control and accurately record complex multistimuli multiresponse experiments, rapidly digitize pertinent information, send this to the central computer and also receive back analyzed results in graphical form. The application of the system to specific research, at the California Institute of Technology, on sight perception systems is illustrated. Particularly pertinent has been its use to accurately determine and analyze the complex flight torque phototropisms of the housefly, Musca domestica. Less sophisticated experiments made before the application of this data processing system were most discouraging. This was due to the extreme variations between single records, the large apparent noise or uncorrelated responses together with the evidence of complex multifrequency responses and variable sensitivity to different components of the stimuli. The application of the computer system resolved the data analysis problems and many of the required stimulus accuracy problems.
This paper describes a new instrument with excellent low frequency response for recording arterial pulse wave forms. It uses a fluid filled chamber and a stiff diaphragm to which a set of semiconductor strain gages are cemented.
A simple, inexpensive electro-optical instrument is described, by which the osmotic fragility curve of red blood cells, as obtained by gradually decreasing the salt concentration of the medium surrounding the cells, can be automatically recorded. Either the direct sigmoid curve or the derivative curve can be recorded.
The paper describes the design and performance of the smallest iron core electromagnetic flow transducer built so far. The design is miniaturized as to the total volume of the device as well as to the size of the artery it accommodates. The use of this transducer for recording of blood flow in the smallest species of animal employed until now in blood flow research is described. Illustrations of pharmacological observations in anesthetized rats are presented.
A new approach to analog simulation and study of the neuron is proposed. This approach is based on recent physiological evidence which indicates that the individual nerve cell is functionally much more complex than the classical view of a synaptic region coupled directly to a spike or impulse-generating region. At least two different intermediate regions have been found. One provides a reliable low-frequency timing or pacemaker function; the other provides nonlinear amplification of both the synaptic and the pacemaker potentials. In addition, the synaptic regions have been found to provide a large variety of complicated interneural transfer functions. In the view presently held by many physiologists, the spatial distribution of these functionally distinct regions within a single neuron would determine its information-processing capabilities. The behavior of each of the functionally distinct regions of the neuron is discussed in this paper. Simple transistor circuits which may be used to simulate individual regions are also described. Groups of these circuits may be connected to form analogs of the entire neuron or any part thereof. Special emphasis is placed here on the synaptic functions, with only a cursory discussion being given for the other regions. It is hoped that networks of the type described in this paper will be of considerable use in future studies of the information processing capabilities of single nerve cells.
The "titration" procedure is reviewed together with its application to the auditory system of the cat. The relevant portion of the auditory system is described by a mathematical model, and calculations based on it show the merit of titration over the direct observation of a stimulus-response ratio. The model yields a good approximation to Desmedt's experimental titration data.
In peripheral organs a logarithmic relationship between stimulus and response holds for a rather wide range of input magnitudes. This relationship is clearly demonstrated for Limulus between the frequency of discharge in the optic nerve, and the intensity of stimulating light. A simple relaxation oscillator is envisioned to model the generation of nerve impulses. The necessary transfer function of the charging circuit of the oscillator is computed so that the frequency of oscillation should be proportional to the logarithm of the magnitude of the input voltage. It is shown that the obtained transfer function can be realized by a tapered RC transmission line. The experimental verification of the derivation is given.
By taking advantage of readily available industrial devices, used in conjunction with a simple auxiliary circuit, an efficient inexpensive blood-flow measuring system can be obtained. As a further advantage, the preamplifier and demodulator-recorder may be detached and used for other purposes. Flow recordings obtained with this system appear to equal or better recordings obtained with commercial integrated electromagnetic blood-flow measuring systems in regard to both frequency response and noise level. The system also exhibits high reliability and ease of operation as well as portability.
The term biological clock is used to designate the phenomenon, displayed by organisms, of pacing activity in a cyclic manner related to environment. Many nocturnal animals, for example, are capable of entraining the onset of their activity with the light-to-dark transition in a periodic light-dark regime in which the period or ratio of light to darkness varies widely. This paper presents the development of an electronic model for simulation of the adaptation of the endogenous circadian rhythm of nocturnal animals due to light stimuli.
The determination of cardiac output and central blood volume is of considerable importance, not only in cardiac research but in the diagnosis and treatment of heart disease. At present, the most clinically adaptable method of determining these parameters is the indicator-dilution technique. However, analysis of indicator-dilution curves is laborious, requiring twenty to forty minutes of a skilled operator's time. A simple instrument has been devised which permits the determination of cardiac output and central blood volume in less than one minute. The computer described in this paper makes use of an electronically-generated curve which is displayed on a CRT, and optically superimposed on the actual indicator-dilution curve. Three manual controls, used to match the curves, yield the desired parameters. The computer may be used to analyze curves within the following ranges: Curve amplitude (2A) = 2.5 to 10 cm; Period (T) = 2.5 to 10 sec; Time constant (CT) = (0.25 to 1) × T sec; Injection (I) = 5 to 12.5 mg; Calibration (M) = 5 to 1.2 cm/mg/liter; Cardiac output = 0 to 48 liters/min; Mean transit time = 25 sec full scale.
An experiment has been carried out to determine pathological and longevity effects caused by chronic microwave irradiation of mice. Two hundred males were exposed daily for 59 weeks to 0.100 w/cm2 for 4.5 minutes. This treatment produced an average body temperature rise of 3.3° C. Histopathology was performed on all dead mice in both irradiated and control group. Changes in body weight, in body temperature response to heating, and in the blood picture were not evident. Testicular degeneration in the form of tubule atrophy and neoplasms of the white cells were indicated. Longevity of the mice did not appear to be affected under the prevailing conditions.
Blood pressure can be measured directly or indirectly. While direct methods provide the maximum quantity of reliable information from probes inserted into the blood stream, indirect methods produce much less disturbance to the subject. Indirect methods are based on the adjustment of a known external pressure to equal the vascular pressure. Systolic and diastolic pressure can be determined intermittently from the pressure that will just collapse the vessel; an approximation of the instantaneous pressure level is obtained from a surrounding chamber adjusted to remove all vessel wall tension. Direct methods can provide continuous, high fidelity recordings of the absolute vascular pressure via a catheter either to transmit the blood pressure through liquid to an external sensor or to carry the signal leads from a miniature internal sensor. External sensors require careful adjustment of the catheter dimensions to obtain optimum dynamic response. Internal sensors provide the maximum dynamic response and avoid acceleration artifacts. Convenience of electrical signal manipulation, display and recording have made electrical transducers increasingly popular.
A method of measuring cardiac output from dyedilution curves recorded by an ear oximeter is described. No sampling of blood is necessary to make the dye-dilution curves quantitative. The inaccuracies inherent in the "end-tail" method of calibration are thus avoided and the technical procedure greatly simplified. Theoretical considerations, circuitry and calibration procedures are discussed. Forty-one cardiac output estimations were made in 15 subjects. Coomassie blue was used as indicator. Comparison was made between the results obtained by the technique under study and by the end-tail venous method. Seven results had to be excluded from the comparison due to manifest inaccuracy of the reference method, which is inherently inaccurate. In spite of this, there was reasonably good agreement. The standard deviation of the differences between simultaneous values by both methods was 14.3 per cent. Fifty-two dye-dilution curves were recorded in seventeen white subjects at rest and during steady-state exercise at loads up to 600 kilogram-meters per minute. Comparison was made between the cardiac output estimates obtained by the technique described and by the "arterial end-tail" method. The standard deviation of the differences between the simultaneous values from the two methods was 14.2 per cent.
This study was undertaken to demonstrate the feasibility of use of computers in extracting clinically useful parameters from electrophysiologic waveforms. The ECG leads were recorded on magnetic tape. The analog signal was sampled 625 times per second and that data was converted to a form suitable for a general-purpose digital computer. Criteria for clinically significant voltage fluctuations of the signal from the baseline within specified time intervals were determined. The computer was programmed to identify those fluctuations automatically. For an output, the computer produces a set of measurements of ECG waveforms from one cardiac cycle in any random 5-sec. portion of a lead. The program can be expanded to include any measurement, but for present purposes it permits determination of amplitude of P, Q, R, S and T waves, ST and PQ segments, and QT and RR intervals. Variables are measured to an accuracy of 1 part in 1000. Measurements conform to those obtainable by careful hand measurement of magnified tracings of the original records. Automatically derived data can be simultaneously used in computer-programmed statistical analysis to permit classification of the tracings into categories of normality or abnormality. The entire automated system can thus become a diagnostic aid to the physician. This paper deals with one phase of a project directed at the development of an automated system to aid in the diagnosis of heart disease.
In the development of a quantitative understanding of physiological reflex arcs it becomes apparent that the concept of pulse-frequency modulation is bound to play an important part. Not only does the discrete nature of these signals introduce some effects of itself, but possibly more significant in the total picture are the dynamical factors introduced by the modulator and demodulator. There is good reason for feeling that in the iris reflex, for instance, a large share of the dynamic behavior is intimately related to the photoreceptors themselves, and possibly a minor role is taken by the synaptic delays.
Using the basic equations for heat balance which have been developed to take into account heat losses by radiation, convection and evaporation, an electrical analog has been constructed to simulate the physiological responses to heat and cold in the nude man. As has been previously shown, physiologic temperature regulation involves three of the basic types of control modes, namely, proportional control, rate control, and some of the characteristics of on-off control. The rate and proportionality constants have been determined experimentally on the assumption that the regulated temperature is the average body temperature. Time constants for the various thermal changes can be determined from the thermal constants of tissue and the response times of the physiological variables of sweating, vasomotor activity and change in metabolic rate. The simulator predicts steady-state situations of rectal temperature, skin temperature, metabolic rate, vasomotor state and evaporative heat loss under both resting conditions and exercise. Dynamic responses to sudden shifts in environmental temperature, air velocity, relative humidity and metabolic rate can be simulated to a considerable extent using equations based on the controls outlined above.