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The mathematical simulation of human blood biochemistry includes the results of detailed chemical analysis of human blood under a variety of chemical stresses. Mathematical simulations of increasing degrees of complexity are developed. A rudimentary blood model assumes the conventional roles of the fixed proteins, the neutral electrostatic charge constraints, and the active cation pump as the major characteristics of hemostatic blood. The microscopic properties of the proteins, particularly their buffering behavior, are incorporated into the model by a mathematical procedure that assumes that the serum albumin and the various globulins represent all of the important buffering power of the plasma fraction. A model of the respiratory biochemistry of the blood, embodying the results of the previous biochemical structural detail, is tested under various conditions. Properties of the mathematical model, such as gas exchange, buffering, and response to chemical stress in the steady state, are practically indistinguishable from those properties of real blood within the limits of the present validation program.

FLUIDMOD is an interactive program for student practice and instruction in the medical treatment of fluid and electrolyte problems in human patients. The FLUIDMOD program uses a mathematical model of the patient so that a student, sitting at a graphics console, may work his way completely through the sequence of steps of a given therapeutic problem. In this manner, he is actively involved in simulated patient management. In addition, FLUIDMOD contains interactive programs to simulate the clinical patient-management environment: doctor's orders, nursing notes, the patient chart and record, etc., are provided. Finally, FLUIDMOD will eventually contain instructional programs to which the student may branch as required. (Author), Prepared in cooperation with Columbia Coll. of Physicians and Surgeons, Babies Hospital, New York, and Johns Hopkins Univ., Baltimore, Md.

The report describes a computer system, BIOMOD, and illustrates its use for the elucidation of a biological process: the movement of fluid and electrolytes through a biological membrane.

Work was begun on a computer system which would accommodate both equilibrium and kinetic computations in the same program. It would also allow the user to write (ordinary nonlinear) differential equations and FORTRAN programs as required for the simulation of his biochemical or physiological problem. This system would therefore allow, in principle, for the iterative calculations required to simulate, for example, equilibrium in each of several compartments, and at the same time, the differential equations of mass and energy transport among compartments. This system, called BIOMOD, is now running. At this Conference a report is given on BIOMOD using a 20-minute movie to show its main characteristics.

The tasks involved in insinuating computer-based technology into the practice of medicine have proved for a variety of reasons considerably more difficult than was first assumed. Clearly, though, certain signs of progress are at hand, and these are explored. The computer is increasingly being used in data handling and automation tasks related to routine activities of health care. Gradually, as we learn how to control costs and to adapt the hardware and software systems to the more complicated and subtle medial care environments, their utility will expand. The state-of-the-art of the utilization of computer technology in medical services is reviewed.

A crucial problem in the clinical treatment of variety of pathological states is determining the acid-base status of the patient. Usually the acid-base status of a sample of blood in vitro, determined by measuring the pH, P(CO2), and either the 'actual bicarbonate' or the 'base excess,' is used as an approximate index of the status of the body. The definition of a precise relation, however, between the buffering characteristics of the blood and of the total body cell mass would permit the status of the body to be determined accurately by the analysis of blood. This study derives the correlation between the arterial-blood composition and the acid-base status of the whole body over a range of experimental conditions in which both respiratory and metabolic status were changed simultaneously. A nomogram for estimating whole body base excess from the pH and p(CO2) of arterial blood has been constructed from experimental data obtained in 54 nephrectomized dogs subjected to hyperventilation, CO2 breathing, NaHCO3 infusion, HCl infusion, and NH4Cl infusion in varying combinations. The data correlation was assisted by a general theoretical model of fluid and electrolyte distribution in the whole body, implemented on a digital computer. (Author), Prepared in cooperation with National Institutes of Health, Bethesda, Md. Dept. of Clinical Chemistry and California Univ., Berkeley. Dept. of Thoracic Surgery.

Clinical investigations, laboratory experiments, and mathematical simulation techniques have demonstrated that current methods of hemodilution extracorporeal circulation are capable of producing significant depression of plasma potassium. This may lead to cardiac arrhythmias in those patients with pre-existing depletion of total body potassium. As predicted by the mathematical model, the simple addition of potassium ion to the crystalloid hemodiluent does not prevent the depression of plasma potassium. However, adjusting the oncotic pressure to approximate normal plasma, together with the addition of potassium chloride, does offer protection from this hypokalemia., Prepared in cooperation with California Univ. Medical Center, Los Angeles. Presented at the Surgical Forum Session of the American Coll. of Surgeons, held at Chicago, Ill., on 12 Oct 70.

The development of a simulation system that would provide both the interactive, user-oriented features of analog computers and the precision, memory, and computing power of the digital computer has been a design objective for many years. This paper reviews the background of present-day continuous systems simulation techniques, with emphasis on interactive, graphic-oriented systems. The state of the art is discussed, particularly as it concerns user convenience, interactive features, the use of block diagram descriptions, and graphic displays. BIOMOD, a system recently developed for simulation of biological systems, is used as an example. Limitations of present-day systems and prospects for near-future development are discussed. (Author)

The document comments on the premise that a technologist has a citizen's responsibility to contribute to and attempt to develop a rational social structure. At the same time there must be a way to leave responsible room for the Arts and Letters, for human needs and feelings, for human fallibility, and for human genius. In short, there must be a way for humans living within a technological society to maintain the upper-hand over the machine and over the organization. (Author), Presented at a Symposium on Global Systems Dynamics, sponsored by the Virginia Univ., Charlottesville, Va., School of Medicine, 17-19 Jun 69.

A study was made of mathematical, computer-based methods of simulating the blood composition of individual clinical patients. Earlier studies developed procedures for constructing models of the respiratory function and acid-base biochemistry of statistically normal human blood. This memorandum extends these procedures and shows that, with sufficient laboratory data, such a model can be derived for individual patients, and conjectures that the blood's chemical pattern may indicate the patient's physical condition. Such models may be useful for clinical and experimental fluid therapy. The models described simulate the steady-state distribution of chemical species (particularly proteins, electrolytes, and water) between the plasma and red blood cells at one instant, but not the kinetics or time-dependent states of such systems. In 30 separate laboratory experiments, a model of individual blood was tested against real blood in vitro, under various chemical stresses. Results indicate satisfactory agreement. (Author)

A crucial problem in the clinical treatment of a variety of pathological states is to determine the acid-base status of the patient. Usually the acid-base status of a sample of blood in vitro, which can easily be determined, is used as a rough index of the status of the body, but the relation between the two has not been thoroughly explored. This study derives the correlation between the arterial-blood composition and the acid-base status of the whole body over a range of experimental conditions in which both respiratory and metabolic status were changed simultaneously. A nomogram for estimating whole body base excess from the pH an pCO2 of arterial blood has been constructed from experimental data obtained in 54 nephrectomized dogs subjected to hyperventilation, CO2 breathing, NaHCO3 infusion, HCl infusion, and NH4Cl infusion in varying combinations. The data correlation was assisted by a general theoretical model of fluid and electrolyte distribution in the whole body, implemented on a digital computer. (Author)

In this study, a series of experiments measured the changes in water and electrolyte distribution in euthyroid and hypothyroid dogs as a result of an infusion of HCl. (Author), Sponsored in part by Public Health Service, Washington, D. C.

Models of fluid and electrolyte distribution in a standard (euthyroid) dog and a hypothyroid dog were developed. The model of the euthyroid dog was altered by adding a new fluid compartment, Colloid, to conform to a hypothesis of body chemistry changes in hypothyroid animals as determined from the literature. Both euthyroid and hypothyroid laboratory dogs received injections of acid solution to provide chemical data for comparing chemical distribution and for validating the models simulating these states. The results proved statistically that hypothyroid dogs respond differently from normal ones to acid infusion. However, the hypothyroid model did not predict these experimental results well. Although laboratory technological problems accounted for many of these discrepancies, additional experiments and other chemical perturbations are necessary to test the biochemical hypotheses formulated in this study. (Author)

Erythrocyte sodium, chloride, and water were significantly different when a group of eight patients with cirrhosis of the liver was compared to a group of normal subjects, but plasma levels were not different. This study demonstrated that patients with cirrhosis can be identified by the analysis of erythrocytes. (Author)

The purpose of this paper is to examine the program and aspirations for the newly created National Center for Health Services Research and Development. The Center, by means of grants and contracts, supports, promotes, and stimulates a national program of health-services research, development, and demonstrations. (Author), Prepared in cooperation with the National Institutes of Health, Washington, D.C.

A detailed report on the structure and use of CHEMIST, a computer program designed to simulate complex chemical equilibria. The study was compiled in response to a growing demand for a reference manual to accompany and document the program. CHEMIST is a program for use by professionals not trained in computer programming. Communication with the program is in English, chemical, and FORTRAN languages. The computer code currently exists in FORTRAN IV for the IBM 7044. In its present form it occupies approximately 25,000 words for the principal part. Additional specialized subroutines not essential to the operation can increase space requirements. The program uses an iterative mathematical programming technique to determine the composition that minimizes the total free energy of a chemical system, subject to system constraints. A detailed program description with examples is given, along with the program subroutines. The References and Selected Bibliography comprise as complete a listing of the literature as is currently possible. This manual will be updated as the CHEMIST program evolves further. (Author)

A feasible solution of a programming problem, in which a positive vector x maximizes a function g(x) under m convex conditions f sub i (x) < or = O usually exhibits certain stable properties and the entire system can be said to be in equilibrium or that it is an equilibrium model. Beginning at a solution, a time transient may be induced in the system by making f and/or g functions of time. Methods for examining such transients on the analog computer are examined with examples. The problem considered here arises because often the behavior of a system in time under the influence of a variation of parameters is as interesting as the initial or final stable states. Typical examples are found in a petroleum fractionating column or a complex chemical equilibrium., Presented at the Symposium on Mathematical Programming, sponsored by The RAND Corp., at the Santa Monica Civic Auditorium, Santa Monica, Calif., 16-20 Mar 59. Available copy will not permit fully legible reproduction. Reproduction will be made if requested by users of DDC. Copy is available for public sale.

The paper reviews the 'classical theory' of fluid and electrolyte balance and then proceeds to list nine important problems implied by the theory for current modeling practice in electrolyte and water balance. The classical theory holds that functional fluid compartments of the body may be regarded, somewhat arbitrarily but conveniently, as homogeneous subdivisions of the body, each separated from the other by a membrane. Thus, we have the plasma, interstitial, intracellular, and transcellular compartments, and sometimes the 'red cell' compartment, the intraperitoneal, and others. Between any two compartments certain physical, chemical, and usually electrical phenomena are evident which alone cause the distribution of electrolytes and fluids which are observed empirically to exist.

The purpose of the symposium was to examine the application of engineering analysis to biology, and to examine some of the results. It is concluded that the problems are so complex that bioengineers are absolutely essential to aid in solving the problems that are now facing biologists. Problems can no longer be solved intuitively. Bioengineers can increase factual biological knowledge by precisely defining the biological problems in engineering terminology., Presented at the Symposium on the Impact of Bioengineering Education, 29-31 Aug 1966, Gatlinburg, Tennessee.