Masuo Shirataka

A model of overall regulation of body fluids

A large-scale model of body fluid regulation was presented for the purpose of studying problems concerning body fluid disturbances and fluid therapy. This model, containing subsystems of circulation, respiration, renal function, and intra and extracellular fluid spaces, was described mathematically as a set of nonlinear differential and algebraic equations of more than 200 variables. A special feature is that the respiratory and renal subsystems are combined into one system, so that acid-base disturbances of body fluid can be simulated over a wide range of time scales. Behavior of the model for various kinds of inputs simulated with a digital computer was in good agreement with a number of experimental results pertaining to body fluid and acid-base disorders. The model presented in this paper is considered to have good applicability to some clinical problems and to be a useful framework for physiological experimental research.

Usefulness of anaerobic threshold in estimating intensity of exercise for diabetics

We examined the utility of the anaerobic threshold (AT) for quantifying the intensity of exercise that a diabetic patient is capable of handling. Thirteen diabetic patients treated with buformin exercised on a bicycle ergometer, and comparison was made with 20 healthy subjects matched for age and sex. The AT was determined from VO2 and VE with a personal computer. The intensity of exercise at the AT was 93 +/- 6 W in diabetic men and 80 +/- 10 W in diabetic women, values that were less than those of healthy subjects (P less than 0.05). There was a negative correlation between the intensity of exercise at the AT and the plasma concentration of buformin (P less than 0.01). There were no significant differences in either plasma lactic acid or pyruvic acid concentration at the AT between healthy subjects and diabetics. The plasma glucose at the AT or after exercise was lower than the baseline values in all subjects (P less than 0.01). The plasma insulin at the AT was lower than the baseline values in healthy subjects (P less than 0.01), but not in diabetics. There were no changes in plasma glucagon in any group. We concluded that determination of the AT is a simple, non-invasive procedure useful for ascertaining the optimal intensity of exercise for diabetics.

Mathematical model of cardiovascular mechanics for diagnostic analysis and treatment of heart failure: Part 1. Model description and theoretical analysis.

The planning of drug therapy for heart failure should involve both the diagnostic analysis of the patient’s defective state and a prediction of the drug effects on the identified state. We have devised a mathematical model of cardiovascular system mechanics, on which both quantitative diagnosis and evaluation of drug effects can be made. The model was composed of systemic and pulmonary circulatory networks including the dynamics of the left and right ventricles. The model of the ventricles can represent both systolic and diastolic problems in heart failure through the parameters of ventricular contractility and diastolic stiffness. Each vascular network was composed of arterial and venous resistances and total vascular capacitance. Patient’s ventricular and vascular parameters were estimated simultaneously from the clinically measurable haemodynamic variables based on the model. Despite the simplicity of the model, the results showed good agreement with clinical and experimental data. The clinically significant haemodynamic classification of heart failure by Forrester et al. (Forrester et al., 1977) was simulated well by the model. This model provides a useful basis for analysing pathophysiological states in heart failure and evaluating drug effects on the disease.

Evaluation of five computer programs in the diagnosis of second-degree AV block

Five electrocardiogram (ECG) analyzing systems were tested with a microcomputer-based ECG signal generator to assess the accuracy of the systems in interpreting Wenckebach periodicity. Although normal sinus rhythm with normal PR intervals and sinus rhythms with first-degree atrioventricular (AV) block were diagnosed by all five systems, second-degree AV block with classic Wenckebach periodicity was routinely misdiagnosed by four of the five systems. No system recognized the atypical Wenckebach periods in a total of 200 trials, misinterpreting the phenomenon as atrial fibrillation, supraventricular rhythm, sinoatrial block, and other rhythm disturbances. In advanced AV block and a variety of ventricular arrhythmias, none of the five systems diagnosed second-degree AV block with Wenckebach periods. Marked unsatisfactory performance with regard to the diagnosis of Wenckebach periodicity indicates the urgent need for accelerated and comprehensive testing of ECG diagnostic equipment. The present generating device was seen as an effective troubleshooter in optimizing the diagnostic competency of computerized ECG systems.

A mathematical model of atrioventricular conduction block using the excitability recovery curve of the myocardial cell

A simple mathematical model of AV conduction block was constructed on the basis of single-cell electrophysiological experiments concerning the rate-dependent property of excitability of the AV nodal cells (the excitability recovery curve, ERC). This ERC was analogous to the phase response curve (PRC) of cardiac pacemaker cells, which the authors had previously used to construct a model of modulated parasystole. Computer simulation was used to reproduce the ERC. The single-cell ERC was then extended to the entire AV node, and this curve was used to formulate a mathematical model of AV conduction block as a nonlinear, first-order difference equation of the successive PR intervals of the ECG. This model predicted a variety of ECG patterns of AV conduction block: normal rhythm, first-degree block, and several second-degree blocks of complex Wenckebach periodicity in relation to the sinus rate and the shape of the ERC. By assuming this model it was possible to identify the underlying ERC of actual ECGs with complex Wenckebach periodicity.

Semi-automatic counting of connexin 32s immunolocalized in cultured fetal rat hepatocytes using image processing.

Connexin 32s (Cx32s) were immunolocalized in fetal rat hepatocytes and their distribution was determined qualitatively. We used image analysis using a quantitative index (QI) of Cx32 (QI Cx32) defined as the area of Cx32s/number of cells in cultured fetal rat hepatocytes. Hepatocytes from livers of fetal rats were separated by collagenase digestion and low centrifugation on gestational day 17. Cells were cultured for 3 days in dexamethasone (DEX)-supplemented medium (Dex0). The medium was replaced with fresh medium and cells were continuously cultured for 3 days with DEX or epidermal growth factor supplemented medium (Dex3 or EGF3). After culture termination, cells were fixed and stained using the fluorescein-labeled antibody method for Cx32s and diaminophenylindole staining for nuclei. Thirty pairs of histological images for Cx32s and nuclei, 180 images in total, were obtained from each condition. The QI Cx32 significantly increased from 284.1 ± 102.0 (mean and SD, n=26) of Dex0 to 428.9 ± 101.0 of Dex3 (n=28) (P<0.05, Kruskal-Wallis test, then Steel-Dwass test). The increase of QI Cx32 was compatible with the morphological observations. The image analysis processing time after preparation for 180 images was reduced from 8h needed for manual operations to 1 min using ImageJ software with our macro routine.

Computer assisted instruction for therapy of heart failure based on simulation of cardiovascular system

Adequate treatment of cardiac failure should reflect both clinical rules and quantitative evaluation of hemodynamics. For the latter we assumed an extensive model of heart and vessels: For the left and right ventricles the EMAX models were assumed with the parameters of contractilities and diastolic compliances. The model of the vessels was composed of systemic and pulmonary vascular networks with arterial, capillary and venous segments. Heart failure of various types was simulated by the model and the optimal therapeutic regimen was formulated. The cardiovasular parameters of patients with heart failure could be esimated from the hemodynamic measurements through the model and the optimal therapy was computed with the technique of nonlinear programming.The simulation thechnique was incorporated in the computer assisted instruction system based on the clinical emirical rules. The program was written with TURBO PASCAL for a microcomputer with CPU 80286. The response time was within a tolerable range for use in the clinical practice.

A 15-year follow-up study on the outcome in patients with early rheumatoid arthritis

This study aimed to investigate the natural course of early rheumatoid arthritis (RA) after treatment for 15 years based on the present data of patients who had been enrolled in a 1 year study of early RA conducted by the Japan Rheumatism Foundation in 1981 and 1982. An examination form was mailed to each doctor who had participated in the previous study requesting them to record the present data of the patients. The patients were requested to fill out the AIMS2 questionnaire. Patients had been randomly assigned into three treatment groups: those treated with gold, with d-penicillamine and without slow acting antirheumatic drugs (SAARDs). Information was obtained concerning 74 of 161 patients who had completed the previous 1 year study. Clinical remission was observed in 20 of 74 patients. The current status of RA by physician’s assessment was reported to be well controlled in 32 of 48 cases (66.7%); however, no remarkable improvement was seen in erythrocyte sedimentation rate (ESR, and the number of painful joints compared with the values at entry 15 years previously. Radiographical stages showed progression and the average score of AIMS2 had deteriorated in most cases. High ESR, progression of joint damage and positive rheumatoid factors at the early stage of RA were suggested to be factors relating to QOL deterioration. These results suggest that it would be difficult to modify the natural course of RA by currently used treatment strategies with SAARDs.

Interprofessional Team-Based Medical Education Program at Kitasato University: Collaboration Among 14 Health-Related Professions

Medical technology is quickly becoming more advanced and more narrowly specialized. At the same time, epidemiological and demographic profiles are changing drastically. Therefore, it would be difficult to provide the utmost health services unless various pieces of knowledge scattered across multiple health-related professions are integrated for practical application. Furthermore, as society’s needs for health services are also changing, it is no longer enough to treat the disease. Hence, the quality of health services is being looked at to humanize the process of diagnosis and treatment and to consider ethical, psychological, and social aspects of services. To provide quality health services, it is imperative for various health-related professionals, who are narrowly specialized, to closely work together as a team. This, in turn, requires urgent training of human resources so that such collaborative teamwork can smoothly take place.

Analysis of Compression Force in the Hip Joint during Impulsive Exercises: A Preliminary Study for Developing Exercise Protocol for Osteoporosis

Past intervention studies on bone remodeling for preventing osteoporosis in elderly women often lack sufficient description of the intensity of the exercise, though bone remodeling is dependent on applied force at specific sites. The effectiveness of exercise in increasing bone density cannot be defined without sufficient description of the intensity and targeted site of the exercise. We conducted kinetic and kinematic analyses of the lower extremities in order to categorize exercise in terms of compression force applied at the proximal end of the femur, to formulate guidelines for prescribing exercise to elderly women. Thirty healthy women aged 18-24 participated in the study. Joint compression force at the proximal end of the femur was measured with the aid of motion analysis devices under several conditions of impulsive loading. Joint compression force at the proximal end of the femur was estimated for twenty-two exercise regimes varying from low to high-impact exercises, including jumping off, stepping down, vertical jumping, and dropping down after heel raises. Some exercises appear to be inappropriate for exercise intervention, because the variability for these exercises is high. Most of the jumping exercises, with coefficients exceeding 0.36, were excluded from further analysis. Of the remaining exercises, four were categorized as statistically different loads, as determined by a posthoc test of one-way analysis of variance of joint compression force. These included jumping off a 10 cm platform, stepping down from a 20 cm platform with the knees in the extended position, stepping down from a 20 cm platform with the knees in a relaxed position, and heel dropping at 80 cycles per minute with the knees in a relaxed position. The joint compression forces during these exercises were 2.32 ± .81, 1.81 ± .59, 1.45 ± .59, and 1.00 ± .27 times as much as the subjects body weight, respectively.