Development of a new aortoscope system for the use of endovascular intervention.

"Balloon aortoscopy" is a technique for viewing inner wall of aorta and used in clinics. By this method, endoluminal aortic surface could be clearly monitored, however, during this period, the aortic blood flow is blocked off by the inflated balloon. To solve this clinical problem, we have been developing a prototype aortoscope system without blocking off aortic flow aiming for the use of an assistive technique for endovascular interventions such as stent-graft placement for aortic aneurysm and have been evaluating through in vitro and in vivo tests. The technique introduced for this purpose was the use of intermittent and instantaneous saline jet controlled by a high-speed electromagnetic valve synchronized to heart beat (diastolic phase). In the previous study, we designed an endoscope with two channels (one for saline discharge and the other for forceps insertion), and confirmed the validity of this method by in vitro and in vivo tests. Based on these findings, in this study, we have newly designed a conventional and low price endoscope system aiming for wide clinical use. From the results of in vitro tests using a mock circulation system, it was confirmed that the newly designed system was capable of visualizing a target installed on an inner surface of the mock system suggesting an availability of the system for an aortoscope without blocking off aortic flow.

Evaluation of a newly designed endoscope for observing inner wall of large arteries for the use of endovascular intervention.

A prototype endoscope for observing inner wall of large arteries was specially designed and evaluated through in vitro and in vivo tests. The purpose of this endoscope is to visualize the inner wall of large arteries, e.g., an aorta, without blocking off the blood stream aiming for the use of an assistive technique for endovascular interventions such as stent-graft placement for aortic aneurysm. The technique newly introduced for this purpose was the use of intermittent high-pressure saline jet synchronized to heart beat (diastolic phase). In the previous studies using commercially available bronchoscopes, we confirmed the validity of the system utilizing this technique [1, 2]. Based on these findings, in this study, we have specially designed a new endoscope with two channels, one for saline discharge and the other for forceps, and evaluated its performance through in vitro and in vivo tests. From the results of in vitro tests using a mock circulation system, it was confirmed that the newly designed endoscope was capable of visualizing a target installed on an inner surface of the mock system. Also confirmed through in vivo tests using swine was that we could observe bifurcation in descending aorta, e.g., left renal artery, without stopping off the blood stream.

Feasibility study on driver's stress detection from differential skin temperature measurement.

Prolonged monotonous driving may lower a driver's awareness level as well as increasing their stress level due to the compulsion to maintain safe driving, which may result in an increased risk of a traffic accident. There is therefore an opportunity for technological assessment of driver physiological status to be applied in-car, hopefully reducing the incidence of potentially dangerous situations. As part of our long-term aim to develop such a system, we describe here the investigation of differential skin temperature measurement as a possible marker of a driver's stress level. In this study, healthy male (n=18) & female (n=7) subjects were investigated under environment-controlled conditions, whilst being subjected to simulated monotonous travel at constant speed on a test-course. We acquired physiological variables, including facial skin temperature which consists of truncal and peripheral skin temperatures (Ts) using thermography, beat-by-beat blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR), and normalized pulse volume (NPV) used as an indicator of local peripheral vascular tone. We then investigated the driver's reactivity in terms of skin temperatures with this background of cardiovascular haemodynamics. We found that the simulated monotonous driving produced a gradual drop in peripheral Ts following the driving stress, which, through interpretation of the TPR and NPV recordings, could be explained by peripheral sympathetic activation. On the other hand, the truncal Ts was not influenced by the stress. These findings lead us to suggest that truncal-peripheral differential Ts could be used as a possible index indicative of the driver's stress.

A preliminary study on driver's stress index using a new method based on differential skin temperature measurement.

Prolonged periods of driving in monotonous situations may lower a driver's activation state as well as increasing their stress level due to the compulsion to maintain safe driving, which may result in an increased risk of a traffic accident. There is therefore an opportunity for technological assessment of driver physiological status to be applied in-car, hopefully reducing the incidence of potentially dangerous situations. As part of our long-term aim to develop such a system, we describe here the investigation of differential skin temperature measurement as a possible marker of a driver's stress level. 10 healthy male subjects were studied, under environment-controlled conditions, whilst being subjected to simulated monotonous travel at constant speed on a test-course. We acquired measurements of relevant physiological variables, including truncal and peripheral skin temperatures (T(s)), beat-by-beat blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR), and normalized pulse volume (NPV) used as an indicator of local peripheral vascular tone. We then investigated the driver's reactivity in terms of cardiovascular haemodynamics and skin temperatures. We found that the simulated monotonous driving produced a gradual drop in peripheral T(s) following the driving stress, which, through interpretation of the TPR and NPV recordings, could be explained by peripheral sympathetic activation. On the other hand, the truncal T(s) was not influenced by the stress. These findings lead us to suggest that truncal-peripheral differential T(s) might be used as a possible index indicative of the driver's stress.

Development of a fully automated network system for long-term health-care monitoring at home.

Daily monitoring of health condition at home is very important not only as an effective scheme for early diagnosis and treatment of cardiovascular and other diseases, but also for prevention and control of such diseases. From this point of view, we have developed a prototype room for fully automated monitoring of various vital signs. From the results of preliminary experiments using this room, it was confirmed that (1) ECG and respiration during bathing, (2) excretion weight and blood pressure, and (3) respiration and cardiac beat during sleep could be monitored with reasonable accuracy by the sensor system installed in bathtub, toilet and bed, respectively.

A new non-invasive method for measuring blood glucose using instantaneous differential near infrared spectrophotometry.

We describe further development of a novel method for non-invasive measurement of blood glucose concentration (BGL), named Pulse Glucometry, based on differential near infrared spectrophotometry. Sequential temporal differences of infrared transmittance spectra from the radiation intensity (I(lambda)) emerging from a fingertip containing an arterial pulse component (DeltaI(lambda)) are analysed. To perform the measurements we developed a new high-speed spectrophotometer, covering the wavelength range from 900 to 1700 nm, scanning at a maximum spectral rate of 1800 spectra/s, with a minimum exposure time of 20 micros. Spectra related only to the pulsatile blood component are derived, thus minimising influences of basal components such as resting blood volume, skin, muscle and bone. We have now improved the performance of the spectrophotometer and in the present paper we describe new in vivo measurements carried out in 23 healthy volunteers undergoing glucose tolerance tests. Blood samples were collected from the cephalic vein simultaneously with radiation intensity measurements in the fingertip every 10 min before and after oral administration of glucose solution for 120 min. BGL values were then predicted using a PLS calibration model and compared with blood values determined by colorimetric assay. The precision and accuracy of the non-invasive determinations are encouraging.

Pulse glucometry: A new approach for noninvasive blood glucose measurement using instantaneous differential near-infrared spectrophotometry.

We describe a new optical method for noninvasive blood glucose (BGL) measurement. Optical methods are confounded by basal optical properties of tissues, especially water and other biochemical species, and by the very small glucose signal. We address these problems by using fast spectrophotometric analysis in a finger, deriving 100 transmittance spectra per second, to resolve optical spectra (900 to 1700 nm) of blood volume pulsations throughout the cardiac cycle. Difference spectra are calculated from the pulsatile signals, thereby eliminating the effects of bone, other tissues, and nonpulsatile blood. A partial least squares (PLS) model is used with the measured spectral data to predict BGL levels. Using glucose tolerance tests in 27 healthy volunteers, periodic optical measurements were made simultaneously with collection of blood samples for in vitro glucose analysis. Altogether, 603 paired data sets were obtained in all subjects and two-thirds of the data or of the subjects randomly selected were used for the PLS calibration model and the rest for the prediction. Bland-Altman and error-grid analyses of the predicted and measured BGL levels indicated clinically acceptable accuracy. We conclude that the new method, named pulse glucometry, has adequate performance for safe, noninvasive estimation of BGL.

Hemodynamic responses during simulated automobile driving in a monotonous situation.

Long hours of automobile driving under monotonous situations may cause the lowering of what we term a driver's activation state (DAS) or in other words the production of drowsiness, resulting in an increased risk of a traffic accident. There is therefore a need to create a newly advanced system focused on the DAS in-car, hopefully thus avoiding potentially dangerous situations. In order to develop such a system as a final goal, we have firstly set out to acquire such cardiovascular variables as beat-by-beat blood pressure (BP), RR interval from ECG and normalized pulse volume (NPV) used as a peripheral vascular tone of alpha-adrenergic sympathetic activity, during presentation to the driver of a screen movie simulating monotonous travel at constant speed on a test-course. Subsequently, we have investigated the reactivity in terms of the driver's cardiovascular hemodynamics. Through the successful monitoring of cardiovascular parameters during the movie presentation obtained in 11 healthy male subjects, the following results were obtained: The monotonous driving produces a statistically significant gradual rise in BP following drowsiness, which could be explained by enhancement of sympathetic activity using a time-frequency analysis of BP and RR. This finding strongly indicates that continuous driving in such monotonous situations can make a driver considerably stressful and thus may cause a gradual increase in BP, and that this gradual BP increase may be used as a possible index relevant to the DAS. This finding was also confirmed by the analysis of NPV, suggesting that the gradual increase in BP during the monotonous driving would be rather caused by a regulation of peripheral vasomotor constriction.

Development of an ambulatory device for monitoring posture change and walking speed for use in rehabilitation.

Monitoring of posture change in sagittal plane and walking speed is important for evaluate the effectiveness of rehabilitation program or brace. We have developed a wearable device for monitoring human activity. However, in the previous system, there still remain several drawbacks for practical use such as accuracy in angle measurement, cumbersome cable arrangements, and so on. In order to improve these practical drawbacks, a new sensor system was designed, and its availability was evaluated. The results demonstrated that the accuracy of this system showed superior to that of the previous, and this system appears to be a significant means for quantitative assessment of the patient's motion.

Nitric oxide contribution to vascular wall oxygen consumption in arterioles.

To study the role of nitric oxide (NO) in regulating oxygen consumption by vessel walls, the oxygen consumption rate of arteriolar walls in rat cremaster muscle was measured in vivo during flow-induced vasodilation and after inhibiting NO synthesis. The oxygen consumption rate of arteriolar was calculated based on the intra- and peri-vascular oxygen tension (P0(2)) values measured by phosphorescence quenching laser microscopy. The peri-vascular PO(2) value of the arterioles during vasodilation was significantly higher than under control conditions, although the intravascular PO(2) values under both conditions were approximately the same. On the other hand, inhibition of NO synthesis caused a significant decrease in both the intra- and peri-vascular P0(2) values of the arterioles. The inhibition of NO synthesis increased the oxygen consumption rate of the walls by 42%, whereas enhancement of flow-induced NO release decreased it by 34%. These results suggest that NO plays an important role not only as a regulator of peripheral vascular tone, but also as a modulator of tissue oxygen consumption by reducing oxygen consumption by vessel walls.

Unconstrained detection of respiration rhythm and pulse rate with one under-pillow sensor during sleep.

A completely non-invasive and unconstrained method is proposed to detect respiration rhythm and pulse rate during sleep. By employing wavelet transformation (WT), waveforms corresponding to the respiration rhythm and pulse rate can be extracted from a pulsatile pressure signal acquired by a pressure sensor under a pillow. The respiration rhythm was obtained by an upward zero-crossing point detection algorithm from the respiration-related waveform reconstructed from the WT 2(6) scale approximation, and the pulse rate was estimated by a peak point detection algorithm from the pulse-related waveform reconstructed from the WT 2(4) and 2(5) scale details. The finger photo-electric plethysmogram (FPP) and nasal thermistor signals were recorded simultaneously as reference signals. The reference pulse rate and respiration rhythm were detected with the peak and upward zero-crossing point detection algorithm. This method was verified using about 24 h of data collected from 13 healthy subjects. The results showed that, compared with the reference data, the average error rates were 3.03% false negative and 1.47% false positive for pulse rate detection in the extracted pulse waveform. Similarly, 4.58% false negative and 3.07% false positive were obtained for respiration rhythm detection in the extracted respiration waveform. This study suggests that the proposed method is suitable, in sleep monitoring, for the diagnosis of sleep apnoea or sudden death syndrome.

Assessing the Effectiveness of Increased FIO2for Enhancing Driver's Activation State Using Simulated Monotonous Driving.

Lowering of what we term a driver's Activation State (AS) during monotonous driving conditions may increase the risk of an accident. To develop an in-car environment that allows active driving - "Biofee dforward System" - we have investigated the effects of applying a stimulus of increased inspired oxygen fraction (FIO2) supply on a driver's AS, using simulated monotonous driving. We used our previously substantiated index of As derived from beat-by-beat blood pressure (BP) response following an electrical stimulus. We have made physiological measurements including BP and found that the increased FIO2stimulus is effective in enhancing the AS. This finding was also confirmed in terms of the autonomic activity balance as well as the lengthening in time for active, safer, driving.

Development of a wearable device capable of monitoring human activity for use in rehabilitation and certification of eligibility for long-term care.

The importance of human posture monitoring is well recognized in the field of rehabilitation, in order to evaluate quantitatively the effectiveness of rehabilitation by a physical therapist. The activity monitoring is also well recognized as being useful in the field of certification of eligibility for long-term care. Assessment of the actual physical condition of the applicant tends to be difficult when determine the level of need for long-term care. Taking these circumstances in consideration, we attempted to measure the activities of patients in rehabilitation using a wearable device for monitoring human activity. The results clearly demonstrated that detailed motion characteristics could be detected during standing up, walking and sitting up as angle changes between specific body segments and as trunk motion acceleration.

Physiological investigation of automobile driver's activation index using simulated monotonous driving.

Monotonous automobile operation in our daily life may cause the lowering of what might be termed an activation state of the human body, resulting in an increased risk of an accident. We therefore propose to create a more suitable environment in-car so as to allow active operation of the vehicle, hopefully thus avoiding potentially dangerous situations during driving. In order to develop such an activation method as a final goal, we have firstly focused on the acquisition of physiological variables, including cardiovascular parameters, during presentation to the driver of a monotonous screen image, simulating autonomous travel of constant-speed on a motorway. Subsequently, we investigated the derivation of a driver's activation index. During the screen image presentation, a momentary electrical stimulation of about 1 second duration was involuntarily applied to a subject's shoulder to obtain a physiological response. We have successfully monitored various physiological variables during the image presentation, and results suggest that a peculiar pattern in the beat-by-beat change of blood pressure in response to the involuntary stimulus may be an appropriate, and feasible, index relevant to activation state.

A new portable device for ambulatory monitoring of human posture and walking velocity using miniature accelerometers and gyroscope.

Measurement of physical activity is one of the key subjects in the field of ambulatory cardiovascular monitoring using such as Holter ECG and so called "ambulatory blood pressure monitor (ABPM)". Rehabilitation and gerontology will also be another fields for the application of the activity monitor. From this point of view, we have developed a portable device for monitoring human posture and walking velocity in ambulatory subjects. In this paper are described, a new sensor system for this purpose using three accelerometers and one gyroscope, its availability for the accurate measurement of human posture and walking velocity, and results of preliminary study using a prototype system for ambulatory monitoring.

Reconstruction of a defect of the rotator cuff with polytetrafluoroethylene felt graft. Recovery of tensile strength and histocompatibility in an animal model.

We reconstructed defects in the infraspinatus tendon u sing polytetrafluoroethylene (PTFE) felt grafts in 31 beagle dogs and examined the mechanical responses and histocompatibility. Except for one infected specimen, all the reconstructed infraspinatus tendons healed. We examined eight specimens each immediately after surgery and at six and 12 weeks. The ultimate tensile strength of the reconstructed tendons was 60.84 N, 172.88 N, and 306.51 N immediately after surgery and at six and 12 weeks, respectively. The stiffness of the specimens at the PTFE felt-bone interface was 9.61 kN/m, 64.67 kN/m, and 135.09 kN/m immediately after surgery and at six and 12 weeks, respectively. Six tendons were examined histologically at three, six, 12 and 24 weeks. Histological analysis showed that there was ingrowth of fibrous tissue between the PTFE fibres. Foreign-body reactionswere found at the margin of the PTFE-bone interface between 12 and 24 weeks. The mechanical recovery and tissue affinity of PTFE felt to bone and to tendon support its use for reconstruction of the rotator cuff. The possible development of a foreign-body reaction should be borne in mind.

Restoration of immunocyte functions by thymosin alpha1 in cyclophosphamide-induced immunodeficient mice.

Thymosin alpha1 (Talpha1) is an oligopeptide hormone originally isolated from the thymus gland, and has been reported to have stimulating effects on the differentiation of T cells and NK cells. These immunostimulating properties have been considered to be useful for improving immune disorders associated with various diseases including cancer, AIDS and hepatitis. Here, we characterized immunostimulating properties of Talpha1 in experimental immunodeficiency of mice that was induced by the administration of cyclophosphamide (CY). Repeated injection of 30-300 microg/kg/day of Talpha1 after CY-treatment significantly accelerated the restoration of the reduced number of CD4+CD8+ T cells in the thymus. Talpha1 administration was effective in restoring the suppressed activities of helper T cells and cytotoxic T cells in CY-treated mice. Talpha1 also had stimulating effects on reduced activity of lymphokine-activated killer cells in CY-treated mice. These results indicate that Talpha1 is stimulatory for both humoral and cellular immune responses, thus providing the immunological basis for the clinical benefit of this compound.

Normalized pulse volume (NPV) derived photo-plethysmographically as a more valid measure of the finger vascular tone.

Normalized pulse volume (NPV) was advocated as a more valid measure for the assessment of finger vascular tone. Based on the optical model in the finger tip expressed by Lambert--Beer's law, NPV is expressed as Delta I(a)/I. Here, Delta I(a) is the intensity of pulsatile component superimposed on the transmitted light (I). Theoretically, NPV seems to be superior to the conventional pulse volume (PV; corresponding to Delta I(a)). Firstly, NPV is in direct proportion to Delta V(a), which is the pulsatile component of the arterial blood volume, in a more exact manner. Relatedly, NPV can be processed as if it is an absolute value. Secondly, the sensitivity of NPV during stressful stimulations is expected to be higher. These expectations were supported experimentally using 13 male students. Firstly, the correlation between cutaneous vascular resistance in the finger tip (CVR) and NPV was higher than that between CVR and PV among all the subjects, although there was not much difference between these correlations within each subject. Secondly, NPV decreased much more than PV during mental stress. Some limitations of the present study were addressed, including the point that certain factors can violate the direct proportional relationship of NPV and PV to Delta V(a).

Unconstrained physiological monotoring in daily living for health care.

This paper deals with the recent development of two types of non-invasive physiological monitoring systems for possible application in an unconstrained manner to normal subjects for health care as well as to patients and/or outpatients with disorders or with life support systems (artificial organs and organ transplantations). One is an ambulatory monitoring system which allows automatic acquisition of blood pressure, cardiac output and other cardiovascular hemodynamic parameters on a beat-by-beat basis using the volume-compensation and transthoracic electrical admittance method. The other is a home monitoring system installed in a lavatory which can measure body and excreta weight together with the ballistocardiogram as an index of cardiac ejecting function in an unaware fashion without attachment of any sensors to the subject's body and without special operations for measurement during toilet use. Outlines of these two systems and monitoring results of laboratory and field testings are presented, and these suggest that the ambulatory and non-conscious physiological monitoring techniques described herein appear promising as a valuable and helpful means for use in research as well as in the practical field of health monitoring at home during daily living.

Effects of periosteum wrapped around tendon in a bone tunnel: A biomechanical and histological study in rabbits.

The present study demonstrated the effects of periosteal autograft on tendon-to-bone healing in the rabbits. In 20 Japanese white rabbits, proximal end of the long digital extensor tendon that was wrapped around by a periosteum was transplanted into a drill hole in the proximal tibial metaphysis. A fresh periosteum was used in the left tibia and a frozen periosteum was used in the right tibia. Six specimens were harvested at each 2, 4, and 6 weeks postoperatively. Radiological features showed progressive remodeling of trabecular bone surrounding the implanted tendon. This remodeling in fresh periosteal graft was earlier than that in frozen graft. Generally, the pull-out strength of the transplanted tendons with a fresh or frozen periosteum increased progressively according to the length of the healing periods. The strength was significantly greater in a fresh periosteal graft than that in a frozen graft at 4 weeks postoperatively. In histological analysis, a 4-week specimen with the fresh periosteal graft showed fibrocartilage formation in the bone tendon interface, whereas the specimens with the frozen graft demonstrated simple approximation of oriented fibrous tissue. In conclusion, the fresh periosteal autograft produced the premature form of fibrocartilagenous attachment in a bone tunnel and provided good mechanical strength.