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.

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.

Hypertensive episodes and circadian fluctuations of blood pressure in patients with phaeochromocytoma: studies by long-term blood pressure monitoring based on a volume-oscillometric method.

A new portable device for the indirect measurement of arterial blood pressure was successfully applied to detect paroxysmal hypertension and circadian fluctuation of blood pressure in patients with phaeochromocytoma. The device utilizes the volume-oscillometric technique, it is equipped with a microprocessor and allows long-term automatic monitoring of indirect blood pressure in the human finger. Compared with conventional fully automated portable devices of the arm-cuff type, our current equipment is lighter, less noisy, and causes less discomfort. With this device repeated measurements can be made without causing stress or discomfort, and without disturbing sleep. The arterial pressure measurement obtained using this device was reliable and reproducible. In some patients certain symptoms, possibly due to phaeochromocytoma, had been observed for several years before the study, although hypertension had not been identified. While these patients had consistently high circulating catecholamine levels, nocturnal falls in blood pressure were clearly documented. This suggests that plasma catecholamines released from the phaeochromocytoma, though excessive, may be of less physiological importance than other regulatory mechanisms concerned with circadian fluctuation of blood pressure, e.g. the sympathetic nervous system and/or hypothalamo-pituitary-adrenal system. This new device has proved to be a reliable means of monitoring long-term blood pressure and is useful in the diagnosis of paroxysmal hypertension in patients with phaeochromocytoma.

Entrainment of respiratory rhythm to respiratory oscillations of arterial PCO2 in vagotomized dogs.

The aim of this study was to demonstrate that the medullary respiratory rhythm generator is capable of entraining to respiratory oscillations of arterial PCO2 (CO2 oscillations). We used 10 anesthetized, paralyzed, vagotomized, and mechanically ventilated dogs. First, rate of mechanical ventilation was manually adjusted so that it matched the dog's spontaneous respiratory rate, which established a constant phase relationship between the mechanical ventilation and the burst of phrenic neurogram (initial phase). Then this phase relationship was temporally disturbed by a brief electrical stimulation of the superior laryngeal nerve (SLN). In the control group, the initial phase and the steady-state phase relationship after SLN stimulation were randomly distributed within the phase plane, implying no interaction between the respiratory center and mechanical ventilation. In contrast, when CO2 output from the lung was increased 2.6-fold above the control level by venous CO2 loading, the initial phase and the steady-state phase after SLN stimulation were locked in such a way that the onset of the burst of phrenic neurogram coincided with the peak of CO2 oscillations. This was not demonstrated when the dog was made hyperoxic. We therefore conclude that the respiratory center could entrain to phasic chemical afferent inputs originating from CO2 oscillations, provided they are considerably amplified.

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.

A correlation analysis between pulse transit time and instantaneous blood pressure measured indirectly by the vascular unloading method.

Linear correlation coefficients (r) between pulse transit time (PTT) and blood pressure (BP) were evaluated on within-subject by within-condition level. Beat-to-beat systolic and diastolic BP was measured noninvasively using the vascular unloading technique (Yamakoshi, Shimazu and Togawa, 1980). PTT was determined from the time interval between the R-wave of ECG and the peak of the finger pulse wave. Five male subjects underwent a 2 min resting (RE), a 1 min cold pressor test (CP), eight 15 sec anagram tests (AN), and another 1 min CP. Significant r values were most frequently obtained for systolic BP and PTT in the RE condition. Under the CP or AN conditions, no consistent tendencies were observed. It was suggested that none of the r values are sufficiently high to warrant the use of PTT as an alternative index of BP. Some factors lowering the r values were discussed.

Fetal and neonatal cerebral oxygen monitoring with NIRS: theory and practice.

Near infra-red spectroscopy (NIRS) is a comparatively new method for monitoring the oxygenation in blood and tissue in the brain of the fetus and the neonate. Absorption of light in the wavelength range 700-1000 nm through such tissue is measured, which is then used to calculate changes in the concentration of cerebral oxygenated and de-oxygenated haemoglobin (HbO2 and Hb) and hence cerebral blood volume (CBV). Studies carried out on several groups of newborn babies have shown clear changes in HbO, Hb and CBV with hypoxia and bradycardia. These changes may well have implications in the occurrence of hypoxic/ischaemic brain injury. Intra partum NIR measurements on the fetal brain have demonstrated clear changes in HbO2, Hb and CBVm, coinciding with the onset of contractions.

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).

An experimental evaluation of isometric placement for extraarticular reconstructions of the anterior cruciate ligament.

We measured the changes in distance between the tibial and femoral attachment points of the extraarticular ACL substitute during knee motion. To measure the changes in distance continuously and directly, a computer-assisted experimental system was developed using an electrolyte-in-rubber transducer. We used 6 cadaveric knees to measure changes in distance of 15 combinations during a simple flexion and extension knee motion. The distance became longer with flexion in each pair of attachment locations. Although the smallest change in distance was obtained between the posterolateral site of the femoral distal metaphysis and a point posterior to the Gerdy tubercle (percent average of the maximum strain was about 12%), it was concluded that the extraarticular ACL reconstruction is not recommended from a standpoint of isometry of the substitute.

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.

Neurogenic factors affecting ventilatory and circulatory responses to static and dynamic exercise in man.

The possible influence of neurogenic factors on respiratory and circulatory responses to continuous static (CSE), rhythmic static (RSE), and dynamic (DE) exercises was studied in 15 healthy young men. Ventilation (VE), oxygen uptake (VO2), cardiac output (Q), and blood pressure (BP) were measured during the steady-state of the exercise. For a given VO2, VE, and respiratory frequency (f) enhanced significantly with increasing frequency of RSE, and for the same frequency, the responses of these variables to RSE were significantly higher than those for DE. Although a similar trend was observed in heart rate (HR) and Q responses to exercises, it was not as strong as for ventilatory responses. These results lead to the conclusion that ventilation and circulation during exercise may be influenced by some neurogenic factors mediated either centrally or peripherally.

A portable instrument for non-invasive monitoring of beat-by-beat cardiovascular haemodynamic parameters based on the volume-compensation and electrical-admittance method.

A new, portable instrument has been developed for simultaneous monitoring of blood pressure, cardiac output and other cardiovascular haemodynamic variables. The measurements are based on the volume-compensation method and the transthoracic electrical admittance method. The instrument is small and light and can be carried by the subject. The portable unit controls the measurement procedures, performs the blood pressure and cardiac output measurement, processes signals and stores almost 32,000 beats of time-series data in a fully automated manner. A conventional personal computer is used to initialize the measurement system, and to reproduce and evaluate the measurement data. The measurement system provides a means to evaluate in detail, without restriction, the subject's cardiovascular haemodynamic responses to daily physical activities as well as to various psycho-physiological stresses. The paper describes a new, portable, cardiovascular haemodynamic instrument and in-the-field test results. Twelve subjects are monitored for trials, 60-210 min, and fewer than 3% of the data in each trial are artifactual. Artefacts are due mainly to body movements.

Ambulatory instrument for monitoring indirect beat-to-beat blood pressure in superficial temporal artery using volume-compensation method.

A portable instrument, based on a volume-compensation technique, is designed for ambulatory monitoring of indirect beat-to-beat blood pressure (BP) in the superficial temporal artery. The instrument consists of a small disc-type cuff and a portable unit carried by the subject. Several components are integrated in the cuff for applying counter-pressure to the artery, i.e. a reflectance-type photo-plethysmographic sensor for arterial volume detection, a pressure sensor for cuff pressure Pc measurement and a nozzle flapper-type- electro-pneumatic convertor for controlling Pc. The portable unit includes volume servo control circuitry and a microprocessor-based signal-processing and recording unit. This automatically performs all the necessary measurement procedures and stores into a memory IC element the processed systolic, mean and diastolic blood pressure data, together with pulse intervals on a beat-to-beat basis from the servo-controlled Pc (indirectly measured BP waveform). With this instrument, momentary changes in BP during ambulatory situations such as bicycle ergometer exercise and daily activities including motorway driving are successfully recorded. From the results of simultaneous measurement of the subject's posture changes, the effect of posture change on blood pressure, e.g. baroreceptor-cardiac reflex, is also clearly demonstrated.

Electrical admittance cuff for noninvasive and simultaneous measurement of haematocrit, arterial pressure and elasticity using volume-oscillometric method.

An improved technique based on the electrical admittance cuff was designed for the non-invasive measurement of haematocrit (Hct), together with blood pressure (BP) and arterial elasticity represented as volume elastic modulus (Ev), in human fingers. This device is made of a rigid annular chamber installed with a surrounding thin-walled tube (cuff), which is filled with electrolyte solution. A tetrapolar method is used to detect the admittance signals, both in the solution and in a finger segment placed through the cuff. With this device, it is theoretically shown that the resistivity of blood flowing into the segment is equal to that of the solution multiplied by the ratio of the admittance variation in the solution to that in the segment. Thus, the blood resistivity and therefore Hct can be non-invasively determined from the electrolyte resistivity and these two admittance variations. On the other hand, BP and Ev are also simultaneously measured from the admittance signals following the gradual change of the chamber pressure based on the volume-oscillometric method. Experiments were successfully made in 14 subjects, showing that the indirect Hct values agreed well with the direct values obtained from sampled blood and that this simple technique was significant for the non-invasive ad simultaneous measurement of these physiological variables.

Ambulatory monitoring of indirect beat-to-beat arterial pressure in human fingers by a volume-compensation method.

Using a volume-compensation technique, a portable device has been designed for the indirect measurement of beat-to-beat arterial pressure and its waveforms in the basal phalanx of fingers of ambulatory subjects. The device consists of (1) a transmission infra-red photoelectric plethysmograph (TIPP) to detect the variation of arterial volume, (2) a pneumatic cuff with an actuator, (3) a servosystem to control the cuff pressure, and (4) a stereo cassette tape recorder. Arterial pressure was determined from the cuff pressure which was controlled by the servosystem so as to maintain the arterial volume constant at the 'vascular unloading' state. This device is equipped with a compensator for any hydrostatic pressure difference between the heart and finger. Thus, the blood pressure at heart level can be obtained for any finger height. The total weight of the device was 1.6 kg. Blood pressure changes during walking, jogging, jumping, and exercises such as side-stepping, Master's two-step test and car driving, have been successfully recorded.

Electric impedance cuff for the indirect measurement of blood pressure and volume elastic modulus in human limb and finger arteries.

A new plethysmograph, the electric impedance cuff, was designed for the indirect measurement of blood pressure, volume elastic modulus Ev and compliance Ca in human limb arteries. This comprises a compression chamber filled with electrolyte solution and a tetrapolar electric impedance plethysmograph whose electrodes are placed inside the chamber; the former for controlling transmural arterial pressure Pt, and the latter for detecting total limb volume Vo, mean arterial volume Va and its variation delta Va. Systolic and mean arterial pressure in the upper arms, forearms and fingers were measured by detecting pulsatile impedance variation during the gradual (3-5 mm Hg per heart beat) increase (or decrease) in chamber pressure by the volume oscillometric technique. Diastolic and pulse pressure delta P were calculated from these pressure values. Compliance Ca = delta V/delta P and volume elastic modulus Ev = delta P/(delta Va/Va) were recorded at various Pt levels, controlled by the compression pressure. Although this is a kind of impedance plethysmograph, the volume change in a limb segment can be detected by this method without passing electric current through the limb.

Vibration technique for indirect measurement of diastolic arterial pressure in human fingers.

Diastolic pressure Pd was indirectly measured by vibrating a finger artery with a 10 Hz sinusoidal pressure variation during a gradual increase (or decrease) in occlusive cuff pressure Pc. Pulsatile arterial volume changes on which sinusoidal variations are superimposed were detected by a transmitted infra-red photoelectric plethysmograph (TIPP). It is known that volume change in an artery shows a maximum amplitude at the transmural pressure Pt level equal to 0 mm Hg due to the nonlinear viscoelastic properties of the arterial wall. For the same reason, the amplitude of the sinusoidal volume variation reached its maximum at the end-diastolic phase, when Pc was controlled to be exactly equal to Pd. The indirect Pd values determined from Pc were compared with those simultaneously measured by a direct method in rabbit forelegs and by the volume-compensation method in human fingers. Using the principle of the volume oscillometric method systolic and mean pressures were also determined by this system.

New technique for time series analysis combining the maximum entropy method and non-linear least squares method: its value in heart rate variability analysis.

A new technique for time series analysis, which is a combination of the maximum entropy method (MEM) for spectral analysis and the non-linear least squares method (LSM) for fitting analysis, is described. In this technique, the MEM power spectral density (MEMPSD) is calculated using a very large lag that could diminish the lag dependence of dominant periods estimated by the MEM analysis. The validity of this large lag is confirmed by the LSM, given that the ten dominant MEM periods are known quantities. To validate the MEM plus LSM technique, it is compared with autoregressive (AR) modelling, by analysing heart rate variability under pharmacological interventions (phenylephrine and trinitroglycerine), using 16 young males. The results indicate that the MEMPSD, when compared with the ARPSD, has numerous periods that could reproduce the original time series much more accurately, as revealed by the LSM analysis. However, both the low- and high-frequency powers with MEMPSD and ARPSDs shift in the expected directions in accordance with the pharmacological effects on the cardiovascular system. The implications of these results are discussed from the theoretical and practical standpoints of the MEM plus LSM technique, compared with AR modelling.

Admittance plethysmographic evaluation of undulatory massage for the edematous limb.

A new apparatus, called Hadomer has been developed for the treatment of peripheral lymphedema and venous disorder. It has cuffs with 5 rooms, through which the air pressure moves from periphery to proximal point, just like surging waves. The peripheral stagnant lymph and venous blood are displaced toward the heart by this pneumatic massage. Hadomer has been applied to more than 400 patients with the edematous limbs, with satisfactory results, such as decrease of swelling, pain and induration. These clinical results have been also confirmed by electrical admittance plethysmography which is useful to measure noninvasively the edematous volume and the blood flow. The admittance of the edematous limbs is high and after massaging with Hadomer it approaches normal range. The blood flow in the diseased limbs is less than the healthy one and it is observed better after pneumatically massaging.

Fully automated health monitoring at home.

The aim of this study was to provide adequate home health monitoring for the elderly at home using fully automated signal measurement with personal identification to support daily health care and to improve quality of life. We attempted to develop a home health monitoring system that did not provide any restrictions during sleep, bathing and excretion. A new room including bath and toilet was constructed. The system consisted of monitoring devices and a computer terminal for collecting data. The data were automatically obtained from monitoring devices situated at the bed, bath and toilet and were transferred to a data terminal and stored for further analysis. Where subjects live with their spouse or family, personal identification is required to store data individually. For the bathtub data, personal identification was performed using ECG data. Sampled data were reduced by wavelet transform and distinguished by a neural network. The data acquisition system is now underway and data are being extensively collected.