Development of an implantable high-energy and compact battery system for artificial heart.

The purpose of this study was to demonstrate the feasibility of the use of an implantable, high-energy, and compact battery system for an undulation pump total artificial heart (UPTAH). The implantable battery system tested consists of six lithium-ion batteries in series, a charge unit, and a charge/discharge control unit. A lithium-ion battery is currently the best energy-storage device because it has more energy density, a better life cycle, and a smaller temperature rise than those of other secondary batteries. The performance of the implantable battery system was evaluated in an in vitro experiment using an electric load that simulated the UPTAH. Also, sufficiently reliable operation of a system for supplying energy to a UPTAH consisting of a transcutaneous energy transmission system (TETS) and an implantable battery system was confirmed in three experiments using goats. The results of the in vitro and in vivo experiments showed that the implantable battery system supplied sufficient current to the UPTAH for maintenance of physiological conditions in the goat with maximum rise in temperature to less than 43 degrees C.

Miniature vibrating flow blood pump using a cross-slider mechanism for external shunt catheter.

The prototype of the miniature vibrating flow pump (VFP) is developed for the external shunt catheter. The cross-slider mechanism is applied to vibrate the tube, which causes the pumping effect. This mechanism results in successful development of the miniature and lightweight VFP. By the use of the prototype VFP, the experiment of the basic pump performance is made in detail based on the authorized procedure in the research field of fluids engineering. The typical H-Q curve of VFP, which is the relationship between the pump head and the flow rate, can be obtained. This result suggests that the miniature VFP developed here can be expected to be used as the booster pump for the external shunt catheter in clinical applications.

Automatic monitoring system for artificial hearts using self organizing map.

This study presents an automatic monitoring system for artificial hearts. The self organizing map (SOM) was applied to monitoring and analysis of an aortic pressure (AoP) signal measured from an adult goat equipped with a total artificial heart. In the proposed system, two different SOMs were used to detect and classify abnormalities in the measured AoP signal. In the first stage, an ordinary SOM, taught with only normal AoP data, was used for detection of abnormalities on the basis of the quantization error in the real-time monitoring task. In the second stage, a supervised SOM was used for classification of abnormalities. The supervised SOM can be regarded as an ordinary SOM with an extra class vector for solving the classification problem. The class vector is assigned to every node in the second SOM as an output weight learned according to Kohonen's learning rule. The effectiveness of detection and classification of abnormalities using these two SOMs was confirmed.

A case of undifferentiated carcinoma of the gallbladder with anomalous arrangement of the pancreaticobiliary ductal system.

Anomalous junction of the pancreaticobiliary duct (AJPBD) is a congenital anomaly associated with gallbladder carcinoma. Especially patients with noncystic dilatation and without dilatation of the biliary tract are at risk of gallbladder carcinoma. A 56-year-old woman with advanced gallbladder cancer associated with AJPBD but without dilatation of the biliary tract was treated at our hospital. Although histologically cancer cells remained in the layer of the proprial mucosa, extensive metastases to lymph nodes including the paraaorta and peripancreas were detected. According to the TNM classification this case was of Stage IVB. The cancer consisted of medullary round cells, and was diagnosed as undifferentiated carcinoma. After surgery poor prognosis was expected, but three years have elapsed with no recurrence. The case is of interest because of two points of discrepancy: the primary cancer did not show deep invasion but demonstrated extensive lymph node metastases; the cancer was histologically malignant but prognosis was relatively good.

[All-trans retinoic acid combined with low-dose cytosine arabinoside treatment for acute myelogenous leukemia with trilineage myelodysplasia--a case report].

AML with trilineage myelodysplasia (AML/TMDS) is recognized as having of poor prognosis due to its resistance to chemotherapy in comparison with de novo AML. An AML/TMDS patient who failed to respond to ordinary induction therapy achieved complete remission with combination therapy consisting of all-trans retinoic acid (ATRA) and low-dose Ara-C. No serious toxicity was observed. ATRA combined with low-dose Ara-C could be an alternative treatment for this kind of patient.

One month survival with the undulation pump total artificial heart in a goat.

The undulation pump is a small continuous flow displacement-type blood pump. The undulation pump total artificial heart (UPTAH) is a unique implantable total artificial heart using undulation pumps. An adult female goat weighing 45.8 kg was used for implantation. The natural heart was replaced with the UPTAH under extracorporal circulation. The cardiac output (CO) was maintained to 100 ml/kg/min by controlling the right pump manually. To prevent lung edema, the left pump was controlled automatically to maintain the left atrial pressure below 20 mm Hg. The CO was maintained for 2 weeks. Thereafter, the CO gradually decreased. The goat suddenly died because of a brain stroke on the 31st postoperative day. At autopsy, the cavity of the left atrial cuff was almost occupied by the big pannus-like thrombus, which was thought to be the cause of death. Improvement of the atrial cuff is necessary to obtain longer survival and is being modified. No thrombus was found inside the pumps. However, temperature rise in a left motor was a problem. Improvement of the efficiency in a motor is necessary. Although many problems still remained, 1 month survival could be obtained with this unique implantable TAH using continuous flow displacement-type blood pumps.

Acute lymphoblastic leukemia accompanied by chromosomal abnormality of translocation (12;17).

This report concerns a female patient with B-precursor acute lymphoblastic leukemia with concomitant expression of CD13 and CD33. A rare chromosomal abnormality, t(2;17)(p13:q21), was detected in 70% of metaphases analyzed. A new subgroup of acute leukemia is proposed, consisting of our case and 12 reported cases with similar chromosomal abnormalities. This subgroup has a poor prognosis and a high incidence of biphenotypic characteristics.

Development of a miniature undulation pump for the distributed artificial heart.

Research of the distributed artificial heart is important not only to acquire the means of individual organ perfusion but also to clarify the characteristics of the organ and the mechanism of blood distribution. To investigate the distributed artificial heart, the miniature undulation pump was developed. The outer diameter and the thickness of the developed pump were 38 mm and 11 mm, respectively. The priming volume of the pump was 3.2 ml. The total size including the motor unit was 38 mm in diameter and 32 mm in length. The total weight was 67.5 g. The total volume was 27.5 ml. The pump was driven with pulse width modulation by using a 1 chip motor controller. More than 5 L/min of continuous output could be obtained. The results showed that the developed miniature undulation pump system had enough performance for individual organ perfusion.

Using one rotary blood pump to produce separate pulsatile circulations in the upper and lower halves of the body.

Separate systemic circulations with pulsatile flow were obtained using 1 rotary blood pump as a left ventricular assist device. The outlet of the pump was divided into 2 conduits, 1 connected to the upper half of the body and the other connected to the lower half. An electric actuator that clamped the 2 outlet conduits alternately provided pulsatile flows. An in vitro experiment showed that the pulsatility phases of the upper and lower halves of the body were complementary with pulsatile flow, and an in vivo experiment showed that controlled flow distributions of continuous flows could be obtained.

Results of animal experiments using an undulation pump total artificial heart: analysis of 10 day and 19 day survival.

An undulation pump is a special rotary blood pump in which rotation of a brushless DC motor is transformed to an undulating motion by a disc in the pump housing attached by means of a special link mechanism. In the blood pump, a closed line between the disc and housing moves from the inlet to the outlet by this undulating disc motion, which sucks and pushes the blood from the inlet to the outlet. Because the same phenomena occurs at both sides of the disc, a continuous flow is obtained when the motor rotational speed is constant. The pump flow pattern can be easily changed from continuous flow to pulsatile flow by controlling the motor drive current pattern. A seal membrane made of segmented polyurethane protects the blood from invading the link mechanism as well as the motor. UPTAH is fabricated with two undulation pumps and two brushless DC motors. Its size is 75 mm in diameter and 80 mm long, and it has one of the great advantage of no compliance chamber required in the system. UPTAHs were implanted under cardiopulmonary bypass (CPB) into the chest cavities of 16 goats, each weighing between 41 and 72 kg. No anticoagulant and antiplatelet agent was used after the surgery. The left atrial pressure was automatically controlled to prevent its elevation and sucking of the atrial wall into the atrial cuff. The following results were obtained: (1) UPTAHs fit well into all the goats; (2) the longest survival was 19.8 days, the cause of death was bleeding from the aortic anastomosis; (3) No thrombus was observed in the blood pump despite no anticoagulant use. Hemolysis depended upon the length of CPB during surgery. When CPB time was within 2 hours, hemolysis level returned to baseline within a few days of the surgery. UPTAH is a promising implantable TAH, because of its small size and easy controllability.

Tumor-like splenic extramedullary hematopoiesis in a patient with myelofibrosis.

A 61-year-old woman, who was diagnosed in 1982 as having polycythemia vera, was admitted to our hospital in July 1998 because of a splenic tumor in an enlarged spleen due to myelofibrosis. As it was difficult to identify the etiology of the splenic tumor, partial splenectomy was carried out. The resected tumor proved to be an extremely proliferative lesion as the result of extramedullary hematopoiesis. Since it is difficult to diagnose the etiology of splenic tumor, the collection and analysis of reports of relevant cases may well facilitate diagnosis.

Analysis of hemodynamic response with 1/R control on biventricular bypass goat.

A conductance and arterial pressure based method (1/R control) to determine the cardiac output (CO) of a total artificial heart (TAH) was developed to provide a central nervous system with control over the output of TAH. In order to clarify the deference in hemodynamic response between natural heart and 1/R control, biventricular bypass was introduced in the goat. After 2 pneumatically driven sac-type blood pumps were connected to the natural heart, the pulmonary artery was totally clamped to acquire 100% right heart bypass, and the ascending aorta was stenosed to acquire about 60 to 90% left heart bypass; 1/R control was performed substituting the output of the right artificial heart for the CO. The results demonstrated that stable control could be achieved. A discrepancy was often seen between the pulse rate (PR) of the artificial heart and the heart rate (HR) in absolute value. However, the relative changes of PR were quite similar to that of HR for the most part, indicating that the responses of 1/R control were the duplication of natural cardiac responses in normal daily activity.

Implantation of the undulation pump total artificial heart in the goat.

The undulation pump total artificial heart (UPTAH) was developed by using small-size continuous-flow displacement-type blood pumps (undulation pump). To clarify and improve the problems accompanied by the implantation in the chest, 14 animal experiments were performed on goats weighing 41.3-79.2 kg. The UPTAH could be implanted in the chest of all goats and was driven with a modulation pulsatile mode. The first problem was the atrial suction effect. This problem could be prevented to some extent by developing the soft disk and by improving atrial cuffs. An automatic detection and releasing of the atrial suction effect was also tried. The next problem was acute lung edema accompanied by the postural change of the animal. Development of the automatic control of left atrial pressure could prevent this problem. Small blood leakage from a pinpoint hole in the seal membrane was the next problem. Improvement of the manufacturing procedure of the membrane prevented this. With these improvements, a 10 day survival could be obtained with this unique implantable total artificial heart.

Present status of the total artificial heart at the University of Tokyo.

At the University of Tokyo, various types of total artificial heart (TAH) systems have been studied since 1959. At the present time, 2 types of implantable TAH have been developed. One is an undulation pump TAH (UPTAH) and the other is a flow transformed pulsatile TAH (FTPTAH). Using the UPTAH, 14 cases of implantation were performed in goats and 10 days' survival obtained. The new type of FTPTAH is under a prototype study. To prevent ring thrombus, a polyurethane membrane valve, a jellyfish valve, has been developed. The longest in vivo experiences with this valve in the TAH blood pump have been 312 days in the left side blood pump and 414 days in the right side blood pump. Conductance and arterial pressure based control (1/R control) can realize the physiological control of the TAH. Using 1/R control, 532 days of survival could be obtained in a goat with a paracorporeal TAH. The technique required to apply this control method to a implantable TAH is under development. We have proposed a new 5 year research project of the implantable TAH entitled "Comprehensive Basic Research on the Development of a Japanese Original Implantable Total Artificial Heart" to The Ministry of Welfare.

Reverse motion of organelles with myosin molecules along bundles of the actin filaments in a Characean internodal cell.

We have visualized bundles of the actin filaments of a Characean internodal cell and investigated the sliding motion of organelles with myosin on the bundles. The investigation revealed that a power spectrum of the sliding velocity time series of the organelle has two remarkable peaks near 4 and 7.5 Hz. This suggests that myosin molecules attached to the organelle not independently but cooperatively produce the sliding force. Moreover, we have found that some organelles move in the opposite direction of their sliding motion for several hundred milliseconds along the bundles. The fluctuation analysis of that motion showed that a power spectrum profile of the reverse velocity time series almost agreed with that of the sliding velocity time series. This result suggests that the dynamics of the reverse motion is the same as that of the sliding motion.

[Dorsal root identification using spinal endoscopy and electro-physiology].

We aimed to develop a method of accurately identifying the dorsal root for the corresponding peripheral afferent nerve under endoscopic observation. We developed an endoscope with an external diameter of 1.8 mm. After small laminectomy on the lower thoracic vertebrae, we inserted this endoscope carefully into the epidural and then subarachnoid spaces. We observed structures in these spaces with the endoscope. We tried to determine the spatial relationship between these electrodes and dorsal root. After identifying each space, we inserted two electrodes into the visualized space to record evoked potentials; a bipolar electrode (protocol 1) and a catheter-type eight polar electrode (protocol 2). Each pole could be distinguished by marks. To stimulate peripheral nerves, we inserted needle-type electrodes into Th 10, 11 and 12 intercostal nerves. We attempted to record potentials from dorsal surface of the cord generated by intercostal nerve stimulus. Protocol 1: We moved the position of the bipolar recording electrodes between Th 9 and L 1 by 1 cm increment, and obtained evoked potentials correspondingly. Protocol 2: We chose the neighboring pairs of poles sequentially from the tip of the catheter for bipolar recording. At the end of each experiment, we dissected the animal and checked the intercostal nerve originating from the root. With the endoscope, we could clearly observe structures in the epidural and subarachnoid spaces. We could record evoked potentials from the dorsal spinal cord with the electrodes located either in epidural or in subarachnoid spaces. Shapes of evoked potentials changed characteristically according to the relative position between the root and the electrode. The largest potentials were obtained when the electrode was nearest to the dorsal root, of which the peripheral nerve was being stimulated. By combining endoscopy with the electrophysiological technique, we could accurately identify the dorsal roots for the corresponding peripheral afferent nerves. This method may be used for the selective dorsal root blockade under the visual field.

[Acute transformation of chronic myelomonocytic leukemia with t(1;3) (p36;q21) abnormality].

A 66-year-old man was given a peripheral blood test because of low grade fever. Leukocytosis was detected, and the blood and bone marrow findings were consistent with those of chronic myelomonocytic leukemia. Three months later the hematological findings were: WBC 58,800/microliter (19% blastoid cells, 22% monocytes), Hb 9.0 g/dl, and a platelet count of 116 x 10(4)/microliters. A bone marrow examination revealed the presence of 52.6% blastoid cells and dysmegakaryocytopoiesis, including micromegakaryocytes. Serum and urinary lysozyme levels were elevated. Karyotypic analysis detected t(1; 3) (p36;q21), but not major bcr/abl mRNA. The patient was given a diagnosis of acute transformation of chronic myelomonocytic leukemia. Despite treatment, he died about 3 months later. t(1;3) is occasionally observed in cases of myelodysplastic syndrome (MDS) and leukemia. Patients with t(1;3) often exhibit dysmegakaryocytopoiesis; furthermore, acute leukemia develops more readily in those who also have MDS. Cases of long-term survival are rare.

Physiological control of a total artificial heart: conductance- and arterial pressure-based control.

To obtain a physiological response by a total artificial heart (TAH), while eliminating the hemodynamic abnormalities commonly observed with its use, we proposed the use of a conductance- and arterial pressure-based method (1/R control) to determine TAH cardiac output. In this study, we endeavored to make use of a variable more closely tied to central nervous system (CNS) efferents, systemic conductance, to provide the CNS with more direct control over the output of the TAH. The control equation that calculates the target cardiac output of the TAH was constructed on the basis of measurement of blood pressures and TAH flow. The 1/R control method was tested in TAH-recipient goats with an automatic method by using a microcomputer. In 1/R control animals, the typical TAH pathologies, such as mild arterial hypertension and substantial systemic venous hypertension, did not occur. Cardiac output varied according to daily activity level and exercise in a manner similar to that observed in natural heart goats. These results indicate that we have determined a control method for the TAH that avoids hemodynamic abnormalities exhibited by other TAH control systems and that exhibits physiological responses to exercise and daily activities under the conditions tested. The stability of the control and the complete lack of inappropriate excursions in cardiac output is suggestive of CNS involvement in stabilizing the system.