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Biomedical subjects

T Isoyama

Publications and source records attributed to T Isoyama.

At least 19 recordsLinked to original sources

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.

Animals

The early haploid male gamete develops a capacity for fertilization after the coalescence of the proacrosomal granules.

We compared the fertilizing capacity of rabbit testicular round spermatids (i) before appearance of the proacrosomal granules (stage -1), (ii) with two to three proacrosomal granules attached to the nucleus (stage -2) and (iii) with one granule attached to the nucleus (stages -3 to -5). Testicular samples were minced and observed via confocal scanning laser microscopy, which allows intracellular observation at high magnification and the subsequent identification of acrosomal granules and round spermatids. Nuclei of round spermatids of stage -1 (group A), -2 (group B), and -3 to -5 (group C) were isolated and injected into mature rabbit oocytes. At 24 and 72 h post-injection the number of cleaved oocytes and morulae/blastocysts, respectively, were significantly lower in groups A and B than group C. These results suggest that the rabbit round spermatid develops fertilizing potential after the stage at which the coalescence of the acrosomal granules occurs.

Acrosome

Development of the undulation pump total artificial heart.

The undulation pump is a small size continuous flow displacement type blood pump that has been developed for an artificial heart. Using undulation pumps, 2 types of implantable total artificial hearts (TAHs), the undulation pump TAH (UPTAH) type 1 (UPTAH 1) and UPTAH type 2 (UPTAH 2) were developed. Both UPTAHs were designed to be small enough to implant into the chest of a goat, the experimental animal. UPTAH 1 could be reduced in size to 75 mm in diameter and 78 mm in length. The weight was 520 g. UPTAH 2 could be reduced in size to 75 mm in diameter and 80 mm in length. The weight was 650 g. UPTAH 2 could be tested in an animal experiment using an adult female goat weighing 52.3 kg. The UPTAH 2 could be implanted successfully into the goat's chest with a good fit. The goat stood after the surgery and extubation and survived for 3 h and 40 min; thus, the potential of the UPTAH for a practical implantable TAH was demonstrated.

Animals

Use of a catecholamine sensor in the control of an artificial heart system.

An electrochemical sensor system to allow real-time measurement and feedback of catecholamine concentrations was developed for use in the control of artificial hearts. Electrochemical analyses were carried out using a carbon fiber working electrode, an Ag-AgCl reference electrode, and a potentiostat. The operating parameters of the pneumatically-driven artificial heart system were altered in accordance with the algorithm for changes in the catecholamine concentration. The minimum detectable concentrations of both adrenaline and noradrenaline in a mock circulatory system using a phosphate-buffered solution were approximately 1-2 ng/ml (10(-8) mol/L). An artificial heart control system utilizing this set-up performed satisfactorily without delay, although sensor sensitivity decreased when placed in goat plasma instead of a phosphate-buffered solution, due to the adsorption of various substances such as plasma proteins onto the electrodes. This study demonstrated the future feasibility of a feedback control system for artificial hearts using catecholamine concentrations.

Adsorption

Composite carcinoid-adenocarcinoma tumor of the stomach: report of a case.

We describe herein the case of an extremely unusual composite carcinoid-adenocarcinoma tumor of the stomach, most of which was found to be carcinoid. The carcinoid tumor component exhibited argyrophilic granules, immunohistochemical localization of chromogranin, and serotonin immunoreaction. Conversely, none of the adenocarcinoma component reacted with argyrophilia, chromogranin, or serotonin. DNA flow cytometric analysis revealed a near-diploid pattern in the carcinoid element and an aneuploid pattern in the adenocarcinoma element. The transitional zone and continuity between the two tumor components were observed. These findings suggest that the tumor originated from the endocrine system, although part of it showed nonendocrine differentiation. The patient died approximately 6 months after the onset of symptoms and an autopsy could not be performed.

Adenocarcinoma

A percutaneously accessible pulsatile left ventricular assist device: modified assist device type 5.

To provide percutaneous access, a new circulatory assist system was developed. We call this newly developed system the modified assist device (MAD). The system is composed of a sac-type blood pump and cannula. Inflow and outflow valves are mounted in the apex and at the side wall 10 cm from the apex of the cannula, respectively. During systole, the blood is sucked from the left ventricle through the inflow valve of the cannula connected to the blood pump, and during diastole, the blood is ejected to the root of the aorta through the outflow valve. In vitro and in vivo evaluations of the pump performance were performed. The maximum flow rate of 1.9 L/min was obtained in the mock circulatory system. In our animal experiment, effective systolic unloading and diastolic augmentation were observed by activation of this system during regular sinus rhythm. In conclusion, the MAD-5 is thought to be percutaneously accessible and increases systemic and coronary flow.

Animals

Basic study to develop the undulation pump for practical use: antithrombogenicity, hemolysis, and flow patterns inside the pump.

The undulation pump (formerly called the precessional displacement pump) is a continuous flow displacement-type blood pump that is being developed as an implantable total artificial heart. A new undulation pump was developed for chronic use and was examined with animal experiment and flow visualization studies. In the animal experiment using a left ventricular bypass in goats, severe hemolysis occurred. After driving for 12 h, thrombus formation inside the pump was found. In the flow visualization studies, the flow pattern showed that the flow inside the pump was a very complicated turbulent flow. Improvement of hemolysis and thrombus formation is important to realize implantable total artificial hearts using undulation pumps.

Animals

New version of flow-transformed pulsatile total artificial heart with no electrical switching valve.

The flow-transformed pulsatile total artificial heart (FTPTAH) is a new pulsatile total artificial heart that consists of a single continuous flow rotary blood pump and blood flow switching valves. It can perfuse the pulmonary and the systemic circulation alternately with pulsatile flow. A new version of the FTPTAH, which consists of one undulation pump (UP), 4 jellyfish valves, and a compensatory chamber, has been proposed. The UP is a reversible continuous flow blood pump, and flow transformation is caused by switching the direction of the motor rotation so that no electrical flow switching valve is needed. A prototype model could perfuse alternately pulmonary and systemic circulation with 3.0 L/min in a mock circulation. Unoxygenated blood in the UP at the end of pulmonary circulation will be stored in the compensatory chamber by shifting a flexible membrane to the direction of the left atrium (LA); therefore, the blood is not sent to the systemic circulation.

Atrial Function

Development of a new apparatus to observe microcirculation chronically in continuous flow blood pump research.

To observe microcirculation chronically is an important key to the successful evaluation of the continuous flow blood pump. In this study, we succeeded in developing a new apparatus by which microcirculation could be observed chronically without a microscope in a conscious animal. The apparatus utilizes a charge coupled device (CCD). A thin living tissue, such as mesentery, is put directly on a highly integrated CCD and is lit up through the tissue with a light-emitting diode (LED). The vascular nets in the tissue are projected onto the CCD like a contact photograph, which is then sent to a television screen and which can be used to analyze their motion and function. A 0.5-inch CCD having 250,000 pixels was used in this study. The cover glass of the CCD was removed, and a fiber optic plate was fixed onto the surface of the CCD for the tissue to be able to contact with the apparatus surface without clearance. The CCD as well as the LED were molded with epoxy resin for electrical insulation. The apparatus was 35 mm wide and 12 mm high with a micro stand for an LED, which can be easily implanted into an animal. The apparatus was implanted into a rabbit for 12 h. The configuration of arterioles and venules, tens of micrometers in diameter, and their motions in subcutaneous tissue could be observed.

Animals

Submucosal tumors of the stomach: a study of 100 operative cases.

BACKGROUND: Mass screening for gastric cancer has been established in Japan, and asymptomatic submucosal tumors are often detected. This retrospective study was made to evaluate the proper surgical management of malignant submucosal tumors of the stomach. METHODS: One hundred submucosal tumors of the stomach were surgically resected, irrespective of symptoms and size. Up to 45% of these tumors, including 44 myogenic lesions, 23 non-Hodgkin's lymphomas, and 11 schwannomas, proved malignant. Myogenic sarcomas were classified in low and high grades according to mitotic rates, cellularity, and pleomorphism. RESULTS: Thirty-five of 55 benign tumors and four of nine low-grade sarcomas underwent enucleation only, without recurrence. The remaining five low-grade and 11 high-grade sarcomas were treated by radical gastrectomy; the 5-year survival was 100% for the former and 80% for the latter. Eighteen patients with lymphomas underwent total or subtotal gastrectomy, and three patients underwent noncurative resection; the 5-year survival rates were 54.2% and 0%, respectively, with a clear significant difference (p < 0.001). Adjuvant chemotherapy was significantly superior to surgery alone (p < 0.05). Other factors did not affect survival of lymphoma. CONCLUSIONS: With these observations, we believe that following the patients with submucosal tumor without surgery is not reasonable. Enucleation will suffice for low-grade sarcomas and benign tumors; high-grade sarcomas can be well treated by gastrectomy. Total or subtotal gastrectomy with systematic lymph node dissection when performed for cure can provide good results for resectable lymphomas.

Adult

Malignant lymphoma of the stomach associated with systemic sarcoidosis.

The case of a patient with gastric malignant lymphoma associated with systemic sarcoidosis is reported. The patient's sarcoidosis was identified by the findings of bilateral hilar lymphadenopathy and secondary glaucoma. Biopsy of a cervical lymph node showed epithelioid cell granuloma; the sarcoidosis was diagnosed 15 years previously. She had been treated with prednisolone for 5 years until 1979. Proximal gastrectomy, splenectomy, and lymph node dissection were done in 1989. The tumor was diagnosed as malignant lymphoma of the diffuse large cell type according to the Working Formulation. There was no infiltration of lymphoma cell in the 45 dissected lymph nodes, but sarcoid nodules were observed in all nodes. Only three cases of gastric malignant lymphoma complicating sarcoidosis have been reported to the authors' knowledge. Further study should be done in support of the concept of a sarcoidosis-lymphoma syndrome.

Aged

Total gastrectomy for gastric cancer in the elderly.

Of 1070 patients with gastric cancers, 292 patients underwent total gastrectomy during 13 years. Sixty patients were more than 70 years of age and 232 were under 69 years. The incidence of well-differentiated carcinomas and poorly differentiated carcinomas was the same in the elderly patients, whereas the latter was dominant in the young patients. However, there was no significant difference between the two groups regarding location, size, macroscopic patterns, extent of lymph metastases, or stage classification. The rates of preoperative surgical risk factors were significantly different between the two groups (p less than 0.01): 90.0% for the elderly and 34.9% for the young patients. However, the rates of postoperative morbidity and mortality were 31.7% and 3.3% for the elderly and 24.1% and 1.3% for the young patients, respectively, with no significant difference. The 5- and 10-year survival rates after curative total gastrectomy were 48.6% and 23.2% for the elderly compared with 49.4% and 33.6% for the young patients, respectively, with no significant difference. A 5-year survival rate after noncurative operation was 0% for the elderly and 6.4% for the young patients. These results indicate that, when performed for cure, total gastrectomy with systematic lymphadenectomy can provide good long-term results for elderly, as well as young, patients.

Age Factors

[A primary choriocarcinoma of the stomach with a review of 45 cases in Japan].

A case of a primary choriocarcinoma of the stomach is reported together with review of 44 cases in the Japanese literature. The patient, a 79-year-old male complaining of severe anemia, was admitted to hospital. As a result of a gastric endoscopy, a carcinoma was diagnosed and a laparotomy was performed. Because of an extensive metastasis, however, the surgery was limited to a palliative proximal gastrectomy. Pathologically, the tumor was a choriocarcinoma, and the HCG in the blood was slightly elevated. Immunohistologically, however, no HCG was detected. Although most cases reported in Japan support the theory of differentiations in gastric carcinomas, this choriocarcinoma suggests a separate type of differentiation in both the function and the morphology or a morphological mimicking.

Aged

The pathophysiology of septic shock: studies of reticuloendothelial system function and liver high-energy metabolism in rats following sublethal and lethal Escherichia coli injection.

Phagocytic indices and the hepatic energy charge (ATP + 1/2 ADP/ATP + ADP + AMP) were studied in rats after intravenous sublethal or lethal injection of live Escherichia coli (12--15 X 10(8) or 4--5 X 10(8) organisms/100 gm of body weight). Phagocytic indices as determined by carbon clearance test were progressively decreased in both groups from 0.063 of control to 0.028 or 0.022 (sublethal or lethal) at 12 hours (P less than 0.001). This was mainly due to marked decrease in carbon uptake in the liver even though a marked accumulation of carbon occurred in the lung. At 24 hours in the sublethal group, the phagocytic index was elevated (P less than 0.01). With regard to the spleen, carbon uptake in the sublethal group remained unchanged, in contrast to the decreased uptake in the lethal group, leading to a significant difference between sublethal and lethal groups (P less than 0.05 or less at six and 12 hours). On the other hand, the hepatic energy charge levels in the lethal group progressively decreased from 0.86 to 0.62 until death (P less than 0.001), while those in the sublethal group remained moderately decreased. Following carbon administration, the hepatic energy charges in the control and lethal groups were decreased, while those in the sublethal group remained unchanged. These results suggest a functional reserve of phagocytic activity in liver and spleen and activated high-energy metabolism in the liver for phagocytosis may play a role in determining survival from bacteremic shock.

Adenosine Triphosphate

The pathophysiology of septic shock: changes in hemodynamics in rats following live E coli injection. An application of the thermodilution method for measurement of cardiac output.

Fifteen anesthetized rats, 273 +/- 9 gm (SEM), were monitored hemodynamically for six hours following an IV injection of a sublethal (4--5) X 10(8) organisms/100 gm body wt, n = 5) or lethal 12--15 X 10(8) organisms/100 gm body wt, n = 5) dose of live Escherichia coli or saline (control, n = 5). A transpulmonary thermodilution method was used for measurement of cardiac output. Changes in the arterial blood temperature and pressure were recorded on a polygraph. In a simulated hydraulic model system, the measured flow rate was well correlated ( r = 0.993, P less than 0.001) with various actual flow readings (30--130 ml/minute). A sublethal dose resulted in a transient hyperdynamic state in the early stage; the cardiac index was increased from the initial rate of 258.2 +/- 9.4 to 312.3 +/- 10.7 ml/minute/kg with a concomitant decrease in the total peripheral resistance from 0.497 +/- 0.019 to 0.367 +/- 0.022 mm Hg/ml/minute/kg which was sustained for 120 minutes after treatment. In contrast, a lethal dose caused a prolonged hyperdynamic state in the early stage followed by a hypodynamic state in the late stage. The cardiac index was increased from 2.54 +/- 4.5 to 306.0 +/- 10.8 ml/minute/kg and the total peripheral resistance was decreased from 0.513 +/- 0.024 to 0.337 +/- 0.015 mm Hg/ml/minute/kg in the early stage, while, in the late stage, the former decreased to 195.0 +/- 13.3 ml/minute/Kg and the latter increased to 0.615 +/0 0.054 m Hg/ml/minute/kg. The mean arterial blood pressure was decreased in both groups in the early stage but maintained above 100 mm Hg. Essentially, no hemodynamic changes were noted in the control group. These results confirm our hypothesis that an injection of live E coli can produce a hyperdynamic state in the early stage as well as hypodynamic state in the late stage, and that serial hemodynamic studies on bacteremia in rats can be done successfully using the thermodilution method.

Animals

Effects of naloxone and morphine in hemorrhagic shock.

The effects of naloxone hydrochloride and morphine sulfate on survival were examined in LD40 hemorrhagic shock in rats. Bolus IV injection of naloxone (1.6 mg/kg) following hemorrhage significantly (p less than 0.025) increased the 24 hour survival rate (14/15, 93%), compared to that in saline-treated animals (13/22, 59%). Supraphysiologic doses of IV morphine sulfate did not adversely influence survival (12/15, 80% at 0.5 mg/kg; 8/15, 53% at 0.1, 0.05, and 0.01 mg/kg). Morphine decreased heart rate during shock in a dose-dependent fashion, but did not affect the blood pressure. Compared to responses in the other groups, naloxone had no effect on blood pressure or heart rate in shock animals during the monitoring interval. These results suggest that: 1) endogenous opioid substances, most likely at much lower blood concentrations than those used in the present experiment, may not be important deleterious factors during shock; and 2) enhancement of survival by naloxone in hemorrhagic shock is probably due to effects other than antiopiate activity.

Animals