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Biomedical subjects

K Nakata

Publications and source records attributed to K Nakata.

At least 649 records · Page 36Linked to original sources

The role of pulsatility in end-organ microcirculation after cardiogenic shock.

To estimate the effectiveness of pulsatility in end-organ microcirculation after cardiogenic shock, experimental studies using swine were done. Cardiogenic shock was produced in 14 pigs by ligating the left anterior descending branches so that mean aortic pressure dropped to 60% of the control value. After inducing shock, left atrial to ascending Ao bypass was initiated. A pneumatic pulsatile pump (Zeon Medical Inc, Tokyo, Japan) was used in seven pigs (Group P) and a centrifugal pump (BP-80, BioMedicus Inc, Minneapolis, MN) in seven (Group NP). In both groups, about half the usual cardiac output was supported for 3 hr, maintaining mean aortic pressure at approximately 100 mm Hg. The pulse pressure was 36.6 +/- 4.6 mm Hg in Group P, and 14.3 +/- 1.5 mm Hg in Group NP. Epicardial and endocardial regional flows recovered after assist in both groups. There were no significant differences between the two groups. However, liver tissue flow, renal cortex flow, and stomach mucous flow in Group P was significantly higher than those of Group NP after support (p < 0.05). In addition, arterial blood ketone ratio in Group P was 0.61 +/- 0.13 vs 0.39 +/- 0.06 in Group NP, a significant difference (p < 0.05). These results suggest that in uneven blood flow distribution of end organs after cardiogenic shock, pulsatility was effective in improving and maintaining function and microcirculation of end organs, preventing multiorgan failure.

Animals↗

Long-term in vivo left ventricular assist device study with a titanium centrifugal pump.

A totally implantable centrifugal artificial heart has been developed. The plastic prototype, Gyro PI 601, passed 2 day hemodynamic tests as a functional total artificial heart, 2 week screening tests for antithrombogenicity, and 1 month system feasibility. Based on these results, a metallic prototype, Gyro PI 702, was subjected to in vivo left ventricular assist device (LVAD) studies. The pump system employed the Gyro PI 702, which has the same inner dimensions and the same characteristics as the Gyro PI 601, including an eccentric inlet port, a double pivot bearing system, and a magnet coupling system. The PI 702 is driven with the Vienna DC brushless motor actuator. For the in vivo LVAD study, the pump actuator package was implanted in the preperitoneal space in two calves, from the left ventricular apex to the descending aorta. Case 1 achieved greater than 9 month survival without any complications, at an average flow rate of 6.6 L/min with 10.2 W input power. Case 2 was killed early due to the excessive growth of the calf, which caused functional obstruction of the inlet port. There was no blood clot inside the pump. During these periods, neither case exhibited any physiologic abnormalities. The PI 702 pump gives excellent results as a long-term implantable LVAD.

Equipment Design↗

Development of an antithrombogenic and antitraumatic blood pump: the Gyro C1E3.

The Gyro C1E3 is a centrifugal blood pump. Its antithrombogenic and antitraumatic blood features were demonstrated by prior studies. Based upon these studies, a mass production model of the C1E3 is becoming commercially available. Therefore, this feasibility study was conducted using the mass production models of the Gyro C1E3 for long-term cardiac assist in ex vivo animal experiments. Five healthy calves were used and 15 pump heads were applied for different time periods (Group 1, 30 days; Group 2, 14 days; Group 3, 10 and 7 days; Group 4, 4 days; and Group 5, 2 days). Activated clotting time (ACT) was kept at 200-250 sec. All five calves demonstrated neither abnormal signs nor abnormal blood examination data throughout the experiment. During necropsy, no thromboembolism was found in any downstream organs. Groups 1-4 showed thrombi inside the pump heads while two pumps in Group 5 had no thrombi formations. Bearing deformation or possible wear did not increase after 2 days of pumping. The C1E3 is capable of long-term assist circulation. However, after 2 days of pumping, careful observation is necessary since thrombi may occur inside the pump when ACT is controlled under 250 sec. During the weaning stage or low flow (under 2 L/min), over 250 sec of ACT is recommended to assure the safety of the patient.

Animals↗

Development of an implantable small right ventricular assist device.

Currently, at least two permanent implantable left ventricular assist devices (LVADs) are used clinically. Unfortunately, there is no small implantable right ventricular assist device (RVAD) available, even though at least 25-30% of this patient population has right ventricular failure. If a small implantable RVAD were available, biventricular assist could support patients with right ventricular failure. A small atraumatic and antithrombogenic RVAD is being developed to meet this clinical need. This small centrifugal blood pump, the Gyro PI pump, is 6.5 cm in diameter and 4.6 cm in height and has three unique characteristics to prevent thrombus formation: (1) the double pivot bearing and magnetic coupling system enable this pump to be completely sealless; (2) the secondary vanes at the bottom of the impeller accelerate the blood flow and prevent blood stagnation; and (3) the eccentric inlet port enables the top female bearing to be embedded into the top housing and decrease blood cell trauma. The inflow conduit consists of a wire reinforced tube and a hat-shaped tip that is biolized with gelatin to create a thrombus resistant material. This conduit is directly implanted into the right ventricle, and the outflow conduit is anastomosed to the PA. The pump can be implanted inside the abdominal wall or in the thoracic cavity. Biocompatibility of this pump was proved in two calves by thrombus free implantation as an LVAD for 284 days and 200 days. Two RVAD implantations were conducted, aiming for 1-month system feasibility studies. During the month, the RVADs operated satisfactorily without any thromboembolic incident. No blood clots or abnormal findings were seen inside the pump, nor were there abnormal findings in the explanted lungs except for small areas of atelectasis. The pump flow was 3.02 +/- 0.38 L/min in calf 1 and 3.75 +/- 1.18 L/min in calf 2. The power requirement was 7.28 +/- 0.43W for calf 1 and 14.52 +/- 3.93W for calf 2. The PaO2 was 72.0 +/- 3.60 mm Hg (calf 1) and 72.0 +/- 7.63 mm Hg (calf 2); PaCO2 was 38.3 +/- 2.17 mm Hg (calf 1) and 34.1 +/- 1.95 mm Hg (calf 2); and SaO2 was 94.1 +/- 1.37% (calf1) and 95.0 +/- 1.95% (calf 2). Gas exchange via the lungs was maintained. These studies indicate that the Gyro PI pump is suitable as a single implantable RVAD, and is a feasible RVAD as a part of a BiVAD system in terms of pump performance and thrombus resistance.

Animals↗

Preclinical evaluation of a hollow fiber silicone membrane oxygenator for extracorporeal membrane oxygenator application.

A silicone membrane hollow fiber oxygenator applicable for use as an extracorporeal membrane oxygenator (ECMO) has been developed in our laboratory. This silicone hollow fiber displays astonishing mechanical stability, is barely compressible or stretchable, and assembles easily while maintaining good gas permeability. The priming volume is 140 cc with a surface area of 0.8 m2. This study evaluated the gas transfer performances and biocompatibility of the oxygenator under ECMO and CPB conditions. In vitro studies that were performed at a blood flow rate of 2 L/min, and revealed O2 and CO2 gas transfer rates of 82.35 +/- 0.56 ml/m2/L/min and 38.72 +/- 2.88 ml/m2/L/min, respectively. The commercially available Kolobow (Avecor 1500) oxygenator was used as the control, and had O2 and CO2 gas transfer rates of 53.8 +/- 0.5 ml/m2/L/min and 24.7 +/- 2.0 ml/m2/L/min. To evaluate blood trauma, Normalized Index of Hemolysis (NIH) was measured according to American Society of Testing and Materials (ASTM) standards. The NIH findings were 0.0112 g/100L at a blood flow of 1 L/min, and 0.0152 g/100L at 5 L/min. Three ex vivo experiments, using a blood flow rate of 1 L/min, were performed with venoarterial bypass, and O2 transfer rate and CO2 transfer rate of the oxygenators were well maintained. This indicates that this preclinical silicone membrane hollow fiber oxygenator has superior efficiency, less blood trauma, and is smaller when compared with the only clinically available Kolobow oxygenator.

Animals↗

Computed tomography of liver sarcoidosis.

A case of sarcoidosis revealed multiple low density areas in the liver on CT. One of these lesions was confirmed by laparoscopic liver biopsy to be a mass of noncaseating granulomas surrounded by necrotic or fibrotic tissues. These lesions disappeared rapidly after steroid therapy.

Adult↗

Role of hepatic artery in haemodynamics in normal and cirrhotic livers in rats.

To examine the degree of influence of the hepatic artery on microcirculation in the liver, microscopic observation of blood flow in the hepatic minute blood vessels and the sinusoids and pressure measurements at key points in hepatic vascular pathways in vivo were performed before and after hepatic artery ligation in normal and cirrhotic rats. In normal rats, portal vein pressure (109 mmH2O) fell 10 mmH2O after hepatic artery ligation, but the pressures of the terminal portal venule, the terminal hepatic venule and the inferior vena cava did not change. In cirrhotic rats, portal vein pressure (206 mmH2O) and terminal portal venule pressure (106 mmH2O) fell 23 and 10 mmH2O after hepatic artery ligation respectively: the pressures in the terminal hepatic venule and the inferior vena cava did not change. These results suggests that the pressure transmitted from the hepatic artery was mostly supplied to the intrahepatic portal vein in normal rats and both to the intrahepatic portal vein and to the sinusoids in cirrhotic rats. In both normal and cirrhotic rats, however, the pressure transmitted from the hepatic artery was about 10 per cent of the initial portal vein pressure, and the blood flow in minute vessels and sinusoids did not change after hepatic artery ligation. Accordingly, it is believed that the hepatic artery plays only a small role in the haemodynamics of the liver in both normal and cirrhotic rats, irrespective of the distribution and manner of the hepatic arterial termination.

Animals↗

Pathogenesis of centrilobular necrosis following congestion of the liver.

The exact pathogenesis of centrilobular necrosis following congestion of the liver is still unknown. We reviewed the clinical data related to systemic circulatory disturbance and histopathology of the liver and the gut in 320 autopsy subjects. Congestion of the liver alone was associated only with atrophy and loss of hepatocytes in centrilobular areas, but not with hepatocellular coagulative necrosis. In many patients with coagulative necrosis of centrilobular hepatocytes and congestion of the liver, fibrin thrombi and neutrophil infiltration in the sinusoids, which are the characteristic histopathological features of the liver in endotoxaemia, were found in and around the necrotic area. Congestion, erosion or haemorrhage of the intestinal mucosa, which may allow entrance of endotoxin into the liver through the portal vein, was seen in such patients. Prolonged hypotension or shock, which may lead to portal endotoxaemia, was present in half the patients with centrilobular necrosis and congestion of the liver. These results suggest that not only congestion of the liver but also portal endotoxaemia may be involved in the pathogenesis of centrilobular necrosis in patients with congestion of the liver.

Adult↗

Differential regulation of albumin gene expression by heparin-binding epidermal growth factor-like growth factor in alpha-fetoprotein-producing and -nonproducing human hepatoma cells.

The effects of heparin-binding epidermal growth factor-like growth factor (HB-EGF) on albumin gene expression were analyzed in alpha-fetoprotein (AFP)-producing and AFP-nonproducing human hepatoma cells, HuH-7 and huH-1/cl.2, in which the AFP silencer is inactive and active, respectively. HB-EGF selectively suppressed the AFP enhancer activity, resulting in decreased levels of both albumin and AFP mRNA in HuH-7 cells. In contrast, HB-EGF did not influence the albumin transcripts in huH-1/cl.2 cells or primary culture of rat hepatocytes, although the AFP enhancer activity was reduced by HB-EGF in huH-1/cl.2 cells as well as in HuH-7 cells. These results indicate that the AFP silencer interacts with the AFP enhancer to block its activity regulating both the albumin and AFP promoters, and that HB-EGF downregulates the albumin gene expression only in the absence of the AFP silencer through the repression of the AFP enhancer activity.

Animals↗

Articular cartilage lesions in ankles with lateral ligament injury. An arthroscopic study.

To investigate intraarticular lesions producing persistent postoperative pain, we arthroscopically examined 31 ankles in 31 patients (15 women and 16 men) with lateral ligament injury. The patients ranged in age from 15 to 33 years, with a mean of 20 years. Nine patients were freshly injured, and 22 patients had chronic injuries. All of the patients underwent arthroscopic examination immediately before the ligament operation. Chondral lesions were found in 89% of the freshly injured ankles and 95% of the ankles with chronic injuries. Most of these lesions were in the medial half of the ankle joint, especially in the anteromedial edge of the tibial plafond. After followup for 1 year postoperatively, persistent pain was noted in 4 patients who had chondral lesions of greater than one-half the thickness of the articular cartilage. Pain and tenderness were localized at the anteromedial joint line, corresponding to the location of the chondral lesions. Chondral lesions of greater than one-half the thickness of the articular cartilage were found in 8 ankles in the chronic injury group, but there were none in the fresh injury group. Thus, in lateral ligament injuries of the ankle, the longer the time elapsed from the initial injury, the more severe the associated chondral lesions became. These chondral lesions appear to cause persistent pain.

Acute Disease↗

Quantitative evaluation after arthroscopic anterior cruciate ligament reconstruction. Allograft versus autograft.

We measured the anteroposterior ligamentous laxity and thigh muscle power in 92 subjects who were rated as successes after they had undergone arthroscopic anterior cruciate ligament reconstruction for unilateral anterior cruciate ligament insufficiency 18 to 36 months previously. The subjects were divided into 2 groups according to the type of graft: fresh-frozen allogenic tendon (N = 47) or central one third of the ipsilateral patellar tendon (N = 45). Instrumented drawer tests in the Lachman position were performed to measure anterior tibial displacement at 200 N (anterior laxity). Thigh muscle power was isokinetically measured with a Cybex II dynamometer. Significantly more anterior laxity was found in the reconstructed knees than in the contralateral normal knees regardless of graft material (paired t-test, P < 0.01), except for the male allograft patients. Although the mean anterior laxity difference between sides for the allograft patients was less than that for the autogenous ones, analysis of variance failed to demonstrate a statistically significant difference between the 2 groups if the comparison was strictly made within the same sex. Thigh muscle tests revealed that extension torque in the reconstructed knees was significantly less than that in the contralateral knees and analysis of variance showed that knee extension torque at 60 deg/sec for the allograft patients was significantly better than that of the autograft ones (P < 0.05). We concluded that the allograft procedure is advantageous over the patellar tendon autograft in terms of better restoration of anterior stability.

Adolescent↗

Collagen fibril populations in human anterior cruciate ligament allografts. Electron microscopic analysis.

We studied human anterior cruciate ligament allograft specimens by quantitative electron microscopy to analyze their collagen fibril populations. The specimens were procured at the time of second-look arthroscopy from the superficial region of the midzone of the anterior cruciate ligament grafts after synovial clearage. The grafts used for the anterior cruciate ligament reconstructions were from fresh-frozen allogenic Achilles, tibialis anterior or posterior, or peroneus longus or brevis tendons and had been implanted 3 to 96 months previously. By 12 months after surgery, the anterior cruciate ligament allografts consisted predominantly of small-diameter collagen fibrils (30 to 80 nm), which resulted in a unimodal pattern in the collagen fibril profile. The number of large-diameter fibrils (90 to 140 nm) within the allogenic tendon grafts had decreased. This predominance of small-diameter collagen fibrils persisted in almost all specimens older than 12 months. The anterior cruciate ligament allografts had collagen fibril profiles that did not resemble normal tendon grafts or normal anterior cruciate ligaments, even several years after surgery.

Achilles Tendon↗

Anterior cruciate ligament reconstruction with multistranded autogenous semitendinosus tendon.

We evaluated 41 knees 24 to 48 months after anterior cruciate ligament reconstruction was performed using multiple autogenous semitendinosus tendons. The ipsilateral free semitendinosus tendon was tripled or quadrupled to make a graft 7 to 10 mm in diameter and more than 60 mm long. When the diameter of the graft was less than 7 mm, an ipsilateral doubled gracilis tendon was also used (in seven cases). Twenty-three patients (56%) returned to their preinjury activity levels. According to the patients' subjective assessment, 34 (83%) graded themselves as normal or nearly normal. No patient reported giving way of the knee or limitation of knee motion. The average anterior laxity difference between the involved knee and contralateral uninjured knee was 1.5 mm at 200 N. Twenty-nine patients (71%) demonstrated an anterior laxity difference of 3 mm or less when the involved knee was compared with the contralateral uninjured knee. Quadriceps muscle strength was 90% compared with the contralateral healthy limb, and hamstring muscle strength was equivalent to the contralateral limb. In our study, tripled or quadrupled semitendinosus free tendons were excellent anterior cruciate ligament grafts for restoring knee stability, recovering thigh muscle power, and preserving knee motion.

Adolescent↗

A case of hepatocellular carcinoma with the sign of Leser-Trelat: a possible role of a cutaneous marker for internal malignancy.

A rare case of hepatocellular carcinoma who developed the complication of the sign of Leser-Trelat is reported. The patient, a 57-year-old male, visited our hospital with complaints of generalized malaise and anorexia. A diagnosis of hepatocellular carcinoma was made based on elevated alpha-fetoprotein measurement, ultrasonography, and hepatic arteriography findings. Chest x-ray film suggested pulmonary metastases of hepatocellular carcinoma. Thereafter, complications of the seborrheic keratosis developed in the trunk and the skin lesion was diagnosed as the sign of Leser-Trelat associated with hepatocellular carcinoma. The patient died of pneumonia 9 months after development of the sign of Leser-Trelat.

Biomarkers, Tumor↗

Most of the patients with cirrhosis in Japan die from hepatocellular carcinoma.

A total of 424 patients with cirrhosis were entered into a registry in Japan. One hundred and seven patients were hepatitis B virus (HBV) associated cirrhosis while 252 were hepatitis C virus (HCV) associated cirrhosis. Patients were followed for a period of 3.3+/-3. 3 years. Fifty-six (80%) of 70 deaths in HBV patients and 151 (90%) of 161 deaths in HCV patients were due to complications associated with hepatocellular carcinoma (HCC). The complication rate of HCC in HCV group was significantly higher than in HBV group. In conclusion, most of the patients with cirrhosis died from HCC.

Adult↗

Alternative splicing of fibronectin transcripts in osteochondrogenic tumors.

BACKGROUND: Fibronectin (FN) acts in many fundamental biological processes including cell adhesion, migration, proliferation and apoptosis. Although FN shows an ubiquitous expression pattern, alternative mRNA splicing modulates tissue-specific molecular heterogeneity at three regions: extra domain-B, extra domain-A and variable region. MATERIALS AND METHODS: In the present study, we analyzed the FN mRNA splicing in osteochondrogenic tumors as well as in various normal tissues using the RT-PCR method. RESULTS: Normal cartilage almost exclusively contained short mRNA lacking alternative exons in all regions. However, 14 osteochondrogenic tumors including osteochondroma, enchondroma, chondroblastoma, chondrosarcoma and osteosarcoma uniformly contained long mRNA with various patterns of alternative exons in the three regions. CONCLUSION: These results indicated that the lack of regulation excluding the alternative exons may be associated with tumorigenesis in chondrocytes.

Alternative Splicing↗

Protective effect of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443), a novel cyclic disulfide, on immunologically induced liver injuries in mice.

The effects of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4- carboxylic acid (SA3443), a novel cyclic disulfide, on new immunological liver injury models were investigated. The first liver injury model included a single injection of rabbit anti-basic liver protein antibody into DBA/2 mice. Serum transaminase activities showed a dose-dependent increase 42 hr after the antibody treatment. SA3443 significantly inhibited the elevation of serum transaminase activity and the histopathological changes of the liver in antibody-treated mice at doses of 100 to 300 mg/kg, p.o. The second hepatic failure model was based on an injection of lipopolysaccharide into BALB/c mice which had been previously treated with heat-killed Propionibacterium acnes (P. acnes). SA3443 reduced the lethal acute hepatic failure at doses of 100 to 300 mg/kg. Moreover, a distinct increase in lymphocyte-activating factor activity was detected in the supernatant of the culture medium of the liver macrophage/Kupffer cells isolated from the rat treated with P. acnes. SA3443, at 10(-6) to 10(-4) M, suppressed the release of the lymphocyte-activating factor activity from liver macrophage/Kupffer cells. These results suggest that SA3443 provides considerable protection against immunological liver injuries, and that the efficacy of SA3443 might be partially related to an inhibition of the increase in lymphocyte-activating factor activity.

Alanine Transaminase↗

Cardiohemodynamic effect of a novel calcium antagonist, SD-3211, in the dog.

The cardiohemodynamic effects of SD-3211, a calcium antagonist possessing a unique structure, were studied in anesthetized open-chest dogs and in conscious dogs. SD-3211 (10-300 micrograms/kg, i.v.) increased coronary and vertebral artery blood flow dose-dependently while lowering blood pressure, indicating a vasodilatation of these arteries. SD-3211 caused a significant increase in heart rate at 10-100 micrograms/kg, but a significant decrease at 300 micrograms/kg. Left ventricular dp dtmax was dose-dependently decreased at the dose range examined, and the change was significant at 300 micrograms/kg. When compared with the cardiohemodynamic effects of diltiazem (10 300 micrograms/kg, i.v.) and nicardipine (1-30 micrograms/kg, i.v.), the selectivity of SD-3211 with regard to vasodilatation as compared to cardiac depression, manifested by a reduction in heart rate and myocardial contractility, was greater than that of diltiazem, but less than that of nicardipine. Furthermore, a comparative study of the effects of orally administered SD-3211 and diltiazem on blood pressure and atrioventricular conduction in conscious, normotensive dogs, demonstrated that SD-3211 had a more potent and long-lasting hypotensive effect, but a much weaker effect on atrioventricular conduction prolongation than diltiazem. Thus, these in vivo cardiohemodynamic studies show that SD-3211 possesses a tissue-selectivity for vasculature, respectively cardiac tissues, which is intermediate between diltiazem and nicardipine.

Anesthesia↗