Search PubMed⌕ Search

Biomedical subjects

H Anai

Publications and source records attributed to H Anai.

At least 109 records · Page 6Linked to original sources
PubMed1986

Partial hepatectomy alters sensitivity of rat hepatocytes to 5-fluorouracil.

The sensitivity to 5-fluorouracil (5-FU) and the metabolism of 5-FU in the regenerating rat liver were investigated in vitro. Determination of cell viability using the succinate dehydrogenase inhibition test showed that the hepatocytes of the partially hepatectomized liver were more sensitive to 5-FU, compared to findings in the case of normal liver. The activities of 5-FU phosphorylation of the 3 pathways were higher in the regenerating than in the intact liver and the peak increase was seen 36 h after partial hepatectomy. The activity of 5-FU degradation decreased to about 30% at 36 h and then gradually increased reaching the normal range at 72 h after partial hepatectomy. These results suggest that the metabolic changes of 5-FU may be one of the causes for increased 5-FU susceptibility in the regenerating liver.

Animals↗
PubMed1986

[In vitro chemosensitivity testing evaluated by intracellular ATP level: ATP assay].

In vitro chemosensitivity was evaluated by bioluminescence ATP assay in 12 human tumors including 7 gastric cancers and 5 colo-rectal cancers. Tumor fragments minced with scissors were exposed to 6 kinds of antitumor drugs: carboquone, adriamycin, aclacinomycin A, mitomycin C, cisplatin and 5-FU at peak plasma concentration or ten times peak plasma concentration. After 3 days at 37 degrees C, each tumor fragment suspension was washed with phosphate-buffered saline, boiled for 3 min and assayed for its intracellular ATP level using the luciferin-luciferase method. The ATP level of the drug-untreated group was 6.01 +/- 4.55 X 10(-10) moles/mg tissue protein in gastric cancers and 9.77 +/- 8.46 X 10(-10) moles/mg tissue protein in colo-rectal cancers. The percentages of cases in which the ATP level was reduced to less than 50% by the antitumor drugs were 70% for carboquone, 11% for adriamycin, 30% for aclacinomycin A, 45% for mitomycin C, 13% for cisplatin and 18% for 5-FU at peak plasma concentration, and 90% for carboquone, 78% for adriamycin, 80% for aclacinomycin A, 82% for mitomycin C, 63% for cisplatin and 82% for 5-FU at ten times peak plasma concentration. The test for chemosensitivity prediction is thus available at peak plasma concentration of antitumor drugs in ATP assay.

Adenosine Triphosphate↗
PubMed1986

[In vitro chemosensitivity of various human tumors evaluated by the succinate dehydrogenase inhibition (SDI) test (2)].

In vitro chemosensitivity was evaluated by succinate dehydrogenase inhibition (SDI) test in 94 human tumors including 59 gastric cancers, 27 colo-rectal cancers and 8 malignant lymphomas. Tumor fragments were exposed to 12 kinds of antitumor drugs at ten times peak plasma concentration. Evaluable rates were 86/94 (91%) for all cases, 56/59 (95%) for gastric cancers, 22/27 (81%) for colo-rectal cancers and 8/8 (100%) for malignant lymphomas. The mean of SD activity was decreased to 48% of that of control cells with aclacinomycin, 49% with carboquone, 53% with actinomycin D, 54% with mitomycin C and 54% with daunomycin for gastric cancers, 59% with adriamycin for colo-rectal cancers and 33% with cyclophosphamide (40487 S), and 33% with actinomycin D, 37% with vinblastine and 39% with adriamycin for malignant lymphomas. When the SD activity was reduced to below 50% by antitumor drugs, the chemosensitivity was defined as positive. The antitumor drugs which had a higher chemosensitive-positive rate were aclacinomycin, carboquone and mitomycin C for gastric cancers, adriamycin for colo-rectal cancers and 40487 S, daunomycin and vinblastine for malignant lymphomas. Our results suggest that the origin of a tumor is a critical factor in its chemosensitivity.

Antineoplastic Agents↗
PubMed1985

[In vitro chemosensitivity of various human tumors evaluated by the SDI (succinate dehydrogenase inhibition) test].

In vitro chemosensitivity was evaluated by SDI test in various human tumors including 1 lymph node metastasis of esophageal cancer, 10 gastric cancers, 4 colo-rectal cancers, 1 hepatoma, 2 lung cancers, 2 breast cancers and 1 gallbladder cancer. Tumor fragments cut with scissors were exposed to twelve kinds of antitumor drugs at five to ten times peak plasma concentration. After 3 days at 37 degrees C, each tumor fragment suspension was washed with phosphate-buffered saline and assayed for succinate dehydrogenase (SD) activity using 3-(4,5- dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) as a hydrogen acceptor. When the SD activity of the drug-treated cells was reduced to below 50% that of control cells, the chemosensitivity to the antitumor drug was considered positive. The chemosensitivity of each tumor varied individually. Mitomycin C or 5-fluorouracil are regularly used to treat gastric cancer patients, but, some specimens of gastric cancer in this study showed a resistance to these drugs and an unexpected sensitivity to other drugs. Our results show that the SDI test is a convenient method for clinical use and gives significant information about drug sensitivity.

Antineoplastic Agents↗
PubMedDate not supplied

Prognosis of patients with gastric cancer and pyloric stenosis: histological differentiation.

The clinicopathology of gastric cancer with pyloric stenosis was examined with special reference to histological differentiation. One hundred sixteen patients treated in Department of Surgery II, Kyushu University Hospital, were classified into differentiated (DT: n = 47) and undifferentiated types (UT: n = 69). The UT group was significantly younger than the DT group (P < 0.05). There were no differences in the incidence of serosal invasion, liver metastasis, lymph node metastasis, and the clinical stage between the groups. The incidence of peritoneal dissemination of the UT group was 41% (28/69), a value significantly higher than the 23% (11/47) for the DT group (P < 0.05). The 5-year survival rates of the DT and UT groups were 27% and 16%, respectively, with survival time for the UT group being significantly less than that of the DT group (P < 0.05). In patients with pyloric stenosis and an undifferentiated adenocarcinoma with the risk of peritoneal dissemination, intensive adjuvant chemotherapy seems essential to improve the prognosis.

Adenocarcinoma↗
PubMedDate not supplied

Expression of P-glycoprotein influences resistance against anthracyclines in clinical gastric carcinomas.

In 58 human gastric cancers, the expression of P-glycoprotein (P-gp) was evaluated immunohistochemically and chemosensitivity was determined using the in vitro succinate dehydrogenase inhibition (SDI) test. Tumors which contained over 75% stained cells were scored as positive, and 14 of 58 cases (24%) were positive. There was no significant correlation between P-gp expression and clinicopathologic features. The succinate dehydrogenase (SD) activity for each drug of P-gp positive and negative tumors was as follows: 81.8 +/- 15.2% vs. 66.3 +/- 16.1% for Adriamycin (ADM), 75.5 +/- 14.2% vs. 59.1 +/- 17.6% for aclacinomycin A (ACR), 71.7 +/- 15.0% vs. 61.1 +/- 14.0% for mitomycin C (MMC), and 57.5 +/- 18.4% vs. 47.0 +/- 16.7% for cisplatin (CDDP). The increase in SD activity was evident in P-gp positive tumors compared with negative ones in cases of ADM (P = 0.0044), ACR (P = 0.0105), and MMC (P = 0.0353). We suggested that P-gp expression is closely related to chemosensitivities of human gastric cancers to anthracyclines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Continuous arterial infusion therapy for severe acute pancreatitis: correlation between CT arteriography and therapeutic effect.

PURPOSE: This study evaluates the relationship between the therapeutic effect of arterial infusion therapy for severe acute pancreatitis and drug distribution on CT-arteriography (CTA). MATERIALS AND METHODS: Eleven patients with severe acute pancreatitis were treated by arterial infusion with use of protease inhibitor and antibiotics. Ten patients had an inflammation of the entire pancreas, while one had pancreatitis localized to the body and tail of the pancreas. The arterial infusion drugs were infused into the celiac artery, splenic artery, inferior pancreaticoduodenal artery, and common hepatic artery. The drug distributions were evaluated by CTA in 10 patients. The duration of arterial infusion ranged from 3 to 39 days. The relationship between the distribution on the CTA and the change in clinical grading of pancreatitis as evaluated by an APACHE II score was studied. RESULTS: Of the nine patients with inflammation of the entire pancreas, six showed the distribution of contrast material to the entire area of pancreatic inflammation (a good distribution) on the CTA, and the remaining three did not show the distribution of contrast material to cover the entire area of pancreatic inflammation (a poor distribution). One patient with localized pancreatitis showed a good distribution. In seven patients with a good distribution, the APACHE II score was decreased from 11.7 points to 4.3 points during follow-up. In the remaining three patients with a poor distribution, the APACHE II score was decreased from 12.3 points to nine points, but was decreased to five points after the additional interventions. One patient without CTA showed a marked improvement in the APACHE II score. No clinically important complications were observed. CONCLUSION: The present study findings suggest that arterial infusion is effective in the treatment of severe acute pancreatitis. A good drug distribution to the area of inflammation is needed to ensure a proper therapeutic effect.

APACHE↗
PubMedDate not supplied

An abdominally placed, implantable left ventricular assist system for long-term use.

An implantable left ventricular assist system was developed for long-term use. The system includes an implantable blood pump, a portable control drive unit (CDU), and a monitoring system. The blood pump was designed to be positioned in the left abdominal wall and was made of segmented polyether polyurethane. A percutaneous drive line connected it to the external CDU. The CDU included a continuous pump performance monitoring system that measured electrical impedance between the two metal connectors of a blood pump. In animal experiments using six adult goats, the pump was installed between the left ventricular apex and the descending aorta, and it was placed in the abdominal wall. No antithrombogenic agents were administered during the course of the experiment. This LVAS was easy to use and provided stable hemodynamic conditions for > 8 weeks. Pump output (Op), estimated by impedance, was linearly related to Op measured with an electromagnetic flowmeter. Pump performance was effectively estimated, and the fill-empty drive was well controlled by impedance. There were no significant abnormal hematologic or blood chemistry values, no signs of infection around the pump pocket (except in one animal), and no obvious thromboembolic symptoms. Maximum flow was 6.7 L/min with use of a prototype portable CDU (dimensions, 500 x 168 x 435 mm; weight, 16 kg). In conclusion, this LVAS is promising for long-term clinical use.

Abdomen↗
PubMedDate not supplied

Development and evaluation of components for a totally implantable artificial heart system.

The authors have been developing an electrohydraulic (EH) artificial heart system for total implantation. This system consists of intrathoracic ventricles, an abdominally placed EH actuator, flexible silicone oil conduits, externally coupled transcutaneous energy transfer (TET) system, transcutaneous optical telemetry (TOT) system, internal battery, and internal control drive unit. Fitting was evaluated in chronic animal experiments as a pneumatic system in 11 goats weighing 55.2 +/- 4.2 kg and 3 calves of 52.3 +/- 1.2 kg. The longest survival time in calves was 111 days, and that in goats was 51 days. The assembled EH pump was implanted in two goats of 49 and 50 kg as an acute experiment, and 4.2-6.7 L/min of cardiac output was maintained. For the TET system, an internal coil 3 cm in diameter was implanted to make an arch covered by skin. Electric energy was transmitted from the external to the internal coil, and energy of about 20 W was carried through wires to an external load. The DC-to-DC efficiency of the system was 76-83% for 40 days. The TOT system with internal light emitting diodes and external photodiodes also was evaluated in a goat. Disalignment of up to 12 mm was tolerated. Although more improvement is necessary, most of the components showed characteristics desirable for a totally implantable system.

Animals↗
PubMedDate not supplied

In vitro and in vivo assessment of an intravenous axial flow pump for right heart assist.

Right ventricular (RV) function is a limiting factor in maintaining systemic circulation with circulatory assist. There is, however, no easy way to institute RV assist, such as the intraarterial axial flow pump (Hemopump) used for left heart assist. In this study, the feasibility and hemodynamic effect of intravenous use of an axial flow pump was examined. A pump system was developed with an outflow cannula and an impeller that were newly designed for intravenous insertion with a Hemopump driving system. The pump system characteristics using goat blood at a hematocrit of 26% indicated that maximum flow at a pressure differential against 40 mmHg is 3.2 l/min at a pump speed of 28,000 rpm. The pump was tested in adult goats by intravenous insertion through a 14 mm, low porosity graft anastomosed to the infrarenal inferior vena cava. The pump was advanced until the tip of the cannula was positioned at the main pulmonary artery, using balloon catheter guidance under fluoroscopy. RV assistance was evaluated by pressure tracing, and aortic flow (AF) measured by electromagnetic flowmeter under 1) induced pulmonary stenosis (PS), and 2) electrically induced ventricular fibrillation (VF) in combination with left heart assist. Under PS, right atrial pressure decreased from 11 to 2 mmHg and AF increased from 1.0 to 4.1 l/min after initiation of the pump. Under VF, AF and aortic pressure were 2.6 l/min and 78 mmHg, respectively, with left ventricular assist. After initiation of the pump, they increased to 4.0 l/min and 98 mmHg, respectively. In chronic experiments using three adults goats for up to 48 hr, levels of plasma hemoglobin and platelet counts were maintained within an acceptable range. There was no prominent damage to the hearts. These data suggest that an axial flow pump introduced by an intravenous approach without thoracotomy is feasible and provides sufficient right heart assist.

Animals↗
PubMedDate not supplied

Development and in vivo evaluation of an implantable left ventricular assist system with an impedance based monitoring and control system.

We have developed an implantable pneumatically driven diaphragm left ventricular assist system (LVAS) for small adults, and an electric impedance based monitoring and control system (Z system). In this Z system, measurement of electric impedance of the blood chamber is performed by charging an alternating current with a constant amplitude between two metal connectors without compromising anti-thrombogenicity. Automatic calibration was performed periodically by measuring trough values of impedance in the blood chamber for several beats while the blood pump was in a full-fill state under preset driving conditions. For precise control of the fill-to-empty (F/E) drive, an automatic trigger level adjustment method was developed. This method is an automatic searching algorithm that identifies the volume change of the last ejection or filling by the Z system and settles the next trigger level to maintain a definite stroke volume. In chronic in vivo evaluation, this LVAS was used in 13 adult goats. The pump was installed between the LV apex and the descending aorta and was placed in the abdominal wall. Pump output ranged from 2.5 to 5.8 L/min, and the Z system provided good monitoring. The F/E drive was achieved satisfactorily by this Z system. The physical condition of the goats was excellent for as long as 19 weeks. Hematologic, hepatic, and renal functions were within the normal range, and no prominent thromboembolic symptoms were observed. A new mobile control drive unit with this Z system is being developed. We conclude that this LVAS with the Z system is promising for long-term use in a clinical setting.

Adult↗
PubMedDate not supplied

Five month survival in a calf supported with an intraventricular axial flow blood pump.

We are studying in vivo an intraventricular axial flow blood pump (Jarvik 2000) designed for long-term left ventricular support. The small (25 cc, 85 g) valveless pump has been placed intraventricularly in seven calves; pumps have functioned for as long as 5 months. In the four most recent long-term studies completed, calves have survived for 70, 120, 155, and 162 days (in that order); weight gain has averaged 0.56 kg/day. One study is ongoing at more than 30 days. Under resting physiologic conditions in the normal calf, the continuous flow pump produces flows of 5-6 L/min with a decreased arterial pulse contour. The device has caused no physiologic complications. Calves in the completed studies had mean free plasma hemoglobin levels of 11.4, 7.1, 6.5, and 4.3 mg/dl, respectively. We have modified the inflow structures of the device, and these results suggest that a thrombus free design with no pannus at or around the inlet of the pump can be achieved. Histopathologic analyses of the heart and kidneys in studies of as long as 5 months show no deleterious effects of this device. These studies demonstrate the feasibility of a small implanted intraventricular blood pump for long-term use. Future developments for permanent implantation will include implanted physiologic control systems, transcutaneous energy transmission systems, and implanted batteries.

Animals↗
PubMedDate not supplied

Development of an intravenous axial flow pump for temporary right heart assist.

In clinical settings, quick application systems with easy access for circulatory support are desired. For left heart assist, an intraarterial axial flow pump (Hemopump) has been developed and applied to clinical cases. However, no simple way has been proposed for right heart assist. We have developed an intravenous axial flow pump for temporary right heart assist and have reported its hemodynamic effect. In this study, in vivo evaluation of this system was performed. The pump system consists of an outflow cannula, an impeller that was newly developed for intravenous use, and a driving system for the Hemopump. A prototype pump demonstrated 3.2 L/min of maximal flow at a pressure differential against 40 mmHg at a pump speed of 28,000 rpm in mock circulation. Application to goats is as follows. A 14 mm low porosity graft was anastomosed to the infrarenal inferior vena cava (IVC). The pump system was inserted into the IVC through the graft and advanced to the right heart using balloon catheter guidance under fluoroscopy, and the tip of the cannula of the pump was positioned at the main pulmonary artery. In acute experiments, this system provided effective right heart assist under induced pulmonary stenosis and induced biventricular failure with left ventricular assist. Chronic animal experiments were performed for as long as 4 hr using adult goats weighing 51-54 kg. There were no difficulties in pump insertion. In one goat, the drive shaft was broken because of kinking of the shaft inside the body, caused by failure in securing the pump. Levels of platelet counts and plasma hemoglobin were acceptable, and there was no prominent damage to heart tissues. In conclusion, an intravenous axial flow pump introduced through a peripheral vein is practicable for temporary right heart assist.

Animals↗
PubMedDate not supplied

Improvement in antithrombogenicity in a centrifugal pump with self wash-out structure for long-term use.

Antithrombogenicity in the initial (NCVC-1) centrifugal pump (CP) developed at our institute is provided by a central balancing hole in an impeller that promotes self wash-out blood flow (Sf) around the impeller. The current CP (NCVC-2) was ameliorated to obtain better antithrombogenicity, where the balancing hole diameter was widened to improve Sf velocity (Vsf), and the edge of a thrust bearing (TB) was rounded to minimize flow separation. Effects of the modifications were assessed in in vitro and in vivo studies. The Vsf of the NCVC-1 and the NCVC-2 evaluated by Doppler velocimeter were 12.8 and 22.1 cm/sec, respectively. Flow around the TB visualized by a light cutting method confirmed less flow stagnation in the NCVC-2. In vivo antithrombogenicity of the CPs was investigated in three goats. A pulsatile VAD (P-VAD) was installed paracorporeally between the left atrium and the aorta. After 3 weeks, the P-VAD was exchanged for the NCVC-2 and the NCVC-1 in sequence. Each CP was driven for 1 week and disassembled. No anticoagulation was used, except for heparin injection at pump exchange. Thrombus at the TB was found in the two NCVC-1s, and two little thrombi were on the impeller of another NCVC-1, whereas a thrombus smaller than 1 mm3 at the TB was noted in one NCVC-2. These results indicate that the NCVC-2 has better antithrombogenicity and Sf around the impeller and the TB.

Animals↗
PubMedDate not supplied

An approach to reducing hemolysis in an axial-flow blood pump.

In an attempt to decrease hemolysis caused by an axial-flow blood pump, we studied whether specific speed (Ns) at a design point (determined by flow in m3/min, pump head in m, and pump speeds in rpm), should be kept within the existing engineering standard range (1000 < Ns < 2500) or whether pump speed should be reduced to a minimum (Ns < 1000). Four pumps (A: 14,000 rpm, B: 18,000 rpm, C: 22,000 rpm, and D: 26,000 rpm), each with an impeller 11.8 mm in diameter, were designed to accommodate a flow rate of 5 L/min and a pressure head of 100 mmHg. At this design point, the Ns of each pump was calculated as A:758, B:974, C:1191, and D:1407. Pump performance was observed, and the total efficiency of each pump was calculated. The hemolysis index (HI) was calculated after simultaneous testing in duplicate of all four pumps using fresh goat blood (anticoagulated with citrate-dextrose solution) in a closed mock-loop circuit. Total efficiency of each pump was calculated as A:49%, B:50%, C:45%, and D:22%. In the first hemolytic test, HIs were measured as A:0.066, B:0.18, and C:0.13; a water seal failed in pump D. In the second test, HIs were B:0.077, C:0.0499, and D:0.12; a bearing failed in pump A. It is concluded that a lower level of hemolysis is associated with a pump speed in the minimum range at the design point, even though Ns is outside the standard range.

Animals↗
PubMedDate not supplied

Detection of total assist and sucking points based on the pulsatility of a continuous flow artificial heart: in vivo evaluation.

Our novel control strategy for a continuous flow artificial heart by detecting the total assist and sucking points based on pump pulsatility was evaluated in acute animal experiments using beagle dogs and our mixed flow pump. The pump was installed as a left ventricular (LV) bypass through a left thoracotomy. To change LV contractility, the left coronary arteries were occluded for 30 min, followed by a 120 min reperfusion. To change LV end diastolic pressure (LVEDP), dextran solution was rapidly infused. To estimate the pump pulsatility without any specific sensor, we calculated the index of current amplitude (ICA), which was obtained from the amplitude of the motor current waveform divided by the simultaneous mean value. To investigate the basic characteristics of the ICA, the pump speed was changed temporarily from 2,300 rpm to 5,000 rpm. In 92% of all measurements, the ICA plotted against the pump speed had a peak point (t-point) that corresponded highly with the turning point from partial to total assistance. The ICA also had a trough (s-point) that corresponded with the beginning of severe sucking in most cases. Only preload significantly influenced pump flow rate at the t-point from among preload (LVEDP), afterload (SAoP), and contractility (max LV dP/dt), by which we can simulate Starling's law of the natural heart. We concluded that a continuous flow artificial heart could be well controlled by detecting the t-point and s-point.

Animals↗