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Biomedical subjects

A Tsuchida

Publications and source records attributed to A Tsuchida.

At least 127 records · Page 7Linked to original sources

Myocardial infarct size-limiting effect of ischemic preconditioning was not attenuated by oxygen free-radical scavengers in the rabbit.

BACKGROUND: The limiting effect of ischemic preconditioning on infarct size has been reported in canine hearts, which contain considerable amounts of xanthine oxidase, a free radical-producing enzyme. Furthermore, a recent study suggested that free radicals generated during preconditioning may contribute to the cardioprotective effect of preconditioning. The present study examined 1) whether preconditioning limits infarct size in rabbits, which, like humans, lack myocardial xanthine oxidase and 2) whether the cardioprotective effect of PC is mediated by free radicals. METHODS AND RESULTS: A branch of the circumflex coronary artery in rabbits was occluded for 30 minutes and then reperfused for 72 hours. Myocardial infarct size and area at risk were determined by histology and fluorescent particles, respectively. Five groups were studied: an untreated control group, a preconditioned group (PC group), a high-dose superoxide dismutase (SOD)-treated preconditioned group (high-dose SOD-PC group), a low-dose SOD-treated preconditioned group (low-dose SOD-PC group), and a SOD-plus-catalase-treated preconditioned group (SOD/CAT-PC group). Preconditioning was performed with four episodes of 5 minutes of ischemia and 5 minutes of reperfusion. The free radical scavengers (30,000 units/kg SOD for high-dose SOD-PC group, 15,000 units/kg SOD for low-dose SOD-PC group, and 30,000 units/kg SOD plus 55,000 units/kg catalase for SOD/CAT-PC group) were infused intravenously over 60 minutes starting 20 minutes before preconditioning. Infarct size as the percentage of area at risk was 45.1 +/- 3.5% (mean +/- SEM) in the control group (n = 11), 13.3 +/- 3.0% in the PC group (n = 12), 9.7 +/- 1.8% in the high-dose SOD-PC group (n = 8), 11.9 +/- 2.2% in the low-dose SOD-PC group (n = 6), and 9.6 +/- 2.3% in the SOD/CAT-PC group (n = 6) (p less than 0.05 versus control for the last four values). The differences in infarct size as the percent of area at risk among the PC, high-dose SOD-PC, low-dose SOD-PC, and SOD/CAT-PC groups were not significant. CONCLUSION: Ischemic preconditioning delays ischemic myocardial necrosis regardless of myocardial xanthine oxidase content. Free radicals are unlikely to have a major role in the mechanism of the preconditioning in rabbits.

Animals↗

Inhibition of thromboxane A2 synthetase failed to limit myocardial infarct size in a rabbit ischemia-reperfusion model.

The role of thromboxane A2 (TXA2) in myocardial necrosis during coronary occlusion and reperfusion was investigated by using a new long-acting TXA2 synthetase inhibitor, DP1904. A rabbit coronary branch was occluded for 30 min and then reperfused for 72h. Infarct size and area at risk were determined histologically and by fluorescent particles, respectively, for 4 groups; a saline receiving control group (C group), a DP1904 treated group (DP group), a heparin treated group (H group), and a DP1904 plus heparin treated group (DP-H group). The H group and DP-H group were included to examine the influence of heparinization on the effect of DP1904. In the DP and DP-H groups, 10 mg/kg of DP1904 was injected i.v. 2h before coronary occlusion, as well as 24 and 48h after reperfusion. This dose of DP1904 (10 mg/kg i.v.) was able to inhibit serum thromboxane B2 formation ex vivo to 1.1% of the control level 2h after its administration, and to 39.5% at 24h, in the rabbit (n = 5). The H and DP-H groups received 1000 units of heparin i.v. 3 min prior to coronary occlusion. The size of the area at risk, heart rate, blood pressure, and rate-pressure products were comparable between the 4 groups. Mortality was not significantly different in any group. Myocardial infarct size as the percentage of area at risk was 43.6 +/- 3.9% in C group (n = 10), 41.1 +/- 4.4% in DP group (n = 9), 47.8 +/- 3.0% in H group (n = 13), and 44.7 +/- 4.0% in DP-H group (n = 10), which were not significantly different. These findings suggest that TXA2 does not contribute directly to myocardial necrosis during coronary occlusion and reperfusion in the rabbit.

Animals↗

T-zone lymphoma in association with systemic lupus erythematosus.

Two patients with systemic lupus erythematosus (SLE) and T-zone lymphoma are described. On admission, both showed arthralgia, generalized lymphadenopathy, hypergammaglobulinemia and positive antinuclear antibody. Lymph node biopsies revealed diffuse infiltration of atypical T-lymphocytes in the expanded interfollicular area (T-zone), a finding characteristic for the T-zone lymphoma. Renal biopsy showed lupus nephritis and neoplastic lymphoid cell infiltration in the glomeruli of one patient, but only diffuse infiltration of neoplastic lymphoid cells and mature plasma cells were observed in the interstitium of the other patient. Both patients responded remarkably well to prednisolone (1 mg/kg/day).

Humans↗

[Variance of signal-averaged electrocardiographic parameters with age in normal children].

The high-frequency components of the surface QRS was analyzed quantitatively in 87 normal infants and children. The subjects were categorized in 4 groups by age; Group A: one day (n = 27), Group B: 1-5 years (n = 20), Group C: 6-10 years (n = 20), Group D: 11-15 years (n = 20), and the results were compared among the 4 groups. Signal-averaging and high-pass, bidirectional and digital filtering were used for analysis. The total duration of the QRS, the duration of the low-amplitude signals (< 40 microV) in the terminal portion of the QRS (U 40), the amplitude of the signals in the QRS (RMS; QRS) and the amplitude of the last 40 msec of the QRS (RMS 40) were measured at high-pass filter frequency settings of 25, 40, 60 and 100 Hz. Statistical analysis was performed with the unpaired t-test. Differences were considered significant if p < 0.05. The results were as follows: 1. At all filters, the durations of the QRS and U 40 were longer in the order of Groups A < B < C < D, and the amplitude of the RMS; QRS and RM 40 were greater in the order of Groups D < C < B < A. 2. There were significant differences in the QRS between the groups at all filters. 3. There were significant differences in U 40 between the groups except between Groups B and C at 25-Hz filter, but at 40-, 60-, 100-Hz filters, there were no significant differences among Groups B, C and D.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Hepatic infusion-chemotherapy of liver metastases from stomach cancer--comparative study for intraarterial group and non-intraarterial group].

Metastasis to the liver was detected in 96 out of 1,825 patients with gastric cancer treated at our department from April 1980 to March 1990, and was respectively found to be synchronous and metachronous in 63 and 33 of the 96 patients. We compared survival durations among these 96 patients according to synchronous or metachronous metastasis by dividing them into the intermittent intra-arterial chemotherapy (FAM) group (18 patients) and non-intra-arterial chemotherapy group (78 patients). In the comparison between the intra-arterial and non-intra-arterial groups, the survival duration was determined to be significantly longer in the intra-arterial group by Wilcoxon generalized test and Cox-Mantel test (p less than 0.01). Among the patients with synchronous metastasis, a significantly longer survival duration was also observed in the intra-arterial group (p less than 0.01). The direct effect of intra-arterial chemotherapy through CT was seen in 56% of the patients in the intra-arterial group. These results indicated the usefulness of FAM hepatic infusion chemotherapy for the treatment of metastasis of gastric cancer to the liver. It is expected that therapeutic results will be much more improved by selecting more effective anticancer drugs in the future.

Aged↗

[Study of intermittent intra-arterial infusion chemotherapy in liver metastases from squamous cell carcinoma].

There are few reports about the methods, amounts, and kinds of dosage about intermittent intra-arterial chemotherapy of liver metastases from primal pathological type's squamous cell carcinoma. Because they are less than liver metastases from adenocarcinoma of colon or stomach. Although it is important of other factors about the operative method of primary focus and metastases of the other parts, it is possible that those cases obtained the good prognosis and protected liver failure, if those liver metastases could be controlled well. In our department from January 1987 to December 1989, 9 cases of inoperative liver metastases of squamous cell carcinoma (esophagus: 4 cases, larynx: 3 cases and cervix of uterus 2 cases) were treated of intra-arterial infusion chemotherapy of FAM (5Fu 500 mg/week, ADM 30 mg/4 weeks and MMC 4 mg/2 weeks) and CDDP methods (only CDDP 10 mg/week). Cases of esophagus carcinoma were treated with FAM method. On the CT-scan one of the cases showed the reduction rate of more than 50% and was a Progressive Response (PC), and the SCC tumor marker decreased in 2 cases. However, 2 other cases died of liver failure. Cases of larynx were treated with FAM and CDDP methods. However, on the CT-scan all of the cases showed No Change (NC) nor decrease in SCC. But thinking of prognosis FAM was better than CDDP. Cases of cervix of uterus were treated with the FAM and CDDP methods. FAM was not different than the CDDP in the prognosis and effect.

Aged↗

Does verapamil limit myocardial infarct size in a heart deficient in xanthine oxidase?

1. The delay of ischaemic myocardial necrosis by verapamil has been reported in the dog heart, which contains a high level of xanthine oxidase, a potential source of cytotoxic free radicals. To test whether the retardation of ischaemic myocyte death by verapamil is not an isolated phenomenon in the xanthine oxidase rich heart, we assessed the effect of verapamil in the rabbit heart, which lacks xanthine oxidase. 2. Verapamil (200 micrograms/kg, i.v. bolus plus 40 micrograms/kg per min) was administered in a group of rabbits (n = 5) to test the haemodynamic response to this agent. The heart rate, blood pressure and left ventricular dp/dt max were reduced by 11, 25 and 57%, respectively, and the plasma concentration of verapamil was maintained at 300-400 ng/mL during the infusion. 3. In other groups of rabbits, the effect of the same dosage of verapamil on the size of myocardial infarct after 20 or 30 min ischaemia and 72 h reperfusion was examined. The verapamil was administered for 45 min, starting 15 min prior to ischaemia. The percentage of area at risk infarcted (%I/AAR) was 15.2 +/- 3.9% in the 20 min ischaemia control group and 15.4 +/- 4.5% in the 20 min ischaemia verapamil group, 49.1 +/- 3.4% in the 30 min ischaemia control group and 41.2 +/- 3.3% in the 30 min ischaemia verapamil group. The %I/AAR was significantly smaller in the 20 min ischaemia control groups and 15.4 +/- 4.5% in the 20 min ischaemia there was no difference in %I/AAR between the control and verapamil treated animals in either the 20 or the 30 min ischaemia groups. 4. These results suggest that verapamil does not delay the transition from reversible to irreversible myocardial injury during coronary occlusion in the rabbit, which like the human, lacks myocardial xanthine oxidase.

Animals↗

[A study of low-dose intermittent intra-arterial infusion chemotherapy for liver metastasis in colorectal cancer].

Since 1985 we have performed low-dose intermittent intra-arterial infusion chemotherapy using an implantable device for inoperable liver metastasis derived from colorectal cancer. We estimated the efficiency of this treatment in terms of effective rates and survival period. We classified subjects into intra-arterial infusion group and general administration group for comparison. The former group was comprised of 54 cases (37 synchronia, 17 heterochronia) treated with low-dose intermittent intra-arterial infusion (FAM ia) from July 1985 to June 1989. The latter comprised 32 cases (17 synchronia, 15 heterochronia) treated with general chemotherapy (general administration of 5-FU and MMC) for three years before December 1986. Of the 37 cases (23 synchronia, 14 heterochronia) evaluated in the intra-arterial infusion group, we recognized 9 PR cases (24.3%; including 5 synchronia, 4 heterochronia). On the other hand, we found only 1 PR case in the general administration group. The 50% survival period in the intra-arterial infusion group was 370 days (380 days synchronia, 340 days heterochronia), against 260 days (270 days synchronia, 250 days heterochronia) in the general administration group. There were no statistically significant differences between the two groups. Although it was not possible for us to obtain satisfactory results in terms of the efficiency of intermittent low-dose intra-arterial infusion treatment, we have been conducting a randomized study considering drug types, drug administration methods, and background of patients to further investigate the efficiency of arterial infusion treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Tissue-type plasminogen activator alone or in combination with thromboxane A2 synthetase inhibitor for ischemic myocardium.

Although the efficacy of tissue-type plasminogen activator (t-PA) for coronary thrombolysis is well established, its direct cardioprotective effect - independent of its thrombolytic effect - is still controversial. In addition, the potentiation of t-PA's direct cardioprotective effect by thromboxane A2 synthetase inhibitor has recently been reported. In this study, the authors examined whether t-PA alone or in combination with DP1904, a thromboxane A2 synthetase inhibitor, is able to salvage ischemic myocardium via a direct action on myocardium. In addition, the effect of these interventions on intramyocardial hemorrhage in reperfused infarcts was assessed. A branch of the coronary artery of the rabbit was occluded for 30 mins and then reperfused for 72 h. Myocardial infarct size and 'area at risk' were determined by histology and fluorescent particles, respectively. The extent of intramyocardial hemorrhage was graded using scores. Rabbits were divided into three groups: control, t-PA and DP1904 plus t-PA. The t-PA was administered intravenously at 500 iu/kg/min for 30 mins starting 5 mins prior to reperfusion. DP1904 was injected intravenously at a dosage of 10 mg/kg every 24 h starting 2 hr prior to coronary occlusion. Mortality was similar and hemodynamic parameters and area at risk were comparable between all three groups. The myocardial infarct size as a percentage of area at risk was 44.5 +/- 3.8% (mean +/- standard error) (n = 9) in the control group, 41.6 +/- 4.6% in the t-PA group (n = 8) and 51.3 +/- 5.2% in DP1904 plus t-PA group (n = 8), not significantly different (ANOVA). Neither were the hemorrhage scores significantly different between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Digoxin clearance and serum beta-2-microglobulin in neonates.

To find reliable indicators of digoxin clearance (CLdig) in the neonatal period, we investigated the linear correlation of CLdig and the reciprocal of CLdig (1/CLdig) with serum beta 2-microglobulin (S beta 2-MG), serum creatinine, blood urea nitrogen, age, and weight on 25 occasions in 21 neonates with congenital heart disease. The S beta 2-MG value showed a significantly closer correlation to 1/CLdig (r = 0.84, p less than 0.0001) than to the other values. The regression equation was (1/CLdig) = 0.15 X (s beta 2-MG) + 0.08. Creatinine and blood urea nitrogen values correlated less closely with 1/CLdig (r = 0.67 and 0.71, respectively). Age and weight had no significant linear correlation with CLdig and 1/CLdig. Determination of s beta 2-MG values allowed an estimate of CLdig by means of the regression equation between s beta 2-MG and 1/CLdig, and permitted a prediction of the required maintenance dose of digoxin. We conclude that s beta 2-MG is a good indicator of CLdig in neonates, and that the determination of s beta 2-MG values may facilitate the advance individualization of digoxin therapy in the neonatal period.

Blood Urea Nitrogen↗

The effect of inotropic dose of dobutamine during reperfusion on myocardial infarct size.

We examined whether dobutamine infusion during reperfusion modifies myocardial infarct size in a rabbit ischemia-reperfusion model. Prior to the infarct size study, the hemodynamic response to dobutamine 5, 10, and 15 micrograms/kg/min i.v. was evaluated in the rabbit model. Ten micrograms/kg/min of dobutamine increased the left ventricular dp/dt max by 34.0 +/- 4.9% (n = 7) and the myocardial blood flow from 0.86 +/- 0.16 to 2.19 +/- 0.57 ml/min/g without change in the collateral blood flow (n = 4). The heart rate, systolic and diastolic blood pressures were elevated by only 4.7 +/- 1.0%, 9.4 +/- 3.0%, and 8.0 +/- 3.7%, respectively (n = 7). In the infarct size study, a coronary branch was occluded for 30 min and then reperfused. Seventy-two hours after reperfusion, the myocardium supplied by the occluded artery (area at risk, AAR) and the infarcted area were determined by fluorescent particles and histology (hematoxylin-eosin and modified Mallory's staining), respectively. In the dobutamine treated group (DB group), 10 micrograms/kg/min of dobutamine were infused for 30 min starting immediately after reperfusion, and a comparable volume of saline was infused in the control group. Hemodynamic parameters and the size of AAR were comparable in the control and DB groups. Myocardial infarct size, expressed as the percentage of AAR, was 45.1 +/- 3.9% in the control (n = 11) and 40.2 +/- 2.4% in the DB group (n = 10), which was not significantly different. These findings indicated that the inotropic dose of dobutamine administered during reperfusion did not cause myocardial necrosis by disturbing the recovery process of the myocardium from ischemic injury.

Animals↗

[Myeloid crisis of chronic myelogenous leukemia showing dramatic response to mithramycin and hydroxyurea combination].

After 4 years of chronic phase, a 22-year-old female with Ph1 (+) chronic myelogenous leukemia developed myelomonocytic crisis. On admission, her Hb was 9.9 g/dl, Plt 4.1 x 10(4)/microliters, WBC 138,000/microliters with 16.5% blasts. Bone marrow contained 38% blasts. She received a combination chemotherapy of mithramycin and hydroxyurea, as reported by Koller et al. Dose of mithramycin was reduced to 20 micrograms/kg. Following 1st and 2nd infusions of mithramycin, severe nasal bleeding was seen. Prednisolone 10 mg/day was given from the 3rd dose of mithramycin with apparent hemostatic effects. Calcium gluconate 3 g/day was administered concomitantly. Her disease responded promptly to this treatment and hematological remission was achieved.

Adult↗

Intraplatelet and urinary serotonin concentrations in systemic lupus erythematosus with reference to its clinical manifestations.

Intraplatelet and plasma serotonin (5-HT) levels were measured in 39 patients with systemic lupus erythematosus (SLE) and in 15 healthy subjects. Urinary 5-HT concentrations were also measured in 32 patients with SLE and 14 healthy subjects. A significantly lower intraplatelet 5-HT level was observed in SLE patients, especially in the active phase with hypocomplementemia (CH50 less than 30 U/ml), 0.17 +/- 0.09 pmol/10(5) platelets, than that in normal controls, 0.36 +/- 0.14 pmol/10(5) platelets (p less than 0.01). Active SLE showed a significantly higher urinary 5-HT concentration, 0.37 +/- 0.15 nmol/ml/mg Cr, than normal controls, 0.21 +/- 0.08 nmol/ml/mg Cr (p less than 0.01). Serial measurements of intraplatelet and urinary 5-HT levels in five patients with SLE revealed a significant correlation between clinical activity and intraplatelet and urinary 5-HT levels. Exogenous 5-HT uptake by platelets in vitro is not altered in patients with SLE. The mechanism of decrease of intraplatelet 5-HT and increase of urinary 5-HT in SLE may be explained by the continuous activation of the blood coagulation within the vessel.

Adolescent↗

Hypoparathyroidism during alpha-INF therapy in a patient with multiple myeloma.

A 66 year-old woman with multiple myeloma developed hypoparathyroidism during combination chemotherapy with melphalan, prednisolone, and alpha-interferon (INF). Seven weeks after commencement of the therapy, the serum calcium (Ca) level decreased to 7.4 mg/dL, and the phosphorus (P) level increased to 7.2 mg/dL; parathyroid hormone (PTH) was at a critically low level. By 13 weeks after discontinuation of alpha-INF, the levels of Ca, P, and PTH had returned to normal values: 8.6 mg/dL, 4.5 mg/dL, and 310 pg/ml, respectively. These changes suggest a strong correlation between hypoparathyroidism and the administration of alpha-INF. Autoantibodies against the parathyroid gland cell were not present in the serum of this patient by indirect immunofluorescent techniques. The mechanism of hypoparathyroidism by alpha-INF could not be identified, but this is the first case of this condition during alpha-INF therapy.

Aged↗

The dual effects of hemodialysis on cardiac function assessed by pulsed Doppler echocardiography.

To assess the effect of hemodialysis on cardiac function, a change of preload due to water removal was considered. In order to keep the preload constant during hemodialysis, extracorporeal ultrafiltration was induced before hemodialysis (step 1), and then hemodialysis without water removal was achieved (step 2). Cardiac performance in 8 patients was evaluated before and at the end of each step using pulsed doppler echocardiography. Step 1: Ultrafiltration was 1350 +/- 410 ml and hematocrit increased significantly. Left ventricular end-diastolic dimension (LVDd) decreased from 40.3 +/- 4.2 (mean +/- standard deviation) mm to 36.1 +/- 4.6 mm (p less than 0.005) and aortic peak flow velocity (PFV) also decreased from 59.9 +/- 16.0 cm/s to 49.0 +/- 11.0 cm/s (p less than 0.005). Step 2: In contrast, after hemodialysis without water removal, the mean velocity of circumferential fiber shortening (mVcf) increased from 1.36 +/- 0.26 circ/s to 1.86 +/- 0.36 circ/s (p less than 0.005). PFV and average acceleration (Aa) increased from 49.0 +/- 11.0 cm/s to 63.8 +/- 11.4 cm/s (p +/- 0.001) and from 750 +/- 220 cm/s/s to 1270 +/- 280 cm/s/s (p less than 0.001), respectively. During this step, serum potassium and osmolality decreased significantly. In conclusion, hemodialysis improves cardiac function under constant preload condition and this is due to the direct effects of hemodialysis by the correction of electrolytes and osmolar components such as uremic toxin.

Adult↗

Inspiratory right ventricular outflow obstruction in a patient with hypertrophic cardiomyopathy.

A patient with familial hypertrophic cardiomyopathy with exertional near syncope is reported. Intra-right ventricular obstruction was demonstrated by hemodynamic studies during inspiration and the Valsalva maneuver with systemic hypotension. Improvement occurred following the administration of propranolol. It was suggested that syncope might be precipitated by hemodynamic changes such as a high output state and a depressed cardiac volume in relation to intra-right ventricular obstruction in patients with hypertrophic cardiomyopathy.

Adolescent↗

Effect of drug administration on experimental renal glomerular thrombosis.

Experimental thrombosis which developed exclusively in glomerular capillary walls was induced in rats by the combined injection of nephrotoxic antiserum (0.2 ml of pooled material) as a preparatory agent and 20 micrograms or more of lipopolysaccharide as a provoking agent. Effects of some antiplatelet and anticoagulant drugs on the glomerular lesions were tested in this experimental glomerular thrombosis. With administration of 2000 units/kg or more of heparin at the time of provoking injection, coagulation time was prolonged for over 5 hr, and the glomerular thrombosis was adequately prevented. Prolongation of prothrombin time (PT) for over 60 sec to prevent thrombosis required warfarin, but with this drug there was only a narrow margin between an effective dose and that which produced a fatal hemorrhage. Low levels of fibrinogen (less than 50 mg/dl) induced by batroxobin seemed to protect partially and high doses of urokinase did not seem to protect from glomerular thrombosis. OP-41483, a derivative of prostacyclin which is about five times more active than PGE1 in inhibiting platelet aggregation, and other anti-platelet drugs except for ticlopidine were not effective in preventing glomerular thrombosis. These findings were in accordance with the fact that thrombocytopenia induced by antiplatelet antiserum did not prevent glomerular thrombosis. Ticlopidine may have a unique and valuable therapeutic potential for the control of this condition.

Animals↗