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Biomedical subjects

K Gotoh

Publications and source records attributed to K Gotoh.

At least 145 records · Page 8Linked to original sources

The relationship between clinical signs and hypercoagulable state in toxemia of pregnancy.

The hypercoagulable state in patients with toxemia of pregnancy was investigated in comparison with normal pregnant women using new coagulation parameters, mainly thrombin-antithrombin III (TAT) complexes, alpha 2-antiplasmin-plasmin complexes (PIP), and D-dimer FDP. When the patients were categorized by the classification of the WHO Study Group (1985), significant increases of TAT complexes and alpha 2-PIP complexes with decreases of the ATIII level were observed in the groups with preeclampsia and severe gestational hypertensive disease as compared to normal pregnant women. A significant increase of D-dimer FDP was observed in a group with severe gestational hypertensive disease. Additionally, the relationship between clinical signs and the hypercoagulable state in the patients was analyzed using canonical correlation analysis as a multivariate analysis. The clinical signs and coagulation parameters had a significantly high correlation of lambda 1 = 0.7219, p less than 0.01. The results showed that clinical signs were associated with simultaneous coagulation abnormalities. The indices obtained from the results of canonical correlation analysis, which were called the clinical index and the coagulation index, should be useful in evaluating the efficacy of anticoagulation therapy.

Adult↗

Relationship between the duration of fetal breathing movements and gestational age and the development of the central nervous system at 25-32 weeks of gestation in normal pregnancy.

In 15 pregnant women with normal pregnancy at 25-32 weeks of gestation, fetal breathing movements (FBM), fetal body movements and fetal heart rate were continuously and simultaneously recorded over a total period of 180 min. The frequency of successive FBM with a duration less than 10 s (apnea period greater than 3 s) showed a significant decrease (p less than 0.01), while the frequency of successive FBM with a duration greater than or equal to 30 s showed a significant increase from 25 to 32 weeks of gestation (p less than 0.001). Strong positive correlations were also demonstrated between the frequency of FBM with a duration of greater than or equal to 30 s and the number of fetal heart rate accelerations per hour, acceleration/fetal body movement ratio, and the value of fetal heart rate long-term variability. These results suggest that the length of the duration of successive FBM represents a useful parameter for the analysis of fetal respiratory patterns, and that a prolongation of the duration of successive FBM of an individual fetus is related to the functional development of the central nervous system.

Central Nervous System↗

Relationship of fetal breathing movement pattern to surfactant phospholipid levels in amniotic fluid and postnatal respiratory complications.

Fetal breathing patterns in 102 patients delivering before 37 weeks of gestation were divided into three types by the duration of successive respiratory activity using an ultrasonic scanner. Approximately 80% of the fetuses with fetal breathing absent or less than 9 s developed neonatal respiratory complications, including 11 cases of severe RDS and 8 cases of apnea of prematurity. However, no infant showing breathing activity of 30 s or more in utero experienced severe respiratory complications after birth. Furthermore, the surfactant phospholipid concentration in amniotic fluid was significantly increased with prolongation of successive fetal breathing activity. These results suggest that the duration of successive fetal breathing movements closely relates with fetal lung development including biochemical and neuromuscular systems in the humans, i.e. functional maturation of the fetal respiratory system, and also that prenatal analysis of breathing patterns may permit evaluation of pulmonary functional capacity after birth.

Amniotic Fluid↗

Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization.

BACKGROUND: Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization. METHODS AND RESULTS: To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization. CONCLUSIONS: We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization.

Allopurinol↗

Beneficial effects of alpha 1-adrenoceptor activity on myocardial stunning in dogs.

This study was undertaken to elucidate whether alpha-1 adrenoceptor activity is beneficial to contractile dysfunction during reperfusion after a brief period of ischemia (stunned myocardium) in 54 open-chest dogs. Contractile dysfunction assessed by fractional shortening (FS) was observed 3 hours after the onset of reperfusion following 15 minutes of complete occlusion of the left anterior descending coronary artery. Pretreatment with prazosin (4 micrograms/kg/min i.c.) further deteriorated contractile dysfunction compared with the untreated condition (12.7 +/- 0.6% versus 6.9 +/- 0.4% with prazosin treatment, p less than 0.001). Conversely, alpha 1-adrenoceptor agonists, methoxamine (1.0 microgram/kg/min i.c.) and norepinephrine (0.24 microgram/kg/min i.c.) with rauwolscine and propranolol, significantly attenuated contractile dysfunction (FS in the methoxamine-treated group, 17.3 +/- 0.3%, p less than 0.001 versus the untreated group; FS in the norepinephrine-treated group, 18.0 +/- 0.9%, p less than 0.05 versus 13.6 +/- 1.1% in the propranolol group). Both adenosine release and hyperemic coronary flow response during the early reperfusion period were significantly attenuated in the prazosin-treated group, and both were enhanced in the alpha 1-adrenoceptor stimulation groups. These results suggest that beneficial effects of alpha 1-adrenoceptor activity may be due to the enhanced release of adenosine. To test the cause-effect relation between the extent of adenosine release and contractile dysfunction during reperfusion, 8-phenyltheophylline was infused to block adenosine receptors in the methoxamine-treated group. The treatment with 8-phenyltheophylline completely abolished (FS, 7.4 +/- 0.3%) the beneficial effect of the enhanced adenosine release by alpha 1-adrenoceptor stimulation. Furthermore, in the prazosin-treated group, adenosine (9 micrograms/kg/min) was additionally infused into the left anterior descending coronary artery 5 minutes before and 2 hours after the onset of reperfusion. Both hyperemic coronary flow and contractile dysfunction (FS, 17.3 +/- 0.3%) recovered to the levels of the alpha 1-adrenoceptor stimulation groups. However, treatment with papaverine could not prevent deleterious effects of prazosin despite the fact that comparable hyperemic flow was obtained. Instead, lactate production up to 10 minutes after the onset of reperfusion was significantly larger (p less than 0.01) despite augmented contractile function in the prazosin-treated and the 8-phenyltheophylline with methoxamine-treated groups compared with the untreated group. The electron microscopic examination revealed no irreversible myocardial injury with and without pharmacological interventions. Thus, we conclude that alpha 1-adrenoceptor activity can reduce the magnitude of myocardial stunning and that its cellular mechanism is due to enhanced adenosine release by alpha 1-adrenoceptor activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗

The influence of experimentally produced oligohydramnios on lung growth and pulmonary surfactant content in fetal rabbits.

To study the effect of oligohydramnios on lung growth and biochemical lung development in fetal rabbits, amniotic fluid was drained through a tube inserted into the maternal peritoneal cavity on the 23 day of gestation. Littermate fetuses without an amniotic shunt were used as controls. The fetuses were delivered abdominally on the 28 day of gestation. In a total of 8 pregnant does, 17 fetuses underwent amniotic shunting and 22 fetuses were used as controls. The amniotic shunt produced a significant reduction in the amniotic fluid volume. There were no differences in the wet weights of the fetal body, liver or brain between the two groups. However, the amniotic shunt significantly decreased the wet weight of the fetal lung, fetal lung wet weight/body weight ratio, and protein concentration per lung as compared to the control fetuses. In the fetal liver and brain tissues, no changes were found in the concentrations of total phospholipids, phosphatidylcholine (PC) or disaturated phosphatidylcholine (DSPC, the main component of lung surfactant) per g of wet tissue and per mg of protein. However, the lungs of the fetuses with amniotic shunts contained significantly more PC and DSPC, and the L/S ratio was higher than in the control fetuses. These results suggest that the oligohydramnios produced by an amniotic shunt causes pulmonary hypoplasia, but raises the pulmonary surfactant content of fetal rabbit lung.

Animals↗

[Fundamental and clinical studies of extracorporeal shock wave lithotripsy (ESWL) for pancreatic duct stones].

The application of ESWL for pancreatic duct stones was studied clinically, and the safety of this technique was also investigated experimentally. In 12 patients suffering from chronic pancreatitis and having calcified stones in the main pancreatic duct, ESWL was performed. None of the patient had received endoscopic pancreatic sphincterotomy before ESWL. Stone disintegration was obtained in all cases, and the main pancreatic duct stones completely disappeared in 9 of 12 cases. As a result, not only exacerbation of pancreatitis was removed, but also the preservation of pancreatic endocrine and exocrine functions was suggested. With regard to complications, no abnormalities were observed experimentally in the pancreatic parenchyma of treated dogs, and similarly no acute symptoms were recognized in the patients with pancreatic duct stones. ESWL for pancreatic duct stones is low in stress for the patient, and is effective for large stones. We therefore conclude that ESWL might be an extremely useful, new non-surgical treatment approach to control of pancreatic duct stones.

Adult↗

[A case of fulminant psittacosis showing Chlamydia in TBLB specimens].

A 55-year-old female was admitted to our hospital because of high fever, nonproductive cough and dyspnea. Initially she had been treated with cephem antibiotics by a local doctor. However, acute respiratory failure due to severe pneumonia developed. The partial pressure of oxygen in arterial blood was 55.5 Torr. Her chest X-ray revealed wide-spread infiltrates with air bronchograms throughout the entire left lung, and pleural effusions were also present in the chest CT scan. Because the patient had a history of the contact with birds, we suspected psittacosis and administered Minocycline immediately. As a result, her clinical condition improved and the abnormal shadow on the chest X-ray film improved markedly in three days. Because the serum titer of a complement fixation test against Chlamydia rose to 1:512, we made the diagnosis of psittacosis. In addition, femoral muscle pain, and a high level of serum GOT, GPT, CK, Aldolase and Myoglobin indicated hepatitis and myositis. In the lung tissue specimens obtained by TBLB performed on the 10th hospital day, slight interstitial pneumonia and intracellular inclusion bodies were found by light microscopy and Chlamydial agents were found electron microscopically.

Antibodies, Viral↗

Enhanced antitumor activity in mice after administration of thermosensitive liposome encapsulating cisplatin with hyperthermia.

The antitumor effect of cisplatin-(CDDP)-encapsulated thermosensitive large unilamellar liposome (ThLip) administration with hyperthermia (HT) was examined in mice bearing Meth A fibrosarcoma. The tumor Pt levels after ThLip administration were increased in response to HT. The targeting index was approximately 3. The antitumor activity of ThLip + HT, as measured by tumor growth delay or tumor weight inhibition, was larger than that of ThLip without HT or a solution with or without HT. The CDDP dose in ThLip + HT to give equivalent tumor growth delay in solution (40 micrograms/mouse) + HT was about 10 micrograms/mouse, and therefore the targeted drug delivery enhancement ratio was about 4. The ratio correlates with the targeting index. The blood urea nitrogen level, as an indicator of CDDP nephrotoxicity, was increased 7 days after the administration of ThLip (40 micrograms CDDP/mouse) with HT. However, this blood urea nitrogen level rise was independent of the activity enhancement by the liposome. These findings suggest that the HT combined CDDP delivery system using ThLip can decrease the effective CDDP dose, thereby increasing its therapeutic index.

Animals↗

Effects of leflunomide on glomerulonephritis induced by antibasement membrane antibody in rats.

Leflunomide (HWA 486, a novel isoxazol derivative), shown to have potent immunosuppressant and antiinflammatory effects, was evaluated for its inhibitory and therapeutic effects on the glomerulonephritis induced in rats by rabbit antiserum against rat glomerular basement membrane. Leflunomide was administered orally to rats at 0.5 and 2 mg/kg/day for 20 days from 2 days before injection of the rabbit antiserum and at 2 mg/kg/day for 14 days from 5 days after the antibody injection. The present study consisting of 2 experiments for inhibitory (I) and therapeutic (II) effects of leflunomide revealed the following effects at 2 mg/kg: in experiment I, significant decreases in (a) urinary total protein, (b) plasma total cholesterol and fibrinogen and (c) thymus weight, and decreased incidences of fibrin deposits in Bowman's space, adhesion of the glomerulus to Bowman's capsule and deposition of rat IgG and C3; and in experiment II, decreases in (a), (b) and (c), though smaller than in experiment I, and decreases deposition of rat C3. Thus, leflunomide had potent inhibitory and limited therapeutic effects on glomerulonephritis, suggesting that the compound is effective in inhibiting the onset and development of glomerulonephritis.

Animals↗

Comparison of amniotic fluid disaturated phosphatidylcholine, phosphatidylglycerol and lecithin/sphingomyelin ratio in predicting the risk of developing neonatal respiratory distress syndrome.

One hundred forty-one amniotic fluid samples were analyzed for disaturated phosphatidylcholine (DSPC), phosphatidylglycerol (PG) and the lecithin/sphingomyelin (L/S) ratio. The L/S ratio was measured by two-dimensional thin layer chromatography. Mature levels (positive) were defined as an L/S ratio of 2:1 or more, a DSPC level of 100 micrograms/ml or more and a detectable level of PG. The DSPC value agreed with the L/S ratio in 114 samples (80.9%). Fourteen of 17 infants with respiratory distress syndrome (RDS) (82.4%) had immature L/S ratios and immature DSPC levels. RDS developed in 16 of 40 (40%) children with immature L/S ratios, and in 15 of 33 (45.5%) children with immature DSPC levels. The true-positive rates of the L/S ratio and DSPC levels were 99.0 and 98.1%, respectively. PG had a low true-negative rate, as only 17 of 67 (25.4%) samples without detectable levels of PG were associated with RDS. However, when PG was present, it had a 100% predictive value of no-RDS. In conclusion, DSPC is nearly equal to the L/S ratio measured by two-dimensional as concerns diagnostic accuracy. PG is useful as an additional index for predicting lung maturation.

Amniotic Fluid↗

[Hepatic arterial infusion chemotherapy using implantable reservoir in colorectal liver metastasis].

Hepatic arterial infusion chemotherapy was performed in 47 cases with colorectal liver metastasis. Methods of hepatic arterial cannulation were as follows: operative insertion of polyvinyl chloride catheter in 12 cases, angiographic insertion of polyethylene catheter via the left high brachial artery in 20 cases and operative implantation of reservoir in 15 cases. Mean durations of chemotherapy were 31 days, 25 days and 115 days, respectively. Chemotherapies were discontinued because of complications and catheter troubles in 7 cases (58%), 8 cases (40%) and 6 cases (40%), respectively. Regression of tumor size was observed only in the group with reservoir. Prolonged therapy is achievable by use of the reservoir. But catheter troubles, including obstruction, infection, extravasation and pseudoaneurysm, are still observed in the course of chemotherapy. Radionuclide study using 99m Tc macroaggregated albumin is useful to detect catheter troubles. We stressed that the proper management of reservoirs is important.

Antineoplastic Combined Chemotherapy Protocols↗

[Role of systemic and pulmonary hemodynamics in genesis pleural effusion in congestive heart failure].

We tried to make an estimate of how pleural effusion occur in congestive heart failure, using right atrial pressure (RA) and pulmonary arterial wedge pressure (PAW) as variables. We calculated the following equation by quoting the data in the past. RA greater than -0.02 x PAW + 13.3. We speculated that when this relationship is satisfied, pleural effusion will appear. We also studied the patients with severe congestive heart failure, dividing them into 2 groups, ie the pleural effusion group (EF) and pulmonary edema group (ED). Compared with ED, EF has a significantly higher RA (RA = 6.1 +/- 1.33 mmHg in EF and 13.3 +/- 2.21 mmHg in ED, mean +/- SE, p less than 0.02) and a significantly lower cardiac index (3.17 +/- 0.26 l/min/m2 vs 2.23 +/- 0.16 l/min/m2, mean +/- SE, p less than 0.01). Therefore, we thought that it was adequate to treat RA and PAW as independent variables. These equations appear to be useful in predicting the development of pleural effusion that's based in the plots of our patients on RA-PAW plane and their relationship to our equations.

Aged↗

Therapeutic efficacy of human recombinant interleukin-2 (TGP-3) alone or in combination with cyclophosphamide and immunocompetent cells in allogeneic, semi-syngeneic, and syngeneic murine tumors.

The potential for a recombinant human interleukin-2 (rIL-2, TGP-3) alone, in combination with cyclophosphamide, and in combination with cyclophosphamide and normal immunocompetent cells to manifest biological activity in vivo was tested using allogeneic, semi-syngeneic, and syngeneic tumor-host systems in mice. The biological activity of rIL-2 was evaluated by the inhibition of the growth of tumors and the inhibition of metastases in short-term assays and, in long-term assays, the prolongation of the survival time of mice bearing subcutaneously (s.c.) or intradermally transplanted tumors. rIL-2 was injected s.c. daily continuously for up to 40 days or intermittently two to four times into mice bearing established tumors. In the short-term assays, the dose and schedule dependence of activity of rIL-2 alone was significantly manifested against sarcoma 180 in ICR mice (allogeneic) by the regression of the tumor, and was confirmed against Meth-A fibrosarcoma in BALB/c mice (syngeneic) by retarding the growth of the tumor. When assessed using these tumor, it was found that the antitumor activity of rIL-2 was schedule-dependent: the growth of tumors was more significantly suppressed when rIL-2 was injected every day for 10 days, starting on the 7th day after tumor transplantation, than when rIL-2 was injected five times every other day or twice every 5th day, even if the total amounts of rIL-2 injected were same. The continuous injection for 10 days was considered to be a standard regimen and the daily effective doses of rIL-2 were 5, 10, and 25 micrograms/mouse. Using the standard regimen and the effective doses, the activity of rIL-2 alone was also observed against two other syngeneic tumors: Colon carcinoma 26 in BALB/c mice, by retarding the growth of the tumor, and Lewis lung carcinoma in C57BL/6 mice by reducing the formation of lung metastases. When assessed using M5076 reticulum cell sarcoma, in a long-term assay, the activity of rIL-2 alone was not manifested in C57BL/6 mice (syngeneic) even when rIL-2 was injected for a long period (20 days) but it was observed in BDF1 (semi-syngeneic) mice. On the other hand, it was found that rIL-2 was effective in combination with cyclophosphamide in prolonging the survival time of C57BL/6 mice bearing the tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Adenosine-induced hyperemia attenuates myocardial ischemia in coronary microembolization in dogs.

We have recently reported that coronary microembolization sustains myocardial ischemia with hyperemic response of coronary blood flow (CBF) induced by massive release of adenosine from the ischemic myocardium. In this study, we tested the hypothesis that this hyperemic flow caused by released adenosine improves myocardial ischemia. In eight dogs (control), microspheres (5.0 X 10(4)/ml of base-line CBF) were repetitively injected until CBF decreased toward zero, and the changes in CBF, fractional shortening, lactate extraction ratio (LER), and adenosine release were studied. In 15 other dogs, an identical procedure was done with an intracoronary infusion of prazosin (4 micrograms.kg-1.min-1, n = 8) or theophylline (0.1 mg.kg-1.min, n = 7) to elucidate the effect of adenosine, since prazosin inhibits release of adenosine from ischemic myocardium and theophylline blocks adenosine receptors. In 16 other dogs, hemodynamic and metabolic parameters were examined with and without these drugs after a single injection of microspheres (1.0 X 10(5)/ml of base-line CBF). In the control group, CBF increased to 170 +/- (SE) 14% of the base-line CBF at 16-30% of maximal embolization. In contrast, intracoronary infusion of prazosin markedly attenuated adenosine release and hyperemic response and significantly deteriorated both fractional shortening and LER. Theophylline also significantly attenuated the hyperemic response and tended to decrease both fractional shortening and LER. A salutary effect of adenosine release was further confirmed by the improvement of ischemic changes in the same dog after withdrawal of prazosin and theophylline associated with an increase in CBF. Thus we conclude that adenosine released from ischemic myocardium improves ischemia in microembolization through the hyperemic response.

Adenosine↗

Beneficial effects of alpha 2-adrenoceptor activity on ischemic myocardium during coronary hypoperfusion in dogs.

We have previously reported that alpha 2-adrenoceptor stimulation enhances adenosine-induced coronary vasodilation. In the present study, we tested the hypothesis that alpha 2-adrenoceptor activity exerts beneficial effects on myocardial ischemia through augmentation of vasodilatory effects of released adenosine. In open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery. Propranolol was infused into the bypass tube to exclude the metabolic effects of norepinephrine. When clonidine (0.24 micrograms/kg/min i.c.) was infused for 10 minutes after reduction of coronary blood flow by partial occlusion of the bypass tube, coronary blood flow was increased by 43% from 27 +/- 1 ml/100 g/min despite no changes in coronary perfusion pressure (38 +/- 5 mm Hg) and a slight decrease in adenosine release. Both fractional shortening and lactate extraction ratio of the perfused area were significantly improved (fractional shortening, 1.8 +/- 1.0 to 10.9 +/- 1.5%, p less than 0.001; lactate extraction ratio, -57.8 +/- 6.5 to -31.9 +/- 2.4%, p less than 0.005). Identical results were observed in the denervated hearts, indicating that the beneficial effect of clonidine is not attributed to the prevention of norepinephrine release from the sympathetic nerve terminals. The beneficial effects of clonidine were prevented by yohimbine, an alpha 2-adrenoceptor blocking agent. An adenosine receptor antagonist, 8-phenyltheophylline, also prevented the beneficial effects of clonidine, indicating that these beneficial effects are mediated by effects of adenosine. Furthermore, the extent of augmentation of coronary flow in the ischemic heart was coincided with that of augmentation of exogenous adenosine-induced hyperemic flow (40%) by clonidine. Production of cyclic AMP in the coronary artery during myocardial ischemia was augmented by clonidine. In 12 other dogs, myocardial ischemia was produced by intracoronary embolization of microspheres (15 microns in diameter). Clonidine enhanced (39%) the hyperemic coronary flow and improved both fractional shortening and lactate extraction ratio. Thus, we conclude that alpha 2-adrenoceptor stimulation can ameliorate myocardial ischemia mainly due to enhancement of vasodilatory effects of adenosine released from the ischemic myocardium.

Acidosis↗