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Biomedical subjects

T Sakabe

Publications and source records attributed to T Sakabe.

At least 19 recordsLinked to original sources

[Assessment of ventriculoarterial coupling in humans by transesophageal echocardiography and radial artery pressure tracing].

To investigate coupling between the heart and arterial system in patients undergoing elective non-cardiac surgery, we determined both the ventricular elastance and the effective arterial elastance in two groups of subjects: normal group, 68 subjects without heart disease; and cardiac group, 33 subjects with heart disease. Left ventricular end-systolic (Ves) and end-diastolic (Ved) volumes were determined by transesophageal echocardiography. By assuming that left ventricular end-systolic pressure (Pes) is close to mean arterial blood pressure (MAP) and that x-axis intercept (Vo) is zero, the ventricular elastance (E'max) was approximated as MAP/Ves, and the effective arterial elastance (Ea) as MAP/(Ved-Ves). In 222 (74%) of the 299 measurements obtained in normal group, Ea/E'max was nearly 0.5, which is a condition for a maximal mechanical efficiency, while in 61 measurements (20%) Ea was almost equal to E'max (Ea/E'max = 1), which is a condition for maximal stroke work from a given end-diastolic volume. In contrast, in cardiac group, Ea/E'max was nearly 0.5 in 56 (41%) of the 137 measurements, while in 42 measurements (31%) Ea/E'max was nearly 1. In addition, although the value of Ea/E'max over 2, which represents severe heart failure, was not observed in normal group, Ea/E'max was over 2 in 10 measurements (7%) in cardiac group. Thus, the present results suggest that, as reported previously in awake patients, ventriculoarterial coupling is set toward higher left ventricular work efficiency in surgical patients without heart disease, whereas in patients with heart disease, ventricular and arterial properties are so matched as to maximize stroke work at the expense of the work efficiency.

Adult

[Effects of isosorbide dinitrate on regional cerebral blood flow and intracranial pressure in cats].

The effects of isosorbide dinitrate (ISDN) on regional cerebral blood flow (rCBF) and intracranial pressure (ICP) were examined in cats. A low dose of ISDN (2.5 micrograms/kg/min) infusion did not show any changes in cerebral hemodynamics. During high dose of ISDN (5.0 micrograms/kg/min) or NTP (5.0 micrograms/kg/min) infusion, mean blood pressure (mBP) decreased by 10 to 20% accompanied by decreased cerebral perfusion pressure (CPP: mBP-ICP), however, rCBF or ICP did not change. It is concluded that intravenous administrations of ISDN in a dose of 2.5-5.0 micrograms/kg/min that produce slight decrease in blood pressure did not influence on cerebral hemodynamics.

Animals

[Nicergoline, an ergot alkaloid, improves ischemic brain damage by ameliorating the decreased cerebral blood flow and metabolism in spontaneously hypertensive rats].

Effects of ergot alkaloids, nicergoline (NIC), on survival rate, brain water content, local cerebral blood flow (LCBF: 14C-iodoantipyrine) and glucose utilization (LCGU: 14C-2-deoxyglucose) were examined after bilateral carotid artery occlusion (BCAO) in spontaneously hypertensive rats. Two series of study were performed; the permanent BCAO and 3-hr-BCAO study. After permanent BCAO, the survival rate at 24 hrs of 32% (8 mg/kg, i.p.) or 38% (16mg/kg) in NIC group was higher than that in non-treated group (12%). At the end of 3-hr-BCAO, the increase in water content (dry-wet) in di-mesencephalon was less in NIC (100 micrograms/kg/min, i.v.) group than that in non-treated group. The decrease in LCBF in caudate-putamen (CP), parietal cortex (PC), thalamus (TH), hypothalamus (HT), and substantia nigra (SN) were less in NIC group than those in non-treated group. At the 2-hr-reperfusion after 3-hr-BCAO, the decrease in LCBF in TH and HT were less in NIC group than those in non-treated group. The LCGU in sensory motor cortex, CP, PC, HT, inferior colliculus and pons-reticular were higher in NIC group than those in non-treated group. From these results, it is concluded that nicergoline may have ameliorative effects on survival rate related to the prevention of decreased cerebral blood flow and metabolism following brain ischemia.

Animals

[Effects of ONO-1016, inhibitor of C1-/HCO3- exchange, on the brain water content and local cerebral blood flow following cerebral ischemia in spontaneously hypertensive rats].

The effects of ONO-1016, as an inhibitor of C1-/HCO3-exchange, on the brain edema and circulatory failure following cerebral ischemia were examined in stroke-prone spontaneously hypertensive rats (SHR-SP). SHR-SP were divided into three groups: control (sham-operation), non-treated, ONO-1016 group, respectively. Cerebral ischemia was produced by bilateral carotid artery occlusion (BCAO) for 1 hr and then following reperfusion. The brain water content and local cerebral blood flow (LCBF) were determined by dry-wet method and 14C-iodoantipyrine method 2 hr after start of reperfusion. ONO-1016 was given intravenously at a dose of 100 micrograms/kg/min prior to ischemia. The brain water content increased in septum (SP), amygdala (AM) in both non-treated and ONO-1016 groups compared from those in control group. However, brain water contents in SP and midbrain were lower in ONO-1016 group than those in non-treated group. LCBFs decreased to 50-80% in SP, cerebral cortex (CT), striatum (ST), hippocampus (HC) and AM in non-treated group, while LCBFs decreased to 60-80% in SP, CT, ST, AM in ONO-1016 group when compared from those in control group. Decrease of LCBF in ST and HC in ONO-1016 group were less severe than those in non-treated group. From these results, ONO-1016 may prevent the brain edema formation associated with hypoperfusion during reperfusion period after ischemia in SHR-SP.

Animals

[Study of pre-operative chemotherapeutic methods for colonic cancer--the concentration in blood and tissues after pre-operative administration of UFT].

As one of the fundamental studies of the pre-operative chemotherapeutic methods in 22 cases with colonic cancer, we studied a progress of the concentration in blood and concentration in tissues including those in the portal vein after administration of UFT. The concentration of 5-FU in blood reached to the peak at 2 hours after administration of UFT and then decreased rapidly, while it was maintained for a long term in comparing with that of 5-FU (oral remedies; tablet and dry syrup). This fact suggested that UFT can be expected for metastatic inhibition and prevention of the recurrence because it showed an effect in free-cancerous cells before and during operation. The anti-tumorous effect was also expected because the concentration of 5-FU in cancerous tissues was significantly higher than that in non-cancerous region. In our study in this time, down staging was considered by pre-operative chemotherapeutic method of colonic cancer in the future because concentration of 5-FU was also highly obtained in metastatic lymph nodes. From the above-mentioned results, pre-operative chemotherapeutic method using UFT was expected as a part of the intensive therapies.

Administration, Oral

[Cerebral effects of isoflurane-induced or PGE1-induced hypotension in dogs].

The cerebral effects of hypotension induced by inhalation of increasing concentrations of isoflurane or intravenous administration of prostaglandin E1 (PGE1) were studied in 15 dogs anesthetized with 1% isoflurane and 50% nitrous oxide during normocarbic (PaCO2 approximately 39 mmHg) and normothermic (37.5 degrees C) condition. Mean arterial pressure (MAP) was decreased stepwise to 25, 40, and 55% of its baseline values. Cerebral blood flow (CBF) was measured using the venous outflow technique. Cerebral metabolic rate for oxygen (CMRO2), cerebral metabolic rate for glucose (CMRgl) and oxygen/glucose index (OGI) were calculated, and cerebrospinal fluid pressure (CSFP) and EEG were also recorded at each decrement in MAP and after resuming the control condition. The CBF, CMRO2, CMRgl, OGI and CSFP responses related to hypotension showed no significant changes from baseline values in both methods. However, CBF values in isoflurane-induced hypotension at 25% and 40% reduction of MAP were significantly higher than those in PGE1-induced hypotension. By increasing concentration of isoflurane, EEG changed from continuous fast wave to high amplitude (100 microV) slow wave (4-6 Hz) and typical burst suppression observed in 3 of 8 dogs. In contrast, no significant EEG changes were seen during PGE1-induced hypotension. These results suggest no adverse effect of isoflurane- and PGE1-induced hypotension on cerebral metabolism or function.

Alprostadil

[Voltage-dependent effects of lidocaine and its metabolite, monoethylglycine xylidide (MEGX), on maximum rate of rise (Vmax) of action potential upstroke in guinea-pig papillary muscles].

We studied the effects of lidocaine and MEGX on the sodium current, using Vmax as an indicator, at an extracellular potassium concentration ([K]o) of 10 mmol.l-1, and compared the present results with those obtained at 5.4 mmol.l-1 [K]o in our previous study. At 10 mmol.l-1 [K]o, both lidocaine (10 micrograms.ml-1) and MEGX (10 micrograms.ml-1) significantly decreased the Vmax at the steady-state of 1 Hz, caused a significant rate-dependent decrease in Vmax, and slowed the recovery kinetics of Vmax. These effects of both agents were more prominent than those obtained at 5.4 mmol.l-1 [K]o, suggesting that MEGX as well as lidocaine produce voltage-or [K]o-dependent blocking effects on Vmax.

Action Potentials

Comparative study of secretion by vagotomized and isotransplanted stomachs in the rat.

An acute observation of gastric secretion by syngeneic stomach transplants in Lewis male rats was compared to the gastric secretory fate of normal, pylorus-ligated, vagotomized, and combined pylorus ligation and vagotomized Lewis rats. A 5 day observation was sufficient before sympathetic fibers and vagal channels could be regenerated. A total of 36 rats were divided into five groups of which group I (ten normals), group II (five vagotomized), group III (pylorus-ligated), group IV (six vagotomized and pylorus-ligated), and group V (five syngeneic stomach-transplanted, five animals served as donors), and those stomachs were intubated to collect gastric juice by housing animals in Bollman cages. Whereas group V animals secreted a mean 24 hr gastric juice volume of 12.5 +/- 6.4 ml with free acid secretion of 0.15 +/- 0.01 mEq/24 hr, animals in groups I, II, III, and IV secreted 24.4 +/- 2.9 ml, 23.3 +/- 1.1 ml, 25.5 +/- 3.4 ml, 22.4 +/- 0.5 ml, respectively, for 24 hr periods with free acid secretions of varying rates. From these observations, the transplanted stomach mean secretory rate averaged half that of the normal stomach.

Animals

Epidural bupivacaine suppresses local glucose utilization in the spinal cord and brain of rats.

Using the 2-[14C]deoxyglucose method, the effects of analgesic doses of epidural bupivacaine (300 micrograms) on local spinal cord glucose utilization (SP-LGU) of the cervical, thoracic, and lumbar regions and local cerebral glucose utilization (BR-LGU) in 38 brain structures were examined in conscious rats. In addition, the effects of intramuscular bupivacaine (300 micrograms) and the spinal cord transection (T2) were examined to determine whether the induced metabolic changes, if any, are related to the drug's systemic effect and/or deafferentation. Lumbar epidural bupivacaine sufficient to produce analgesia decreased SP-LGU in the thoracic (18-28%) and lumbar (21-29%) spinal cord but not in the cervical cord. Epidural bupivacaine decreased BR-LGU (15-26%) in 35 of 38 structures examined. With intramuscular bupivacaine, SP-LGU remained unchanged in almost all regions, while BR-LGU was significantly decreased (11-23%) in 23 structures. Plasma concentrations of bupivacaine in the epidural and intramuscular groups were comparable. With spinal cord transection alone, SP-LGU significantly decreased with varying degrees depending on the structure examined, but BR-LGU did not decrease in 36 of 38 structures examined. These results indicate that analgesic doses of epidural bupivacaine decrease SP-LGU, probably reflecting decreased neuronal activity of the spinal cord, and that reduced BR-LGU by epidural bupivacaine is most likely due to the drug's systemic effect rather than deafferentation.

Analgesia, Epidural

[Differential effects of isoflurane and nitrous oxide on cerebral blood flow, metabolism and electrocorticogram after incomplete cerebral ischemia in the rat].

Differential effects of isoflurane (ISOF) and N2O on cerebral blood flow, metabolism and electrocorticogram (ECoG) were examined in rats subjected to 15 min-incomplete cerebral ischemia. In the first study, regional cerebral blood flow (rCBF) and ECoG were measured during and after ischemia. In the second study, local cerebral blood flow (LCBF) and glucose utilization (LCGU) were determined at 60 min after reperfusion. In the N2O group, rCBF in both the cerebral cortex and hippocampus decreased significantly to less than 10% of the pre-ischemic value during ischemia, and it increased to 170% at 10 min after reperfusion. The ECoG became flat during ischemia and reappeared at 21 min after reperfusion. In the ISOF group, rCBF decreased significantly to 25% during ischemia and returned to the preischemic value after reperfusion. The ECoG became flat during ischemia and reappeared at 14 min. In the N2O group, LCBFs decreased significantly to 40-50% of the pre-ischemic values in the forebrain. LCGUs decreased significantly to 30-50% in all structures of the forebrain. In the ISOF group, LCBFs decreased significantly to 60-80% in the forebrain, but were not different in other structures. LCGUs did not differ from pre-ischemic values in all structures except for in the thalamus and habenula. These results may indicate cerebral protective effects of ISOF on incomplete cerebral ischemia in rats.

Animals

[Chemosensitivity of human head and neck tumors detected by human tumor clonogenic assay].

Chemosensitivity of human head and neck tumor was evaluated by human tumor clonogenic assay. Among eight of head and neck tumors seven squamous cell carcinomas such as tongue, gingiva, maxillary sinus, pharynx and one malignant fibrous histiocytoma (MFH) of maxillary sinus and four anti-cancer agents BLM, CDDP, 5-FU and MMC were used. Five of eight tumors were succeeded to evaluate the sensitivity. Positive rates except MFH were BLM 100% (3/3), CDDP 25% (1/4), 5-FU 33% (1/3). These results are similar to recent clinical experiments except CDDP.

Bleomycin

[Radio- and radio-chemosensitivity of human head and neck cancer cell line detected by human tumor clonogenic assay].

The radiosensitivity and radio-chemosensitivity of 3 series of human cancer cell lines were evaluated by human tumor clonogenic assay. The sources of cell lines were gingiva carcinoma (Ca9-22), uterus carcinoma (Hela) and gastric carcinoma (MKN-45). BLM and CDDP were used, and chemosensitivity of gingiva carcinoma tended to be higher than other cell lines. Radiosensitivity was same as MKN-45. Isobologram were employed for quantitation of the interaction between the irradiation and anti-cancer agents. In Ca9-22, the interaction of between gamma-rays, BLM and CDDP was supra-additive. Hela was also supra-additive, but in MKN-45, the interaction of between gamma-rays and BLM was sub-additive.

Bleomycin

[Availability of intermittent chemotherapy by reservoir in liver metastasis of colo-rectal cancer].

From August 1986 to May 1989, in 18 cases of liver metastasis from colo-rectal cancer, intermittent chemotherapy was undergone by implantation reservoir in the subcutaneous. Intra-arterial infusion chemotherapy was under taken in 6 cases, and intra-portal vein chemotherapy in 12 cases. 5-FU 500 mg + MMC 10-6 mg was infused through implantable reservoir once every two weeks. CDDP and ADM were also infused in one case. Infusions averaged 12.4 times, and the most was 24 times in the group of intra-arterial infusion chemotherapy. In the group of intra-portal vein infusion chemotherapy, infusion averaged 12.4 times, with the highest at 35 times. In liver metastasis (H3), there is no significant difference between intra-arterial infusion chemotherapy and intra-portal vein infusion chemotherapy, revealing the cumulative survival rate. And the reservoir group compares with the 14 cases of hepatectomy and the 9 cases of systemic chemotherapy in cumulative survival rate. As a result, there was no significant difference between the group with the reservoir and the systemic chemotherapy group in H1 cases and H2 cases, revealing a median survival rate in these treatment groups. The median survival of reservoir group was 8.3 months, and that of the hepatectomy group was 20.6 months in H2 cases. In the H3 cases, the median survival of the reservoir group was 9.6 months, and that of the systemic chemotherapy group was 10.3 months. Reservoir was implanted in three cases to prevent recurrence after hepatectomy. As a result, two of three cases have survived for 20 months and 10 months, respectively.

Adult

Calcium entry blockers in cerebral resuscitation.

This paper reviews postischemic events which might influence the neurologic injury following cerebral ischemia. The influence of diverse calcium entry blockers (CEB) on postischemic cerebral blood flow (CBF) and neurologic outcome is presented. The role of intracellular calcium (Ca) accumulation in neuronal injury is discussed. Although a number of diverse experiments appear in the literature using several, different types of CEB, e.g., nimodipine, lidoflazine, flunarizine and nicardipine, they appear to have different cerebral effects. There is no solid consistent evidence that CEB prevent Ca loading following cerebral ischemia. At least one CEB appears promising, namely, nimodipine. Since the mechanisms of action of CEB in cerebral ischemia remain obscure, further studies appear necessary and warranted.

Animals

Metabolic activation of intercortical and corticothalamic pathways during enflurane anesthesia in rats.

The purpose of this study was to examine the effects of enflurane on local cerebral glucose utilization (LCGU), and to provide further insight into the mechanism of the epileptogenic properties of enflurane. Twenty-four male Wistar rats were divided into four groups; three groups with intact cortex received 0.5, 2, or 4% enflurane, and one group with unilateral cortex excised received 4% enflurane. LCGU was measured at each anesthetic concentration using the autoradiographic 2-[14C]deoxyglucose method. LCGU in ten of 33 structures examined during 2% enflurane decreased by 19-33%, and LCGU in 22 structures during 4% enflurane decreased by 19-65%, when compared with that during 0.5% enflurane. While LCGU, in most structures, decreased in a dose-related manner, LCGU in the corpus callosum, thalamic ventrobasal complex, and hippocampal CA3 field during 4% enflurane increased by 31-70%, compared with that during 0.5% and/or 2% enflurane. With unilateral cortical excision during 4% enflurane, the increase in LCGU in the ventrobasal complex was obliterated in the excision side, and the increase in the corpus callosum was attenuated. High LCGU in the hippocampal CA3 field and contralateral ventrobasal complex was not affected with cortical excision. These results indicate that intercortical and corticothalamic pathways are metabolically activated during deep enflurane anesthesia, suggesting that the epileptogenic property of enflurane is related to activation of these pathways.

Anesthesia, Inhalation

[Transcatheter hepatic arterial chemoembolization using microencapsulated mitomycin C (MMCmc)].

Thirty-six patients with hepatocellular carcinoma were treated by hepatic arterial chemoembolization of microencapslated mitomycin C (MMCmc). The infusion cannulae were placed in the hepatic artery by the Soldinger method, and 10 to 40 mg of MMCmc was injected 1 to 4 times (total doses, 10-110 mg). The evaluation of anti-tumor effects revealed 12 partial responses in 27 evaluable lesions and response rates were 44%. The serum AFP levels were decreased in 70% of patients. The survival rate for 12 months was 35% in all patients, but 67% at Stage III. The control of liver function is also important, because the hepatic failure and esophageal varices were the main causes of death. Side effects such as fever and pain were seen in 70%, but they were mild.

Adult

[Clinical study of controlled-release preparation of mitomycin C in the treatment of inoperable cancer patients].

The composite substance of Mitomycin C (MMC) and polymer by low temperature radiating polymerization has a characteristic of slow release, the possibility of applying it to local chemotherapy was clinically studied. Buttom-formed preparation (MMC 20 mg) and needle-formed preparation (MMC 5 mg) were applied to the lesions, respectively, by sewing and piercing in 220 cancer patients with non resectable infiltrative lesions. The treatment had a pain-relieving effect in 70 out of 117 cases (60.0%) of painful cancer in the pancreas, biliary duct, liver, etc, and improved the symptoms of digestive organs in 31 out of 93 cases (33.3%). However, the tumor-reducing effect was recognized only in minute localized lesions of hepatic cancer, etc., and the survival period was not prolonged. The treatment caused no severe side effects. From the above results, the local chemotherapy with slow-releasing MMC preparation was concluded to be a useful means of palliative therapy in non-resectable, though its formulation may to be further improved.

Clinical Trials as Topic