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Biomedical subjects

T Sakabe

Publications and source records attributed to T Sakabe.

At least 19 recordsLinked to original sources
PubMed1996

Prognostic factors for patients with colon or rectal carcinoma treated with resection only. Five-year follow-up report.

BACKGROUND: The prognostic factors and natural history of recurrence in patients with colorectal carcinoma who underwent curative resection and no other therapy were analyzed. METHODS: The object of analysis was the potentially curative resection only subgroup in the randomized clinical trial (RCT) that we performed. Cox's proportional hazards model was used mainly to analyze recurrence rates during the first 5 years after surgery. RESULTS: The analysis was performed on a subgroup of the RCT (279 patients with colon carcinoma and 293 patients with rectal carcinoma). Five-year disease free survival rates were 76.3% and 56.5% for colon and rectal carcinomas, respectively. The prognostic factors for recurrence for colon carcinoma patients were different from those with rectal carcinoma. For colon carcinoma, only Dukes stage was significant, whereas for rectal carcinoma, Dukes stage, age, location of the tumor, and serosal and venous invasion by cancer cells were prognostic factors. Log-transformed disease free survival rates were linear in Dukes Stage B and biphasic in Dukes Stage C for both colon and rectal carcinoma. The two phases in Dukes Stage C intersected at 2.85 and 3.04 years, respectively. The annual hazard value was high for the first 3 years in both colon and rectal carcinoma. CONCLUSIONS: We conclude that follow-up of patients with colorectal carcinoma who undergo potentially curative resection is of particular importance in the first 3 years after surgery. Furthermore, the usefulness of adjuvant chemotherapy can be adequately evaluated from data yielded during this postoperative period.

Chemotherapy, Adjuvant↗
PubMed1996

Prognostic factors of colorectal cancer. Results of multivariate analysis of curative resection cases with or without adjuvant chemotherapy.

One thousand two hundred fifty-four cases (610 colonic and 644 rectal cancers resected during 2 years from 1984 and followed up for more than 5 years) were entered from 140 institutions in Japan and analyzed by means of Cox's proportional hazards model. The analyzed pathologic variables were the size and depth of invasion, Dukes' stage, venous invasion, lymphatic permeation, and other clinical features, such as the sex and age of the patient and location of the tumor. The extent of dissection, serum carcinoembryonic antigen (CEA) level, and the presence or absence of adjuvant chemotherapy were also analyzed. Adjuvant chemotherapy consisted of three arms for both colonic and rectal cancers. For colonic cancer, arm I was a combination of i.p. (intraportal) and i.v. mitomycin C (MMC) + p.o. 5-fluorouracil (5-FU); arm II was i.v. MMC + p.o. 5-FU; and arm III was surgery only. For rectal cancer, arm IV was a combination of i.a. (inferior mesenteric artery) and i.v. MMC + p.o. 5-FU; arm V was i.v. MMC + p.o. 5-FU; and arm VI was surgery only. As for the factors affecting the disease-free survival of the patient, multivariate analysis disclosed nodal involvement, venous invasion, an elevated CEA level, and the lower part of the rectum. The effect of adjuvant chemotherapy on the patient's survival was proven for rectal cancer but not for colonic cancer. We conclude that these factors should be considered in setting the stage of tumor pre- and postoperatively.

Aged↗
PubMed1996

Preservation of the ration of cerebral blood flow/metabolic rate for oxygen during prolonged anesthesia with isoflurane, sevoflurane, and halothane in humans.

BACKGROUND: In several animal studies, an increase in cerebral blood flow (CBF) produced by volatile anesthetics has been reported to resolve over time during prolonged anesthesia. It is important to investigate whether this time-dependent change of CBF takes place in humans, especially in clinical situations where surgery is ongoing under anesthesia. In this study, to evaluate the effect of prolonged exposure to volatile anesthetics (isoflurane, sevoflurane, and halothane), the CBF equivalent (CBF divided by cerebral metabolic rate for oxygen (CMRO2) was determined every 20 min during anesthesia lasting more than 4h in patients. METHODS: Twenty-four surgical patients were assigned to three groups at random to receive isoflurane, sevoflurane, or halothane (8 patients each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 MAC before surgery and then 1.5 MAC for the 3 h of surgical procedure. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 60 mmHg, using phenylephrine infusion, if necessary. CBF equivalent was calculated every 20 min as the reciprocal of arterial-jugular venous oxygen content difference. RESULTS: CBF equivalent at 0.5 MAC of isoflurane, halothane, and sevoflurane was 21 +/- 4, 20 +/- 3, and 21 +/- 5 ml blood/ml oxygen, respectively. All three examined volatile anesthetics significantly (P<0.01) increased CBF equivalent in a dose-dependent manner (0.5, 1.0, 1.5 MAC). AT 1.5 MAC, the increase of CBF equivalent with all anesthetics was maintained increased with minimal fluctuation for 3 h. The mean value of CBF equivalent at 1.5 MAC in the isoflurane group (45 +/- 8) was significantly (P<0.01) greater than those in the halothane (32 +/- 8) and sevoflurane (31 +/- 8) groups. Electroencephalogram was found to be relatively unchanged during observation periods at 1.5 MAC. CONCLUSIONS: These results demonstrate that CBF/CMRO2 ratio is markedly increased above normal and maintained during prolonged inhalation of volatile anesthetics in humans. It is impossible to determine whether these data indicate a stable CBF or whether CBF and CMRO2 are changing in parallel during the observation period. The unchanging electroencephalographic pattern suggests that the former possibility is more likely and that the increase of CBF produced by volatile anesthetics is maintained over time without decay, which has been reported in several animal studies. It also is suggested that isoflurane possesses greater capability to maintain global CBF relative to CMRO(2) than does halothane or sevoflurane. time.)

Adult↗
PubMed1995

A saponin conjugated with 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one from Dolichos lablab.

A new 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP)-conjugated saponin, lablab saponin I, was isolated from the hypocotyl of hyacinth bean (Dolichos lablab). The structure was elucidated by 1H NMR and 13C NMR spectroscopy and chemical techniques as 3-O-[alpha-L-rhamnopyranosyl- (1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D-glucuronopyranosyl(1 -->)]-22-O- [2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one(2'-->)]-3 beta, 22 beta, 24-trihy-droxyolean-12-en-28-al. SOD (superoxide dismutase)-like activity depended upon the DDMP group and the aldehyde group (C-28) of the aglycone was observed in the order of lablab saponin I > glutathione > soyasaponin beta g > maltol. The soybean saponin Bb, lacking the DDMP moiety was found not to exhibit the SOD-like activity.

Carbohydrate Conformation↗
PubMed1995

[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↗
PubMed1994

Contractile force and resting tension in the presence of halothane and increased extracellular potassium or decreased extracellular pH in isolated guinea pig atria.

To gain a better understanding of the direct actions of halothane on myocardial function in ischaemia, we studied the effects of increasing extracellular potassium concentration and decreasing extracellular pH (acidosis), alone or in combination with halothane, on the contractile force and resting tension in isolated atria. Guinea pig left atria were superfused with Tyrode's solution and stimulated at 1 Hz. Isometric contractile force and resting tension were measured using a force displacement transducer. Perfusate potassium concentrations were increased from 5.4 mmol.L-1 to either 8.1 mmol.L-1 or 10.8 mmol.L-1 by adding KCl to the standard Tyrode's solution, and its pH was decreased from 7.4 to either 7.0 or 6.5 by decreasing bicarbonate. In standard Tyrode's solution (potassium 5.4 mmol.L-1, pH 7.4), halothane 0.5-2% reduced contractile force in a dose-dependent manner (P < 0.05); the effective concentration of halothane for 50% inhibition of contractile force (IC50) was 1.3%. Both increasing extracellular potassium and decreasing extracellular pH decreased the contractile force in a potassium- or pH-dependent fashion. The negative inotropism of halothane (1%) was not altered by increasing potassium concentrations, whereas 1% halothane caused a greater decrease in contractile force at pH 6.5 than at pH 7.4. Halothane (1%) enhanced the acidosis (pH 6.5)-induced increases in resting tension. Arrhythmias were produced in one of eight preparations during acidosis, while four of eight preparations demonstrated arrhythmias during acidosis in the presence of halothane. These data suggest that acidosis and halothane may have a synergistic interaction on the contractile force and resting tension of the atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1994

[Effects of volatile anesthetics on force interval relationships in guinea-pig atrial preparations].

Depressant effects of halothane, enflurane and isoflurane on isolated guinea-pig left atrial muscles bathed in Tyrode's solution at 30 degrees C were examined. Contractions were elicited by stimulation through external field electrodes while tension was recorded continuously. Frequency-force relationships at stimulation rates of 0.1, 0.2, 0.5 and 1 Hz were studied. The pD2 values of these volatile anesthetics at each stimulation rates were not different significantly, suggesting the frequency-independent depressions of these anesthetics. Interval-strength relationships at time intervals of 0.3-20 sec during 1 Hz-stimulation were also studied. Mechanical restitution curves after converting to logistic function reached a peak at 8-20 sec and were fitted well to double exponential functions with time constants of 200-600 msec (k1) and 2-6 sec (k2). All volatile anesthetics depressed the magnitude constants for fast response in a dose dependent manner. Accordingly, at high concentrations, mechanical resuscitation curves tended to fit single exponential function. Halothane and enflurane did not alter time constant k1, k2 significantly, while isoflurane increased k2 significantly. These results suggest that the mechanisms of myocardial depressant effects are different between these anesthetics.

Anesthetics, Inhalation↗
PubMed1994

[The optimal period for orally administered fluoropyrimidines as an adjuvant chemotherapy for gastric cancer--a pilot study using 5-FU tablets compared with surgical operation alone].

Long-term oral administration of fluoropyrimidines such as 5-fluorouracil (5-FU) or tegafur is commonly used as an adjuvant chemotherapy for gastric cancer, but the optimal period or optimal total doses of fluoropyrimidines have not been studied. Two hundred cases of macroscopical Stage II and III curatively resected gastric cancer patients were entered in this study, and divided into three groups (6 months group: mitomycin C was given i.v. at day 0 and day 1 and 5-FU tablets were orally administered at a dose of 200 mg/day for 6 months. 12 months group: MMC was given the same as for the 6 months group and 5-FU tablets were administered for 12 months. Surgery alone group: No chemotherapy, operation only). As the result, 185 cases were eligible. There was no significant difference between the 6 months group and the 12 months group among Stage II patients. Although there was also no significant difference between the 2 groups in Stage III patients, the survival curve of 12 months group was always higher than in the 6 months group. When comparing with surgery alone group, 5-year survival of the 12 months group was always higher than in the surgery alone group of Stage III patients; however, the survival rate in the 6 months group was worse than in the surgery alone group at Stage II and III. These results suggest that MMC i.v. and 12 months or over administration of 5-FU tablets is useful for Stage III gastric cancer patients, and that cooperative study is required comparing with surgery alone in Stage II patients.

Administration, Oral↗
PubMed1994

[Differential effects of isosorbide dinitrate and nitroprusside on pial vessel diameter in cats].

Changes in pial vessel diameter combined with regional cerebral blood flow (CoBF) during infusion of vasodilating drugs, isosorbide dinitrate (ISDN) 5 micrograms/kg/min and nitroprusside (NTP) 5 micrograms/kg/min, compared with haemorrhagic hypotension were studied in cats anesthetized with halothane (1.0%). Pial arteries and veins were measured by image-splitting technique and were each divided into three groups according to the reference diameter: I; < 50 microns, II; 51 < microns < 100, III; 101 < microns. With either drug, the mean blood pressure (mBP) decreased by 10-20%. There was significant decrease in cerebral vascular resistance with ISDN compared with haemorrhagic hypotension while CoBF (H2 clearance) remained unchanged. Dilatation of pial arteries depending on vessel size with ISDN was two-hold compared with haemorrhagic hypotension without any change in all veins. Consistent and significant dilation of veins (I and II) was observed only during NTP infusion. These findings indicate the differential effect of ISDN and NTP on pial arteries and veins.

Animals↗
PubMed1993

Enflurane increases the adrenaline threshold for the development of slow responses in isolated canine trabeculae.

To determine if enflurane has different effects on myocardial sensitivity to adrenaline than those previously reported for halothane, we have studied the enflurane-adrenaline interaction in isolated canine trabeculae using doses of adrenaline necessary to produce slow responses (adrenaline threshold for the development of slow responses, ATSR) as an indicator. The preparations were depolarized in Tyrode's solution containing potassium chloride 26 mmol litre-1, then adrenaline concentrations in the solution were increased stepwise. Enflurane 1% had no significant effect, but 2% and 4% significantly increased the ATSR two-fold and seven-fold, respectively. To investigate the influence of enflurane on the adrenaline-adrenoceptor interaction, we studied the effects on the ATSR of 2% enflurane alone or in combination with either prazosin 8 ng ml-1 or metoprolol 17 ng ml-1. Compared with the ATSR obtained with 2% enflurane alone, alpha 1-block with prazosin did not alter, but beta 1-block with metoprolol significantly increased the ATSR (three-fold). These effects on enflurane are qualitatively as well as quantitatively similar to those reported previously for halothane. Thus, assuming that the MAC value for enflurane is about 2-2.5 times greater than that for halothane, the effects of enflurane on slow channel conductance (antiarrhythmic effects of enflurane) might be about two to three times greater than those of halothane at equivalent depth of anaesthesia. Such differences may explain in part the clinical observation that ventricular arrhythmias are less likely with enflurane than with halothane.

Animals↗
PubMed1993

[Assessment of left ventricular contractility (Emax) and arterial load (Ea) in humans by transesophageal echocardiography and radial artery pressure tracing].

We determined both the slope of the left ventricular end-systolic pressure-volume relation (Emax), which is a measure of contractility independent of loading conditions, and the slope of the arterial end-systolic pressure-stroke volume relation (Ea), which is a measure of arterial load independent of ventricular function, in 10 patients undergoing elective noncardiac surgery. Left ventricular end-systolic volume (Ves) was measured by transesophageal echocardiography and instantaneous left ventricular end-systolic pressure (Pes) was estimated from the dicrotic notch pressure in the radial artery. Emax was calculated during afterload reduction (nicardipine 30 micrograms.kg-1 iv), and the correlation of Emax to either Pes/Ves ratio or MAP (mean arterial blood pressure)/Ves ratio was accomplished in order to investigate whether these indices were clinically useful measurements of ventricular function or not. Ea was also calculated from the data obtained before and 2-3 min after nicardipine iv. The averaged Emax and x-axis intercept (Vo) were 3.11 mmHg.ml-1 and -3.8 ml, respectively. The correlation coefficient obtained between Emax and Pes/Ves was 0.96, and that obtained between Emax and MAP/Ves was 0.97. Ea decreased significantly (P < 0.05) following intravenous nicardipine, demonstrating a decreased arterial load. The direction of changes in Ea was similar to that reported previously in systemic vascular resistance. From these results, we conclude that measurement of Emax (or Pes/Ves, MAP/Ves) and Ea using transesophageal echocardiography and radial artery pressure tracing is feasible and these are a useful tool to estimate left ventricular performance and arterial load during surgery.

Blood Pressure↗
PubMed1993

[Study of pre- and post-operative chemotherapy with oral 5-FU in patients with gastric cancer. Study Group of Pre- and Post-Operative Oral 5-FU in Gastric Cancer].

A cooperative study group consisted of 37 medical institutions evaluated the utility of pre- and post-operative chemotherapy with oral 5-FU by comparing with the historical controls of the patients treated with operation alone who were registered in Japanese Gastric Cancer List. Of 634 patients entered in this trial, 366 patients received curative operation at macroscopical stages II and III were studied as eligible cases. The relative 5-year survival at macroscopical stage II and III was 68.6% with 5-FU, significantly higher than 62.6% with operation alone (p < 0.05). Particularly, 5-year survival at macroscopical stage III was markedly different between 57.1% with 5-FU and 42.7% with operation alone. In order to make more effective comparison with the historical controls in this 1-arm trial, the background factors in 5-FU and control groups were matched in the ratio of 1:2 or 1:3 with respect to the following 4 factors: tumor site, S, N and macroscopical tumor type (by Kajitani's classification). As a result, the 5-year survival at macroscopical stages II and III was significantly higher with 5-FU (67.5%, 69.1%) than with operation alone (59.9%, 59.8%), and in particular this tendency was more marked at macroscopical stage III. These results suggest the usefulness of adjuvant chemotherapy in macroscopical stage III gastric cancer.

Administration, Oral↗
PubMed1992

[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↗
PubMed1992

[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↗
PubMed1991

[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↗