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Biomedical subjects

T Ochiai

Publications and source records attributed to T Ochiai.

At least 217 records · Page 12Linked to original sources

The treatment of lymph node metastasis from esophageal cancer by extensive lymphadenectomy.

During the period between 1965 and the end of 1988, 560 patients with esophageal cancer were surgically treated in our University hospital. In an attempt to improve patient survival, three-field lymphadenectomy of the bilateral neck, mediastinum and abdomen was performed in 117 patients treated since 1983. The present study was undertaken to reveal the substantial rate of lymph node metastasis in esophageal cancer and to decide if three-field lymphadenectomy is mandatory or not for surgery of esophageal cancer. Despite the increased radicality of the operation, the mortality and morbidity rates decreased in the 1980's compared to the earlier periods, the operative death being 12.5 per cent in the 1960's, vs. 2.0 per cent in the 1980's. Moreover, the mortality rate of the patients receiving the three-field lymphadenectomy was as low as 2.6 per cent. The metastatic rate of cervical nodes in the patients receiving three-field lymphadenectomy was 32.5 per cent, while that of mediastinal and abdominal nodes was 47.0 per cent and 46.0 per cent respectively. The metastatic rate in the mediastinum was high in the bilateral recurrent nerve lymph nodes, bifurcation nodes and paraesophageal nodes, while in the abdomen, it was high in the bilateral paracardial nodes. Recurrent nerve paralysis, which had been rarely seen was observed in 12.0 per cent of the patients. Metastasis from esophageal cancer is often seen in the cervical nodes, however, the clinical importance of three-field lymphadenectomy will be decided by the data of patient survival in the near future.

Abdomen↗

Pharmacological studies on (4S)-1-methyl-3-[(2S)-2-[N-((1S)-1-ethoxycarbonyl-3-phenylpropyl)amino] propionyl]-2-oxo-imidazolidine-4-carboxylic acid hydrochloride (TA-6366), a new ACE inhibitor: I. ACE inhibitory and anti-hypertensive activities.

TA-6366 and its active metabolite 6366A inhibited swine renal angiotensin converting enzyme (ACE) activity with IC50s of 9900 and 2.6 nM, respectively. TA-6366 (0.05-0.5 mg/kg, p.o.) inhibited the angiotensin I (AT-I)-induced pressor response in rats. 6366A augmented bradykinin (BK)-induced contraction of guinea pig ileum more potently than captopril. However, when the augmentation on BK-induced hypotension in rats was used as an indicator, TA-6366 was less active than captopril. TA-6366 increased plasma renin activity and plasma AT-I concentration. Oral administration of TA-6366 lowered the blood pressure in two-kidney one-clip renal hypertensive rats at 0.5 to 2 mg/kg and in spontaneously hypertensive rats (SHRs) at 2 to 10 mg/kg. The antihypertensive effect of TA-6366 was approximately 5 times more potent than that of captopril and almost as potent as that of enalapril. In SHRs, the antihypertensive action of TA-6366 was intensified in potency when administered repeatedly. The duration of action was longer than those of captopril and enalapril. However, TA-6366 had no substantial effect on the blood pressure in DOCA/saline hypertensive rats. These results indicate that TA-6366 is a potent and long lasting antihypertensive agent and that its antihypertensive action is attributable to the inhibition of ACE.

Angiotensin-Converting Enzyme Inhibitors↗

[Evaluation of immunotoxicity testings using azathioprine-treated rats: the International Collaborative Immunotoxicity Study (Azathioprine)].

The immunotoxicological effects of azathioprine (AZP) were examined by enhanced histopathological and function tests in the rat which is routinely used in toxicological tests. Male F344 rats were orally administered AZP in doses of 0, 2.5, 12.5 and 25.0 mg/kg/day for 28 days. Reductions in the organ weights of the thymus, spleen, liver, kidney, and testis in a dose-dependent manner were confirmed. Hematological examination revealed a marked decrease in the number of WBCs, which was associated with a decrease in the number of lymphocytes. In the femoral bone marrow, a significant reduction in the total cell number attributed to the decrease in the number of lymphocytes and granulocytes was observed. Histopathologically, atrophy and obfuscation of the corticomedullary junction in the thymus, the decrease of lymphocytes in the thymus and spleen, and the disappearance of germinal centers in the lymph nodes were observed. As for the functional testings, azathioprine treatment did not affect remarkably the PFC number and the NK cell activity per unit spleen cell number. However, the total spleen cell number per spleen was decreased in a dose-dependent manner. Therefore, the total functional activities (PFC and NK) per spleen were decreased. Thus, in the AZP-treated F344 rats, it was shown that the enhanced histopathological tests were useful to evaluate potential risks to the immune system.

Animals↗

[A simple method of extracorporeal membrane oxygenation (ECMO)--2: The effects of ECMO (arterio-venous shunt) on the arterial blood gases measured for 24 hours].

In eight anesthetized mongrel dogs with thiopental, diazepam and pancuronium bromide, ECMO with arterio-venous shunt was performed under hypoventilation for 24 hours. The blood flow through the ECMO which was connected between the femoral artery and vein was approximately 40% of the cardiac output. Hypoventilation was induced to decrease PaO2 to around 40mmHg and increase PaCO2 to around 80 mmHg. The ECMO improved the abnormal parameters, which were induced by the hypoventilation, to almost normal range (PaO2 80mmHg, PaCO2 30mmHg) for 24 hours. Furthermore, there were no abnormalities in cardiovascular and other systems during ECMO.

Animals↗

[Effect of high dose etoposide, adriamycin, cisplatin (EAP) therapy with autologous bone marrow transplantation in gastric cancer].

A clinical usefulness of high dose EAP therapy with autologous bone marrow transplantation for gastric cancer was investigated. Three patients with advanced gastric cancer (one recurrent and 2 inoperable) with measurable lesions were treated with high dose EAP therapy consisting of VP-16 1200 mg/m2, ADM 80 mg/m2 and CDDP 80-120 mg/m2, and then 1 x 10(7)/kg of cryopreserved autologous bone marrow cells were transfused intravenously. All patients were recovered from aplastic period without any severe complications. Measurable lesions, namely, stenosis of prepyloris lesion, lymph node metastasis and invasion into pancreas in 3 patients with gastric cancer were reduced or diminished. It seemed that high dose EAP therapy with autologous bone marrow transplantation was safe and an useful strategy, especially for advanced gastric cancer.

Adult↗

[Immunotherapy and quality of life].

In order to examine the quality of life with immunotherapy, a survey was conducted on 17 advanced gastric or colon cancer patients receiving LAK immunotherapy and on 10 patients receiving EAP chemotherapy as a control. Performance status of patients at the time of treatment was similar between the groups. Many patients on EAP therapy complained of severe side effects, such as loss of hair, nausea and vomiting, and appetite loss. None of the patients on LAK therapy complained of such effects on the contrary, favorable effects were found. Appetite increased in some patients and tenderness of the liver disappeared in others. As for the continuance of the treatment, two thirds of EAP patients declined, and all LAK patients replied in the affirmative. The data suggest that LAK immunotherapy is better than EAP chemotherapy from the standpoint of the quality of life.

Antineoplastic Combined Chemotherapy Protocols↗

[Effects of stress on colon in the canine].

In order to clarify the effects of stress on the colon, functions of the colon in conscious dogs were examined by using strain gauge force transducers and periodical X-ray pictures. Immediately after loading the stress, the motility of colon increased, while 2 weeks after loading the stress the motility of the colon had decreased. Under these circumstances all dogs with dysfunctions of right colon had diarrhea, while dogs with dysfunctions of left colon had no diarrhea. This stress model did not result in the formation of ulcers and dogs had intestinal dysfunction and diarrhea. Therefore, this stress model may be an appropriate method in which to study diarrhea and irritable bowel syndrome.

Animals↗

Studies on angiotensin converting enzyme inhibitors. 4. Synthesis and angiotensin converting enzyme inhibitory activities of 3-acyl-1-alkyl-2-oxoimidazolidine-4-carboxylic acid derivatives.

(4S)-1-Alkyl-3-[[N-(carboxyalkyl)amino]acyl]-2-oxoimidazolidine-4- carboxylic acid derivatives (3) were prepared by two methods. Their angiotensin converting enzyme (ACE) inhibitory activities and antihypertensive effects were evaluated, and the structure-activity relationships were discussed. The dicarboxylic acids 3a-n possessing S,S,S configuration showed potent in vitro ACE inhibitory activities with IC50 values of 1.1 X 10(-8)-1.5 X 10(-9) M. The most potent compound in this series, monoester 3p, had an ID50 value of 0.24 mg/kg, po for inhibition of angiotensin I induced pressor response in normotensive rats and produced a dose-dependent decrease in systolic blood pressure of spontaneously hypertensive rats (SHRs) at doses of 1-10 mg/kg, po.

Angiotensin-Converting Enzyme Inhibitors↗

Optimal serum trough levels of FK506 in renal allotransplantation of the beagle dog.

The present study was performed to estimate the optimal serum trough levels of FK506 (FK) for prophylactic use and for the treatment of acute rejection in renal allotransplantation of the beagle dog. The serum trough levels of an immunosuppressive dose of FK 1.0 mg/kg p.o. ranged from 0.1 to 0.4 ng/ml. The data indicate that the effective serum trough level is about 100 times lower than that of cyclosporine, as was already observed in previous in vitro studies. Combining treatment with a nonimmunosuppressive dose of cyclosporine of 2.5 mg/kg could lower the effective trough levels of FK. By the combining treatment, 2 out of 5 renal recipient dogs survived with well-functioning grafts as long as 60 days with the trough levels between 0.04 and 0.07 ng/ml. High-dose 5-day i.m. FK treatment of 0.5 or 1.0 mg/kg was effective in the reversal of acute rejection, with peak serum trough levels during successful rejection therapy ranging between 0.28 and 3.7 ng/ml. Two dogs died of malaise or pneumonia with peak trough levels of 2.25 and 2.78 ng/ml. Among the wide range of the effective trough levels for successful acute rejection therapy, those above 2.0 ng/ml seem to be toxic in some renal-transplanted dogs.

Administration, Oral↗

Effects of combination treatment with FK506 and cyclosporine on survival time and vascular changes in renal-allograft-recipient dogs.

In our previous experiments studying the effects of FK506 on renal allografting in the dog, we encountered two major problems. One problem was anorexia and the other problem was vascular changes mainly in the recipient heart. Anorexia was generally dose dependent, but the vascular changes were seen to be more prominent at lower doses rather than at higher immunosuppressive doses. The present study was undertaken to study these two problems. A nonanorexic, vascular change-related, nonimmunosuppressive dose of FK506 was combined with a low dose of cyclosporine or prednisolone in beagle dogs after renal allografting. Treatment with either FK506 alone at a dose of 0.32 mg/kg or cyclosporine alone at 2.5 mg/kg was not effective in prolonging renal recipient survival. The recipient dogs died of rejection, and a variety of vascular changes were observed in the hearts of both groups. Combined treatment with FK506 and cyclosporine at these same doses resulted in statistically significant prolongation of the survival time of the renal recipient (P less than 0.01), and histologic studies showed that the frequency and severity of the vascular changes were suppressed in the recipient receiving the combined treatment. The combination of FK506 and prednisolone at 0.5 mg/kg was not effective in prolonging survival. Furthermore, the extent of vascular changes was similar to those found in recipients receiving FK506 alone. The data suggest that combined treatment with low doses of both FK506 and cyclosporine acted synergistically in prolonging canine renal allografts and that the vascular changes frequently seen at low doses of FK506 were reduced by additional immunosuppression with a low dose of cyclosporine.

Animals↗

[Validity of estimating left ventricular relaxation and filling dynamics by Doppler trans-mitral flow].

To evaluate the validity of estimating left ventricular (LV) diastolic function using the Doppler transmitral flow profile, the relationship of transmitral flow to LV relaxation and LV filling dynamics was observed. A total of 54 subjects, including patients with ischemic heart disease, idiopathic cardiomyopathy, and normal persons were examined. LV filling dynamics were assessed in 20 of them who had no regional wall motion abnormality or irregular LV geometry. Peak velocity of rapid filling (R) and acceleration of rapid filling (AR) at the mitral annular level were measured as indices of transmitral flow during the rapid filling period. LV relaxation was evaluated according to the time constant of LV isovolumic pressure decline (T) using the method of Weiss et al. The correlation coefficient between R and T was -0.27 and that between AR and T was -0.16, indicating lack of correlations. The v-wave of pulmonary wedge pressure (PWPv) was measured as an index for left atrial driving pressure during the rapid LV filling period. Multiple regression analyses of R or AR as dependent variables and T and PWPv as independent variables revealed significant correlations (r = 0.66 and r = 0.59). The peak transit rate (PTR = R/TVI) and atrial transit fraction (ATF = TVIa/TVI) were determined from the time integral of the transmitral flow velocity (TVI = time velocity integral during diastole, TVIa = time velocity integral during the atrial contraction phase). Also, the peak filling rate (PFR) during the rapid filling and atrial filling fraction (AFF) were determined by left ventriculography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Over two years survival of intra-arterial infusion chemotherapy in gastric cancer with liver metastases].

Between 1977 and April in 1989, long-term survivors (over two years) by intra-arterial infusion chemotherapy in gastric cancer patients with liver metastases were examined. The materials were 5 patients (4 synchronous, 1 metachronous metastases) among 21 P0H (+) gastric cancers. The extent of liver metastases shows 1 H1 and 4 H2. Reduction surgery was performed in 4 H2 patients (2 S2 + 3, 1 S4, 1 S6) and postoperative intra-arterial infusion chemotherapy via the catheter in the common hepatic artery was done to control the residual liver metastases. Continuous intra-arterial infusion chemotherapy with the regimen of FML (5-FU, MMC, Lentinan) revealed 100% response rate (3 CR, 1 PR). In a patient with metachronous metastases, PR was obtained with MA (MMC, ADM) + one-shot intra-arterial infusion of LAK cells. Among 5 patients, one with synchronous metastases has survived 35 months, followed by a patient who died after 32 months and two patients who died after 27 months. A patient with metachronous metastases has survived for 24 months.

Aged↗