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Biomedical subjects

Y Kasai

Publications and source records attributed to Y Kasai.

At least 181 records · Page 10Linked to original sources

[Phase II study of THP (2''R)-4'-0-tetrahydropyranyladriamycin) in breast cancer].

In a phase II study of THP, fifty-six patients with advanced or recurrent breast cancer were evaluated, and a response rate of 23.2% including 1.8% with complete response and 21.4% with partial response, was obtained. Response rates of THP varied according to the location of metastasis and the highest rate was shown to be 38.5% in patients with soft tissue metastasis. The median dose for inducing response was 100 mg with a range from 60 mg to 160 mg. Toxicities such as leukopenia and gastrointestinal disorders were observed during THP treatment. The favorable response to THP was close to that of adriamycin, but it was noteworthy that a lower frequency of alopecia occurred.

Adult↗

[Phase II study of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with solid tumors. Multi-Institutional Cooperative Study].

A Phase II Study of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with various solid tumors was carried out by 44 cooperative study institutions. Seven hundred fifty-six patients administered the drug intravenously were entered into this study. Of these, 499 patients were evaluated for objective responses. THP was given mainly at a dose of 40 to 60 mg/body every 3 to 4 weeks or 20 to 30 mg/body once a week. Response rates were 18.8% for head and neck cancer, 13.1% for stomach cancer, 21.4% for breast cancer, 22.2% for bladder cancer, 30% for renal pelvic and urinary tract tumor, 26.8% for ovarian cancer and 24.2% for uterine cancer. Overall response rate was 15.4% including 10 complete responses and 67 partial responses. Adverse reactions were similar to those previously reported in the phase I study, including gastrointestinal toxicities and myelosuppression. Alopecia and stomatitis, which are major side effects of other anthracyclines, were rather mild. Incidence of ECG changes was 2.8% and no congestive heart failure was observed.

Adult↗

Revision of porto-enterostomy in congenital biliary atresia.

For the patients with insufficient bile flow following porto-enterostomy for congenital biliary atresia, removal or resection of granulation or scar tissue at the porta hepatis has been performed. Of 11 reoperations, constant bile excretion was obtained in four. Sufficient resection of scar tissue at the porta hepatis was most important for revision of porto-enterostomy. For resection of scar tissue, a special scissors devised by us was used.

Bile↗

Atrial natriuretic factor inhibits the hypertension induced by chronic infusion of norepinephrine in conscious rats.

To assess the physiological role of atrial natriuretic factors in the regulation of blood pressure and sodium-water excretion, we studied the chronic effects of continuous infusion of a synthetic atrial natriuretic factor of 25 amino acids for up to 3 days on systolic blood pressure, urine volume, and urinary excretion of sodium, prostaglandin E2 and kallikrein in conscious rats, and also evaluated the antihypertensive effect of this substance in rats with hypertension caused by chronic infusion of norepinephrine. Continuous infusion of atrial natriuretic factor (150 micrograms/kg per day) into the jugular vein via osmotic minipumps did not induce any changes in systolic blood pressure, urine volume, and urinary excretion of sodium, prostaglandin E2, and kallikrein for up to 3 days, compared with those in vehicle-infused rats. When the same dose of atrial natriuretic factor was administered simultaneously with 1.8 mg/kg per day of norepinephrine infused intraperitoneally by osmotic minipumps, the systolic blood pressure of conscious rats rose on day 1 to only 127.3 +/- 6.3 mm Hg compared with the rise to 146.3 +/- 1.6 mm Hg when norepinephrine alone was infused (P less than 0.05). The antihypertensive effect of atrial natriuretic factor was sustained for 3 days in rats infused with norepinephrine. The administration of atrial natriuretic factor to rats made hypertensive by 3 days of infusion with norepinephrine alone returned the blood pressure to control levels, and the antihypertensive effect was sustained throughout the experimental period lasting for 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Decreased urinary active and inactive kallikrein by chronic infusion of vasopressin in conscious rats.

To assess possible interactions of circulating vasopressin with the synthesis or activation of renal kallikrein, we studied the effect of chronic infusion of vasopressin (7.2 U/kg/day i.p.) for 6 days on the urinary excretion of total and active kallikrein in conscious rats. We determined urinary total, active and inactive kallikrein by measuring kallikrein activity using a kininogenase assay before and after the treatment with trypsin (200 micrograms/ml). Chronic infusion of vasopressin induced sustained decreases in urinary total, active and inactive kallikrein excretion, but did not affect the ratio of active to total kallikrein. The infusion of vasopressin induced significant increases in circulating levels of vasopressin (248.1 +/- 35.2 pg/ml in vasopressin-infused rats (n = 7) compared to 95.5 +/- 14.6 pg/ml in vehicle-infused rats (n = 7), p less than 0.001) and in weight gain (39.6 +/- 1.3 g in vasopressin-infused rats (n = 7) compared to 29.1 +/- 3.3 g in vehicle-infused rats (n = 7), p less than 0.05), and also sustained decreases in water intake and urine volume, but it did not induce any change in urinary sodium excretion. Circulating levels of angiotensin II was decreased by chronic infusion of vasopressin. Thus, the present study suggests that the elevation of circulating vasopressin levels induces a decrease in the synthesis of renal kallikrein.

Animals↗

[Cefminox concentration in tissues and clinical efficacy of cefminox in acute peritonitis].

Cefminox sodium (CMNX, MT-141), a new semisynthetic cephamycin, having marked resistance to beta-lactamase, and a broad spectrum of antibacterial activity against various bacterial species, including Haemophilus influenzae, Serratia marcescens and Citrobacter freundii, CMNX has higher activity in vivo than in vitro. For therapeutic purpose, CMNX was given in a daily dose of 0.5 g (0.5 g X 1) to 2 g (1 X 2) by intravenous drip infusion for 4 to 8 days to 24 cases with acute peritonitis (17 cases with acute appendicitis, 1 with localized peritonitis after gastrectomy, 1 with diffuse peritonitis due to perforative duodenal ulcer and 5 with panperitonitis due to intestinal obstruction). The clinical response was rated excellent in 9 cases, good in 14 cases and fair in 1 case and poor in none. No adverse effect was observed. There were 29 strains isolated organisms included 12 Escherichia coli, some Enterococcus faecalis and Pseudomonas aeruginosa. These isolated organisms were eradicated after CMNX treatment, except a strain of E. faecalis was decreased. In 19 cases of them, 16 cases with acute peritonitis due to acute appendicitis and 3 cases with acute panperitonitis due to intestinal obstruction, CMNX was administered intravenously in a dose of 1 g (1 case was 0.5 g) before or during the operation, and tissue specimens and body fluids samples were taken during the operation. CMNX concentration was determined to a bioassay with Escherichia coli NIHJ or Vibrio vercolans ATCC 8461 as the test organisms. CMNX concentrations in purulent ascites were 47.2 +/- 38.5 micrograms/ml (n = 23), those in infected appendix wall were 32.2 +/- 21.7 micrograms/g (n = 16), that in pus in appendix were 22.1 +/- 24.3 micrograms/ml (n = 8) and that in other non infected tissues were 24.3 +/- 22.0 micrograms/g (n = 8). CMNX concentrations in infected tissues were higher than the non infected tissues. In the 3 cases with empyemic appendicitis, CMNX levels in pus in appendix were more higher than that in appendix wall itself. Therefore, CMNX sodium appears to be a very useful drug when used for chemotherapy on acute peritonitis.

Acute Disease↗

Effect of anti-alpha-fetoprotein serum on human hepatoblastoma.

There is no definitive treatment of hepatoblastoma. Except for radical resection, the prognosis of unresectable cases remains pessimistic. Therefore, the development of new anticancer drugs for this tumor is urgently needed. Using the human hepatoblastoma cell line (c-HB-3) we demonstrated that horse anti-alpha-fetoprotein containing serum suppressed proliferation of the hepatoblastoma cells. This effect was dependent on the duration of exposure and the concentration of anti-alpha-fetoprotein serum.

Animals↗

Renal prostaglandin E in the hypotensive mechanism of MK-421 in conscious rats.

To assess the role of renal prostaglandin E in the hypotensive mechanism of MK-421, we evaluated the effects of chronic infusion of MK-421 (6 mg/kg/day i.p.) on systolic blood pressure and urinary prostaglandin E excretion in conscious rats in states of sodium repletion or depletion and also during chronic infusion of norepinephrine (1.8 mg/kg/day i.p.) or vasopressin (7.2 U/kg/day i.p.). The hypotensive effect of MK-421 was greater in sodium depleted than in sodium repleted rats. The hypertensive effect of norepinephrine or vasopressin was inhibited by the simultaneous administration of MK-421. MK-421 induced an increase in the excretion of urinary prostaglandin E, in both sodium repleted and depleted rats. However, simultaneous administration of MK-421 had no influence on the increase in urinary prostaglandin E excretion induced by norepinephrine or vasopressin. In addition, the combined administration of MK-421 with indomethacin (10 mg/kg/day s.c.) still abolished the hypertensive effect of norepinephrine or vasopressin. The disparate effect of MK-421 on urinary prostaglandin E excretion suggests that the renal prostaglandin system is not essential for the mechanism of the hypotensive effect of MK-421.

Angiotensin I↗

Renal kallikrein-kinin system and the depressor effect of angiotensin converting enzyme inhibitors MK 421, SA 446, and captopril in rats.

Responses in urinary kallikrein and kinin excretion and systolic blood pressure to MK 421, SA 446 or captopril were studied in normotensive rats fed on a regular or a low sodium diet to assess the role of renal kallikrein-kinin system in their hypotensive effect. MK 421, SA 446 or captopril were infused at a rate of 6 mg/kg/day by osmotic minipump implanted intraperitoneally for up to 6 days. The magnitude of fall in systolic blood pressure was greater on a low sodium diet when compared to on a regular diet, whereas the pattern of the fall was similar on both diets. The magnitude of falls in plasma angiotensin II and aldosterone concentration induced by MK 421, SA 446 and captopril was not significantly different between both regular and low sodium diets. Urinary kallikrein and kinin excretion and sodium excretion were increased during infusion of MK 421, SA 446 or captopril on a low sodium diet, however any significant changes were not found in each of them on a regular diet. The present results suggest that on a low sodium diet the augmented hypotensive response to angiotensin converting enzyme inhibitors in the rats might be due to the enhanced renal kallikrein-kinin system in addition to suppressed renin-angiotensin system.

3-Mercaptopropionic Acid↗

Chronic effects of norepinephrine and vasopressin on urinary prostaglandin E and kallikrein excretions in conscious rats.

To assess in vivo functional interactions of vasopressor substances, norepinephrine and vasopressin, with renal prostaglandins and kallikrein-kinin system which are responsible for the vasodepressor mechanism in the kidney, we evaluated chronic effects of norepinephrine (1.8 mg/kg/day ip) and vasopressin (7.2 U/kg/day ip) on urinary prostaglandin E excretion and urinary kallikrein excretion in conscious rats. Both norepinephrine and vasopressin induced a sustained increase in systolic blood pressure. Norepinephrine induced slight but significant increases in urinary prostaglandin E excretion and urinary kallikrein excretion which were sustained for up to 6 days. Vasopressin induced a marked increase in urinary prostaglandin E excretion which was sustained for up to 6 days, whereas it induced a sustained decrease in urinary kallikrein excretion. Circulating angiotensin II levels was not changed by norepinephrine, but was decreased by vasopressin. These results indicate that renal prostaglandin E may not correlate with renal kallikrein-kinin and renin-angiotensin system in the responses to norepinephrine and vasopressin, and that vasopressin may be a more potent stimulator of the synthesis or release of renal prostaglandin E.

Angiotensin II↗

[Evaluation of cefotaxime for postoperative infection in surgery].

Cefotaxime (CTX) was microbiologically and clinically studied in surgery. CTX shows excellent antibacterial activity in vitro against Gram-negative bacilli including E. coli. Klebsiella spp., and Proteus spp. in comparison with cefmetazole (CMZ) and cefazolin (CEZ). Antibacterial activity of CTX is found to be superior to that of CEZ and equal to that of CMZ against Gram-positive bacteria (S. aureus and S. epidermidis). The antibacterial activity of CTX against anaerobic bacteria exceeds that of CEZ and almost equal to that of CMZ. It also showed minimum inhibitory concentration values which, clinically speaking, offer great expectation. CTX is also superior to CMZ and CEZ in its antibacterial activity against P. aeruginosa. Clinical studies were carried out in the group A for which CTX was administered a drug of first choice for postoperative infections in surgery, and in the group B for which CTX was administered as a drug of second choice since the antibiotic of first choice had been ineffective for these cases. As a result, high effective rates were obtained in both groups (80.3% for the group A, and 77.1% for the group B). With reference to the group B, an effectiveness rate of 100% was obtained for the cases in which CEZ had been ineffective and 55.6% was obtained for 10 cases in which mainly combination of CMZ had been ineffective. Side effects appeared in 3 cases (1 case each of tinnitus and malaise, vomiting and nausea, and fever) with an incidence rate of 1.46%. Abnormal clinical laboratory findings appeared in 4 cases (1 case each of leukopenia and increase in GOT and GPT; eosinophilia; increases in platelet and monocyte; and increases in GOT, GPT and A1-P) with an incidence rate of 1.95%.

Adolescent↗

[Indication of minimized regional operation for primary liver cancer].

In the cirrhotic patient with inadequate liver functional reserve, curative standard resection due to anatomic basis often lead to liver failure postoperatively. Therefore, prognosis and resectability remained unsatisfactory for these patients. Definition of minimized regional operation which is performed to the patient with decreased functional reserve of the liver is not clearly determined. In our department, definition of minimized regional operation is made as follows. 1. The liver is impaired to more than moderate degree. (Child B and C or decreased liver functional reserve) 2. Maximum tumor diameter is less than 5 cm. 3. The extent of resection is less than subsegmentectomy. Study of 23 patients undergoing this minimized regional operation was made and the result is as follows. In relation of extent of resection to tumor diameter, in patients with less than 3 cm tumor recurrence developed only in one (7.6%) of thirteen patients undergoing minimized regional operation and none of four undergoing conventional standard resection. While in patients with more than 3 cm tumor, recurrence was found in two (25%) of eight patients with minimized regional operation and three (60%) of five patients with resection of one segment. In relation of the extent of resection to tumor capsule, in patients with less than 3 cm tumor with capsule, minimized regional operation and three standard resections were performed and in none of which recurrence developed. In patients with less than 3 cm tumor without capsule, recurrence developed in one of four patients undergoing minimized regional operation. While in patients with more than 3 cm tumor, recurrence developed in two (25%) of eight patients with tumor possessing capsule and three (60%) of five patients without capsule. As a result, in patients with less than 3 cm tumor diameter, minimized regional operation is acceptable with little recurrence but in patients with more than 3 cm tumor with or without capsule, anatomic lobe resection is necessary and resection of more than two segments is mandatory if functional reserve of the liver allows. In our department, extent of resection is determined by the functional reserve of the liver which is graded into three degree. For subsegmentectomy, following laboratory date has to be met: ICG-Rmax greater than 0.4, sigma IRI/sigma BS greater than 0.2, Ch-E greater than 500 IU/1, Total Bil. less than 2.5 mg/dl, S-Alb greater than 3.0 g/dl, GPT less than 300 IU and HPT greater than 50%.(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic Disease↗