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Biomedical subjects

N Koyanagi

Publications and source records attributed to N Koyanagi.

At least 19 recordsLinked to original sources
PubMed1994

Synthesis and antitumor activities of novel 6-5 fused ring heterocycle antifolates: N-[4-[omega-(2-amino-4-substituted-6,7-dihydrocyclopenta [d]pyrimidin-5-yl)alkyl]benzoyl]-L-glutamic acids.

Novel antifolates with a 6-5 fused ring system, 6,7-dihydrocyclopenta [d]pyrimidine, (3a,b and 4a,b) were synthesized on the basis of combined modification of the heterocycle and bridge regions of the folate molecule. The synthetic method involves (1) synthesis of key intermediates of tert-butyl 4-[omega-(2-substituted-3-oxocyclopentanyl) alkyl]benzoates (8a,b and 9a,b) by a carbon-carbon radical coupling of tert-butyl 4-(omega-iodoalkyl)benzoates (7a,b) with 2-substituted-2-cyclopenten-1-ones (5 and 6) utilizing tributyltin hydride, (2) cyclization of either the methyl enol-ethers derived from the 2-cyanocyclopentanones (8a,b) or the 2-(methoxycarbonyl)cyclopentanones (9a,b) themselves by treatment with guanidine which leads to 6,7-dihydrocyclopenta [d]pyrimidines with a 4-(tert-butoxycarbonyl)phenylalkyl group (11a,b and 14a,b), (3) deprotection to the corresponding carboxylic acids (12a,b and 15a,b), and (4) amidation with diethyl glutamate and deesterification. Potent dihydrofolate reductase inhibition and highly potent cell growth inhibition were found with 2,4-diaminopyrimidine-fused cyclopentene compounds containing the trimethylene (3a) or ethylene bridge (3b) but not with the corresponding 2-amino-4-hydroxy analogs (4a,b). Compounds 3a and 3b were more growth inhibitory to several tumor cell lines (P388, colon 26, colon 38, and KB) than was methotrexate, with 3a being the most potent. Both 3a and 3b gave increases in the lifespan of P388 leukemic mice comparable to that observed with MTX. Both compounds were therapeutic against colon 26 colorectal carcinoma in mice. Compound 3a was highly effective against LC-6 non-small cell lung carcinoma in nude mice.

Animals↗
PubMed1994

In vivo tumor growth inhibition produced by a novel sulfonamide, E7010, against rodent and human tumors.

The search for compounds active against solid tumors has led us to the discovery of a novel sulfonamide, E7010 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4- methoxybenzenesulfonamide), which inhibits tubulin polymerization. When administered orally, E7010 showed good antitumor activity against various rodent tumors and human tumor xenografts. In tests on mouse tumor, E7010, administered in doses of 25-100 mg/kg daily for 8 days, inhibited the growth of colon 38 carcinoma inoculated s.c. in mice by 60-99%. E7010 was active against s.c. inoculated M5076 fibrosarcoma (75% tumor growth inhibition), s.c. inoculated Lewis lung carcinoma (84% increase in life span), and i.p. inoculated P388 leukemia (118% increase in life span). In a test on rat tumor, E7010 inhibited the growth of SST-2 mammary carcinoma inoculated s.c. in rats by 84%. In tests on s.c. inoculated human tumor xenografts, E7010, when administered orally, showed a broad spectrum of activity. E7010 inhibited the growth of: four kinds of gastric cancer, H-81, H-111, SC-2, and SC-6 by 60-78%; three kinds of colon cancer, H-143, COLO320DM, and WiDr by 58-83%; three kinds of lung cancer, LC-376, LC-6, and LX-1 by 63-82%; and two kinds of breast cancer, H-31 and MX-1 by 79-87%. In studies on drug-resistant P388 leukemia, E7010 was effective against vincristine-resistant P388, cisplatin-resistant P388, and 5-fluorouracil-resistant P388 sublines in mice. Because of its good activity against rodent tumors and human tumor xenografts, E7010 is currently undergoing Phase I clinical trials.

Aminophenols↗
PubMed1992

Sclerotherapy vs. esophageal transection vs. distal splenorenal shunt for the clinical management of esophageal varices in patients with child class A and B liver function: a prospective randomized trial.

Ninety-six patients with good liver function (Child class A or B) and esophageal varices were randomly assigned to one of three groups given different treatments: endoscopic injection sclerotherapy (n = 32), esophageal transection (n = 32) or distal splenorenal shunt (n = 32). Five patients (5.2%) had to be excluded from this study because severe chronic pancreatitis made separation of the distal splenic vein from the pancreatic bed difficult. Esophageal transection was performed for these patients. No deaths occurred during the 30 days of treatment. The 5-yr cumulative bleeding rates were 0%, 5.9% and 12.9% in the endoscopic injection sclerotherapy, esophageal transection and distal splenorenal shunt groups, respectively (no statistical significance). In no case in the three groups did death occur because of variceal bleeding. Sixteen patients died, mainly because of underlying liver disease; four were in the endoscopic injection sclerotherapy group, five were in the esophageal transection group and seven were in the distal splenorenal shunt group. No statistically significant difference in survival rate among the three groups was found. These results show that endoscopic injection sclerotherapy is a satisfactory alternative to esophageal transection or distal splenorenal shunt for the clinical management of patients with esophageal varices.

Esophageal and Gastric Varices↗
PubMed1992

Endoscopic injection sclerotherapy for 1,000 patients with esophageal varices: a nine-year prospective study.

We report here the results of endoscopic injection sclerotherapy performed in 1,000 consecutively treated Japanese patients with esophageal varices. This prospective study covered the period from 1982 to 1990. Variceal bleeding was controlled in 215 (97.7%) of 220 patients. Esophageal varices were completely eradicated in 778 patients (77.8%); the mean number of sessions was 4.2. In only 3 of the 778 patients did esophageal varices of the same size recur. Small, dilated, venous vessels that required additional sclerotherapy in follow-up endoscopy at 3-mo intervals appeared in 171 (22.2%) of 778 patients. The cumulative nonbleeding rate at 5 yr was 94.5% in patients in whom the varices had been eradicated. Deaths caused by upper gastrointestinal bleeding accounted for 2.6% of cases, whereas the rates of liver failure and hepatoma were 4.6% and 47.3%, respectively. The 5-yr cumulative survival rate was 54.1% in patients without concomitant hepatoma; it was 12.0% in patients with hepatomas. Multivariate analysis showed that hepatoma, Child classification, indication (acute, elective or prophylactic) and eradication were independent factors that significantly influenced survival time. This study clearly shows that close follow-up with endoscopy and complete eradication lead to significant reduction in bleeding from esophageal varices and reduction of mortality related to this bleeding.

Endoscopy↗
PubMed1992

[Surgical versus non-surgical treatment in patients with esophageal varices--a prospective randomized study].

In Japan, non-shunting procedures and selective shunt such as esophageal transection (ET), and distal splenorenal shunt (DSRS) have been widely performed. A prospective randomized trial was done to assess the effects of EIS and DSRS for treating patients with esophageal varices. Ninety-six Japanese with good liver function (Child A or B) and large esophageal varices were randomly assigned to one of three groups given different treatments; (EIS, n = 32), (ET, n = 32) and (DSRS, n = 32). Five patients (15.6%) of the DSRS group has to be excluded from this study, because of severe chronic pancreatitis. No patient died within 30 days of the treatments. The 5-year cumulative bleeding rates were 0%, 4.3% and 12.1% in the EIS, ET and DSRS groups, respectively, with no statistical significances. In no case in the three groups did the death occur because of variceal bleeding. Nineteen patients died mainly due to the underlying liver disease; 5 in the EIS, 5 in the ET and 9 in the DSRS group. There was no statistically significant difference in the survival rates among the three groups. We conclude that EIS is a satisfactory alternative to ET or DSRS for the management of patients with large esophageal varices.

Adult↗
PubMed1992

Comparative effects of 5% ethanolamine oleate versus 5% ethanolamine oleate plus 1% polidocanol for sclerosing esophageal varices.

Sixty-six patients with portal hypertension and esophageal varices due to liver cirrhosis were randomized to receive either 5% ethanolamine oleate (EO) or 5% EO plus 1% polidocanol (EOP) as a sclerosant for endoscopic injection sclerotherapy (EIS). The two groups were well matched with regard to age, sex and the severity of liver disease. In no patient in the two groups was there any major complication, such as esophageal perforation or esophageal bleeding. Eradication of esophageal varices was attained with an average of 4.7 and 4.3 sessions of endoscopic injection sclerotherapy in the ethanolamine oleate and polidocanol groups, respectively. Data on one patient in the ethanolamine oleate group had to be excluded because he left the hospital after 2 sessions of endoscopic injection sclerotherapy. Esophageal ulcers occurred earlier in the polidocanol group (after an average of 2.8 weeks) than in the ethanolamine oleate group (3.8 weeks), the difference being statistically significant (P < 0.01). The rate of occurrence of esophageal stricture requiring more than 2 sessions of bougienage was significantly (P < 0.01) higher in the polidocanol group (16/33, 48%) than in the ethanolamine oleate group (4/32, 12%). This study suggests that the two sclerosants have equal efficacy for treating patients with esophageal varices. With polidocanol there was ulceration and stricture in the distal esophagus.

Drug Combinations↗
PubMed1989

Esophageal transection may well be the approach of choice for patient with portal venous obstruction and esophageal varices.

Thirty patients with esophageal varices, portal venous obstruction and a histologically proven normal liver underwent either one of 2 different types of surgery. Shunt surgery was performed on 20 patients: 9 had a mesocaval shunt, 3, a splenorenal shunt, 4, a left gastric venacaval shunt, and 4, a distal splenorenal shunt. Conversely, direct interruption was performed on the other 10 patients; 6 underwent an esophageal transection, and 4 underwent a resection of the proximal stomach. Re-hemorrhage occurred in 7 of the former 20 patients but not in any of the 10 on whom the direct interruption method was used. In 6 of these 7 patients who experienced rebleeding, subsequent direct interruption surgery led to control of the bleeding. One patient died of a variceal hemorrhage one month postoperatively. The total 10 year cumulative survival rate was 86.3 per cent. In the light of these findings, we believe that methods of direct interruption, such as esophageal transection, may well be the approach of choice for patients with esophageal varices caused by extrahepatic portal venous obstruction.

Adolescent↗
PubMed1988

Recurrence of varices after oesophageal transection: intra-operative and postoperative assessment by endoscopy.

Intra-operative and postoperative endoscopy were used in 16 patients with portal hypertension to investigate whether intra-operative elimination of oesophageal varices by oesophageal transection with devascularization leads to prevention of variceal recurrence and rebleeding. Intra-operative elimination of the varices was achieved in 12 patients. In ten patients the varices recurred and in two cases rebled, during the follow-up period of 6-43 months (average 25 months). Of the ten patients with recurrent varices, eight (including the two who bled acutely in the postoperative period) successfully underwent endoscopic injection sclerotherapy. Postoperative endoscopy was performed at 5-monthly intervals. It is concluded that intra-operative elimination of the varices will not prevent recurrence and that a closer follow-up using endoscopy more than three times a year is a significant aid in the management of these patients.

Adult↗
PubMed1988

Preoperative computed tomography and scintigraphy to facilitate the detection of accessory spleen in patients with hematologic disorders.

Accessory spleens of 1.5 cm in size were preoperatively identified by the combined use of computerized tomography and splenic scintigraphy in two patients with hematologic diseases. After the accessory spleen had been removed from the first patient, who had persistent hereditary spherocytosis and had undergone a splenectomy 15 months before, a postoperative decrease in hyperbilirubinemia was noted. In the other patient who had idiopathic thrombocytopenic purpura, a successful accessory splenectomy was done at the same time as her splenectomy, and was followed by 6 months' complete remission. These events indicate that preoperative investigations using computerized tomography and scintigraphy are indispensable for ruling out an accessory spleen in those patients for whom splenectomy needs to be done in order to alleviate hematologic disorders.

Female↗
PubMed1988

Prognostic blue varices as a discriminant factor of variceal hemorrhage: amendment of the criteria of endoscopic findings of esophageal varices.

Up until now, the endoscopic findings related to hemorrhage from esophageal varices have been red color signs (RCS) and the fundamental bluish color (Cb) of the varices. Although most investigators agree with the former, there is considerable dispute regarding the latter "blue varices". In order to identify the "risky" type of blue varices, prognostic varices (P-Cb) were specifically defined as being featured by a fully expanded appearance with a glossy surface, like an over-inflated balloon. Three hundred and nineteen collected patients with esophageal varices, including 114 bleeders, were retrospectively assessed and the P-Cb was found to have a significant correlation to the bleeding history. The P-Cb should be taken into account when attempting to predict bleeding of blue varices. The general rules for recording endoscopic findings of esophageal varices, as determined in 1980, should thus be amended.

Color↗
PubMed1988

Increased platelet count as a screening test for distal splenorenal shunt patency.

Hypersplenism was not relieved by distal splenorenal shunting in 46 of 47 Japanese patients with nonalcoholic cirrhosis of the liver. However, the platelet count significantly increased by 40 percent of the preoperative value, whereas the increment in the white blood cell count was nil. Though the platelet count in 47 patients with a patent shunt did not significantly differ from that in another 7 patients with an occluded shunt, the rate of increase was significantly higher in those with patency than in those with early occlusion throughout the postoperative period and in those with late occlusion 6 months after operation. The increased rate of the platelet count can thus serve to screen patients for shunt patency.

Adult↗
PubMed1988

A prospective randomized study comparing the effects of large and small volumes of the sclerosant 5% ethanolamine oleate injected into esophageal varices.

The safety efficacy and complications of injections of large and small volumes of 5% ethanolamine oleate (EO) were examined prospectively in the sclerotherapy of esophageal varices in 39 consecutive cirrhotic patients. Twenty patients were randomly allocated to the large-volume group (LVG) injected with up to 30 ml per session, and 19 to the small-volume group (SVG) injected with up to 15 ml per session. The two groups were comparable with regard to age, etiology and severity of liver disease. Post-injection bleeding occurred in 15.8% (3/19) after 1-3 sessions in the SVG and in 0% in the LVG. The LVG showed a significantly higher rate of decrease in variceal size (95.0% vs 53.2%, p less than 0.05) and disappearance of red color signs (RCS) on the variceal surface (95.0% vs 52.6%, p less than 0.01) one week after the initial session. The treatment period and number of sessions of endoscopic injection sclerotherapy (EIS) for eradication of varices were significantly (p less than 0.01) smaller in LVG than in SVG (LVG: 2.7 +/- 0.6 sessions over 4.2 +/- 0.7 weeks vs SVG: 5.4 +/- 0.9 sessions over 6.0 +/- 1.6 weeks). There were no life-threatening complications, and the incidence of minor complications did not differ between the two groups. The persistence of RCS and the occurrence of post-injection bleeding may imply that esophageal varices are not always completely obliterated despite 1-3 sessions in the SVG. We conclude that the large volume of EO is superior to the small volume for repeated EIS to eradicate esophageal varices.

Adult↗
PubMed1988

Effects of argon laser on vascular materials.

The laser has been shown to vaporize arterial atheromatous plaque, but little information is available about its effect on various vascular materials. This study attempts to determine a safe margin for laser graft thrombectomy. An 18 watt argon laser with a 2 mm metal-encased sapphire tip fiberoptic system was used. Specimens such as autogenous vein, polytetrafluoroethylene (PTFE), and Dacron grafts as well as polypropylene and PTFE sutures were harvested from amputated human legs. Laser energy was delivered from the tip of the fiberoptic system while perpendicular to and in direct contact with these materials. The effects were examined histologically and compared by determining the bursting pressure of the grafts and the breaking strength of the sutures. The results indicate that seven sections of autogenous vein grafts and 11 sections of PTFE grafts were perforated by laser delivery of 32.9 +/- 9.9 and 50.0 +/- 7.1 joules, respectively, whereas two sections of Dacron grafts were easily perforated after only 10 joules was delivered. The bursting pressure of PTFE and autogenous vein grafts after laser application was determined to be more than 300 mm Hg. The breaking strength of 6-0 PTFE sutures was compared before and after receiving 200 joules by contact laser application. No significant difference was found; in a before laser application the breaking strength was 585.0 +/- 9.6 gm compared with 560.0 +/- 16.4 gm after laser application (n = 4, p greater than 0.1). However, 6-0 polypropylene sutures were easily melted after receiving 10 joules of laser energy.(ABSTRACT TRUNCATED AT 250 WORDS)

Argon↗
PubMed1988

Lack of preventive effect of branched-chain amino acid solution on postoperative hepatic encephalopathy in patients with cirrhosis: a randomized, prospective trial.

The purpose of this randomized, prospective study was to determine whether the infusion of branched-chain amino acid (BCAA)-enriched solution had a preventive effect for treating postoperative hepatic encephalopathy in patients with cirrhosis. Among the 56 patients with cirrhosis, 29 were given BCAA-enriched solution, and 27 were given the conventional amino acid solution for 14 days postoperatively. These groups were indistinguishable with regard to clinical and laboratory criteria at entry, except by sex. The molar ratio of BCAA to aromatic amino acids in the BCAA group was increased postoperatively, whereas the ratio in the control group was decreased, the difference being statistically significant. Among the 29 who received BCAA, three (10.3%) had hepatic encephalopathy; two died and one recovered. Of the 27 control patients, hepatic encephalopathy occurred in three (11.1%); one died and two recovered. There was no significant difference in rate of occurrence of hepatic encephalopathy between the groups. Thus the infusion of BCAA-enriched solution apparently had no preventive effect with regard to hepatic encephalopathy for patients with cirrhosis who underwent surgical treatment.

Amino Acids↗
PubMed1988

An ultrasonic duplex system facilitates detection of portal hemodynamic changes following selective shunts for esophageal varices.

We used an ultrasonic duplex system (US system) to assess portal hemodynamics in 52 patients with liver cirrhosis and esophageal varices, who underwent 2 types of distal splenorenal shunt (DSRS), conventional DSRS (group A, 8 patients) or DSRS with splenopancreatic disconnection (group B, 44 patients). The portal blood flow rate (PBF) was determined in 64 out of 70 patients (91.4%) and the shunt flow rate (SVF) in 39 out of 42 patients (92.9%) who had angiographically confirmed patent portal vein and shunt vein, during the peri- and postoperative period. In group A, a remarkably small amount of postoperative PBF (193 ml/min) and a concomitant increase in SVF (1039 ml/min) were evident. Such ultrasonic findings were compatible with a reduction in portal vein diameter, in accordance with the poor portal perfusion grade of the liver, and a transpancreatic stealing of the portal blood flow to the shunt, as evidenced by postoperative angiography. In contrast, the reduction in PBF was minimal, that is 663 ml/min preoperatively to 562 ml/min at discharge, and 536 ml/min at late follow-up, in group B patients. Significant alterations in portal circulation of the group B patients were not evident angiographically. This US system is most useful to assess portal hemodynamics in patients with a selective shunt.

Adult↗