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Biomedical subjects

M Hashizume

Publications and source records attributed to M Hashizume.

At least 19 recordsLinked to original sources

Endoscopic injection sclerotherapy for esophageal varices associated with concomitant portal venous thrombus of hepatocellular carcinoma.

Between 1983 and 1994, we treated 51 patients with esophageal varices and portal trunk and main branch invasion of hepatocellular carcinoma, using endoscopic injection sclerotherapy. Variceal bleeding was controlled in 28 of 29 patients (96.6%), esophageal varices were completely eradicated in 28 (54.9%), and only 2 of 28 (7.1%) bled from small, dilated, venous vessels after eradication. The cumulative nonbleeding rate at 3 years was 87.5%. Death caused by hepatocellular carcinoma accounted for 89.4% of the patients, whereas the rate of bleeding from esophageal varices was 4.3%. Variables significantly associated with the duration of survival were Okuda's clinical stage, alpha-fetoprotein, eradication of esophageal varices by sclerotherapy, and treatment of hepatocellular carcinoma, as determined in a univariate analysis. Multivariate analysis showed that eradication of esophageal varices by sclerotherapy, Okuda's clinical stage, and age were independent factors which significantly influenced survival time. We propose that complete eradication of esophageal varices and close follow-up using endoscopy may lead to a reduction in bleeding from esophageal varices, and hence may reduce mortality rates related to this bleeding.

Carcinoma, Hepatocellular

Increased prostacyclin content in gastric mucosa of cirrhotic patients with portal hypertensive gastropathy.

Plasma levels and gastric mucosal contents of prostaglandin (PG) E2 and prostacyclin were determined in cirrhotic patients with portal hypertensive gastropathy (PHG), in cirrhotic patients without PHG and in healthy controls. PGE2 and 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) levels were measured in 30 cirrhotic patients and 10 controls, using radioimmunoassay. Of 30 cirrhotics, 13 had PHG of the fundus and the corpus. Plasma concentrations of 6-keto-PGF1 alpha in the cirrhotic patients were significantly higher than in the controls (p < 0.01), but there was no significant difference between cirrhotics and controls with regard to plasma levels of PGE2. The gastric mucosal contents of 6-keto-PGF1 alpha in the fundus was significantly higher in cirrhotics with PHG than those without PHG (p < 0.05) and controls (p < 0.01). However, the gastric mucosal contents of PGE2 in the fundus were not significantly different in cirrhotics with and without PHG. The gastric mucosal contents of 6-keto-PGF1 alpha significantly correlated to the plasma levels (r = 0.37, p < 0.05), but there was no significant correlation between plasma levels and gastric mucosal contents of PGE2. Since prostacyclin has vasodilator and gastric acid inhibitory effects, we speculate that high contents of prostacyclin in the gastric mucosa may have some role in the pathogenesis of PHG.

6-Ketoprostaglandin F1 alpha

Modulation of extraluminally induced vasoconstrictions by endothelium-derived nitric oxide in the canine basilar artery.

The present study was undertaken to investigate the role of endothelium in extraluminally induced vasospasm of the cerebral artery using isolated perfused canine basilar arteries. The extraluminal applications of high K+ and prostaglandin F2 alpha (PGF2 alpha) induced concentration-dependent vasoconstriction. Both constrictive responses were significantly enhanced by denuding endothelium. Additionally, the responses in the endothelium-intact arteries were markedly augmented by intraluminal perfusion with NG-monomethyl-L-arginine (L-NMMA). These results suggest that the inhibition of nitric oxide (NO) synthase in endothelium enhances increase in transmembrane Ca(2+)-influx which is a common constrictive mechanism to the vasoconstrictors. The augmentative action induced by L-NMMA was inhibited by intraluminal perfusion of L-arginine, but not by D-arginine. Furthermore, the augmentation was not observed in the arteries without endothelium. These results suggest that the endothelium may have a great significance on responsiveness to extraluminal vasoactive substances and that endothelium-derived NO may modulate the extraluminally induced vasoconstriction which is responsible for cerebral vasospasm after subarachnoid hemorrhage.

Amino Acid Oxidoreductases

Prognostic significance of hepatic vein waveform by Doppler ultrasonography in cirrhotic patients with portal hypertension.

OBJECTIVE: We prospectively evaluated the prognostic value of the flat hepatic vein waveform, measured by Doppler ultrasound, in cirrhotic patients with portal hypertension. METHODS: The Doppler pattern of right and left hepatic veins in a series of 120 consecutive cirrhotic patients with portal hypertension but without hepatocellular carcinoma was examined, together with clinical and biochemical parameters. RESULTS: Flat waveform of the right hepatic vein was recognized in nine patients and that of the left hepatic vein was seen in 13. After a mean follow-up of 13.6 +/- 9.7 months, 17 patients died, all from liver failure. In the univariate analysis, variable significantly associated with the duration of survival were age, etiology of the liver cirrhosis, upper gastrointestinal bleeding after start of the study, Child-Pugh score, ascites, encephalopathy, prothrombin index, bilirubin, albumin, and flat Doppler waveform in the right and left hepatic veins. Multivariate analysis showed that flat Doppler waveform in the right hepatic vein, bilirubin, and prothrombin index were independently related to survival. CONCLUSIONS: The prognostic accuracy in cases of cirrhosis with portal hypertension is significantly improved with acquisition of information obtained from hepatic vein waveform by Doppler ultrasound.

Adult

Recurrent rectal bleeding from portal hypertensive colopathy in a patient with hemorrhoids.

In a 62-yr-old woman who complained of recurrent rectal bleeding, hemorrhoids with mucosal prolapse were found. Virus-related cirrhosis also was present. Colonoscopy revealed spontaneous bleeding from two rectal ectasias (portal hypertensive colopathy) located 9 cm from the anus. Endoscopic hemostasis was achieved with a heater probe, and there has been no recurrent hemorrhage. Colonoscopy is important in ruling out hemorrhage from portal hypertensive colopathy when rectal bleeding occurs in the presence of portal hypertension.

Angiodysplasia

Feasibility of laparoscopic cholecystectomy for patients with a nonvisualized gallbladder on drip infusion cholangiography.

We report here the operative findings, the incidence of successful laparoscopic treatment, and the perioperative complications in patients with nonvisualized gallbladder on drip infusion cholangiography (DIC). Eighty-five patients with a nonvisualized gallbladder on DIC were entered into the study. None of the patients had a minimal adhesive gallbladder; 51 to 85 patients (60.0%) had moderate adhesive gallbladders, and 34 (40.0%) had severely adhesive ones. The rate of successful laparoscopic treatment, including laparoscopy-assisted abdominal surgery, was 97.6% (83 of 85 patients). Perioperative complications occurred in only three patients (3.5%), and there were no deaths related to the operation. Thus, when patients with a nonvisualized gallbladder on DIC undergo laparoscopic cholecystectomy, meticulous procedures must be carried out; however, as the rate of successful laparoscopic treatment is high, cholecystectomy under laparoscopy is feasible for experienced surgeons.

Cholangiography

Effect of beta-alanyl-L-histidinato zinc on protein components in osteoblastic MC3T3-El cells: increase in osteocalcin, insulin-like growth factor-I and transforming growth factor-beta.

The effect of beta-alanyl-L-histidinato zinc (AHZ) on protein components in osteoblastic MC3T3-E1 cells was investigated. Cells were cultured for 3 days at 37 degrees C in CO2 incubator in plastic dishes containing alpha-modified minimum essential medium supplemented with 10% fetal bovine serum. After the cultures, the medium was exchanged for that containing 0.1% bovine serum albumin plus various concentrations of AHZ or other reagents, and the cells were cultured further 3 or 6 days. The homgenate of cells was analyzed with SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The presence of AHZ (10(-7) to 10(-5) M) caused an appreciable increase of many protein components in cells. Especially, the 67 killo-dalton (kDa) and 44 kDa proteins which are the major components from control cells were clearly increased by the presence of AHZ. Furthermore, the concentrations of osteocalcin, insulin-like growth factor-I and transforming growth factor-beta in the culture medium secreted from osteoblastic cells were markedly increased by the presence of AHZ (10(-6) and 10(-5) M). The effect of AHZ was a greater than that of zinc sulfate (10(-6) and 10(-5) M). The present findings suggest that AHZ can increase many proteins which are involved in the stimulation of bone formation and cell proliferation in osteoblastic cells.

Carnosine

Hepatic metastasis after laparoscopic cholecystectomy for polypoid gallbladder cancer followed by radical surgery.

While laparoscopic cholecystectomy is being increasingly performed on patients with gallbladder disease, this approach in cases of polypoid lesions in the gallbladder may not always be justified. We report here a case of early development of intrahepatic metastasis after laparoscopic cholecystectomy for polypoid gallbladder cancer; wedge resection of the gallbladder bed and dissection of regional lymph nodes had to be done. When a malignancy of the gallbladder is suspected during preoperative examinations, open cholecystectomy should be done.

Adenocarcinoma, Papillary

Effect of zinc-chelating dipeptides on osteoblastic MC3T3-E1 cells: activation of aminoacyl-tRNA synthetase.

The effect of zinc-chelating dipeptides on osteoblastic MC3T3-E1 cells was investigated. As zinc compounds, we used zinc sulfate, AHZ, di(N-acetyl-beta-alanyl-L-histidinato)zinc (AAHZ), and di(histidino)zinc (HZ). Cells were cultured for 72 h in the presence of zinc compounds (10(-8)-10(-5) M). The effect of AHZ (10(-7) and 10(-6) M) to increase protein and deoxyribonucleic acid (DNA) contents in the cells was the greatest in comparison with those of other zinc compounds. Zinc sulfate and HZ at 10(-7) M did not have an effect on the cellular protein content. AHZ (10(-6) M) had a potent effect on cell proliferation, although zinc sulfate (10(-6) M) had no effect. beta-Alanyl-L-histidine (10(-6) and 10(-5) M) did not have an appreciable effect on the cells. Those effects of AHZ (10(-6) M) on osteoblastic cells were completely abolished by the presence of cycloheximide (10(-6) M). AHZ (10(-8)-10(-5) M) directly activated [3H]leucyl-tRNA synthetase in the cell homogenate, whereas the effect of zinc sulfate was seen at 10(-6) and 10(-5) M. The present study suggests that the chemical form of zinc-chelating beta-alanyl-L-histidine (AHZ) can reveal a potent anabolic effect on osteoblastic cells, and that AHZ directly stimulates protein synthesis.

3T3 Cells

Synthesis and pharmacological evaluation of phenolic 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols as a new norepinephrine potentiator.

2-Methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline-4-ol(PI-OH) (2a) and its derivatives form a new class of compounds possessing norepinephrine (NE) potentiating activity. As a new series of compounds, the isomeric 4-(4-hydroxyphenyl)- and 4-(3-hydroxyphenyl)-2-methyl-1,2,3,4- tetrahydroisoquinolin-4-ols (3a and 3b), and 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinolin-4-ol (3c) were prepared and their NE potentiating activities were evaluated. The 4-(4-hydroxyphenyl) analogue (3a) had only moderate activity and the 4-(3-hydroxyphenyl) analogue (3b) possessed a slightly higher activity than PI-OH. The 4-(3,4-dihydroxyphenyl) analogue (3c) was the most active compound and the pD2 value was 7.71 +/- 0.06 (activity ratio; 26.9 fold) at a concentration of 3 x 10(-6) M. These results indicate the importance of dihydroxyphenylethanolamine moiety of 3c for the inhibition of NE uptake.

Animals

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

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

Improvement of large intestinal absorption of insulin by chemical modification with palmitic acid in rats.

The intestinal absorption of 125I-labelled palmitoyl insulin was examined following administration into in-situ closed large intestinal loops of rats. When mono- and dipalmitoyl insulins (Palins-1 and Palins-2, respectively) were administered in polyoxyethylene hydrogenated castor oil (HCO 60) micellar system into intestinal loops, a marked increase in plasma radioactivity and a corresponding disappearance of residual radioactivity in the intestinal lumen were observed in the following rank order: Palins-2 greater than Palins-1 greater than native insulin. In addition, the derivatives were more stable than native insulin in the mucosal tissue homogenates of the large intestine. These results suggest that chemical modification of insulin with palmitic acid may not only increase the lipophilicity of insulin but also reduce its degradation, resulting in the increased transfer of insulin across the large intestinal mucous membrane. The linoleic acid-HCO 60 mixed micelles system did not have a significant effect on the large intestinal absorption of radioactivity associated with the lipophilic insulin analogues.

Animals

[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