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Biomedical subjects

S Fujiyama

Publications and source records attributed to S Fujiyama.

At least 73 records · Page 4Linked to original sources

Clinical evaluation of endoscopic injection sclerotherapy for bleeding esophageal varices in liver cirrhosis with hepatocellular carcinoma.

Endoscopic injection sclerotherapy (EIS) for rupture of esophageal varices was carried out in 13 patients of liver cirrhosis with hepatocellular carcinoma (HCC). Sclerotherapy was performed by intravariceal injections of 5% ethanolamine oleate. According to the manual for the staging of cancer, these HCCs were classified as Stage I in 1 case, II in 1 case, III in 2 cases, and IV in 9 cases. There was no difference between post EIS prognosis and stage. Child's classification of these patients were class A in 1 case, B in 5 cases, and C in the remaining 7 cases. Only in 1 case of Child's A and 1 case of Child's B who were less advanced clinically and were free from icterus and ascites did EIS produce favorable results, it arresting esophageal variceal hemorrhage and led to a relatively good outcome. We suggest that emergency EIS for rupture of esophageal varices should be performed in patients with relatively good general conditions, irrespective of the stage of HCC.

Adult↗

The prevalence of anti-HCV antibodies in hemodialysis patients.

The prevalence of antibodies to hepatitis C virus (anti-HCV) was assessed in 489 hemodialysis patients and 152 members of the staff of dialysis units, using an Ortho HCV Ab ELISA Test. Of the 489 patients, 100 (20.4%) had anti-HCV, a significantly greater rate than was found in either staff members (0.7%, P less than 0.01) or local healthy blood donors (1.1%, P less than 0.001). Anti-HCV positivity was apparently related to the duration of hemodialysis.

Adult↗

Evaluation of the KCL-163 ELISA test for detecting antibodies against hepatitis C virus in patients with non-A, non-B chronic hepatitis.

A specific ELISA test (KCL-163) for detecting anti-hepatitis C virus antibody (anti-HCV) has been developed (Kaketsuken). Using the KCL-163, 183 serum samples obtained from patients with non-A, non-B hepatitis (NANBH) were examined. We also tested and compared results with Ortho HCV ELISA (C100) and C825 ELISA. Of these 183 samples, 139 (76%), 121 (66%), and 88 (48%) were positive with KCL-163, C100 and C825, respectively. These results showed that there were patients with NANBH caused by HCV who were seronegative in C100 ELISA. KCL-163 ELISA is applicable for the diagnosis of HCV infection in these patients.

Chronic Disease↗

Detection of antibodies to hepatitis C virus (anti-HCV) in patients with various liver diseases, by an ELISA (KCL-163) test consisting of synthetic peptides corresponding to an HCV genome.

In 1989, the Chiron group developed an enzyme immunoassay system (C100) for detecting antibodies to hepatitis C virus (anti-HCV). In our examinations, the positive rate was 65.3% of the total number of patients (199) with non-A, non-B (NANB) liver disease. Additionally, a specific ELISA system (KCL-163) was developed by Kaketsuken (Kumamoto, Japan) based on synthetic peptides corresponding to an HCV genome of a Japanese isolate. In this study, we measured antibodies to HCV by KCL-163, and compared the results of KCL-163 with that of C100 in patients with various liver diseases. Our emphasis was on the discrepancies between the results of the two types of ELISA. We concluded that it was not sufficient to diagnose hepatitis C only by assay systems based on the C100-3 region of an HCV genome, and that KCL-163 was superior to C100 in its specificity and sensitivity in the diagnosis of hepatitis C.

Enzyme-Linked Immunosorbent Assay↗

Gastric mucosal hexosamine content in various liver diseases.

Since gastric mucosal lesions are frequently encountered in patients with liver disease, we measured the levels of gastric mucosal hexosamine. In chronic hepatitis patients, hexosamine levels were reduced in both the antrum and corpus as compared with those in normal controls, while values in the advanced liver cirrhosis group (total bilirubin greater than 5 mg/dl) were lower than in the less advanced group. Although the presence or absence of esophageal varices had no influence on hexosamine, higher concentrations were found in patients with the red color sign (+) in comparison with those with negative red color sign (-). One month after endoscopic injection sclerotherapy of esophageal varices, hexosamine did not change, but decreases were seen in both the antrum and corpus at 3 months. We observed an increase in gastric mucosal blood flow after treatment with teprenone, a new antiulcerative agent, in normal controls. Gastric mucosal hexosamine increased significantly after teprenone treatment in both chronic hepatitis and liver cirrhosis groups. From these results, we conclude that hexosamine has a defensive action against gastric lesions in various liver diseases.

Anti-Ulcer Agents↗

Transrectal portal scintigraphy with I123 iodoamphetamine in liver diseases.

Using transrectal portal scintigraphy with I123 iodoamphetamine, we calculated the portosystemic shunt index and investigated the portal hemodynamics in patients with various liver diseases. The shunt index tended to increase in the order of chronic hepatitis, primary biliary cirrhosis, compensated liver cirrhosis, and decompensated liver cirrhosis. An increase in the stage of esophageal varices (assessed endoscopically) also tended to be associated with an increase in the shunt index. The shunt index correlated significantly with both the ICG test and the spleen index. Accordingly, measurement of the shunt index by this method appeared to accurately reflect the existence and severity of portosystemic shunting, and to be of value in the evaluation of portal circulatory abnormalities. However, no clear differences were found in the shunt index following hepatic arterial injection chemotherapy for hepatocellular carcinoma, or endoscopic injection sclerotherapy for esophageal varices.

Amphetamines↗

The inhibitory effect of probenecid on renal excretion of famotidine in young, healthy volunteers.

Effects of coadministration of probenecid on pharmacokinetic behaviors of famotidine, an H2-receptor antagonist, after oral administration, were studied in eight young, healthy volunteers. They received an oral 20 mg dose of famotidine with and without coadministration of oral 1500 mg doses of probenecid. The mean area under the serum famotidine concentration-time curve up to 10 hours was increased by coadministration of probenecid from 424 +/- 19 (SEM) to 768 +/- 39 ng.hr/ml. The mean urinary excretion rate of unchanged famotidine, the mean amount of unchanged famotidine excreted in urine up to 24 hours and mean renal clearance were decreased by coadministration of probenecid. The mean tubular secretion clearance of famotidine was decreased from 196.2 +/- 21.4 to 22.0 +/- 4.2 ml/min. These data suggest that probenecid, which is a classical inhibitor of renal tubular secretion of organic anions, inhibits the renal tubular secretion of famotidine, which exists partly in a cationic form under physiological pH conditions.

Adult↗

Removal of famotidine by haemodialysis in elderly anuric patients.

The effect of haemodialysis on the pharmacokinetics of oral famotidine has been studied in five elderly anuric patients. Famotidine 20 mg was administered in a cross-over design to patients on and not on haemodialysis. The elimination rate constant of haemodialysis (k) was 4.6-fold larger than the systemic elimination rate constant (ke). Although the mean maximum serum concentration of famotidine during haemodialysis (141.5 ng.ml-1) was not significantly lower than that without haemodialysis (195.6 ng.ml-1), the AUC up to 5 h during haemodialysis was significantly decreased to 58.1% of the value without it. The data suggest that famotidine is dialysable by haemodialysis.

Aged↗

Atrial natriuretic peptide in liver cirrhosis with mild ascites.

To clarify the involvement of atrial natriuretic peptide (ANP) in the pathogenesis of liver cirrhosis, we measured plasma ANP in patients with various stages of cirrhosis and in age-matched normal subjects. Urinary cyclic guanosine monophosphate (cGMP) was also measured as a marker of active biological ANP. In addition, effects of exogenous synthetic human ANP (0.5 micrograms/kg) on renal functions were examined in normal subjects and in cirrhotics without ascites or with mild ascites. Plasma ANP levels were not significantly different among these 3 groups. Urinary cGMP concentrations were significantly higher in both cirrhotics without ascites and cirrhotics with mild ascites, (340 pmol/ml, P less than 0.05 and 496 pmol/ml, P less than 0.01 respectively) than normal subjects (95 pmol/ml). In normal subjects, marked increases in urinary volume (UV), sodium excretion (UNaV), fraction excretion of sodium (FENa) and free water clearance (CH2O) were induced after ANP infusion, and significant recoveries were subsequently observed in these parameters. However, in cirrhotics, the responses to ANP infusion of UV, FENa and CH2O were far less dramatic. The response of UV, UNaV and FENa in cirrhotics with mild ascites was delayed compared to cirrhotics without ascites. These results suggest that the blunted natriuretic responsiveness to ANP is contributory to the pathogenesis of initial sodium retention in cirrhotics.

Ascites↗

5'-Nucleotide phosphodiesterase isozyme-V in hepatocellular carcinoma and other liver diseases.

The clinical usefulness of serum 5'-nucleotide phosphodiesterase isozyme-V (5'-NPD-V) assay as a serological marker for hepatocellular carcinoma was evaluated. Serum levels of 5'-NPD-V were measured by polyacrylamide gel electrophoresis in 536 Japanese patients with various diseases, including 120 patients with hepatocellular carcinoma. Icteric serum was not an indicator for the measurement of this isozyme, because jaundice gave a non-specific false-positive reaction. In 99 cases of hepatocellular carcinoma without jaundice, 73 (74%) had positive 5'-NPD-V and 24 (24%) showed levels greater than (+ +). The diagnostic value of this isozyme for hepatocellular carcinoma was relatively high, especially in patients with low or negative AFP levels. Diagnostic application for serum 5'-NPD-V assay to small liver tumors was limited. 5'-NPD-V showed false-positive results even in certain cases of benign liver diseases such as chronic hepatitis and liver cirrhosis, but cases with positivities stronger than (+ +) were few. Moreover, the test might be useful for the prediction of liver metastasis in cancer patients, since positive rates were significantly higher in cases with liver metastasis than in those in the non-liver metastasis group.

Adult↗

Immunogenicity and safety of recombinant yeast-derived hepatitis B vaccine in haemodialysis patients.

The immune response of 32 haemodialysis patients vaccinated with a recombinant yeast-derived hepatitis B vaccine (YHB vaccine) was compared with that of healthy adults and of another haemodialysis patient group vaccinated with the plasma-derived vaccine (PHB vaccine). Twenty-two patients were immunized 3 times (months 0, 1 and 6) intramuscularly with a 20 micrograms dose, and ten patients with a 40 micrograms dose of the YHB vaccine. All members of the former group (100%) and nine of the latter group (90%) were anti-HBs positive after 3 vaccinations (months 7); anti-HBs concentrations with geometric mean titres (GMTs) of 82.3 mIU/ml and 242.1 mIU/ml, respectively, the difference being statistically in significant. The 87 healthy control group participants were vaccinated according to the same schedule but with 10 micrograms per dose, and 98% of them were anti-HBs positive by month 7, with a GMT of 198.3 mIU/ml. The patients responses were higher at each time point than those of 53 dialysis patients vaccinated in an earlier study with either 20 micrograms or 40 micrograms PHB vaccine. Two additional inoculations led to a substantial elevation of the anti-HBs titre in most of the haemodialysis patients; GMTs by month 12 being 506.8 mIU/ml and 979.5 mIU/ml for the 20 micrograms and the 40 micrograms dose respectively. No serious side-effects were observed over the one-year period of study. From these results, it was concluded that the YHB vaccine is highly immunogenic and could replace the PHB vaccine even in dialysis patients.

Adult↗

[A case of multiple tumors].

A 54-year-old man was admitted to our clinic for a further examination of rectal and liver tumors, after which a rectal cancer, a hepatocellular carcinoma (HCC), a hemangioma of the liver a retroperitoneal cyst, and a submucosal tumor of the stomach (SMT) were diagnosed by means of a colonoscopy, a gastroscopy, and US, CT, and angiography, these tests also revealing elevated CEA and AFP levels. A hepatic subsegmentectomy and a Miles's operation, as well as an enucleation of other liver tumors and an SMT, were performed and a retroperitoneal cyst was removed. The histopathological finding of the rectal cancer was a moderately differentiated adenocarcinoma, while the liver tumors were determined as being an HCC of the trabecular type, adenomatas revealing hyperplasia, a hemangioma, and the SMT showing a benign leiomyoblastoma.

Adenocarcinoma↗

A case of type Ia glycogen storage disease complicated by hepatic adenoma.

A 31-year-old male patient with type Ia glycogen storage disease was admitted to our department complaining of general fatigue and right hypochondriac pain. He exhibited massive hepatomegaly with systemic hypoglycemia, lactic acidosis, hyperuricemia, hyperpyruvatemia and hyperlipemia. The failure of blood glucose levels to increase after a glucagon loading test, and a reduced lactate level on glucose tolerance test were also observed. Various imaging techniques suggested hepatic adenoma with hemorrhage in the tumor, which was confirmed histologically. There was a complete absence of glucose 6-phosphatase activity, as determined by an enzyme assay on resected liver specimens, which proved the case to be type Ia glycogen storage disease. We also reviewed all previously reported cases of hepatic tumor and glycogen storage diseases. We conclude that, since hepatic adenoma is not rare in this disease, and is complicated by hemorrhage, rupture and malignancy, careful follow-ups are necessary.

Adult↗

[Clinical trial of inactivated hepatitis A vaccine].

A clinical trial was carried out for a lypophilized inactivated hepatitis A vaccine in order to confirm its safety and antibody response. The vaccine used for the study has been developed by Denka Institute of Biological Science (Lot. D-01), Chiba Serum Institute (Lot. C-01) and The Chemo-Sero-Therapeutic Research Institute (Lot. K-02). Thirty-six volunteers were selected and employed for the present study from healthy male adults carrying no antibody against hepatitis A virus (HAV). They were divided into three dose groups; 1.0 microgram, 0.5 microgram and 0.25 microgram viral protein respectively. Each groups were injected intramuscularly 3 times with 0, 1 and 6 months interval. As the results, though, slight side effects such as local pain were found in 16 cases out of 99 total injected, but no abnormal value was observed in the blood and urine examinations. On the other hand, the mean values of serum anti-HAV at 2 months after the first injection in 1.0 microgram, 0.5 microgram and 0.25 microgram dose-groups were 562 mIU/ml, 323 mIU/ml and 134 mIU/ml, respectively, and at the 7 months, 3630 mIU/ml, 1288 mIU/ml and 1000 mIU/ml, respectively. Namely, the high immunogenicity and safety of the vaccine were confirmed in this trail.

Adult↗

Hepatic arterial injection chemotherapy with cisplatin suspended in an oily lymphographic agent for hepatocellular carcinoma.

A method to prepare cisplatin suspended in an oily lymphographic agent, Lipiodol (LPS), has been established to deliver cisplatin to hepatocellular carcinoma (HCC) by the hepatic artery. Seventy-one patients, one Stage I, 16 Stage II, 16 Stage III, and 38 Stage IV, were treated with LPS therapy. A partial response was obtained in 33 cases (46.5%), a minor response in 20 cases (28.2%), and no change in 18 cases (25.3%). In 34 patients whose serum alpha-fetoprotein (AFP) levels were greater than 400 ng/ml, the serum AFP levels decreased in 31 patients (91.2%). The AFP decreased by more than 50% in 25 cases (73.5%) and more than 75% in 19 cases (55.9%). The plasma des-gamma-carboxy prothrombin (DCP) levels decreased in all of the 26 DCP-positive patients. The survival rate was 77% at 6 months and the 1-year survival rate was estimated to be 55%. The patients treated with LPS therapy survived longer compared with patients given Lipiodol containing neocarzinostatin by the hepatic artery. Complications such as acute gastroduodenal mucosal lesions (24%), cholecystitis (2.8%), pancreatitis (7%), delayed jaundice (7%), and hepatic encephalopathy (4.2%) were observed after therapy. The peak plasma platinum (Pt) concentrations determined as ultrafilterable Pt occurred 5 to 20 minutes, and 5 to 60 minutes as total Pt after the end of LPS injection. The Pt concentrations in the tumor tissues were 42 times higher in four operated cases and 7.1 times higher in six autopsy cases than those in the nontumorous tissue. These results suggest that LPS selectively accumulates in the HCC, is long-lasting and gradually releases the drug. In addition it is effective as a new anti-cancer therapy for hepatocellular carcinoma.

Adult↗

Pharmacokinetics of famotidine in elderly patients with and without renal insufficiency and in healthy young volunteers.

The pharmacokinetics of the H2-receptor antagonist famotidine, after oral administration of a 20 mg tablet, has been studied in 10 elderly patients with normal renal function (CLCR greater than or equal to 59 ml.min-1, Mean = 80 ml.min-1), 5 elderly patients with renal insufficiency (CLCR less than or equal to 38 ml.min-1, Mean = 15 ml.min-1), and 6 healthy young volunteers. Elimination half-life in the elderly patients with renal insufficiency was significantly prolonged compared to the elderly patients with normal renal function and the young volunteers. The correlation coefficient between creatinine clearance and the elimination rate constant of famotidine was 0.672. Mean urinary recovery of unchanged drug up to 24 h in the young volunteers was 44%. The mean renal clearance of famotidine in the young volunteers (270 ml.min-1) was substantially greater than the creatinine clearance, 128 ml.min-1, which suggests the possibility of tubular secretion of famotidine.

Adult↗

[Clinical usefulness of plasma PIVKA-II assay and its limitations in patients with hepatocellular carcinoma].

Plasma abnormal prothrombin (protein induced by vitamin K absence or antagonist-II: PIVKA-II) was evaluated as a serological marker for hepatocellular carcinoma (HCC). Its plasma levels were measured by enzyme immunoassay using an anti-PIVKA-II monoclonal antibody in 1010 patients with various diseases. Of 192 patients with HCC, 116 (60%) had abnormal PIVKA-II levels greater than 0.1 AU/ml. Elevation of PIVAK-II levels was observed rarely in chronic hepatitis, liver cirrhosis and other malignant tumors. Plasma PIVKA-II levels in HCC increased with tumor size. Normal levels were observed in patients with tumors measuring 2 cm or less in diameter. As a result, diagnostic application of plasma PIVKA-II levels to small liver tumors is limited. The sensitivity of PIVKA-II in the diagnosis and monitoring of HCC was increased by serial and simultaneous determinations of AFP, because high PIVKA-II levels were observed more often in low AFP-producing HCC patients. In some patients with HCC, plasma PIVKA-II levels decreased after surgical resection of the tumor or chemoembolization with cisplatin suspended in Lipiodol (LPS), but later rose again with recurrence of the disease. Elevated plasma PIVKA-II levels were not related to low vitamin K concentration in the serum. In fact, in many patients vitamin K administration resulted in only a moderate reduction of PIVKA-II levels. From these results, plasma PIVKA-II assay by the EIA method using a monoclonal antibody is a useful tool for the diagnosis and monitoring of HCC, particularly in HCC patients with low AFP levels.

Biomarkers↗