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Biomedical subjects

N Murashima

Publications and source records attributed to N Murashima.

At least 55 records · Page 3Linked to original sources
PubMed1997

The long term efficacy of glycyrrhizin in chronic hepatitis C patients.

BACKGROUND: Hepatocellular carcinoma (HCC) occurs in patients with hepatitis C virus-RNA positive chronic liver disease. It is important to prevent HCC with drug administration. METHODS: A retrospective study was undertaken to evaluate the long term preventive effect of Stronger Neo-Minophagen C (SNMC) on HCC development. SNMC is a Japanese medicine that is commonly administered to patients with chronic hepatitis C to improve the serum alanine aminotransferase (ALT) level. Of 453 patients diagnosed with chronic hepatitis C retrospectively in the study hospital between January 1979 and April 1984, 84 patients (Group A) had been treated with SNMC; SNMC was given at a dose of 100 mL daily for 8 weeks, then 2-7 times a week for 2-16 years (median, 10.1 years). Another group of 109 patients (Group B) could not be treated with SNMC or interferon for a long period of time (median, 9.2 years) and were given other herbal medicine (such as vitamin K). The patients were retrospectively monitored, and the cumulative incidence of HCC and risk factors for HCC were examined. RESULTS: The 10th-year rates of cumulative HCC incidence for Groups A and B were 7% and 12%, respectively, and the 15th-year rates were 12% and 25%. By Cox regression analysis, the relative risk of HCC incidence in patients not treated with SNMC (Group B) was 2.49 compared with that of patients treated with SNMC (Group A). CONCLUSIONS: In this study, long term administration of SNMC in the treatment of chronic hepatitis C was effective in preventing liver carcinogenesis.

Adult↗
PubMed1997

Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity-determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection.

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are predictive factors of poor response to interferon therapy in patients with chronic hepatitis C. To further examine the factors predicting the response to interferon in patients with genotype 1b infection, we analyzed 110 consecutive patients with HCV who were treated with a total of 624 million units of lymphoblastoid interferon alfa. Thirty-six patients (33%) were responders, while the remaining 74 patients (67%) were nonresponders. Multivariate analysis showed that a high virus titer (assessed by serum core protein level, P = .0021) and the presence of more than two amino acid substitutions in the interferon sensitivity-determining region (ISDR) (P = .0036) correlated significantly with the response to interferon therapy. Because mutations analyzed by direct sequencing of polymerase chain reaction (PCR) products may reflect artifacts of direct sequencing, we further analyzed quasispecies of HCV in this region by cloning and sequencing. Although PCR-based analysis of responders with multiple amino acid substitutions in the ISDR showed the presence of a small amount of wild-type strain in their serum, the results obtained by direct sequencing and cloning were essentially the same. A longitudinal study of quasispecies in 2 patients who showed a dramatic change in the virus titer showed no conversion from wild type to mutant or vice versa. Our results indicate that amino acid substitutions and virus load are independent predictors of the response to interferon therapy. The ability of some patients with no mutation in the ISDR or high virus load to eliminate the virus suggests the presence of other unidentified factors, host or viral, that influence the response to interferon therapy.

Adult↗
PubMed1997

Effect of arterial administration of a high molecular weight anti-tumor agent, styrene maleic acid neocarzinostatin, for multiple small liver cancer--a pilot study.

To assess the efficacy of the zinostatin derivative, the anti-tumor agent, styrene-maleic acid neocarzinostatin, in treating multiple small liver cancers, 29 patients with multiple hepatocellular carcinoma of 3 cm or less in diameter were treated with intraarterial injections of this high molecular weight agent, mixed with Lipiodol. Computed tomography 3 months after the first therapy showed complete deposition of Lipiodol in the entire area of the original tumor in 8 patients (27.6%), 50%-99% deposition in 4 (13.8%), 10%-49% in 10 (34.5%), and less than 10% in 7 (24.1%). After repeated injections, Lipiodol deposition in the entire area of the original tumor was found in 11 patients (37.9%). The degree of Lipiodol deposition depended on the angiographic vascularity of the tumor and on the images of the computed tomogram during arterial portography. Although complete deposition of Lipiodol was found in all tumors in 10 (58.8%) of the 17 patients with well demarcated round hypervascularity, only 1 (8.3%) of 12 patients with ill demarcated tumors showed complete deposition of Lipiodol in the tumors. Taking into account that hypervascularity on angiograms was closely correlated with the degree of Lipiodol accumulation on computed tomograms taken later, it appears that well demarcated round-shaped liver cancer is the best candidate for styrene-maleic acid neocarzinostatin therapy.

Adult↗
PubMed1997

Time course of histological changes in patients with a sustained biochemical and virological response to interferon-alpha therapy for chronic hepatitis C virus infection.

BACKGROUND/AIMS: Although biochemical and virological responses to interferon-alpha therapy for chronic hepatitis C virus infection have been extensively studied, long-term changes in liver histology have not been well documented. METHODS: We retrospectively analyzed 105 paired liver biopsy specimens taken before and after treatment from 93 patients who persistently showed biochemical remission and an absence of viremia for up to 68 months. RESULTS: The grading scores for necroinflammatory and fibrotic activity in the liver biopsy specimens decreased significantly after interferon-alpha therapy. Histological scores graded according to Knodell's components improved significantly in every category after interferon-alpha therapy. However, inflammatory cell infiltrates remained within the portal tracts for long periods; necroinflammation in the periportal and lobular regions were absent in most of the post-therapy specimens. The cumulative disappearance rate, calculated using the Kaplan-Meier method, was significantly lower for portal inflammation than for periportal or lobular necroinflammation but was equivalent to that for histological disease activity. On univariate analysis, age and fibrosis at the onset of treatment were significant factors influencing the response of histological disease activity to interferon-alpha therapy (p=0.025 and 0.049, respectively). Using Cox's proportional hazard analysis, age was the only significant independent predictor of histological response to treatment (p=0.035). CONCLUSIONS: Clinical remission of chronic hepatitis C virus infection is associated with histological resolution of necroinflammation in the periportal and lobular regions. Host-related factors are likely to influence whether early remission of inflammation after interferon-alpha therapy occurs.

Adult↗
PubMed1997

A prospective randomized administration of 5'-deoxy-5-fluorouridine as adjuvant chemotherapy for hepatocellular carcinoma treated with transcatheter arterial chemoembolization.

A prospective randomized trial was conducted to evaluate the efficacy of long-term oral administration of low-dose 5'-deoxy-5-fluorouridine (5'-DFUR) as an adjuvant chemotherapy, following transcatheter arterial embolization (TAE) in 40 patients with hepatocellular carcinoma (HCC). Forty eligible patients were randomized into two groups: 20 with TAE plus 5'-DFUR (400 mg/day) and 20 with TAE alone. A good necrosis rate or decrease in size of more than 70% of the original tumor mass was attained in 14 by the TAE plus 5'-DFUR arm, and in 12 by the TAE arm at 3 months after the first TAE. Although all five patients with HCC and 70-99% necrosis rate after the first TAE in the TAE alone arm showed a less than 70% necrosis rate at 12 months, four of the seven patients with a 70-99% necrosis in the TAE plus 5'-DFUR arm retained a necrosis of more than 70% at 12 months after the first TAE. The appearance rate of ascites and/or encephalopathy in patients with chemotherapy was not different from that of patients with TAE alone. One-year survival rates in the TAE plus 5'-DFUR arm and the TAE alone arm were 75.0% and 85.0%, 2-year rates were 64.2% and 66.2%, and 3-year rates were 64.6% and 49.7%, respectively. There was no significant difference in the survival curves. In conclusion, adjuvant therapy with 5'-DFUR was well tolerated without significant side effects, and it might maintain a good necrosis state of HCC after TAE. In order to confirm a beneficial effect of the chemotherapy on the survival period, a study using more patients and longer observation periods will be required.

Adult↗
PubMed1997

[Cranial MRI in the patients with chronic liver disease (CLD)].

We examined cranial MRI in 62 patients with CLD. Abnormal finding that high intensity area in symmetrical bilateral basal ganglia other than globus pallidum was found on both T-1 weighted images (T1WI) and fat suppression (chemical shift selective) images. This MRI finding was observed in 32 of 41 patients with cirrhosis while 1 of 21 patients with chronic hepatitis. This MRI finding was irreversible. The incidence of this MRI finding was correlated with severity of CLD and was statistically significant between in the patients with chronic hepatitis and those with cirrhosis. The contributing factors to the incidence of this MRI finding were severity of CLD and total bilirubin level by an analysis with logistic regression model. This MRI finding was detected clearer in a fat suppression imaging than in T1WI. The cause of this MRI finding was supposed not fat related substance by the finding of fat suppression imaging. This MRI finding would be useful for prediction of severity of CLD.

Adult↗
PubMed1996

Relationship between pretreatment viremia level and response to interferon-alpha therapy in chronic hepatitis C differs in viral type 1 and 2 infections.

To determine the contribution of virus-related factors to long-term remission of chronic hepatitis C infection, we analyzed viral type and viremia level in 185 patients who had undergone a six-month course of interferon-alpha therapy. These virus-related factors were measured by an enzyme-linked immunosorbent assay with use of viral type-specific antigens and the branched DNA (bDNA) signal amplification assay, respectively. Sustained and long-term sustained responses were achieved in 55% and 50% of the patients, respectively. Transient or no responses were observed in 30% and 15% of the patients, respectively. Thirty-five percent of viral type 1 patients and 82% of viral type 2 patients had long-term sustained responses. Forty-two percent of bDNA-positive and 71% of bDNA-negative patients experienced long-term sustained responses. On multivariate analysis, viral type, Knodell's intralobular score, and viremia level were strong independent predictors of long-term sustained response (P < 0.0001, = 0.0060, and 0.037, respectively). Viremia level, however, was a significant predictor only in viral type 1, not type 2, patients. The relation between pretreatment viremia level and response to interferon-alpha therapy in chronic hepatitis C differs in viral type 1 and 2 infections.

Chronic Disease↗
PubMed1996

A randomized, double-blind, controlled trial of natural interferon-beta therapy for e-antigen-negative chronic hepatitis B patients with abnormal transaminase levels.

Intermittent interferon (IFN) therapy appears to be effective for patients with e-antigen-negative chronic hepatitis B who exhibit abnormal fluctuations of alanine aminotransferase (ALT) levels and histological evidence of disease progression. To determine the optimal dose of IFN in such patients, we studied the effects of natural IFN-beta in a prospective, randomized, double-blind, controlled trial in 36 patients with e-antigen-negative chronic hepatitis B who repeatedly demonstrated abnormal fluctuations in ALT levels. Thirty-six patients were randomly assigned to three groups, receiving doses of: 0.3 MIU IFN (group 1; n = 12), 1 MIU (group 2; n = 12), or 3 MIU (group 3; n = 12), administered twice per week for 24 weeks. Patients were regarded as responders if ALT levels remained within the normal range and HBV-DNA tested negative for 6 months after the initiation of the therapy. According to this criterion, treatment was effective in 16.7% of the patients (2/12) in group 1, 33.3% (4/12) in group 2, and 75% (9/12) in group 3, the efficacy rate in group 3 being significantly higher than that in the other two groups. However, in 12 of the 15 responders, (80%) ALT levels were frequently elevated again within 3 years of the termination of IFN therapy. Although IFN was effective in controlling the manifestations of hepatitis in terms of e-antigen-negative patients who exhibited abnormal fluctuations in ALT, it appears that continuous treatment with intermittent high-dose IFN is necessary to maintain ALT levels within the normal range.

Adult↗
PubMed1996

Hepatitis C virus subtype 3b infection in a hospital in Japan: epidemiological study.

To elucidate the epidemiology of infection with hepatitis C virus (HCV) subtype 3b (a rare subtype thought to have originated in Southeast Asia) in Japan, we examined the genotypic subtype in 1397 patients with HCV-related chronic liver diseases. Of 1330 patients with identified HCV RNA genotypes. 960 had subtype 1b, 243 had subtype 2a, 97 had subtype 2b, 14 (1.1%) had subtype 3b, and 16 had other types of HCV or mixed subtypes. The age, gender, and severity of liver disease in patients with HCV subtype 3b did not differ from these features in patients with other subtypes. Eleven of the 14 patients with the 3b subtype had once worked at Company A in Tokyo, Japan. Multivariate logistic analysis showed that working history at that company was independently associated with the incidence of the subtype; the risk ratio was 207.2 (P < 0.0001). All 11 patients from Company A had received medical services, between 1953 and 1981, at Clinic C, which undertook medical care of the company staff. All 11 patients had received repeated intramuscular or intravenous injections for treatment of various diseases or for preventive vaccination for contagious diseases. The rare HCV subtype 3b, appeared to have been transmitted among the employees of a company through the performance of certain medical practices.

Adult↗
PubMed1996

A pilot study of corticosteroid priming for lymphoblastoid interferon alfa in patients with chronic hepatitis C.

Interferon treatment reduces the serum level of hepatitis C virus (HCV) and improves inflammatory activity, but relapse is frequently observed. In an attempt to develop a new therapeutic strategy that may reduce relapse and cure the disease, we evaluated the effect of corticosteroid priming on lymphoblastoid interferon alfa in an open randomized clinical trial. The level of HCV RNA increased significantly during corticosteroid priming (from 5.60 [median] to 21.0 x 10(5) Eq/mL; P = .0004) but decreased to the pretreatment level 4 weeks after cessation of corticosteroid (7.0 x 10(5) Eq/mL; P = .07). Sustained normalization of alanine transaminase (ALT) level and virus clearance, confirmed by negative results for HCV RNA using reverse-transcription nested polymerase chain reaction (PCR), were observed over a period of 6 months in 8 of 19 (42.1%) corticosteroid-primed patients, compared with 6 of 19 patients (31.6%) treated with interferon only. A "rebound" of ALT after the withdrawal of corticosteroid was observed in only 2 of 19 patients primed with corticosteroid, but both showed sustained responses. Multivariate analysis for factors predictive of the sustained response indicated that HCV titers measured immediately before interferon therapy and HCV genotype were statistically significant (P = .006 and P = .025, respectively). Our results indicated that corticosteroid priming has a marginal benefit over treatment with interferon alone and that large-scale clinical trials are necessary to determine whether interferon with corticosteroid priming is more effective than interferon alone.

Adult↗
PubMed1995

Diagnosis of hepatocellular carcinoma by concanavalin A affinity electrophoresis of serum alpha-fetoprotein.

BACKGROUND: Concanavalin A (Con A) affinity electrophoresis of serum alpha-fetoprotein (AFP) can distinguish hepatocellular carcinoma (HCC) from other malignancies when the serum AFP concentration is elevated. However, Con A has not been able to distinguish HCC from benign chronic liver disease such as cirrhosis or chronic hepatitis. METHODS: The Con A affinity electrophoresis of serum AFP was analyzed in patients with a serum AFP concentration greater than 50 ng/mL by antibody affinity electrophoresis and Western blotting in an attempt to distinguish hepatocellular carcinoma from benign chronic liver disease. Before the assay, the serum AFP concentrations were adjusted between 100 ng/ml and 300 ng/ml by concentrating or diluting the samples. RESULTS: Of 180 patients with HCC, 44 (24%) had a single band and 91 (51%), 35 (19%), and 10 (6%) had 2, 3, and 4 bands, respectively. All 35 patients with chronic hepatitis had a single band. All but 1 of 72 patients with cirrhosis had a single band. Multiple AFP bands on Con A affinity electrophoresis appear to be diagnostic of HCC. This method has a sensitivity of 76%, a specificity of 99%, a positive predictive value of 99%, and a negative predictive value of 71% for detecting HCC. The number of AFP bands correlated with serum AFP concentration and tumor size in patients with HCC. CONCLUSIONS: This assay is useful for distinguishing HCC from benign chronic liver diseases.

Adult↗
PubMed1994

[The expression of neural cell adhesion molecule (NCAM), neural invasion and recurrence patterns in rectal cancer--a study using anti-NACM (neural cell adhesion molecule) antibody].

Neural invasion may be one of the main causes of local recurrence, but its mechanism has not been sufficiently clarified. We previously reported that the expression of NCAM on cancer cells was correlated with neural invasion in pancreatic cancer. In this study, we examined the neural affinity of rectal cancer cells and the relationship between neural invasion and recurrence patterns of rectal cancers. A total of 64 rectal adenocarcinoma were examined. Specimens from 17 patients (27%) revealed perineural invasion. The incidence of neural invasion increased with the frequency of venous invasion and the degree of lymph node metastasis, but not significantly. The incidence of the expression of NCAM in rectal cancer cell was 45.3 percent. Neural invasion of rectal carcinoma was significantly related to the expression of NCAM (p < 0.05). NCAM immunocytolocalization was classified into the focal type, and the diffuse type. Concerning the recurrence type, 8 of 9 cases that developed local recurrence showed either presence of neural invasion or expression of NCAM. Liver metastasis was associated with absence of neural invasion or NCAM expression. The expression of NCAM may contribute to local recurrence, whereas the absence of NCAM may predict liver metastasis.

Adenocarcinoma↗
PubMed1994

Hepatocellular carcinoma with splenic metastasis developing after 16 years of chemotherapy for chronic myelogenous leukemia: a case report.

A case of hepatocellular carcinoma (HCC), which developed during chemotherapy for chronic myelogenous leukemia (CML), is presented. A 55-year-old Japanese man, who had received an alkylating agent for 16 years, was diagnosed as having HCC with clinically evident splenic metastases. The patient died of the HCC rupture three months after diagnosis. The autopsy revealed the HCC to have developed from the non-cirrhotic liver. In the present case, DNA damage due to the long-term chemotherapy with the alkylating agent for CML may have endowed the HCC induced by post-transfusion hepatitis and alcohol abuse with an aggressive proliferative potential. This is the first report on HCC in association with CML.

Busulfan↗
PubMed1990

[A case of complete remission in brain metastasis from lung adenocarcinoma with EAP (etoposide, adriamycin, cisplatin)].

A 61-year-old male patient who developed brain metastasis 6 months after the lung resection for adenocarcinoma was treated with the 3 courses of EAP (Etoposide 150 mg/body/course, ADR 40 mg/body/course, CDDP 100 mg/body/course). Although our doses were lesser than Preusser's, symptoms soon subsided, and brain CT revealed a complete disappearance of metastases 16 days after the beginning of the first EAP course. During 5 months of CR, the patient had enjoyed his common daily life, the relapse, however, occurred. Since brain metastasis is life threatening, such an effective regimen like EAP should be made further studies to it.

Adenocarcinoma, Papillary↗