PubMed Health⌕ Search

Biomedical subjects

H Kumada

Publications and source records attributed to H Kumada.

At least 19 recordsLinked to original sources
PubMed2002

In-phantom two-dimensional thermal neutron distribution for intraoperative boron neutron capture therapy of brain tumours.

The aim of this study was to determine the in-phantom thermal neutron distribution derived from neutron beams for intraoperative boron neutron capture therapy (IOBNCT). Gold activation wires arranged in a cylindrical water phantom with (void-in-phantom) or without (standard phantom) a cylinder styrene form placed inside were irradiated by using the epithermal beam (ENB) and the mixed thermal-epithermal beam (TNB-1) at the Japan Research Reactor No 4. With ENB, we observed a flattened distribution of thermal neutron flux and a significantly enhanced thermal flux delivery at a depth compared with the results of using TNB-1. The thermal neutron distribution derived from both the ENB and TNB-1 was significantly improved in the void-in-phantom, and a double high dose area was formed lateral to the void. The flattened distribution in the circumference of the void was observed with the combination of ENB and the void-in-phantom. The measurement data suggest that the ENB may provide a clinical advantage in the form of an enhanced and flattened dose delivery to the marginal tissue of a post-operative cavity in which a residual and/or microscopically infiltrating tumour often occurs. The combination of the epithermal neutron beam and IOBNCT will improve the clinical results of BNCT for brain tumours.

Boron Neutron Capture Therapy↗
PubMed2001

Therapeutic effects of stronger neo-minophagen C at different doses on chronic hepatitis and liver cirrhosis.

Stronger neo-minophagen C (SNMC), a glycyrrhizin (GL) preparation, has been extensively used with considerable success in Japan for the treatment of chronic hepatitis. The aim of the present study was to elucidate the efficacy of administering massive doses of 100 ml/day to patients in whom standard administration (40 ml/day) for 2 weeks did not show sufficient improvement. A comparative study was conducted by dividing at random 100 cases (56.2%), out of a total of 178 enrolled, into two groups, one for the administration of 100 ml/day for 3 weeks (group A) and the other for administration of 40 ml/day for 3 weeks (group B). Cases were rated 'markedly improved'or 'improved' according to their ALT levels (defined respectively as <1.2 times and 1.2-1.5 times the normal upper level 3 weeks after treatment). Except those who dropped out or were otherwise not eligible for analysis, 44 and 46 cases were analyzed. In group A, 23 of 44 cases (52.3%) were rated 'improved' or better whereas only 12 of 46 (26.1%) in group B were 'improved' or better. Group A showed significant improvement compared to group B (P=0.017), thus documenting the greater efficacy of administering SNMC at 100 ml/day compared to only 40 ml/day.

Journal Article↗
PubMed2001

Efficacy of IFN therapy based on duration period of negative HCV-RNA during IFN administration.

We assessed the relationship between the duration period of negative hepatitis C virus (HCV)-RNA during interferon (IFN) therapy and the efficacy after prolonged IFN therapy in patients with HCV-genotype 1b and high virus load of more than 1 mega equivalents/ml (Meq/ml) retrospectively. A total of 100 patients who had HCV-genotype 1b and a high virus load of more than 1 Meq/ml and were treated with natural IFN-alpha for more than 12 months were enrolled in this trial. These patients were given 6 MU of IFN daily for 8 weeks, followed by three times weekly for another more than 44 weeks. The HCV-RNA pattern during IFN therapy according to negative or positive of the serum HCV-RNA by reverse transcription nested polymerase chain reaction (RT-nested PCR) from 2 months after the initiation of IFN to the termination of IFN were classified as follows: group 1: constant negative HCV-RNA (n=41 cases), group 2: constant positive HCV-RNA (n=35 cases), group 3: HCV-RNA pattern except for group 1 or group 2 (n=24 cases). A complete response (CR) was defined as negative HCV-RNA by RT-nested PCR at two points, 3 and 6 months after the completion of IFN therapy. CR rate was 58.5% (24 cases) in group 1, but CR rate in group 2 or group 3 was 0%. In group 1, the CR rate was 100% (10/10) in patients with negative HCV-RNA constantly for period of more than 24 months during IFN therapy. On the other hand, all patients who had positive HCV-RNA 2 months after the initiation of IFN did not get CR. In conclusion, it seems to us that the attainment of constantly negative HCV-RNA for the period of more than 24 months during IFN therapy is highly related to CR.

Journal Article↗
PubMed2001

Risk factors of hepatitis C virus-related liver cirrhosis in young adults: positive family history of liver disease and transporter associated with antigen processing 2(TAP2)*0201 Allele.

The aim of this study was to clinically characterize young patients with hepatitis-C-related cirrhosis. We compared 27 patients with liver cirrhosis (Group LC) who were anti-HCV positive, aged 40 years or less at the time of diagnosis, with 323 consecutive patients with HCV-related chronic hepatitis (Group CH) matched for age and gender. Furthermore, Group LC was divided into two arbitrary groups (29-35 years, n = 8 /36-40 years, n = 19), based on the age of patients at the time of diagnosis of liver cirrhosis. Patients' characteristics and family history were investigated, and the frequency of transporter associated with antigen processing 2 (TAP2) was determined. A family history of liver disease was present in 40.7% of Group LC but in 18.0% of Group CH (P < 0.05). The younger the age of diagnosis of cirrhosis in Group LC, the higher the frequency of a positive family history (29-35 years, 87.5%; 36-40 years, 21.1%, P < 0.05). The frequency of TAP2*0201 was significantly higher in young adult patients with HCV-related liver cirrhosis than in HCV carriers with normal ALT (P < 0.05), and tended to be higher than in uninfected normal subjects (P = 0.05). The cumulative survival rate of cirrhosis patients with family history of liver diseases was significantly lower than that of cirrhosis patients without such history (P < 0.05). Our findings suggest that a positive family history of liver disease and TAP2*0201 polymorphism may be risk factors for HCV-related liver cirrhosis in young adults.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Genotype may correlate with liver carcinogenesis and tumor characteristics in cirrhotic patients infected with hepatitis B virus subtype adw.

To identify the influence of hepatitis B virus (HBV) genotype on development of hepatocellular carcinoma (HCC) and clinical outcome in chronic HBV infection, 26 consecutive cirrhotic patients infected with HBV subtype adw were investigated prospectively. HBV serology was undertaken using subtype-specific antibodies against hepatitis B surface antigens. The HBV genotype was determined by sequencing directly the polymerase chain reaction products of the HBV S gene. When HCC occurred, patients underwent transcatheter arterial embolization therapy. If tumor necrosis was incomplete, additional embolization therapy was carried out after a 3- to 4-month interval. At a median follow-up of 14.1 years (range 2.2 to 31.7), HCC occurred in 9 (35%) of 26 patients. Nineteen patients were infected with genotype B and 7 with genotype C. Four of the 19 genotype B patients (21%) and 5 of the 7 genotype C patients (71%) developed HCC (P = 0.058). Patient age (<45 years or 45 < or = ) at diagnosis of cirrhosis was the only significant independent factor influencing liver carcinogenesis by multiple logistic regression analysis and Cox's regression analysis (P = 0.0069 and 0.029, respectively). When analysis was limited to the age of 45 years or more at the last visit, genotype was the only contributory factor to HCC development by univariate analysis (P = 0.038). Whereas genotype B patients responded well to embolization therapy and had no recurrence of HCC for a prolonged period of time, genotype C patients showed poor responses and died of hepatic failure due to rapid HCC progression despite embolization therapy. The cumulative incidence of survival was significantly higher in the genotype B group (P = 0.0049). The HBV genotype correlated with the development of HCC, response to embolization therapy, and recurrence of HCC. Determination of HBV genotype may be useful in predicting outcomes in HBV subtype adw-related cirrhosis.

Adult↗
PubMed2001

Incidence of the appearance of the red color sign on esophageal varices and its predictive factors: long-term observations of 359 patients with cirrhosis.

PURPOSE: The red color sign observed by endoscopic examination is a reliable predictive factor for variceal bleeding. The aim of this study was to calculate the incidence of the appearance of the red color sign and to evaluate its predictive factors. METHODS: Endoscopic examination was repeatedly performed in 359 consecutive patients diagnosed as having liver cirrhosis with or without esophageal varices, during a median follow-up period of 2651 days. RESULTS: The incidence of the appearance of the red color sign on esophageal varices at the end of the tenth year was compared among patients without varices (11.4%), those with small varices (45.4%), and those with mid-size varices (65.0%). The difference was significant (P < 0.0001). The number of varices (P = 0.0010), size of varices (P = 0.0064), platelet count (P = 0.0168), and alpha-fetoprotein level (P = 0.0207) were significantly correlated with the appearance of the red color sign, as estimated by the multivariate Cox hazard model. To exclude the influence of carcinogenesis, observation was stopped when hepatocellular carcinoma was discovered. Additive predictive factors with significance were: number of varices (P = 0.001), size of varices (P = 0.027), and platelet count (P = 0.0315). CONCLUSIONS: Endoscopic signs of esophageal varices and platelet count were significant predictors for the appearance of the red color sign.

Color↗
PubMed2001

Twice-daily administration of interferon-beta for chronic hepatitis C is not superior to a once-daily regimen.

PURPOSE: Although interferon (IFN) is commonly used for the treatment of chronic hepatitis C virus (HCV) infection, eradication of the virus occurs in only a small proportion of patients with genotype 1b and a high virus titer. Modified IFN therapies have been tried, with only limited benefit. Recently, the administration of IFN-beta twice per day has been reported to be more effective than the usual once-daily administration regimen. The aim of this study was to evaluate whether twice-daily IFN results in a sustained response in patients with chronic HCV infection with genotype 1b, and a high virus titer. METHODS: Twenty patients with genotype 1b and high HCV RNA level (more than 1 MEq/ml by branched DNA probe assay) were randomly assigned to receive either twice-daily 3 MU of IFN beta (group A) or once-daily 6 MU of IFN-beta (group B) for 4 weeks. All patients received a further daily dose of 6 MU IFN-beta for 12 weeks, followed by IFN-alfa three times a week for 16 weeks. RESULTS: Although a rapid fall in HCV RNA levels was noted in group A, a sustained response was observed in only one of nine patients in this group, and none of group B. Adverse effects of IFN were more frequent and pronounced in group A than in group B. CONCLUSIONS: We conclude that further modification, which combines the early strong anti-viral effects of the twice-daily regimen with long-term sustained response, is necessary for effective therapy of HCV patients with genotype 1b and high HCV RNA levels.

Adult↗
PubMed2001

Interferon therapy for flare-up of hepatitis B virus infection after emergence of lamivudine-induced YMDD motif mutant.

A 61-year-old man with chronic hepatitis B was treated with interferon (IFN)-alpha for flare-up after the emergence of a lamivudine-induced YMDD motif mutant. The YMDD mutant emerged 13 months after the initiation of lamivudine therapy. Despite this, lamivudine therapy was continued. Acute exacerbation occurred 25 months after the emergence of the YMDD mutant. Treatment with IFN-alpha resulted in rapid loss of hepatitis, B virus DNA, resolution of hepatitis, and clinical recovery.

Amino Acid Motifs↗
PubMed2001

Evaluation of quantitative measurements of hepatitis C virus RNA to predict sustained response to interferon by genotype.

Hepatitis C virus (HCV) virus load is one of the most important predictive factors for the outcome of interferon (IFN) therapy. Recent technological advances have allowed a more precise measurement of HCV load. However, the exact cutoff values that could be used to predict the outcome of IFN have not been established for each assay. Five recent quantitative assays were evaluated for the measurement of HCV (Amplicor monitor ver 1.0, Amplicor monitor ver 2.0 (GT), Amplicor monitor ver 2.0 (Cobas), Quantiplex branched DNA amplification (bDNA) ver 2.0 and HCV core protein level by enzyme immunosorbent assay) in 209 consecutive patients with chronic hepatitis C, who received IFN therapy. The results of the two second generation Amplicor monitor tests (GT and Cobas) showed the best correlation (r = 0.930), but the other tests also showed relatively good correlations (r = 0.646-0.925). Each method predicted the effect of IFN with comparable predictive efficacy, ranging from 77.0 to 80.8%. Receiver operating characteristic (ROC) curve analysis showed that Amplicor monitor ver 2.0 and bDNA ver 2.0 are superior in predicting the response in genotype 2a. The best cutoff value for predicting the response to IFN was different by genotype, which should be considered in selecting candidates for IFN treatment.

Adult↗
PubMed2001

Randomized controlled clinical trial of lymphoblastoid interferon-alpha for chronic hepatitis C.

Objective: Most of chronic hepatitis C patients with HCV-genotype 1 and a high virus load fail to eradicate the HCV-RNA by the interferon (IFN) or IFN/ribavirin therapy. But in these patients, IFN is often effective with regard to normalization of alanine aminotransferase (ALT). We had therefore the following two randomized controlled clinical trials to evaluate the effect of IFN which reduce ALT and maintain normalization of ALT. One approach (study 1) was to compare the efficacy of a 6 month course of three different dosages of recombinant IFN-alpha-2a in patients with chronic hepatitis C associated with HCV-genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml. Another approach (study 2) was to make clear the significance of an additional 6 month course of IFN in patients who had biochemical response during the first 6 month course of IFN (study 1). Methods: (1) Study 1; 45 patients with HCV-genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml were randomly assigned into three equal groups; group 1 was treated with 3 million units (MU), group 2 with 6 MU and group 3 with 9 MU. They were treated with IFN 3 times weekly for 6 months. Biochemical response was defined as normalization of ALT at the 6 month after initiation of IFN; (2) Study 2; Subsequently, of 23 patients with biochemical response by the first study, 22 were randomly assigned to two groups; patients in group A were continued to receive 3 MU of IFN-alpha-2a three times a week for an additional 6 months and patients in group B were discontinued IFN therapy. Results: (1) Study 1; One patient in group 1, three in group 2 and five in group 3 withdrew from IFN therapy because of IFN-related side-effects. Biochemical response was 10 (66.7%) patients of group 1,8 (53.3%) of group 2 and 5 (33%) of group 3 by the intention-to-treat (ITT) analysis. The biochemical response rate in group 1 was slightly higher than that in other two groups by the Cochran Armitage two-tailed test (P=0.066). With respect to serum HCV-RNA level, one patient in group 1, six patients in group 2 and four patients in group 3 became negative for HCV-RNA by reversed transcription nested-polymerase chain reaction (RT nested-PCR) at the end point of first 6 month course of IFN; (2) Study 2; The maintenance rate of ALT normalization was 88.9% (9/11) in group A and 11.1% (2/11) in group B. The maintenance rate of ALT normalization in group A was significantly higher than that in group B by the Fisher exact's test (P=0.0089). With respect to serum HCV-RNA level by RT nested-PCR, four patients in group A had negative HCV-RNA at the end of an additional IFN therapy. On the other hand, all the patients in group B had positive HCV-RNA at the same time. Conclusion: Our data suggested that a prolonged IFN therapy using a dose of 3 MU of IFN-alpha-2a is safe strategy to reduce ALT and to maintain ALT normalization in patients with HCV-genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml.

Journal Article↗
PubMed2001

Rapid decrease of plasma HCV RNA in early phase of twice daily administration of 3 MU doses interferon-beta in patients with genotype 1b hepatitis C infection: a multicenter randomized study.

Virological response to interferon (IFN) is poor in patients with plasma levels of HCV RNA higher than 1 Meq/ml and genotype 1b hepatitis C viral infection. In 60 patients, a randomized control study was conducted to compare 3 MU of IFN-beta twice daily for four weeks (group A) and 6 MU once a day for four weeks (group B) followed by a four-week administration of 6 MU once a day. The plasma levels of HCV RNA, determined by an amplicore-monitor method, for patients in group A were significantly lower than those for group B at the fourth and eighth day of IFN administration, and complete virological responses were noted in two patients from group A but none in group B. It is concluded that twice daily administration of 3 MU IFN-beta is more effective than once a day 6 MU in the early phase of IFN therapy.

Female↗
PubMed2001

Role of protein kinase C in the reduction of infarct size by N-methyl-1-deoxynojirimycin, an alpha-1,6-glucosidase inhibitor.

Preischaemic treatment with N-methyl-1-deoxynojirimycin (MOR-14), an alpha-1,6-glucosidase inhibitor, attenuates glycogenolysis and lactate accumulation during ischaemia and markedly reduces infarct size in rabbit hearts. In the present study, we have investigated whether protein kinase C (PKC), a principal mediator of ischaemic preconditioning, is also involved in the cardioprotective effect of MOR-14. To assess the effect of PKC inhibition on infarct size in MOR-14-treated hearts, 38 rabbits were subjected to 30 min of ischaemia followed by 48 h of reperfusion. Infarct size, as a per cent of area at risk, was significantly smaller in rabbits administered 100 mg kg(-1) of MOR-14 10 min before ischaemia (17+/-2%, n=10), than in a control group (46+/-5%, n=10). This beneficial effect of MOR-14 was abolished when 5 mg kg(-1) of chelerythrine, a PKC inhibitor, was given 10 min prior to MOR-14 injection (39+/-4%, n=10), although chelerythrine alone did not alter infarct size (43+/-4%, n=8). Further, chelerythrine had no effect on MOR-14-induced attenuation of glycogen breakdown and lactate accumulation in hearts excised at 30 min of ischaemia. Immunoblot analysis of PKC in homogenates of Langendorff-perfused rabbit hearts revealed that MOR-14 significantly increased levels of PKC-epsilon in the particulate fraction at 20 and 30 min of ischaemia and in the cytosolic fraction at 30 min of ischaemia. Taken as a whole, our data suggest that PKC acts downstream of the inhibition of glycogenolysis by MOR-14 to reduce infarct size. Thus, activation of PKC is a more direct mediator of the cardioprotection afforded by MOR-14 than is inhibition of glycogenolysis.

1-Deoxynojirimycin↗
PubMed2001

Long-term interferon therapy for 1 year or longer reduces the hepatocellular carcinogenesis rate in patients with liver cirrhosis caused by hepatitis C virus: a pilot study.

BACKGROUND AND METHODS: In order to elucidate the influence of a long-term administration of interferon on the appearance rates of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-related cirrhosis, we retrospectively analyzed 694 patients with cirrhosis. A total of 113 patients underwent interferon therapy, including 25 patients with a long-term administration of interferon for 1 year or more, and the other 581 patients received no antiviral drugs. RESULTS: Crude cumulative appearance rates of HCC in the interferon and the untreated groups were 14.1, and 28.4% at the end of the 5th year, and 36.7 and 52.5% at the end of the 10th year, respectively (P = 0.0028). As there was a waiting time between diagnosis and treatment (median 2.0 months, average 21.3 months) in the treated group, Cox proportional hazard analysis using a time-dependent covariate was introduced to evaluate the anticarcinogenic effect of interferon. Although male sex, higher alpha-fetoprotein, older age, lower albumin concentration, and lower platelet count significantly increased the carcinogenesis rate, interferon was not a significant contributing factor to the carcinogenesis rate as a whole (hazard ratio = 0.83, P= 0.32). When the patients with interferon were divided into two groups according to therapy duration, long-term interferon therapy significantly decreased the hepatocellular carcinogenesis rate after an adjustment by significant covariates (hazard ratio = 0.28, P= 0.0048). CONCLUSION: When interferon is administered for 12 months or longer, effective cancer prevention will be achieved, even in patients with HCV-related cirrhosis.

Adult↗
PubMed2001

Muscle weakness in a Japanese family of Arg1239His mutation hypokalemic periodic paralysis.

Familial hypokalemic periodic paralysis is an autosomal dominant disorder. Recently, three predominant mutations were found in the muscle dihydropyridine-sensitive calcium channel alpha 1-subunit gene. We present a Japanese family that displays one of these, the Arg1239His mutation. All the affected individuals of this family displayed this mutation. Two cases had a history of recurrent episodes of muscle weakness and difficulty in running before their first paralytic attack. It is suggested that there are no racial differences with this mutation, and that mild muscle weakness occurs not only after but also preceding the first attack.

Adult↗
PubMed2001

Lamivudine therapy for spontaneously occurring severe acute exacerbation in chronic hepatitis B virus infection: a preliminary study.

OBJECTIVE: The nucleoside analogue lamivudine, a potent inhibitor of hepatitis B virus replication, has shown notable results in treating chronic hepatitis B. However, lamivudine has not been specifically tested for effectiveness against spontaneously occurring severe acute exacerbations of hepatitis in patients chronically infected with this virus. We addressed this issue in a pilot study. METHODS: Ten patients with chronic hepatitis B developed severe acute exacerbation spontaneously during follow-up; 3 of them developed hepatic failure shortly before entering the trial. Lamivudine was administered long-term to the 10 patients at a daily oral dose of 100 or 300 mg. RESULTS: All 3 patients with hepatic failure at initiation of treatment recovered dramatically. Of the remaining 7 patients, 5 recovered rapidly with lamivudine, but 2 progressed quickly to hepatic failure despite treatment. One died of sepsis and the other of multiorgan failure. In the 8 survivors, serum alanine transaminase activity decreased rapidly to normal with lamivudine therapy, and serum hepatitis B virus DNA level declined rapidly to undetectable levels. Serum total bilirubin concentrations normalized somewhat later. Prothrombin time improved steadily and gradually. Hepatitis B e antigen elimination or seroconversion was achieved in 3 survivors. No adverse effects were noted in any patient. All survivors had good quality of life with long-term lamivudine monotherapy. CONCLUSIONS: Lamivudine is effective, safe, and well tolerated by patients with spontaneous, severe, acute exacerbation complicating chronic hepatitis B virus infection, even in the presence of hepatic failure. Lamivudine appears to be an attractive therapeutic option and may represent the best choice.

Acute Disease↗
PubMed2001

Pathogenic significance and organic virus levels in patients infected with TT virus.

Previous reports documented the recovery of a DNA virus from a patient with posttransfusion non-A-G hepatitis and named TT virus (TTV). Although the virus was initially detected as a causative agent of hepatitis, there is doubt about its pathogenicity. The aim of this study was to clarify the relationship between TTV and liver diseases. Histopathological examination of liver biopsies from 14 patients with TTV genotype 1 positive non-B, non-C and non-G chronic hepatitis showed mild fibrosis and periportal/piecemeal necrosis. Using the real-time detection (RTD)-PCR method, we found that TTV DNA levels of genotype 1 in liver samples from 3 such patients were 100- to 1,000-fold higher than those in the paired serum samples. Further investigation using various tissues from 2 autopsies of patients with hepatitis C with hepatocellular carcinoma revealed that the concentrations of TTV DNA in the liver were also higher than in serum samples. However, the highest TTV DNA concentrations in these 2 autopsies were found in the lung and bone marrow, respectively. Our results suggest that TTV may replicate in various tissues including the liver and may cause only mild liver damage.

Adult↗