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Biomedical subjects

T Kumada

Publications and source records attributed to T Kumada.

At least 19 recordsLinked to original sources

Difference of HBV genotype distribution between acute hepatitis and chronic hepatitis in Japan.

BACKGROUND: Recently genotype A which is rare in the patients in chronic hepatitis B (CHB) was frequently noted in patients with acute hepatitis B (AHB). To investigate their clinical and virological features, we studied the AHB patients in the past 5 years. PATIENTS AND METHODS: 98 patients with AHB and 80 patients with CHB admitted to our hospital between 1998 and 2003 were studied. RESULTS: Genotype A was not found in CHB but was frequently noted in AHB (p < 0.001). Comparison of the clinical features of acute hepatitis between the two major genotypes, A and C, homosexual and heterosexual with multiple partners were frequently seen among genotype A patients (p < 0.001). On the other hand, infection from steady partner showed a tendency to be more frequent in genotype C (p = 0.065). In genotype A, the levels of HBVDNA on admission was higher (p = 0.007) and AHB has significantly more frequently progress to chronic infection than in genotype C (p = 0.028). Phylogenetic analysis of genotype A revealed that almost all strains from homosexual men belonged not to the African type A1 but to the Western type A2. CONCLUSION: Genotype A has increased recently among AHB in Japan. This fact may correlate to promiscuous intercourse in high risk group. Prophylactic efforts should be considered to prevent the prevailing of genotype A.

Acute Disease↗

Endoscopic management and follow up of Dieulafoy lesion in the upper gastrointestinal tract.

BACKGROUND AND STUDY AIMS: Dieulafoy's lesion is an important cause of upper gastrointestinal bleeding, and the safety and efficacy of endoscopic treatment have been widely accepted. The aim of this study was to evaluate the effectiveness of endoscopic management, including hemoclipping and injection methods, for bleeding Dieulafoy lesions in the upper gastrointestinal tract. PATIENTS AND METHODS: Between 1995 and 2003, 61 patients with bleeding Dieulafoy lesions underwent endoscopic treatment. The available hemostatic methods were hemoclipping, hypertonic saline-epinephrine injection, and pure ethanol injection. Clinical data, endoscopic features, and treatment outcome were analyzed retrospectively. RESULTS: Comorbid conditions were present in 39 patients (64 %). Active bleeding was noted in 20 patients (33 %). Hemoclipping was a selected treatment in 48 patients (79 %). Initial hemostasis was achieved in 61 patients (100 %). One patient had rebleeding 6 days after the initial procedure but was successfully treated endoscopically. The 30-day mortality was 0 %. During follow-up, for a mean of 47 months, 15 patients (25 %) died of causes unrelated to the Dieulafoy lesion. Two patients had recurrent bleeding due to non-Dieulafoy gastric ulcer, and responded to endoscopic therapy. We encountered no patients who required surgery. CONCLUSIONS: Dieulafoy lesion can be successfully managed by endoscopic treatment. The long-term outcome is acceptable.

Adolescent↗

Liver dysfunction among workers handling 5-nitro-o-toluidine.

BACKGROUND: 5-Nitro-o-toluidine is an aromatic nitro amino compound. While other aromatic compounds are known to damage the human liver and are registered as toxic substances, toxicity information concerning 5-nitro-o-toluidine is lacking. AIMS: To investigate the hepatotoxicity of 5-nitro-o-toluidine. PATIENTS AND METHODS: Of 15 workers in the same factory who handled 5-nitro-o-toluidine, three were hospitalised with symptoms of acute liver dysfunction. Suspecting a link between liver dysfunction and working conditions, we correlated workplace factors with clinical findings in all 15 workers. RESULTS: Blood biochemistry tests indicated liver damage in seven of 15 study subjects. Workers who handled 5-nitro-o-toluidine and nitrosyl sulphuric acid often loosened their respiratory protective equipment shortly after 5-nitro-o-toluidine powder had been dispersed into the air of the room. No potential hepatotoxins were present except for 5-nitro-o-toluidine. Six of the affected workers had handled 5-nitro-o-toluidine 12 to 20 times; the seventh worker had handled the powder three times; and the other eight workers without liver dysfunction had handled the material once or twice. No other significant differences in background were evident between the affected and unaffected workers, such as age, sex, or protective measures. Histological findings during recovery from liver damage were similar to those of acute viral hepatitis. None of the 15 subjects has demonstrated liver damage since the factory was closed. CONCLUSIONS: A link between liver dysfunction and 5-nitro-o-toluidine exposure is suggested by greater severity of liver dysfunction associated with more episodes of handling.

Acute Disease↗

Induction of angiotensin converting enzyme in neointima after intravascular stent placement.

BACKGROUND: To investigate the morphological changes of the arterial wall and the expression of angiotensin converting enzyme (ACE) in the arterial wall after stent placement in a canine model. METHODS: Seventeen mongrel dogs underwent stent placement (Gianturco's Z stent) in the aorta. Six animals were sacrificed at 4 weeks after stent implantation, and the other 5 animals at 12 weeks. The normal aorta was harvested from 6 dogs. The specimens were stained with hematoxylin-eosin (H&E) as well as by immunohistochemistry (smooth muscle specific a-actin, and ACE). Histomorphometric analysis was performed using the sections stained with H&E and smooth muscle specific a-actin. RESULTS: The total intimal area was significantly increased at all time points as compared with the control aorta. The a-actin positive intimal area was also significantly increased at all time points as compared with the control aorta. In the control aorta, luminal endothelial cells as well as a-actin positive medial cells occasionally exhibited faint cytoplasmic staining for ACE. In the 4- and 12-week stented aorta, a-actin positive cells in the neointima and media as well as macrophages in the adventitia stained strongly positive for ACE. CONCLUSIONS: ACE was induced in the neointima after stent placement of the canine aorta. Considering its multiple biological actions, ACE may be associated with the pathogenesis of neointimal hyperplasia after stent placement.

Actins↗

Impact of diabetes mellitus on the prognosis of patients with hepatocellular carcinoma.

BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) have coexisting cirrhosis or chronic hepatitis, often complicated by diabetes mellitus. In the current study, the authors evaluated the impact of diabetes mellitus on the prognosis of patients with HCC. METHODS: Among 581 patients with HCC who had been diagnosed and treated between 1990 and 1999, survival was compared between those patients with and those patients without diabetes mellitus. The rate of disease recurrence after treatment also was analyzed. RESULTS: Ninety-two patients (15.8%) had diabetes mellitus. There was no significant difference with regard to patient characteristics (i.e., age, gender, or alcohol intake) or liver function between those patients with and those patients without diabetes mellitus. No differences were observed in survival between patients with diabetes mellitus and patients without it. Among the 195 patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension, the survival of the 32 patients with diabetes mellitus was significantly poorer than that of the 163 patients without diabetes mellitus (P = 0.0273), despite no apparent difference in liver function between the 2 groups. On multivariate analysis, diabetes mellitus was found to be an independent factor predicting lower survival after treatment (P = 0.0077) among patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension. No difference in the rate of recurrence was observed between the two groups in all the patients and in those patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension. CONCLUSION: The results of the current study indicated that the presence of diabetes mellitus worsens the prognosis of patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension; it appears to impact prognosis in patients with HCC when HCC is treatable, based on the size and the number of lesions. However, diabetes mellitus did not appear to affect the prognosis in the general population of patients with HCC. Based on the current study data, diabetes mellitus does not appear to modify the progression of HCC and its recurrence after treatment, but it does appear to worsen the prognosis of patients with HCC by means of a rapid decline in remnant liver function caused by repeated treatment of HCC.

Aged↗

Analysis of hepatocellular carcinoma tumor growth detected in sustained responders to interferon in patients with chronic hepatitis C.

BACKGROUND: By analyzing a tumor growth of hepatocellular carcinoma (HCC) detected in sustained responders (SR) to interferon (IFN) therapy for chronic hepatitis C, we sought to determine the duration of follow up in SR that would be sufficient to detect HCC. In addition, we sought to elucidate the presence of HCC, which truly developed after the eradication of hepatitis C virus (de novo HCC development). METHODS: Tumor volume doubling time (DT) was calculated in a total of 46 cases of HCC detected in SR after IFN therapy. Based on DT, the annual growth rate was estimated for each tumor. Survival was compared between patients with HCC < or = 30 mm and patients with HCC > 30 mm in diameter. RESULTS: Doubling time in SR was similar to the previously reported DT of HCC irrespective of IFN therapy. However, extensive DT was observed in three HCCs despite relatively poor differentiation, which may represent de novo HCC development. In the analysis of tumor growth, all HCCs grew to exceed 20 mm in estimated diameter between 6 months and 7 years after the end of IFN therapy. Better survival was observed in patients with HCC < or = 30 mm in diameter compared with patients with HCC > 30 mm (P = 0.0107). In surviving patients, recurrences of HCC were very infrequent. CONCLUSIONS: We may be able to detect most HCC in SR between 6 months and 7 years after IFN therapy. However, we cannot neglect the presence of de novo HCC development after the eradication of HCV, which makes it difficult to determine completely sufficient follow-up duration after IFN therapy in this population.

Antiviral Agents↗

Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein.

BACKGROUND AND AIM: The Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) has been reported to be a highly useful marker for hepatocellular carcinoma (HCC) compared with a conventional serum AFP concentration, which allows earlier detection of HCC compared with using other imaging modalities and predicting prognosis after therapy. A collaborative prospective study involving nine Japanese hospitals was conducted to analyze the relationships between the tumor characteristics of a HCC patient and the percentage of AFP-L3/AFP total at the initial detection. METHODS: Between 1 October 1996 and 30 September 1997, a total of 388 patients with newly diagnosed HCC were registered. RESULTS: The cut-off level of the percentage of AFP-L3 was altered from 15 to 10%. The AFP-L3-positive HCC patients demonstrated the characteristics of having an advanced tumor, such as the number of tumors, maximum diameter, tumor spread, portal vein invasion, tumor stage, and tumor classification. With the conventional cut-off level of 15% of the percentage of AFP-L3, the malignant characteristics were more definite than that of 10%. However, no significant differences of serum AFP concentration were observed for malignant characteristics such as maximum diameter and histopathological grading. CONCLUSION: Serum AFP concentration does not reveal a malignancy of HCC, however, the AFP-L3-positive HCC has biologically malignant characteristics, especially portal vein invasion and lower tumor classification, and is an advanced tumor regardless of small tumor size and lower serum AFP concentration. As AFP-L3 shows the tumor characteristics, its presence should be an important factor in the determination of therapy and prognosis of patients.

Aged↗

Interferon responsiveness in patients infected with hepatitis C virus 1b differs depending on viral subtype.

BACKGROUND: Genotype 1b of hepatitis C virus (HCV) comprises mainly three subtypes, each named for its geographic prevalence (worldwide, W; Japan, J; and not in Japan, NJ). AIM: To characterise the newly identified subtypes of genotype 1b and to review factors associated with response to interferon (IFN) for each subtype. PATIENTS: Chronic hepatitis patients (80 men and 41 women; mean age 48.5 years, range 20.7--69.3) with HCV genotype 1b (W type, n=41; J type, n=38) or genotype 2a (n=42) were treated according to the same IFN protocol. Forty four patients (36.4%) negative for serum HCV RNA six months after cessation of treatment were considered complete responders. METHODS: Factors associated with complete response were investigated. RESULTS: Genotype 2a patients had lower viral loads (odds ratio 0.11 (95% confidence intervals (CI) 0.049--0.256)) and a better IFN response (odds ratio 0.25 (95% CI 0.117--0.552)) than genotype 1b patients whereas W type and J type patients had similar viral loads and responses to IFN. IFN response in W type patients was associated with female sex (odds ratio 0.23 (95% CI 0.055--0.983)) and low viral load (odds ratio 84.00 (95% CI 14.04--502.6)) whereas response in J type patients was related to transfusion history (odds ratio 7.20 (95% CI 1.443--35.91)), low viral load (odds ratio 117.0 (95% CI 17.82--768.3)), and genetic mutation in the interferon sensitivity determining region of the virus (odds ratio 0.08 (95% CI 0.013--0.553)). Multivariate analysis found low viral load (odds ratio 64.19 (95% CI 14.66--281.06)) to be the only significant independent factor associated with IFN response. CONCLUSIONS: Factors associated with IFN responsiveness in HCV infection differ with viral subtype.

Adult↗

Effect of the dose and duration of interferon-alpha therapy on the incidence of hepatocellular carcinoma in noncirrhotic patients with a nonsustained response to interferon for chronic hepatitis C.

OBJECTIVE: We evaluated the effect of dose and duration of treatment with interferon (IFN)-alpha on the incidence of hepatocellular carcinoma (HCC) after IFN treatment in patients with chronic hepatitis C. METHODS: A total of 291 noncirrhotic patients with chronic hepatitis C without hepatitis B virus coinfection in whom hepatitis C virus (HCV) was not eradicated by IFN-alpha therapy were retrospectively analyzed. The incidence of HCC after IFN therapy was compared according to the total dose or duration of treatment. RESULTS: Patients were followed up for 6-117 months after the end of IFN treatment. The duration of IFN treatment (< or =24 vs. >24 weeks) had no effect on the incidence of HCC. However, the incidence of HCC was significantly lower in patients who received >500 million units of IFN as a total dose than in patients who received < or =500 million units of IFN (p = 0.0480), and the total dose of IFN (>500 million units) was an independent factor affecting the incidence of HCC (p = 0.0405). In addition, when focusing on patients whose histology was F2 or F3 before IFN treatment, the suppressive effect of the total dose of IFN (>500 million units) was emphasized (p = 0.0049 in generalized Wilcoxon test and p = 0.0178 in multivariate analysis). CONCLUSIONS: Patients with chronic hepatitis C should receive more than 500 million units of IFN when IFN is used to decrease the incidence of subsequent HCC.

Adolescent↗

Feature-based control of attention: evidence for two forms of dimension weighting.

In three experiments, I examined whether prior knowledge of a target feature dimension is useful for guiding spatial attention to the target in a variety of tasks: visual search (Experiments 1A and 1B), texture segregation (Experiment 2), and visual enumeration (Experiment 3). Experiment 1A used a simple search task and found that reaction times for blocks in which a target was defined within a single feature dimension were shorter than those for blocks in which a target was defined across dimensions (within-dimension facilitation: WDF). Intertrial facilitation (ITF; Müller, Heller, & Ziegler, 1995), a dimension-based priming effect from one trial to the immediately following one, was also observed. Both WDF and ITF disappeared when the same stimuli were used under a compound search task (Experiment 1B), in which participants responded to an attribute of the target in a feature dimension different from its defining dimensions. Experiments 2 and 3 showed that WDF and ITF are not necessarily contingent upon each other: In a texture discrimination task, only WDF was found; in an enumeration task for six or seven targets, only ITF was found. These results show that the two forms of dimension weighting, WDF and ITF, are mediated by different mechanisms. WDF was eliminated when focal attention to targets was required, suggesting that feature-based modulation is limited as a source for controlling spatial attention (Kumada, 1999). ITF was correlated with type of response, suggesting dimension-specific response mechanisms (Cohen & Shoup, 1997).

Adult↗

Characteristics and course of small hepatocellular carcinomas in patients with hepatitis C virus types 1 and 2.

The associations between types of HCV and tumor characteristics and recurrence and survival after treatment of small HCC were investigated. Viral genotype-specific antibodies were measured in sera obtained at the time of diagnosis of HCC, in 92 patients with HCC < or = 2 cm in diameter who were treated between 1990 and 1998. The degrees of tumor differentiation and angiographically-evaluated hypervascularity were compared between patients infected with HCV type 1 and those with type 2. Survival, time to recurrence, and patterns of recurrence after initial treatment also were compared. On pathologic evaluation, 6 of 21 HCC (28.6%) in patients with HCV type 2 were well-differentiated, whereas 28 of 48 HCC (58.3%) in patients with HCV type 1 were well-differentiated (P = 0.0229). HCC in patients with HCV type 2 showed hypervascularity more frequently than HCC in patients with HCV type 1, with tumor staining evident by digital subtraction arteriography in 17 of 22 patients with HCV type 2 (77.3%) vs. 20 of 50 in patients with HCV type 1 (40.0%, P = 0.0036). Survival and overall recurrence rates were similar in patients infected with HCV type 1 and with HCV type 2 (P = 0.5537). In the analyses of patterns of recurrence, recurrences in patients infected with HCV type 2 were relatively more likely to be intrahepatic metastases (P = 0.0342), that was closely related to the differentiation of HCC. Multicentric occurrence of HCC was a more frequent type of recurrence in patients with HCV type 1 (P = 0.1619), and infection of HCV type 1 was an independent factor for multicentric occurrence in multivariate analysis (P = 0.0021). In HCC < or = 2 cm in diameter, HCV type 2 is associated with more progression of HCC than HCV type 1, whereas patients with HCV type 1 may be at higher risk for multicentric HCC occurrence after the treatment of HCC.

Aged↗

Japan-specific subtype of hepatitis C virus genotype 1b, J subtype, has relatively low pathogenicity.

The prognostic implication of viral genotype 1b for hepatitis C virus (HCV) infection has been controversial, possibly due to the pathogenetic heterogeneity of genotype 1b. We analyzed two newly delineated subtypes of HCV genotype 1b subtypes with respect to progression of liver disease. Patients with chronic HCV 1b infection (113 total, including 18 with chronic persistent hepatitis, 60 with chronic active hepatitis, 19 with cirrhosis, and 16 with hepatocellular carcinoma with cirrhosis) were studied to elucidate the factors associated with progression of liver disease. Factors evaluated included sex, age at diagnosis, blood transfusion history, and HCV genotype 1b subtype (W subtype or J subtype). W subtype was identified more often in association with chronic active hepatitis than with chronic persistent hepatitis (P = 0.0089), and more often in patients with cirrhosis than in those without (P = 0.0044). The age-, sex-, and transfusion history-adjusted odds ratios with respect to histological activity and presence of cirrhosis for W subtype compared to J subtype were 6.966 (1.856 to 26.145) and 6.397 (1.506 to 27.179), respectively. Age at diagnosis was the most important risk factor for predicting development of cirrhosis and carcinoma. In conclusion, the W subtype of HCV 1b is associated closely with histologically active disease and development of cirrhosis, whereas the Japan-specific J subtype has relatively low pathogenicity. HCV genotype 1b, therefore, is heterogeneous in its pathogenicity.

Adult↗

Effects of fibronectin bonding on healing of high porosity expanded polytetrafluoroethylene grafts in pigs.

BACKGROUND: We developed a new fibronectin bonding to expanded polytetrafluoroethylene (ePTFE) and previously reported that, in a dog carotid implant model, fibronectin bonding improves graft healing in high porosity ePTFE grafts. The purpose of this study was to further investigate the effect of the fibronectin bonding on graft healing in a pig carotid implant model. METHODS: Fifteen pigs received a high porosity ePTFE graft treated with the fibronectin bonding (fibronectin-bonded graft) on one side and an untreated graft (non-bonded graft) on the contralateral side. The grafts were explanted at intervals of 3 and 6 weeks and subjected to histological studies. RESULTS: At 3 weeks, the neointima of fibronectin-bonded grafts was better organized than that of non-bonded grafts. At 6 weeks, the morphologic features of the neointima were the same in fibronectin-bonded and non-bonded grafts. The neointima was completely organized. CONCLUSIONS: Together with the previous results with the dog model, fibronectin bonding could be expected to improve healing of the high porosity ePTFE grafts in humans.

Animals↗

[A new development in interventional radiology for hepatocellular carcinoma].

In Japan, interventional radiology (IVR) treatments such as transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), and intraarterial infusion chemotherapy play an important role in the treatment of hepatocellular carcinoma because of the associated cirrhosis (impairment of liver function) and occasional multicentricity. With progress in catheters, embolic materials, and imaging equipment such as the so-called "IVR-CT", superselective TAE and precise evaluation of tumor lesions has become feasible. However, the impact of TAE on survival in patients with hepatocellular carcinoma remains to be determined because no survival benefit was seen in four of five randomized controlled trials (RCTs) in Europe and Eastern countries, in which TAE was compared with no treatment (3 trials), i.v. 5-fluorouracil (1 trial), or tamoxifen (1 trial). To resolve questions arising from these results, a fair number of trials, particularly RCTs are needed in Japan.

Carcinoma, Hepatocellular↗

Electron spin echo study of long-lived radicals which cause mutation in gamma-ray irradiated mammalian cells.

Long-lived radicals, produced by gamma-ray irradiation of mammalian cells at room temperature, cause mutation and morphological transformation in the cells. The local environment near the long-lived radicals in irradiated cells was investigated here by the analysis of electron spin echo envelope modulation (ESEEM) spectra. The number of hydrogen (deuterium) atoms surrounding the long-lived radical, which may correspond to the number of water molecules, was estimated roughly as one or two. It is postulated that the long-lived radicals are generated in the interior of biopolymers. The radicals are not produced by the reaction of OH radicals, but mainly by the decomposition of biopolymer which absorbed directly the energy of the ionizing radiation.

Albumins↗

The effect of retreatment with interferon-alpha on the incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

BACKGROUND: Interferon (IFN) has been reported to have beneficial long term effects that reduce the occurrence of hepatocellular carcinoma (HCC), even in patients who do not have complete responses to IFN. The authors evaluated the effect of retreatment with IFN-alpha on the long term prognoses of those with incomplete responses to their initial IFN-alpha treatment. METHODS: Among 271 patients with incomplete responses to initial IFN-alpha treatment who had received sufficient dose and duration (a total dose of more than 350 megaunits administered over a period longer than 12 weeks) between October 1989 and September 1997, 63 patients received retreatment and 208 did not. The authors retrospectively compared the incidence of HCC between patients who received retreatment and those who did not. RESULTS: There were no significant differences in the clinical characteristics between these two groups. The cumulative incidence of HCC was significantly lower among the patients who had retreatment, and retreatment with IFN-alpha was the only factor that correlated with the lower incidence of HCC in multivariate analysis. The results were similar when the 12 patients with complete responses to retreatment were excluded from the analysis. CONCLUSIONS: Retreatment with IFN-alpha appeared to have the additional effect of suppressing the development of HCC in patients who had incomplete responses to the initial treatment, even when the hepatitis C virus was not cleared (i.e., a complete response was not achieved) with retreatment. Further prospective study is required.

Adolescent↗