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Biomedical subjects

Kenji Ikeda

Publications and source records attributed to Kenji Ikeda.

At least 109 records · Page 6Linked to original sources
PubMed2003

Efficacy of prolonged interferon therapy for patients with chronic hepatitis C with HCV-genotype 1b and high virus load.

BACKGROUND: In patients with hepatitis C virus (HCV)-genotype 1b and a high virus load, of more than 1 Meq/ml by the DNA probe assay, the clearance of HCV-RNA was achieved in only 10% with a 6-month interferon (IFN) course. We therefore assessed the efficacy of prolonged IFN therapy in patients with HCV-genotype 1b and a high virus load. METHODS: A total of 51 patients with HCV genotype 1b who were given 6 million units (MU) of natural IFN-alpha daily for 8 weeks followed by three-times-weekly treatment with natural IFN-alpha for 16 weeks, were enrolled in this trial. These 51 patients were randomly assigned to one of two schedule groups at the time of termination of the first IFN therapy. The 48-week-group patients (n = 25) were given 6 MU of natural IFN-alpha by intramuscular injection three times weekly for 24 weeks, beginning within a week after the termination of the first IFN therapy. The 72-week-group patients (n = 26) were given 6 MU of IFN-alpha by intramuscular injection three times a week for 48 weeks, beginning within a week after the termination of the first IFN therapy. The therapeutic efficacy was evaluated 24 and 30 months after the initiation of the first IFN treatment. A virological response (VR) to IFN therapy was defined as the normalization of serum alanime amino transferase (ALT) level (ALT less, similar 50 IU) and HCV-RNA negativity at the two time points. Biochemical response (BR) was defined as the normalization of serum ALT, but positivity for HCV-RNA, assessed by commercial Amplicor HCV qualitative assays, at the two time points. RESULTS: The efficacy of IFN treatment was assessed in relation to the IFN administration schedule by intention-to-treat (ITT) analysis and per-protocol analysis. With respect to the IFN regimen, VR occurred in 16.6% (4/24) of the patients in the 48-week-group with additional IFN and in 20% (5/25) in the 72-week-group with additional IFN by ITT analysis. The BR rate was 33.3% (8/24) in the 48-week group and 48% (12/25) in the 72-week group. CONCLUSIONS: We found that prolonged IFN therapy could be a worthwhile treatment strategy for patients with HCV genotype 1b and a high serum virus load.

Adult↗
PubMed2003

Long-term prognosis by lamivudine monotherapy for severe acute exacerbation in chronic hepatitis B infection: emergence of YMDD motif mutant and risk of breakthrough hepatitis -- an open-cohort study.

BACKGROUND/AIMS: Comparison of long-term prognosis in patients with chronic hepatitis B treated with lamivudine, with or without severe acute exacerbation (SAE). METHODS: In chronic hepatitis B HBeAg-positive patients on lamivudine monotherapy, 21 patients with SAE were retrospectively compared with 63 patients without SAE. Both groups were matched for age and sex. We investigated the efficacy and problems associated with monotherapy with respect to SAE. RESULTS: In SAE and non-SAE, HBeAg seroconversion rates were 21.1 vs. 27.6%, 20.0 vs. 50.0%, and 14.3 vs. 66.7% at 1, 2, and 3 years, respectively. YMDD mutant emerged later in SAE than in non-SAE, but the emergence rates in SAE almost exceeded those of non-SAE from 2 years (rates of about 35%). DNA breakthrough (hepatitis B virus DNA becoming detectable after a period of negativity, accompanied by emergence of YMDD mutant) and breakthrough hepatitis (alanine aminotransferase becoming abnormal after a period of normalization, accompanied by DNA breakthrough) also appeared later in SAE than in non-SAE, but the rates in SAE exceeded those of non-SAE at 3 years. CONCLUSIONS: Our results suggest that Japanese genotype C-dominant hepatitis B patients with SAE seem to be at greater risk of re-exacerbation after temporary relief of the initial SAE by long-term lamivudine monotherapy, compared with those without SAE.

Adult↗
PubMed2003

The influence of hepatitis B virus genotype on the development of lamivudine resistance during long-term treatment.

BACKGROUND/AIMS: Genotype-dependent development of lamivudine resistance in hepatitis B virus (HBV) has not been reported. METHODS: We determined the cumulative rate of emergence of YMDD motif mutant in 213 Japanese patients with chronic hepatitis B infected with genotype A, B, or C and treated with lamivudine for more than 1 year. RESULTS: The emergence rate of lamivudine resistance was independent of the genotype (A, B, and C). In contrast, the emergence rate was significantly higher in the Ba ("a" stands for Asia) subgroup of HBV than in Bj ("j" for Japan) subgroup (P<0.05). For genotype C (HBV/C), the emergence rate in hepatitis B e antigen (HBeAg)-positive was significantly higher than in HBV/C-HBeAg-negative (P<0.05), but the rate in HBV/B-HBeAg-positive was similar to HBV/B-HBeAg-negative. Only four patients with HBV/C developed severe acute exacerbation of hepatitis accompanied by emergence of YMDD mutant, but none of the patients with other genotypes developed such complication. CONCLUSIONS: Our results suggest that lamivudine resistance in HBV does not seem to depend on the genotype but rather on the subgroup of HBV/B. The results also suggest that lamivudine resistance according to HBeAg state might be different between HBV/B and HBV/C. Large-scale prospective studies of each genotype should be conducted in the future to confirm these findings.

Adult↗
PubMed2003

Immunohistochemical study of brain-derived neurotrophic factor and its receptor, TrkB, in the hippocampal formation of schizophrenic brains.

Recently, the pathogenesis of schizophrenia has been investigated from the perspective of neurodevelopmental dysfunction theory. On the other hand, it has been indicated that neurotrophic factors, such as nerve growth factors, brain-derived neurotrophic factor (BDNF), and neurotrophin-3, are significantly involved in the development and functional differences of central nervous system (CNS). Some reports proposed that the dysfunction of these factors could explain the pathogenesis of schizophrenia possibly. In this study, the authors investigated immunohistochemically the distribution and/or morphology of BDNF and TrkB, its peculiar receptor, in the hippocampal formation of schizophrenic brain. As a result, BDNF-positive pyramidal cells in the CA2 and neurons in the CA3 and the field of the CA4 were intensely stained compared to those of normal control. Staining of TrkB-positive neurons showed a signet-ring like shape in the hippocampus of normal control brains. Such figures were not observed on staining of those neurons from schizophrenic brains. In the control cases, TrkB-immunopositive varicose fibers were frequently seen. Those observed differences between schizophrenic and normal cases may indicate the existence of dysfunction of BDNF and TrkB in schizophrenic brain, and this dysfunction may be one of the factors involved in the pathogenesis of schizophrenia.

Adult↗
PubMed2003

Serum levels of gamma-globulin and total bilirubin influence the prevalence of multiple extrahepatic complication in patients with hepatitis C virus infection.

Patients with chronic hepatitis C virus (HCV) infection develop various extrahepatic complications. In this study, we analyzed as following. (1) The prevalence and interrelation of multiple extrahepatic manifestations. (2) Exact factors that are related to multiple extrahepatic manifestations. Consecutive autopsies of 261 cases with HCV infection that had undergone autopsy in 1988-1998 were enrolled. One hundred and forty consecutive patients who had gastro enteric carcinoma and underwent autopsy after death in our institution during the same period were used as controls. These 140 patients did not have hepatitis virus and chronic hepatitis or liver cirrhosis histologically. The prevalence of glomerulonephritis (GN), sialadenitis, thyroiditis, and idiopathic pulmonary fibrosis (IPF) was determined histologically. 'Multiple extrahepatic complications' was defined as the presence of two or more of the above four extrahepatic complications. Multiple logistic regression analyses of the risk for the multiple extrahepatic manifestations were performed. GN was present in 58.6% (153 cases), sialadenitis in 16.1% (42 cases), thyroiditis in 7.7% (20 cases), and IPF in 5% (13 cases) in cases of HCV infection. In addition, 37 out of 261 (14.2%) and seven (2.7%) cases had two and three extrahepatic complications, respectively. Multivariate analysis showed that multiple extrahepatic complications correlated with high serum gamma-globulin levels (>/=2.5 g/dl) and high serum total bilirubin levels (>/=1.2 mg/dl) about 1 year before death. Moreover, about 70-80% of patients with sialadenitis, IPF, or thyroiditis had other extrahepatic manifestations. HCV-positive patients with high serum gamma-globulin or high total bilirubin are at high risk of multiple extrahepatic complications.

Journal Article↗
PubMed2003

Randomized trial of prolonged interferon retreatment for chronic hepatitis C patients with HCV-genotype 1b and high virus load.

The aim of this study was to examine whether 78 week course of interferon (IFN) retreatment could improve the beneficial effect of IFN in chronic hepatitis C patients compared with 52 week course of IFN retreatment. Inclusion criteria were biopsy-proven chronic hepatitis, serum HCV-RNA level of more than 1 Meq/ml, HCV-genotype 1b, abnormal serum alanine aminotransferase (ALT), and transient negative conversion for HCV-RNA during the initial course of IFN therapy. Forty-one patients were randomly assigned to two groups, receiving total doses of: 1410 MU for 52 weeks (a 52 week-group: n=20), or 1995 MIU for 78 weeks (a 78 week-group: n=21). But three patients (one in the 52 week-group and two in the 78 week-group) were withdrawn from the study due to a transfer, refusal after randomization, and occurrence of malignant lymphoma before IFN retreatment, respectively. Therefore remainder 38 patients were studied about efficacy of IFN administration. A virological response (VR) to IFN therapy was defined as HCV-RNA negativity by the reverse transcription nested polymerase chain reaction both 3 and 6 months after the completion of IFN retreatment. A biochemical response (BR) was defined as normalization of ALT but positive HCV-RNA both 3 and 6 months after the cessation of IFN therapy. According to these criteria, VR was 36.8% (7/19) in the 52 week-group and 21.1% (4/19) in the 78 week-group. BR was 5.3%(1/19) in the 52 week-group and 21.1% (4/19) in the 78 week-group. There was no significant difference between the 52 week-group and the 78 week-group with respect to the effect of IFN. We conclude that 52 week course of IFN retreatment may be a sufficient strategy if patients, who have HCV-genotype 1b and high virus load, show negative HCV-RNA and normal ALT level during the first IFN therapy.

Journal Article↗
PubMed2003

Usefulness of serum KL-6 for early diagnosis of idiopathic pulmonary fibrosis in patients with hepatitis C virus.

The aim of this study was to evaluate when the serum level of KL-6, a sensitive marker for idiopathic pulmonary fibrosis (IPF), rise prior to clinical onset of IPF. Eight hepatitis C virus (HCV)-positive patients with IPF were enrolled in this trial. The serum samples of these eight patients were stored -80 degrees C every 1-3 month during a follow-up period and enzyme-linked immunosorbent assay (ELISA) for KL-6 was done at the same time. Diagnosis of IPF was based on computed tomography and/or histology. Diagnosis of clinical onset of IPF was based on presence of dyspnea, dry cough, and audible fine crackles. At 1 year before clinical onset of IPF, the sensitivities of serum marker for IPF were 75% (6/8) for KL-6, 25% (2/8) for each of lactic acid dehydrogenase (LDH) and C-reactive protein (CRP). At 2 years before clinical onset of IPF, the sensitivities of the same serum markers were 62.5% (5/8), 12.5% (1/8) and 0% (0/8), respectively. The sensitivity of KL-6 at 1 and 2 year before clinical onset of IPF was significantly higher compared with LDH and CRP. Our results indicate that many future patients with IPF may have high levels of serum KL-6 at 1 or 2 years before clinical onset of IPF, suggesting that changes in serum KL-6 level can provide useful information for the early diagnosis of IPF in patients with HCV.

Journal Article↗
PubMed2003

Two distinct subgroups of senile dementia of Alzheimer type: quantitative study of neurofibrillary tangles.

The heterogeneity of senile dementia of Alzheimer type (SDAT) has been suggested by some authors clinically and neuropathologically. The heterogeneity of SDAT was investigated based on quantification of NFT combining Braak and Braak's neuropathological staging and the density of NFT in various areas of the cerebral cortex. Brain tissues were examined from 16 autopsy cases with clinically late onset dementia (> age 65) and neuropathologically diagnosed dementia of Alzheimer type (DAT). Gallyas-Braak staining was used for the quantification of NFT. The density of NFT was examined in the precentral gyrus, middle temporal gyrus (T2), parahippocampal gyrus and the amygdaloid nucleus. The 16 cases studied were divided into two groups depending on the number of NFT in the cortex (cut-off score: 5/mm2): the AD-like group (NFT > or = 5/mm2) and the common group (NFT < 5/mm2). The density of NFT in the precentral gyrus (t(3.225) = -9.007, P = 0.002) and T2 (t(3.365) = -3.774, P = 0.027) in the AD-like group was significantly higher than those in the common group. However, no significant difference was observed in the parahippocampal gyrus between the two groups (t(14) = -0.318, NS). Moreover, there were no significant differences between the two groups as regards age at onset and the duration of the illness. The present study revealed the possible existence of two subgroups in SDAT having significantly different NFT densities in various areas of the cerebral cortex without any significant difference in their duration of illness. This classification has no relationship to Braak and Braak's staging, which depends only on the distribution of NFT, irrespective of their density. Arai et al. revealed that the NFT density in AD was significantly higher than in SDAT. We suggest that the neuropathological findings of the AD-like group in SDAT resemble those of presenile AD.

Age of Onset↗
PubMed2003

Pick body disease and Pick syndrome.

Diagnostic criteria for Pick's disease have been criticized from many different viewpoints. This confusion is mainly derived from the ambiguity of this term 'Pick's disease' (PD), which may imply either purely histological findings, such as Pick body (PB), or a characteristic clinical syndrome that could occur even in the absence of PB. This taxonomic confusion will be circumvented by introducing the diagnostic term 'Pick body disease' to designate patients with the characteristic argyrophilic inclusions purely on histological grounds. In parallel, employment of 'Pick syndrome' to describe the time-honored clinical features may be more convenient and less confusing than PD because PD implies either the presence of PB or the clinical features, two aspects not necessarily linked to each other. Three-dimensional reconstruction of PB confirmed that tau-like immunoreactivity was accentuated at their periphery, as was recognized with the Bodian method. Preferential affinity of three-repeat tau pathology, as seen in Pick body disease, to the Bodian over the Gallyas method is distinct from the reversed affinity (the Gallyas over the Bodian method) of four-repeat tau pathology, as seen in corticobasal degeneration and in argyrophilic grains. This preference of silver staining is compatible with the mixed three- and four-repeat tau pathology, as seen in NFT of the Alzheimer's type, which are stained with both the Bodian and Gallyas staining. This will provide a practical basis on which to differentiate these disorders based on their distinctive tau species and possible relation of tau species to staining profile on these silver methods.

Brain↗
PubMed2003

Consistently low hepatitis B virus DNA saves patients from hepatocellular carcinogenesis in HBV-related cirrhosis. A nested case-control study using 96 untreated patients.

BACKGROUND: To elucidate the influence of serum hepatitis B virus (HBV) load on hepatocellular carcinogenesis in cirrhotic patients, HBV-DNA was sequentially measured. PATIENTS AND METHODS: Among 160 consecutive patients with HBV-related cirrhosis who received no anti-viral therapy, serial assay of HBV-DNA concentration was available in 146 (91.3%): 48 developed hepatocellular carcinoma (HCC) and 98 did not during a median of 11.7 years. HBV-DNA of 10(3.7) copies/ml or less was considered as low. RESULTS: Of the 48 cases with eventual HCC development (group A), 9 showed intermittently high HBV-DNA, and the other 39 persistently high values. Among 48 age- and sex-matched control patients (group B) selected from the 98 HCC-free patients, 9 had continuously low HBV-DNA, 13 showed a settled down course of HBV-DNA, 9 intermittently high, and the remaining 17 patients demonstrated continuously high HBV-DNA. High HBV-DNA in the last 3 years was significantly associated with carcinogenesis (group A; 0/48 vs. group B; 22/48, p < 0.0001). No patient with a continuously low HBV-DNA for the last 3 years developed HCC. CONCLUSION: Persistence of high HBV-DNA concentration suggested an increased risk of carcinogenesis. Sequential analysis of HBV-DNA is important in the assessment of the carcinogenesis risk.

Adult↗
PubMed2003

Precore wild-type hepatitis B virus with G1896 in the resolution of persistent hepatitis B virus infection.

OBJECTIVE: Factors influencing the resolution of persistent hepatitis B virus (HBV) infection were sought for. METHODS: The loss of hepatitis B surface antigen (HBsAg) from serum was correlated with mutations in HBV DNA for a hepatitis B e antigen (HBeAg)-minus phenotype in patients infected with HBV genotype C and positive for HBeAg at presentation. RESULTS: HBeAg turned negative in all the 22 patients in whom HBV infection resolved, but only in 11 of the 25 patients with severe liver diseases (100 vs. 44%, p = 0.0001). The precore wild type (G1896) persisted significantly more frequently in the 22 patients in whom HBV infection resolved than in the 11 patients who developed decompensated liver cirrhosis or hepatocellular carcinoma (15/22 or 68% vs. 1/11 or 9%, p = 0.005). The double mutation in the core promoter (T1762/A1764) was comparably frequent in the two groups of patients at presentation (14/22 or 64% vs. 7/11 or 64%) and >15 years thereafter (18/22 or 82% vs. 10/11 or 91%). CONCLUSION: The precore wild type (G1896) would seem to facilitate the resolution of HBV infection, while the precore mutant (A1896) may induce severe liver diseases in patients with HBeAg-positive chronic hepatitis who have lost HBeAg from serum.

Adult↗
PubMed2003

Histological improvements after a three-year lamivudine therapy in patients with chronic hepatitis B in whom YMDD mutants did not or did develop.

OBJECTIVE: The long-term effects of lamivudine and the influence of YMDD mutants on the histology of chronic hepatitis B are not known. METHODS: 3-year lamivudine therapy was given to 16 patients with chronic hepatitis B. YMDD mutants did not develop in 9 patients (group A), while they appeared in the remaining 7 patients (group B). RESULTS: Biochemical and virological responses were invariably achieved in the 9 patients without YMDD mutants, while virological breakthroughs with or without biochemical relapses occurred in all 7 patients with such mutants. All 16 patients accomplished histological improvement, with the total histology activity index (HAI) score decreasing from 11.3 +/- 3.0 to 4.1 +/- 1.7 (p < 0.001). The total HAI score decreased from 11.6 +/- 3.8 to 3.4 +/- 1.3 in the 9 patients in group A (p < 0.001). Although to a significantly lesser extent (p < 0.02), the total HAI score also decreased in the 7 patients in group B from 10.9 +/- 1.0 to 5.0 +/- 1.7 (p < 0.001). CONCLUSION: The results obtained indicate that 3-year lamivudine therapy can induce histological improvements, regardless of the appearance of YMDD mutants accompanied by virological breakthroughs and biochemical relapses.

Adult↗
PubMed2003

Efficacy of lamivudine therapy and factors associated with emergence of resistance in chronic hepatitis B virus infection in Japan.

OBJECTIVE: Several reports have examined the efficacy of long-term lamivudine therapy and the risk factors involved in emergence of viral resistance in Japanese patients with hepatitis B virus (HBV) infection. However, the patient cohorts in such studies are relatively small. METHODS: We analyzed 234 chronically HBV-infected Japanese patients who were treated with lamivudine for more than 12 months. They comprised patients with HBV genotype A (n = 8), genotype B (n = 21), genotype C (n = 203) and other HBV genotypes (n = 2). RESULTS: In most patients, lamivudine resulted in normalization of alanine transaminase (ALT) levels at 6 and 12 months, and suppression of serum HBV DNA to undetectable levels by the branched chain DNA probe assay (bDNA). Rates of ALT normalization and non-detection of HBV DNA were higher among patients with genotype B than genotype C disease. The proportions of patients who achieved HBeAg loss were 27, 42 and 45% after 6 months, 1 year and 2 years, respectively. The emergence of mutations was not different among genotypes A, B and C by the Kaplan-Meier method. Multivariate analyses identified high HBV DNA level (bDNA >or=100 MEq/ml) as an independent factor associated with emergence of the YMDD motif mutation in all patients. Among patients with genotype C disease, which is the predominant HBV genotype in Japan, multivariate analysis also identified high HBV DNA level and HBeAg positivity as factors associated with emergence of resistance. CONCLUSION: Patients exhibiting these factors at the commencement of lamivudine treatment must be monitored carefully at regular intervals for emergence of viral resistance.

Adult↗
PubMed2003

Recurrence rate and prognosis of patients with hepatocellular carcinoma that developed after elimination of hepatitis C virus RNA by interferon therapy. A closed cohort study including matched control patients.

BACKGROUND: Although hepatocellular carcinoma does develop after sustained response to interferon (IFN) in patients with chronic hepatitis C, details on the clinical prognosis have not been elucidated yet. PATIENTS AND METHODS: Among 12 patients with liver cancer arising after hepatitis C virus (HCV) elimination, 10 patients with potentially curative ablation were prospectively analyzed. Matched control patients were chosen from a patient list of surgical resection on the basis of age, sex, cancer stage, and severity of liver disease. Control patients were recruited with a ratio of 1:4, and all the control patients had positive HCV-RNA. RESULTS: One (10.0%) of 10 patients with virus elimination and 31 (77.5%) of 40 control patients eventually developed cancer recurrence during the same follow-up period. Cancer recurrence rates of the 10 cases and 40 controls were 10.0 and 55.3% at the 3rd year, and 10.0 and 72.2% at the 5th year, respectively. The recurrence rate in the 10 cases of virus elimination was significantly lower than that of control patients (p = 0.012). CONCLUSION: Although hepatocellular carcinogenesis after elimination of HCV-RNA by IFN treatment did rarely occur, the recurrence rate after radical therapy was significantly lower than that of untreated or non-responsive patients.

Antiviral Agents↗
PubMed2003

A pilot study of thymosin alpha1 therapy for chronic hepatitis B patients.

OBJECTIVE: The efficacy of thymosin alpha 1 (Talpha1) in patients with chronic hepatitis B still requires confirmation. We, therefore, evaluated the efficacy of therapy in patients with chronic hepatitis B. METHODS: Sixteen patients were randomly assigned into one of two groups, treated with 0.8 mg of Talpha1 (low dose group; n = 8) or 1.6 mg Talpha1 (high dose group; n = 8), administered six times weekly for two weeks, followed by twice weekly for another 22 weeks. Responders were defined as patients having clearance of hepatitis B e antigen by radioimmunoassay and negativity of hepatitis B virus (HBV)-DNA by branched DNA signal amplification and normalization of serum alanine aminotransferase (ALT) 24 months after initiation of Talpha1 therapy. Transient acute exacerbation was defined as an increase of more than 300 IU/I in serum ALT level during Talpha1 therapy. RESULTS: The response rate was 37.5% (6/16). Talpha1 therapy had a significant effect when, 1) transient acute exacerbation was present (p = 0.0029), 2) the serum HBV-DNA level was < 100 Meq/ml prior to the commencement of Talpha1 therapy (p = 0.0063). The difference between low and high dose groups was not statistically significant (p = 0.608). CONCLUSION: The results of this trial show that: 1) a 24-week course of Talpha1 could be a worthwhile strategy for chronic hepatitis B patients with a serum HBV-DNA level of less than 100 Meq/ml; and 2) patients with a transient acute exacerbation during Talpha1 therapy generally often respond well.

Adjuvants, Immunologic↗
PubMed2003

[An autopsy case of argyrophilic grain dementia with abundant neurofibrillary tangles].

We reported an autopsy case of "senile dementia" showing neuropathologically abundant neurofibrillary tangles(NFT) and argyrophilic grains(AG) without senile plaques. A Japanese woman developed memory disturbance when she was 70 years old. The patient was hospitalized at age 80 and a cranial CT scan revealed bilateral mild atrophy of the temporal lobes and mild enlargement of the lateral ventricle, especially in the inferior horn. She died at the age of 80. Autopsy showed that her brain weighted 1220 g. Numerous NFT were found in the entorhinal (trans-entorhinal) region, subiculm, CA1-CA4, dentate gyrus, amygdala, nucleus basalis of Meynert, substantia nigra, and locus coeruleus. Furthermore, numerous AG were seen in the temporal lobe(T3, T4), amygdala, prominently in the basolateral nuclei. Obvious neuronal loss with gliosis was noted in the temporal lobes, including the hipocampal regions. Few senile plaques was detected in temporal lobe(T4). Sarkosyl-insoluble tau extracted from the temporal lobe consisted predominantly of four-repeat tau isoforms. To our knowledge, this is the first report of argyrophilic grain dementia complicated with tangle only dementia.

Aged↗