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Biomedical subjects

M Asaka

Publications and source records attributed to M Asaka.

At least 55 records · Page 3Linked to original sources

The relationship between consumption of antimicrobial agents and the prevalence of primary Helicobacter pylori resistance.

BACKGROUND: Primary and acquired resistance to the antimicrobial agents is a primary reason for the failure of Helicobacter pylori eradication therapies. We assessed the primary antibiotic resistance rates of H. pylori to three different antibiotics and its relationship due to the annual antibiotic consumption in Japan during the period prior to approval of anti-H. pylori therapy in Japan. MATERIALS AND METHODS: Antibiotic susceptibility was tested using the agar dilution method for clarithromycin, amoxicillin and metronidazole. Isolates were considered resistant when the MIC value was > 8 mg/l for metronidazole, > 1 mg/l for clarithromycin and < 0.5 mg/l for amoxicillin. RESULTS: Helicobacter pylori isolates were obtained from 593 Japanese patients from 1995 to 2000. Primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin was found in 11%, 9% and 0.3% strains, respectively. The proportion with clarithromycin resistance significantly increased from 7% in 1997-98 to 15.2% in 1999-2000 (p =.003). During the same period the metronidazole resistance rate also increased from 6.6% in 1997-98 to 12% in 1999-2000 (p =.02). The prevalence of clarithromycin and metronidazole was related to the annual consumption of these antimicrobial agents. CONCLUSION: Resistance rates for both clarithromycin and metronidazole appear to reflect the annual consumption of these agents. The high rate of clarithromycin resistance in Japan suggests that the effectiveness of clarithromycin-based therapies may be compromised in the near future.

Anti-Bacterial Agents↗

Analysis of mixed chimerism in patients after allogeneic stem cell transplantation using a capillary electrophoresis system.

We analyzed mixed chimerism (MC) after allogeneic stem cell transplantation (SCT) using a capillary electrophoresis system with four kinds of fluorescence-labeled primers for microsatellites (D3S1359, D6S89, ACTBP2, HGH). The sensitivities of all microsatellites were at least 3%. The present method is sufficiently rapid: only 3-4 h are needed to perform all the procedures. For analysis of MC in 30 patients who had undergone allogeneic SCT, heterozygosity of all microsatellites was over 88% and informativeness of ACTBP2 and HGH was over 73%. We analyzed MC using this technique to determine whether it was useful for prediction of the prognosis of 22 patients who had undergone allogeneic SCT. MC was more frequently observed in patients who were treated without total body irradiation (TBI) than in patients who were treated with TBI (p = 0.009). MC was also seen in a larger percentage of patients without acute graft-versus-host disease (p = 0.027). Six patients developed graft failure or relapse among 12 patients with MC. The graft failure or relapse was higher in patients with MC than in patients with complete chimerism (CC) (p = 0.009) especially if they were over 30 years of age (p = 0.0005). In contrast, graft failure or relapse was not higher in patients with MC compared with patients with CC under 30 years of age (p = 0.78). These results show that MC is an important predictive factor, especially in patients over 30 years of age.

Adolescent↗

Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation.

Hypovasculature is an outstanding characteristic of pancreatic cancers in imaging diagnosis, suggesting that blood supply is poor in pancreatic cancer tissues. Despite poor blood supply, pancreatic cancer cells survive and proliferate in severe hypoxia and nutrient deprivation. To demonstrate how pancreatic cancer cells adapt themselves to hypoxia and nutrient deprivation, we investigated the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) protein and HIF-1-inducible genes in human pancreatic cancer cell lines in comparison with other cancer cell lines. We found that HIF-1alpha protein was constitutively expressed in 15 of 20 pancreatic cancer cell lines (75%) but in none of other cancer cell lines tested in this study. The cells with constitutive expression of HIF-1alpha were more resistant to apoptosis induced by hypoxia and glucose deprivation than those without constitutive expression of HIF-1alpha. Transfection with HIF-1alpha transformed the latter cells resistant to apoptosis and increased in vivo tumorigenicity. Furthermore, anaerobic metabolism-associated genes, Glut1 and aldolase A, were more highly expressed in the cells with constitutive expression of HIF-1alpha than in the cells without it. These results suggest that constitutive expression of HIF-1alpha contributes to the survival and proliferation of pancreatic cancer cells in hypoxia and glucose deprivation through the activation of anaerobic metabolism.

Animals↗

Exfoliative esophagitis early after autologous peripheral blood stem cell transplantation.

Two patients with non-Hodgkin's lymphoma (NHL) suffered from hematemesis due to exfoliative esophagitis early after autologous peripheral blood stem cell transplantation (PBSCT). The chemotherapy regimens used for these 2 patients were the same and consisted of high-dose ranimustine, carboplatin, etoposide, and cyclophosphamide (MCVC regimen), which have been widely used in autologous PBSCT for NHL in Japan. Esophageal bleeding in both patients was stopped by conservative treatment without any special endoscopic manipulations. Gastrointestinal bleeding after hematopoietic stem cell transplantation is usually caused by viral infections, graft-versus-host disease, or conditioning chemo-radiotherapy. Although severe esophagitis is common in patients receiving stem cell transplantation, the exfoliative form detected by endoscopic examination has not been reported. We conclude that high-dose chemotherapy and frequent vomiting during treatment are risk factors for lower-esophageal bleeding in these cases.

Adult↗

Avascular necrosis in the femoral head secondary to bone marrow infarction in a patient with graft-versus-host disease after unrelated bone marrow transplantation.

We previously reported a case of bone marrow infarction attributable to acute graft-versus-host disease (GVHD) in a patient with acute lymphoblastic leukemia after unrelated bone marrow transplantation (BMT). Although the bone marrow infarction-induced arthralgia in this patient improved, severe arthralgia appeared again with exacerbation of chronic GVHD, and the arthralgia was strongly correlated with the clinical course of chronic GVHD, i.e., the course of symptoms such as dermal and hepatic GVHD and ocular dryness. Finally, the patient developed avascular necrosis (AVN) in the right femoral head. Serum interleukin (IL)-6 and IL-10 levels were high at the onset of arthralgia but low during remission, and levels of interferon-gamma were undetectable throughout the period of arthralgia. Based on the clinical course and these data, chronic GVHD was thought to have been the major cause of the AVN. Since IL-10 antagonizes various other cytokines that induce GVHD, the increase in IL-10 might have inhibited the development of GVHD.

Adult↗

Peripheral T-cell lymphoma in a patient with osteopetrosis.

Osteopetrosis is a rare genetic disorder in which the function of osteoclasts is defective, resulting in impaired bone resorption. This disease is usually accompanied by myelosuppression due to decreased marrow space and by osteomyelitis, especially in the submandibular bone. We report the case of a 72-year-old woman with an autosomal dominant form of osteopetrosis who suffered from peripheral T-cell lymphoma. Accurate clinical and pathological diagnoses and staging were difficult due to nonspecific reactive hyperplasia of the lymph nodes, even though we used several scintigraphic techniques and [18F]fluorodeoxyglucose positron emission tomography. We also paid special attention to myelosuppression and exacerbation of osteomyelitis after combination chemotherapy. Severe infectious complications were avoided by early administration of G-CSF for leukocytopenia and by continuous oral administration of antibiotics. The patient achieved complete remission after four courses of chemotherapy and this status has been maintained for 6 months.

Aged↗

Chronic eosinophilic leukemia with t(6;11)(q27;q23) translocation.

We report a rare case of chronic eosinophilic leukemia (CEL) with a chromosomal abnormality of t(6;11)(q27;q23). The patient was diagnosed as having thyroid cancer with metastases to the lung and cervical lymph nodes in 1993. Percutaneous ethanol injection therapy (PEIT), total thyroidectomy, and radiotherapy were performed. The patient was also diagnosed as having prostatic cancer with bone metastasis in July 1999, and hormonal therapy was performed. At the time of the diagnosis of prostatic cancer, leukocytosis with eosinophilia was also revealed. Thereafter, cytogenetical analysis and reverse transcriptase polymerase chain reaction (RT-PCR) analysis of bone marrow showed t(6;11)(q27;q23) translocation and MLL/AF6 fusion products, respectively. No transcripts of the BCR/ABL chimeric gene were found by RT-PCR in bone marrow. Analysis of serum cytokines revealed a slight elevation of GM-CSF but no elevation of IL-3 or IL-5. Tissue damage due to infiltration of eosinophils was not observed throughout the clinical course. On the basis of the cytogenetic and molecular abnormality, the patient was diagnosed as having CEL, rather than reactive eosinophilia due to thyroid or prostatic cancer or other reactive inflammation. This is the first case report of CEL with t(6;11)(q27;q23) translocation.

Aged↗

Combined hepatocellular carcinoma and cholangiocarcinoma growing into the common bile duct.

We report a patient with combined hepatocellular carcinoma and cholangiocarcinoma (HCC-CC) growing into the common bile duct (CBD) and showing obstructive jaundice within 2 years of the onset of the disease. The patient was a 59-year-old Japanese man in whom, at the age of 57 years. a hepatic tumor was discovered by diagnostic imaging during follow-up of hepatitis B surface antigen (HBsAg)-positive liver cirrhosis. The tumor was diagnosed as HCC. Epirubicin was injected twice, intraarterially. The patient then received oral etoposide therapy for the next 14 months. The treatment was initially effective, but approximately 2 years after the hepatic tumor was discovered, local recurrence of the tumor and a tumor thrombus in the CBD were discovered. Although he was treated with percutaneous transhepatic biliary drainage (PTBD), to reduce obstructive jaundice, the jaundice was irreversible and he died of severe hepatic failure. The autopsy findings confirmed that the hepatic tumor was HCC-CC, in which the HCC and CC components expressed alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9), respectively, which accurately reflected the disease process. The underlying mechanism of the growth of HCC-CC into the CBD may differ from the underlying mechanism of the development of icteric-type HCC.

Bile Ducts, Intrahepatic↗

Attributable risk of H. pylori in peptic ulcer disease: does declining prevalence of infection in general population explain increasing frequency of non-H. pylori ulcers?

Recent reports in the United States have found that fewer peptic ulcers are due to Helicobacter pylori than previously believed. The aim of this study is to determine if the declining prevalence of H. pylori infection in the general population can account for the apparent increase in the frequency of non-H. pylori ulcers. A total of 396 patients with peptic ulcer or ulcer scar were enrolled in this study. The pre-1950 population consisted of 149 patients with gastric ulcers and with 44 duodenal ulcers. The post-1950 population consisted of 96 patients with gastric ulcers and 107 with duodenal ulcers. The frequency of H. pylori-negative gastric ulcers was 5.4% in patients born before 1950 and 4.2% in patients born after 1950, and the frequency of H. pylori-negative duodenal ulcers was 0% and 1.9%, respectively. There are no statistical differences between the two populations in gastric and duodenal ulcers. H. pylori seropositivity was 74.9% in asymptomatic volunteers born before 1950 and 20.7% in those born after 1950 (P < 0.01) in the general population. The attributable risk of H. pylori infection in peptic ulcer diseases was not affected by the prevalence of H. pylori infection in the general population in Japan. This suggests that the apparent increase in frequency of non-H. pylori ulcers in the United States is not simply due to the declining prevalence of infection. Other explanations for non-H. pylori ulcers should be sought.

Adult↗

Cyclosporin A-induced encephalopathy after allogeneic bone marrow transplantation with prevention of graft-versus-host disease by tacrolimus.

A 21-year-old woman with severe aplastic anemia received an allogeneic bone marrow transplant (allo-BMT) from an HLA-matched and ABO-matched sibling donor after conditioning with cyclophosphamide, rabbit ATG (Lymphoglobuline; Aventis-Pharma), and total lymphoid irradiation. She had a long history of cyclosporin A (CsA) therapy before conditioning. She complained of severe headache and convulsions on day 0, and findings on magnetic resonance images suggested CsA-induced encephalopathy. CsA was immediately stopped, and tacrolimus for prevention of graft-versus-host disease (GVHD) was started on day 2. Hematological engraftment was observed on day 14 without serious GVHD. Prompt diagnosis, replacement of immunosuppressive agents, and careful monitoring of serum drug concentrations are thought to have contributed to the patient's good clinical course, since CsA-induced encephalopathy tends to be recurrent but to improve completely without any sequelae.

Adult↗

Efficacy of triple therapy with rabeprazole for Helicobacter pylori infection and CYP2C19 genetic polymorphism.

BACKGROUND: Rabeprazole is a new, potent, proton pump inhibitor. The metabolism of rabeprazole is less dependent on CYP2C19 genetic polymorphism. METHODS: A total of 102 Helicobacter pylori-positive patients with gastric ulcer were randomly allocated to three groups: rabeprazole 10 mg (RAC10), rabeprazole 20 mg (RAC20) or rabeprazole 40 mg (RAC40) plus amoxicillin 750 mg and clarithromycin 200 mg twice daily for 7 days. CYP2C19 genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: All-patients-treated-based eradication rates in patients treated with RAC10, RAC20 and RAC40 were 83%, 77% and 90%, respectively, and per protocol-based eradication rates were 83%, 80% and 90%, respectively. The eradication rates in the three groups were not significantly different. There was also no significant difference between the all-patients-treated-based eradication rate in CYP2C19 extensive metabolizers and that in poor metabolizers (86% vs. 77%). Adverse events were 12% in extensive metabolizers and 23% in poor metabolizers, and the difference in these incidence rates was also not statistically significant. CONCLUSIONS: Triple therapy with 10 mg of rabeprazole combined with amoxicillin/clarithromycin is effective for Japanese patients with H. pylori infection, and the H. pylori eradication rate is not affected by CYP2C19 genetic polymorphism.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Evaluation of the cost-effectiveness of Helicobacter pylori eradication triple therapy vs. conventional therapy for ulcers in Japan.

BACKGROUND: Helicobacter pylori eradication triple therapy with a combination of lansoprazole, amoxicillin and clarithromycin was approved in Japan in September 2000. AIM: To compare the cost-effectiveness of this eradication therapy with conventional histamine-2 receptor antagonist therapy in Japan. METHODS: We established two Markov models for gastric and duodenal ulcers. The model design was based on the Japanese H. pylori eradication guideline and a specialist's opinions, and the model inputs were obtained from a literature review. The models predict the direct medical costs, number of disease-free days and cost per disease-free day for 5 years. RESULTS: In the gastric ulcer model, the expected total costs of eradication and conventional therapies per patient were yen169 719 and yen390 921, respectively; the expected numbers of disease-free days were 1454 days and 1313 days, respectively. In the duodenal ulcer model, the expected total costs were yen134 786 and yen324 689, respectively; the expected numbers of disease-free days were 1503 days and 1387 days, respectively. The sensitivity analyses showed that the results of the base case analysis were robust. CONCLUSIONS: This eradication therapy is less costly and more effective than conventional therapy for the treatment of gastric and duodenal ulcers in a Japanese medical setting.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Detection of AP12-MALT1 chimaeric gene in extranodal and nodal marginal zone B-cell lymphoma by reverse transcription polymerase chain reaction (PCR) and genomic long and accurate PCR analyses.

t(11;18)(q21;q21) has been recognized as a characteristic chromosomal translocation in mucosa-associated lymphoid tissue (MALT)-type lymphoma, and recent studies have demonstrated that this translocation results in the chimaeric transcript of API2 (apoptosis inhibitor 2)-MALT1 (mucosa-associated lymphoid tissue lymphoma translocation gene 1). In this study, we used reverse transcription polymerase chain reaction (RT-PCR) to analyse the incidence of this fusion product in a large series of MALT lymphoma, nodal marginal zone B-cell lymphoma (nMZBCL) and extranodal diffuse large B-cell lymphoma (DLBL) cases. RT-PCR analysis revealed that 17 of the 95 (17.9%) MALT lymphomas but none of the nine nMZBCLs or 16 DLBLs had API2-MALT1 fusion transcripts. The incidence of API2-MALT1 varied among MALT lymphomas arising from different sites and was highest for pulmonary MALT lymphomas (10 out of 16 cases, 62.5%). The presence of the API2-MALT1 fusion gene was also confirmed by long and accurate (LA)-PCR with genomic DNA, and the result correlated well with that obtained with the RT-PCR assay, thus demonstrating the usefulness of LA-PCR for the detection of the API2-MALT1 fusion gene.

Humans↗

Guidelines in the management of Helicobacter pylori infection in Japan.

BACKGROUND: In preparation of the approval of Helicobacter pylori therapy by the Japanese national health system, the board of directors of the Japanese Society for Helicobacter Research decided to prepare guidelines on the diagnosis and treatment of H. pylori infection for physicians in routine medical practice. METHODS: A guidelines preparation committee was formed and six meetings were held. Then, in December 1999, a consensus meeting was held in Kobe to obtain the opinions of general practitioners as well as experts from Europe, North America, and Asia. RESULTS: Helicobacter pylori eradication therapy is recommended in gastric or duodenal ulcer patients. Helicobacter pylori eradication therapy is recommended or gastric mucosa associated lymphoid tissue (MALT) lymphoma but it should be done at specialist institutions. The significance of H. pylori eradication therapy is still under evaluation in patients with hyperplastic polyps, chronic atrophic gastritis, non-ulcer dyspepsia and in patients after endoscopic mucosal resection of gastric cancer and after gastrectomy for gastric cancer. When diagnosing H. pylori infection, at least one of the tests requiring endoscopic biopsy (e.g. rapid urease test, histology, or culture) and tests not requiring biopsy (e.g. measurement of H. pylori antibody or urea breath test) should be used. Multiple tests are recommended to increase the accuracy. The drugs of first choice currently covered by the national health insurance system in Japan are: lansoprazole (30 mg) 1 capsule twice daily, amoxicillin (250 mg) 3 capsules twice daily, and clarithromycin (200 mg) 1-2 tablets twice daily. These three drugs should be administered after breakfast and dinner for 1 week. CONCLUSION: These guidelines are intended for utilization in routine medical practice after the Japanese national health system begins to cover the management of H. pylori infection.

Amoxicillin↗

A multicenter, double-blind study on triple therapy with lansoprazole, amoxicillin and clarithromycin for eradication of Helicobacter pylori in Japanese peptic ulcer patients.

BACKGROUND: Two triple therapies with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of Helicobacter pylori were studied in multicenter, double-blind fashion to evaluate the eradication rate of H. pylori and safety of eradiation treatment in Japanese patients with H. pylori-positive active gastric ulcers or duodenal ulcers. METHODS: Patients were randomly chosen for the control treatment of LPZ 30 mg twice a day (b.i.d.; Group A-LPZ-only) or the test treatments of LPZ 30 mg plus AMPC 750 mg and CAM 200 mg b.i.d. (Group B-LAC200) and LPZ 30 mg, AMPC 750 mg and CAM 400 mg b.i.d. (Group C-LAC400). All eradication treatments lasted for a period of 7 days. Successful eradication was assessed by culture and gastric histology 1 month after completion of the ulcer treatment. RESULTS: The eradication rates of H. pylori in the full analysis set were 0% in Group A-LPZ-only, 87.5% in Group B-LAC200 and 89.2% in Group C-LAC400 for gastric ulcer and, 4.4% in Group A-LPZ-only, 91.1% in Group B-LAC200 and 83.7% in Group C-LAC400 for duodenal ulcer. The eradication rates of Group B-LAC200 and Group C-LAC400 were 89.2% (95% CI: 84.8-93.7%) and 86.4% (95%CI: 81.5-91.3%) in total in the full analysis set, 89% (95% CI: 84.3-93.7%) and 85.3% (95%CI: 80.1-90.5%) in the per protocol set. The eradication rates in Groups B-LAC200 and group C-LAC400 were statistically significantly higher than the rate in Group A-LPZ-only for both gastric ulcer and duodenal ulcer patients (p <.0001 for both). CONCLUSION: A satisfactorily high H. pylori eradication rate was obtained in Japanese ulcer patients with the triple therapy regimen consisting of LPZ 30 mg, AMPC 750 mg, and CAM 200 mg b.i.d.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Atrophic gastritis and intestinal metaplasia in Japan: results of a large multicenter study.

BACKGROUND: This study evaluated the relationship between Helicobacter pylori infection, atrophic gastritis and intestinal metaplasia in Japan. MATERIALS AND METHODS: This was a multicenter study performed in 21 centers in Japan. A total of 2455 individuals were enrolled. H. pylori status was determined by validated ELISAs. Atrophic gastritis was diagnosed by histology, endoscopy with Congo Red dye scattering or the Kimura-Takemoto endoscopic classification. RESULTS: Atrophic gastritis increased from 9.4% in those less than 20 years of age to > 70% in those aged 60 or older and was strongly associated with H. pylori infection. The overall prevalence of atrophic gastritis in H. pylori infection was 82.9% (1272/1534) compared with 9.8% (90/921) among uninfected (OR = 44.8; 95% CI = 34.7-57.8). Intestinal metaplasia was present in 43.1% (542/1258) of H. pylori positive persons compared with 6.2% (51/823) among the uninfected (OR = 11.5; 95% CI = 8.5-15.5). Atrophic gastritis in H. pylori positive Japanese was very high in the younger generation (38.5% in those aged 20 or less and 58.5% in those 21-30). CONCLUSIONS: Atrophic gastritis and intestinal metaplasia were strongly associated with H. pylori and not with aging. The fall in prevalence of H. pylori in Japan has not been associated with a corresponding fall in the prevalence of atrophic gastritis among those with H. pylori infection. The high prevalence of the precursor lesion, atrophic gastritis with intestinal metaplasia, among those with H. pylori infection suggests that the risk of development of early gastric cancer will continue to remain high in Japan.

Adult↗

Endoscopic screening for early esophageal cancer by iodine staining in patients with other current or prior primary cancers.

BACKGROUND: Although early diagnosis of esophageal carcinoma is an important determinant of outcome, early stage carcinomas are rarely detected on routine endoscopic examination. Iodine staining may be useful in the detection of early stage esophageal carcinoma, especially in high-risk populations. In a prior study, 29.2% (68/233) patients with superficial esophageal carcinoma (SEC) undergoing resection at our hospital had other nonesophageal primary carcinomas, suggesting that patients with nonesophageal primary cancers are at increased risk for the development of esophageal cancer. The aim of the current study was to determine whether endoscopic screening with iodine staining is useful for the detection of SEC in patients with a history of non-esophageal cancers. PATIENTS AND METHODS: In a prospective study, 331 patients with nonesophageal primary cancers were screened for esophageal cancer by endoscopic examination with iodine staining. All patients were men 55 years of age or older. RESULTS: Nine patients (2.7%) with SEC were identified. Among these patients, 7 with mucosal cancer were treated by endoscopic mucosal resection, and 2 with submucosal cancer were treated by surgical resection or radiation therapy. Five patients (1.5%) were found to have cancer confined to the epithelium or the lamina propria. These lesions were difficult to detect by conventional endoscopic screening and were cured by endoscopic mucosal resection. After exclusion of 51 patients with head and neck cancer, the incidence of SEC was still 2.1% (6/280), higher than reported in prior screening studies. CONCLUSIONS: All men with a history of nonesophageal primary cancers should undergo endoscopic screening for esophageal cancer. Endoscopic iodine staining in such patients may be useful in screening for early stage esophageal carcinoma.

Aged↗