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Biomedical subjects

Hiroto Miwa

Publications and source records attributed to Hiroto Miwa.

At least 19 recordsLinked to original sources
PubMed2006

Clinicopathological features of nonpolypoid colorectal tumors as viewed from the patients' background.

BACKGROUND: This study was performed to characterize the clinicopathological features of colorectal tumors with flat-, depressed-, or protruded-type morphology (hereafter referred to simply as flat, depressed, or protruded lesions). METHODS: There are two major types of colorectal tumor: polypoid (protruded) and nonpolypoid (flat and depressed). A total of 130 lesions from 130 patients with colorectal submucosal invasive cancer were classified into three groups according to their macromorphology seen during endoscopy: flat (laterally spreading) and depressed nonpolypoid tumors and protruded polypoid tumors. The following factors in the patients' background were evaluated: indication for colonoscopy, age, and family history of colorectal cancer in first-degree relatives (i.e., parents, siblings, children). We also compared the following characteristics of the tumors: size, location, depth of submucosal invasion, vascular invasion, and frequency of synchronous and metachronous tumor lesions. RESULTS: The incidence of abnormal findings on follow-up studies after polypectomy as an indication for colonoscopy was significantly higher among patients with flat lesions (4/24, 16.7%) and depressed lesions (3/22, 13.6%) than among those with protruded lesions (1/84, 1.2%) (P < 0.01, P < 0.01). Patients with flat lesions (65.8 +/- 7.6 years old) were significantly older than those with protruded lesions (P < 0.05). The patients with flat tumors had a significantly higher rate of a family history of colorectal cancer (6/24, 25.0%) than patients with protruded or depressed lesions (P < 0.01, P < 0.05). The protruded lesions were significantly larger than the depressed lesions (size 13.3 +/- 6.7 mm) (P < 0.05), and the flat lesions (24.1 +/- 10.1 mm) were significantly larger than either the protruded or depressed lesions (P < 0.01, P < 0.01). Seventy-five percent (18/24) of the flat lesions were located in the right colon, and this proportion was significantly higher than that among the protruded or depressed lesions (P < 0.01, P < 0.01). The mean +/- SD depth of submucosal invasion was 1218 +/- 1034 microm in the flat lesions, 2392 +/- 1869 microm in the depressed lesions, and 2761 +/- 1929 microm in the protruded lesions, representing a significant difference (P < 0.05, P < 0.0001). Of the 24 patients with flat lesions, 9 (37.5%) showed vascular invasion; this proportion was significantly lower than that among patients with the depressed or protruded lesions (P < 0.01, P < 0.01). Patients with depressed lesions tended to have higher incidence of synchronous and metachronous malignant polyps than those with protruded or flat lesions. CONCLUSION: It is important to examine the morphology of colorectal tumors when diagnosing them and planning the treatment strategy, including follow-up, after resection of nonpolypoid tumors. It is useful to know the patient's family history so nonpolypoid tumors can be accurately diagnosed.

Aged↗
PubMed2006

Activated platelets as a possible early marker to predict clinical efficacy of leukocytapheresis in severe ulcerative colitis patients.

BACKGROUND: Leukocytapheresis (LCAP) is an effective adjunct for patients with active ulcerative colitis (UC). Because LCAP may have the potential to remove and modulate not only leukocytes but also platelets, we evaluated the correlation between activated platelets and the therapeutic response to LCAP. METHODS: Fourteen patients with severe UC received weekly LCAP for 5 consecutive weeks. Their average clinical activity index (CAI) and endoscopic index (EI) were 9.6 +/- 3.4 and 10.9 +/- 1.0, respectively. Their peripheral blood was sampled before and after every LCAP and stained with fluorescent antibodies to the activation-dependent surface antigens of platelets (CD63, CD62-P) prior to flow cytometry. Endoscopic evaluations were performed after the last LCAP. RESULTS: Clinical remission (CAI < 4) was induced in 50% of the patients (7/14) after 5 weeks, and there were no significant differences observed in clinical background between the responder group (RG) and the nonresponder group (NG). In the RG, the populations of CD63(+) (P < 0.03) and CD62-P(+) (P < 0.05) platelets were significantly decreased after the first LCAP, and their reduction ratio decreased gradually with repeated LCAP. A significant improvement of the EI score, especially mucosal damage, was achieved in RG (P < 0.04) but not in NG. CONCLUSIONS: These results indicate that the therapeutic responses to LCAP were reflected in modulations of population and/or platelet functions, especially after the first session. The decrease of such activated platelets immediately after the first LCAP may be an early marker for predicting the response in patients with severe UC.

Adolescent↗
PubMed2006

Effect of a gastro-protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan.

BACKGROUND AND AIM: Although mucosal protective agents have been used frequently for treatment of symptomatic gastritis, there has been no well-controlled study of functional dyspepsia. The aim of this study was to assess the efficacy of a 4-week treatment with rebamipide for the relief of overall dyspeptic symptoms and the improvement in quality of life from an untreated baseline in Japanese patients with functional dyspepsia. METHODS: In a double-blinded, randomized, placebo-controlled, single-center study, 81 patients with functional dyspepsia were recruited and treated with rebamipide (100 mg, t.i.d.) or placebo for 4 weeks. Symptoms were assessed at baseline and at the end of the study period by a symptom questionnaire. Quality of life was evaluated by the QPD 32. RESULTS: Data was analyzed for symptoms from 38 patients who received rebamipide and 33 patients who received placebo treatment. Overall symptoms were significantly improved in both the rebamipide and placebo treatment groups from the untreated baseline after 4 weeks of treatment, and the mean changes in overall symptoms were not significantly different between the groups. However, the improvement in symptom score was significantly greater in the treatment arm than in the placebo arm for three items, which were bloating, belching, and pain or discomfort that was relieved after a meal. Regarding quality of life, social restriction and pain intensity were significantly improved in the rebamipide treatment group in per-protocol analysis (P = 0.048 and P = 0.031, respectively). CONCLUSIONS: Although rebamipide was not significantly better than placebo in reducing overall symptoms by 4 weeks' treatment, it may partially improve the symptoms. It may also be beneficial in improvement of quality of life in Japanese patients with functional dyspepsia.

Adult↗
PubMed2006

[Brain function in IBS patients].

Irritable bowel syndrome(IBS) is functional disorder that is characterized by abdominal pain and changes in stool habits, and possibly related to abnormal brain-gut communication. Recent studies using brain imaging suggest the brain functions of IBS patients may be possibly different from that of control. We, in this article, review the recent knowledge regarding this point.

Brain↗
PubMed2006

[Post-infectious IBS].

Irritable bowel syndrome (IBS) is a mulitifactorial disease. Bacterial gastroenteritis has been known as a risk factor of IBS. Current evidence shows a strong association between colonic infection and inflammation with development of IBS.

Gastroenteritis↗
PubMed2005

Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis.

BACKGROUND: The esophageal tight junction is responsible for the paracellular sealing of the epithelium. Alteration of the expression of tight-junction proteins plays crucial roles in the pathogenesis of some human diseases. The aim of this study was to investigate the distribution and expression pattern of tight-junction proteins in the esophageal mucosa of control rats and rats with reflux esophagitis. METHODS: Chronic acid reflux esophagitis was experimentally induced by operation in rats. The animals were killed on days 7 and 14 after the operation. The thickness of the mucosa and the 5-bromo-2-deoxyuridine (BrdU) labeling index were assessed. The expression pattern of the tight-junction proteins claudin 1-4 and occludin in the esophageal mucosa was investigated by immunofluorescence staining and Western blotting in the controls and esophagitis rats. RESULTS: In the esophagitis model, the thickness and BrdU labeling index increased with time. In control rats, claudin-1, -3, and -4 were localized on the cellular membranes of esophageal epithelial cells, mainly in the spinous and granular layers, while claudin-2 was not detected in any layer. Occludin was seen on the cellular membranes in all esophageal mucosal layers. In the esophagitis rats, the expression of claudin-1 was increased both in the plasma membrane and in the cytoplasm around the erosion in the spinous and granular layers. The expression of claudin-4 and occludin shifted to the cytoplasm from the plasma membrane in the spinous and granular layers. In contrast, the expression of claudin-3 was decreased in the spinous and granular layers. CONCLUSIONS: The localization and the expression patterns of tight-junction proteins were different in the controls and the rat esophagitis model. The expression of claudin-3 in the esophageal mucosa was decreased, while that of claudin-1 was increased. It is postulated that these alterations in tight-junction proteins most likely increase the permeability of the esophageal the epithelium, thereby impairing the defense mechanism of this epithelium.

Animals↗
PubMed2005

Treatment of functional dyspepsia with antianxiety or antidepressive agents: systematic review.

BACKGROUND: The pathophysiology of functional dyspepsia (FD) has not been elucidated precisely; accordingly, effective management of FD has not yet been found. Until now, treatment with antianxiety or antidepressive agents has been empirically applied; however, the efficacy of these treatments has not been established. We carried out this study to estimate the efficacy of these treatment approaches by systematically reviewing the literature concerning trials with agents that are efficacious against anxiety, neurosis, or depression. METHODS: Articles were searched from the MEDLINE database up to October 2003, using the terms, "antianxiety agents", "antidepressants", and "dyspepsia", and from reference lists of published articles. Finally, studies in which the effectiveness of drugs was clearly stated were selected from the retrieved articles. RESULTS: Thirteen articles, on 1717 patients, were selected from among 90 articles retrieved through our literature search. In 11 of the 13 studies, dyspeptic symptoms were improved significantly by treatment. Statistical analysis of 4 trials showed a significant benefit of treatment with antianxiety or antidepressive agents (pooled relative risk, 0.55; 95% confidence interval [CI], 0.36-0.85), although funnel plots were asymmetric. CONCLUSIONS: Antianxiety or antidepressive agents may be effective in the treatment of FD patients, though further clinical trials are necessary.

Anti-Anxiety Agents↗
PubMed2005

Effects of hepatocyte growth factor on rat inflammatory bowel disease models.

Hepatocyte growth factor (HGF) is a hepatotrophic factor and, also, functions as an epithelial growth factor. We examined the therapeutic effects of HGF on rat inflammatory bowel disease models induced by trinitrobenzensulfonic acid or dextran sulfate sodium. Recombinant human HGF was continuously administered at 50 microg/body/day using an intraperitoneally implanted pump for 7 days. Treatment of HGF reduced the ulcerated area, histological damage score, mucosal myeloperoxidase activity, and epithelial apoptotic rate but did not increase epithelial mitotic rate and immunohistochemical labeling indexes of proliferating cell nuclear antigen, Ki-67, and bromodeoxyuridine as indexes of epithelial cell proliferation in either model. We then examined the epithelial localization of the HGF receptor c-met and identified it on the surface epithelia, where apoptosis was observed, but did not find it in the proliferative zone. These results suggest that HGF exhibits therapeutic effects via anti-inflammation including antiapoptosis rather than epithelial cell proliferation in these inflammatory bowel disease models.

Animals↗
PubMed2005

Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up.

OBJECTIVE: It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC. MATERIAL AND METHODS: Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3-5 months and 12-14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method. RESULTS: The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3-5 and 12-14 months after the end of treatment compared with those in the control group (p=0.001-0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002-0.049). No serious drug-related toxicity was observed during the trial. CONCLUSIONS: The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

Adolescent↗
PubMed2005

Influence of antimicrobial treatment for Helicobacter pylori infection on the intestinal microflora in Japanese macaques.

Eradication treatment for Helicobacter pylori is known to cause mild but relatively frequent adverse effects. Some adverse effects such as diarrhoea and soft stools are related to disruption of the composition of the intestinal microflora. This study investigated the microfloral changes resulting from administration of an eradication regimen using proton pump inhibitor (PPI), amoxycillin and clarithromycin. Twenty-eight laboratory-bred Japanese macaques either were administered eradication treatment by this regimen for 7 days or received no medication. Faecal samples were collected for analysis on days 0, 8 and 15, and both aerobic and anaerobic cultures were performed. Among aerobic bacteria, Streptococcus had significantly decreased by day 8, while Enterococcus and Enterobacteriaceae had significantly increased. However, the total number of aerobic bacteria was not significantly decreased from pretreatment levels 1 day after completion of treatment. The number of anaerobic bacteria did not change significantly by day 8. However, the number of Lactobacillus and the detection rate of Bifidobacterium, Peptostreptococcus and Veillonella significantly decreased by day 8, although the number of Bifidobacterium, Peptostreptococcus and Veillonella had almost recovered up to the pretreatment levels 1 week after completion of treatment (day 15). These results suggest that the alterations in the composition of the intestinal microflora caused by the antimicrobial regimen that excludes metronidazole are different from those caused by the regimen including this drug. However, the alterations in bacterial microflora had almost reversed 7 days after completion of treatment in these macaques, which supports clinical findings that diarrhoea or soft stools in humans resolve relatively quickly after a similar treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

[Carcinogenesis in ulcerative colitis-associated colon cancer and surveillance colonoscopy].

It has been widely accepted that long-standing cases with ulcerative colitis, especially pancolitis have higher risk of complicating colitic cancer. Colitic cancer often appears as multi-focal invasive features with un-differentiated histology. Therefore, endoscopic diagnosis of precancerous or cancer associated dysplastic lesions. Surveillance colonoscopy has preventing effects for developing colitic cancer. In western world, annual surveillance colonoscopy with multiple stepwise has been adopted. In Japan, surveillance colonoscopy with targeted biopsies assisted by chromoendoscopy and/or magnifying endoscopy has proven to be efficacious in finding such lesions.

Colitis, Ulcerative↗
PubMed2004

Adsorptive Monocyte-granulocytapheresis (M-GCAP) for refractory Crohn's disease.

Six patients with active Crohn's disease (CD) unresponsive to conventional medications (CM) were treated with Monocyte-granulocytapheresis (M-GCAP). CD patients who scored 200-400 points in Crohn's disease activity index (CDAI) in spite of receiving CM, including enteral nutrition, for at least 2 weeks were enrolled in our double series trial. Each series had 5 weekly M-GCAP and 2 follow-up weeks, and each M-GCAP treated 1,800 ml of patient's peripheral blood. After the 1st series, patients who decreased more than 50 points on the CDAI were deemed responders and enrolled in the second series. Patients with a CDAI score less than 150 points were considered in remission. The patients' quality of life was evaluated using an index (IBDQ) before and after the 1st series. The CDAI was significantly decreased comparing before and after the 1st series (258.2 +/- 36.2 vs. 166.5 +/- 16.6; P < 0.02). 50% of patients (3/6) responded to the therapy, and one case (16.7%) could be induced to remission. Significant removal was revealed only for white blood cells (25.6 +/- 16.9%; P < 0.05), especially granulocytes (29.5 +/- 22.5%; P < 0.05). A statistically significant improvement of IBDQ was revealed in the responders' group (162.3 +/- 17.2 vs. 189.3 +/- 11.5; P < 0.03). M-GCAP could be an effective adjunctive therapy for active CD patients unresponsive to CM allowing them to maintain a high QOL. However, it might be difficult to improve patients who could not be induced to remission after the 1st series by applying another series.

Adult↗
PubMed2004

Second-line treatment for Helicobacter pylori infection in Japan: proton pump inhibitor-based amoxicillin and metronidazole regimen.

BACKGROUND: Recent studies have reported that proton pump inhibitor (PPI)/amoxicillin (A) metronidazole (M) therapy for Helicobacter pylori infection provides a sufficient cure rate in Japan in patients who have failed first-line treatment with PPI/amoxicillin and clarithromycin (AC). To validate the efficacy of this regimen as second-line therapy, our experience with second-line treatment using a PPI/AM regimen was reviewed. METHODS: We analyzed data on 151 patients who had been prescribed a 10-day PPI/AM re-treatment regimen after eradication failure of 1 to 2 weeks' first-line PPI/AC therapy. The PPI/AM regimen was given according to results of susceptibility testing (S+) in 31 patients. The group that had undergone susceptibility testing was further divided into two subgroups according to dosage: standard dose of omeprazole (O)/AM (n = 11) and double dose of lansoprazole (L)/AM (n = 20). The PPI/AM regimen was given without susceptibility testing (S-) to 120 patients. These patients were also divided into two subgroups according to whether they received omeprazole or lansoprazole: OAM (n = 61) and LAM (n = 59). Cure rates and adverse effects in each group were analyzed. RESULTS: The intention-to-treat (ITT)-based cure rate with/without susceptibility testing was 93.5% (95% confidence interval [CI], 79%-99%) and 87.5% (95% CI, 80%-93%), respectively (not significant [NS]). The ITT-based cure rate in S+/S- for OAM and S+/S- for LAM was 90.9% (95% CI, 59%-100%)/82% (95% CI, 70%-91%), and 95% (95% CI, 75%-100%)/93.2% (95% CI, 84%-98%), respectively (NS). Adverse effects were seen in 26.3% and 32.5% of patients in the OAM group and the LAM group, respectively (NS). CONCLUSIONS: The 10-day PPI/AM re-treatment regimen is safe and effective, suggesting its usefulness as second-line treatment in Japan in patients who have failed initial treatment with the PPI/AC regimen.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Enteropathy-type T-cell lymphoma expressing NK-cell intraepithelial lymphocyte (NK-IEL) phenotype.

Enteropathy-type T-cell lymphoma (ETL) is an intraepithelial T-lymphocyte (T-IEL) tumor. The tumor cells are usually CD3+, CD4-, CD8+, and contain cytotoxic granule associated proteins. We report on a CD3-negative CD56-positive enteropathy-associated lymphoma (ETL). This is the first case report of CD3-negative, CD56-positive, CD94-negative, and CD161-positive ETL. ETL cells originate from intraepithelial T-lymphocytes of the intestine. CD3-negative intraepithelial lymphocytes are known as natural killer (NK)-IELs. The phenotype of NK-IELs is also CD3-negative, CD56-positive, CD94-negative, and CD161-positive, while most normal NK cells express CD56 and CD94. CD3-negative lymphoma cells in this report also expressed CD56 and CD161, but not CD94. Because Southern blotting analysis showed a rearrangement of T-cell receptor (TCR) Cbeta in this case, the tumor is classified as an ETL. Based on the findings, NK-IELs may originate from T-cells, not NK-cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Recurrent peptic ulcers in patients following successful Helicobacter pylori eradication: a multicenter study of 4940 patients.

OBJECTIVE: Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection. METHODS: This was a multicenter study involving 4940 peptic ulcer patients who were H. pylori negative after successful eradication treatment and were followed for up to 48 months. The annual incidence of ulcer relapse in H. pylori-cured patients, background of patients with relapsed ulcers, time to relapse, ulcer size, and site of relapsed ulcers were investigated. RESULTS: Crude peptic ulcer recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric, duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively. Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5% and 1.3%, respectively. The recurrence rate was significantly higher in gastric ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs were significantly higher in those with gastric ulcer recurrence compared to duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at the same or adjacent sites as the previous ulcers). CONCLUSIONS: Curative treatment of H. pylori infection is useful in preventing ulcer recurrence. Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer tended to recur at the site of the original ulcers.

Alcohol Drinking↗