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Biomedical subjects

Takashi Shimoyama

Publications and source records attributed to Takashi Shimoyama.

At least 19 recordsLinked to original sources
PubMed2003

Poorly controlled ulcerative colitis treated by colectomy during remission induced by extracorporeal leukocyte removal therapy.

Both monocyte-granulocytapheresis (M-GCAP) and leukocytapheresis (LCAP) are categorized as extracorporeal leukocyte removal therapies (ECCTs). These therapies have been recognized as efficient adjuncts for patients of steroid-resistant ulcerative colitis (UC). This study aimed to consider the adaptation and the limitation of these new therapies from the clinical standpoint based on a case of UC showing strong resistance to high-dose continuous steroid injection therapy. The patient successfully underwent a scheduled colectomy while maintaining remission after applying M-GCAP and LCAP independently. Surgical therapy was chosen because of a deep ulcer in the patient's sigmoid colon, which was assumed to constitute a future risk for perforation. This case suggests that combining ECCT with steroid therapy can maintain such poorly controlled and high-risk UC patients safely for the scheduled colectomy while improving the prognosis by reducing the dosage of steroid efficiently prior to operation.

Adult↗
PubMed2003

Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis.

BACKGROUND: 6-Mercaptopurine (6-MP) and azathioprine (AZA) have been used in patients with Crohn's disease (CD) and ulcerative colitis (UC) for reducing the dose of steroids and maintaining remission. However, some patients treated with 6-MP/AZA develop bone marrow suppression, one of the most serious side effects. The aim of this study was to evaluate the efficacy and safety of low-dose AZA (0.6-1.2 mg/kg per day) for maintaining remission in patients with UC. We also investigated the relationship between bone marrow suppression and thiopurine methyltransferase ( TPMT) mutation in the Japanese population. METHODS: Study 1. To investigate the frequency of TPMT mutation, findings for 82 patients among 141 patients with UC or CD who were treated with AZA or 6-MP were analyzed retrospectively. Polymerase chain reaction (PCR) methods were used to analyze allele mutations of the TPMT gene. Study 2. A multicenter prospective trial was performed. The subjects were 22 patients with UC with presence of remission for 3 months or more. They were treated with 50 mg/day of AZA, and we evaluated the remission rate at 6 months, adverse side effects, and changes in prednisone doses after the initiation of AZA. RESULTS: Study 1. Seventy-four (91%) of the 82 patients analyzed had no TPMT mutation, 7 (8%) had one mutant allele, and 1 (1%) had two mutant alleles. Of the total of 141 patients, 4 (44%) of the 9 patients who were treated with 50 mg/day of 6-MP or 100 mg/day of AZA developed bone marrow suppression, although no mutation of TPMT was seen in any of these patients. On the other hand, 8 (6%) of the 132 patients who were treated with 30 mg/day of 6-MP or 50 mg/day of AZA developed bone marrow suppression. Seven of 8 patients (88%) who developed bone marrow suppression with a low dose of AZA had a mutant TPMT allele. Study 2. In the 17 patients who could continue taking low-dose AZA for 6 months, 15 (88%) maintained remission. Of 8 patients treated with low-dose prednisone (5-10 mg/day), 3 patients (38%) could discontinue oral prednisone and 4 (50%) could reduce its dose. Six of the 22 patients (27%) had some adverse side effects. These side effects were ameliorated, or disappeared spontaneously, or disappeared with the discontinuation of AZA. CONCLUSIONS: A dose of 50 mg/day of AZA is effective and safe for maintenance of remission in the Japanese population. Investigation of the TPMT allele may be useful for predicting the appearance of bone marrow suppression, when low-dose 6-MP or AZA is given.

Adult↗
PubMed2003

Follow-up survey of a large-scale multicenter, double-blind study of triple therapy with lansoprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in Japanese peptic ulcer patients.

BACKGROUND: To evaluate histopathological changes and effects on inhibition of ulcer recurrence, a follow-up survey was performed in Japanese patients with Helicobacter pylori-positive active peptic ulcers. These patients had previously participated in a large-scale multicenter trial of triple therapy with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of H. pylori. METHODS: Patients who had been treated with LPZ only or a combination of LPZ, AMPC, and CAM for a period of 7 days and in whom ulcer healing had been confirmed after treatment were grouped according to successful or failed eradication of H. pylori. They were examined endoscopically to determine whether ulcers had recurred. The updated Sydney system was applied to study histological changes after H. pylori eradication therapy, compared with baseline. RESULTS: Twelve months after treatment for H. pylorieradication, gastric ulcers had recurred in 11.4% of those with successful H. pylorieradication and in 64.5% of those with unsuccessful H. pylori eradication. Duodenal ulcers had recurred in 6.8% of patients for whom H. pylori eradication was successful and in 85.3% of patients in whom eradication failed. These findings proved that H. pylori eradication significantly reduced ulcer recurrence ( P < 0.0001 for both types of ulcers). Histopathological findings of inflammation and activity grade in both gastric and duodenal ulcers were more favorable in patients with successful eradication than in those with unsuccessful eradication. CONCLUSIONS: H. pylori eradication significantly inhibited ulcer recurrence in Japanese peptic ulcer patients. Histopathological findings were also improved with regard to inflammation and activity (neutrophils) in patients in whom H. pylori eradication was successful.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Extracorporeal monocyte granulocytapheresis was effective for a patient of erythema nodosum concomitant with ulcerative colitis.

We report an erythema nodosum (EN) patient whose condition became apparent during the clinical course of ulcerative colitis (UC). The patient relapsed frequently in spite of taking a high dose adrenocortical steroid during his morbidity period of UC. Monocyte-granulocytapheresis (M-GCAP) was combined with 5-aminosalicylic acid 2250 mg/day peroral and once a day of steroid enema. Monocyte-granulocytapheresis was performed once a week for 5 weeks, and succeeded in inducing clinical remission for both UC and EN. The immunological and clinical connections between UC and EN have never been fully elucidated. In this case, because the symptoms of UC and EN revealed parallel improvement after his inflammatory reaction had been brought under control by combining M-GCAP therapy, we hypothesize that the onset of EN appeared as a result of the patient's long-term, treatment-resistant immuno-disturbance, which first appeared as symptoms of UC. Immunomodulative effects induced by M-GCAP might help to control other chronic non-specific inflammations not concerned with targeted organ(s).

Adult↗
PubMed2003

Inflammatory liver steatosis caused by IL-12 and IL-18.

Acute fatty degeneration in the liver is caused by various agents, such as aspirin, valproic acid, and ibuprofen, that directly inhibit mitochondrial beta-oxidation of fatty acid and oxidative phosphorylation. Endogenous molecules, such as cytokines and hormones, are also known to mediate microvesicular steatosis in liver failure. In this study, we examined how interleukin-12 (IL-12) and IL-18 cause steatosis in the liver. Administration of these cytokines in combination caused marked hepatosteatosis and weight loss in mice. There were marked increases in levels of interferon-gamma (IFN-gamma), nitrite (NO(2)/NO(3)), and fibrinogen in the circulation in these mice. On the other hand, the ATP concentration and blood flow in the liver were significantly reduced. These changes, except the production of IFN-gamma and NO, were partially inhibited by Z-VAD-fmk, a synthetic tripeptide inhibitor for NO-induced caspases. These results indicate that IL-12 and IL-18 may mediate inflammatory hepatosteatosis through impairment of the microcirculation, which leads to mitochondrial dysfunction in hepatocytes.

Adenosine Triphosphate↗
PubMed2003

Dietary fat attenuates the benefits of an elemental diet in active Crohn's disease: a randomized, controlled trial.

OBJECTIVES: Although an elemental diet has been established as the primary treatment for patients with Crohn's disease, the influence of dietary fat on the elemental diet remains unclear. We have designed the first randomized, controlled trial for elemental diets containing different fat percentages in patients with active Crohn's disease. METHODS: Each patient was randomized to receive one of three dose levels of fat in an elemental diet (Elental) for 4 weeks: 10 patients received low fat (3.06 g/day), 10 patients received medium fat (16.56 g/day) and eight patients received high fat (30.06 g/day). The additional fat was composed of long-chain fatty acids. All patients were evaluated using the International Organization of Inflammatory Bowel Disease rating, plus C-reactive protein level and erythrocyte sedimentation rate, which were measured at weekly intervals. RESULTS: Although the International Organization of Inflammatory Bowel Disease rating, C-reactive protein level and erythrocyte sedimentation rate in the low-fat group decreased, the values in the medium- and high-fat groups fluctuated during the study. The remission rate after 4 weeks in each group was 80%, 40% and 25% for patients in the low-, medium- and high-fat groups, respectively. CONCLUSIONS: When the fat consisted of long-chain triglycerides, a high amount of this fat in the elemental diet formula decreased its therapeutic effect against active Crohn's disease.

Adult↗
PubMed2003

Evaluation of the effects of strain-specific antigen variation on the accuracy of serologic diagnosis of Helicobacter pylori infection.

It has been suggested that enzyme immunoassay (EIA) kits validated in one region may yield variable diagnostic performance results in different regions, possibly due to strain-specific differences in antibody responses in different populations. We tested (13)C-urea breath test-characterized serum samples from 109 U.S. patients and 288 Japanese patients using enzyme immunoassay with different preparations of high-molecular-weight cell-associated (HM-CAP) antigens that are conserved across Helicobacter pylori strains. Replicate antigens were prepared from five H. pylori clinical isolates. Eight antigen preparations were evaluated: two of U.S. origin and six of Japanese origin. The accuracies achieved with the eight antigen preparations ranged from 94.4 to 96.3% with the U.S. samples. With the Japanese samples the accuracies achieved ranged from 92.3 to 97.2%. Use of a pool of HM-CAP antigens prepared from isolates from Japan resulted in a higher median enzyme immunoassay value and slightly fewer samples with indeterminate results compared to the results obtained by use of the U.S. standard HM-CAP antigen for H. pylori-positive patients (accuracies, 97.2 and 92.3%, respectively), suggesting that variations in performance between both antigen source and patient population might be reduced by using antigens pooled from several strains.

Antibodies, Bacterial↗
PubMed2003

Multicenter randomized controlled trial for the treatment of ulcerative colitis with a leukocytapheresis column.

The administration of steroids is not always effective for the treatment of ulcerative colitis (UC). Their long-term use often causes adverse effects which sometimes result in their stoppage and acute exacerbation. Therefore, an alternative treatment is necessary in order to decrease steroid dosage and avoid the clinical problems associated with steroids. Methods The effectiveness and adverse effects of a leukocytapheresis (LCAP) were investigated in a controlled multicenter trial with randomized assignment of 76 active-stage UC patients in two groups. In the LCAP group (39 patients), LCAP weekly for 5 weeks as an intensive therapy was added to the on-going drug therapy, while steroids were maintained but not increased, and then LCAP was gradually reduced to once every 4 weeks as a maintenance therapy. In the high dose prednisolone (h-PSL) group (37 patients), PSL was added or increased 30 approximately 40 mg/day for moderately severe and 60 approximately 80 mg/day for severe patients and then gradually tapered. Findings The LCAP group showed a significantly higher effectiveness (74% vs. 38%; p=0.005) and lower incidence of adverse effects (24% vs. 68%; p<0.001). The patients were able to continue the trial for a longer period in the LCAP group than the h-PSL group (p=0.012). Clinical activity and endoscopic indexes showed the LCAP group had better improvements than the h-PSL group. Interpretation The results of the trial show that LCAP permits a reduction in total PSL dosage and is more effective and safer than high-dose PSL administration for intensive therapy, and LCAP may maintain remission longer than PSL.

Adult↗
PubMed2003

[Suitable diagnostic methods for H. pylori infection after eradication therapy].

Urease test, histology, culture, urea breath test(UBT) and stool antigen test are accurate tests for Helicobacter pylori diagnosis. General practitioners are now going to test peptic ulcer disease patients with these tests before and after in Japan. To test with high accuracy after eradication therapy, it is important that examination should be done over 4 weeks after cessation of treatment with PPI and antibiotics. UBT and stool antigen test are suitable tests for diagnosis of Helicobacter pylori infection after treatment.

Helicobacter Infections↗
PubMed2003

[The present status and problems of Helicobacter pylori eradication therapy with a special reference to gastric cancer].

Since the eradication therapy of Helicobacter pylori(H. pylori) for peptic ulcer was covered by Japanese health insurance at 2000 November, this therapy has been generalized in Japan. However, some problems have cropped up at the time, for example, emergence of clarithromycin resistant bacterium etc. On the other hand, investigation of relation between H. pylori and gastric cancer is making progress. Uemura, et al. demonstrated H. pylori had an important role for gastric carcinogenesis by the elegant prospective study in 2001. Under the present circumstances, the Japanese society of Helicobacter Research has to reconsider the guideline for eradication therapy. In this paper, we would like to state the present status and problems of eradication therapy of the current guideline for eradication therapy, especially focusing on gastric cancer.

Animals↗
PubMed2003

Treatment of ulcerative colitis patients by long-term administration of germinated barley foodstuff: multi-center open trial.

Germinated barley foodstuff (GBF), which mainly consists of dietary fiber and glutamine-rich protein, is a prebiotic for ulcerative colitis (UC). In our previous study, we carried out a clinical trial of GBF with mildly to moderately active UC patients and showed that GBF treatment was able to attenuate the symptoms of UC in a relatively short-term. The aim of this study was to investigate the efficacy of long-term administration of GBF in the treatment of UC in a multi-center open trial. Twenty-one patients with mildly to moderately active UC received 20-30 g of GBF for 24 weeks in an open-label protocol while baseline treatments (5-amino-salicyrate compounds and/or steroids) were continued. The response to the GBF treatment was evaluated using a clinical scoring and after 24 weeks of observation, the GBF group showed a significant decrease in clinical activity index (especially, the degree of visible blood in stools and the presence of nocturnal diarrhea) compared with the control group (p<0.05). No side effects related to GBF were observed. In conclusion, GBF can reduce the clinical activity of UC over long-term as well as short-term administration. Nutraceutical GBF therapy may have a place in long-term management of UC, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

Adult↗
PubMed2003

[Complete response of primary tumor in a case of advanced gastric cancer with liver metastasis treated by TS-1 plus divided administration of CDDP].

A 62-year-old female patient was hospitalized for general fatigue and appetite loss. Type 3 gastric cancer (moderate differentiated adenocarcinoma) with liver metastasis (S8) and direct invasion to the retro-peritoneal space and duodenal third portion was detected by endoscopic and radiographic examination. This case was judged to be unresectable from these findings. TS-1 plus divided administration of CDDP was performed. TS-1 (100 mg/day) was administrated from day 1 to 21 followed by 14 days rest as one course. CDDP (20 mg/m2) was infused for 2 hours on day 1, 8, and 15. One course was done in the hospital, and the following 2 courses as ambulatory treatment. Grade 2 neutropenia was observed as an adverse reaction. At the completion of 3 courses, partial response in the primary tumor, complete response in the duodenal third portion and no change in the liver metastasis were assessed by examination. Because of this remarkable down-staging, distal gastrectomy and radiofrequency ablation (RFA) for liver metastasis were performed. There was no evidence of direct invasion to the other organs from the primary tumor in intraoperative findings. Pathological examination revealed the disappearance of carcinoma cell in the resected stomach and the surrounding lymphnodes. In conclusion, this chemotherapy regimen has an excellent antitumor effect with low toxicities. Therefore, this regimen was comparatively safe for outpatients and was an effective neo-adjuvant chemotherapy.

Adenocarcinoma↗
PubMed2002

Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn's disease, respectively.

The importance of tumor necrosis factor (TNF)-alpha and the TNF receptor gene polymorphisms in the etipathogenesis of inflammatory bowel disease (IBD) has not been elucidated. DNA from peripheral blood samples was obtained from 124 patients with Crohn's disease (CD), 106 patients with ulcerative colitis (UC), and 111 unrelated healthy controls. We examined two single nucleotide polymorphisms (SNPs) of the TNF-alpha gene, TNF (-308 G/A and -238 G/A), an SNP of the TNF receptor superfamily member 1A gene, TNFRSF1A(also known as TNFR1), at codon 12 in exon 1 (CCA/CCG), and two SNPs of the 1B gene, TNFRSF1B (also known as TNFR2), (1466 A/G and 1493 C/T). There was a difference in the carrier frequency for haplotype AG (-308 A, -238 G) between UC patients and the controls (OR=4.76, 95% CI=1.53-14.74, P<0.01). We found a significant difference in carrier frequency for haplotype AT (1466 A, 1493 T) of the TNFRSF1B gene between CD patients and the controls (OR=2.13, 95% CI=1.08-4.21, P<0.05). The significance proved to be greater in CD patients with both internal and external fistula (OR=4.8, 95% CI=1.73-13.33, P<0.01), and in those who were poor responders ( n=22) to our treatments, which consisted of nutritional therapy, medical therapy and surgical therapy (OR=9.24, 95% CI=3.37-25.36, P<0.001). This study suggests that one of the genes responsible for UC may be the TNF gene, or an adjacent gene, and that TNFRSF1B gene polymorphisms contribute greatly to the increased onset risk of CD and to the disease behavior.

Adolescent↗
PubMed2002

Treatment of ulcerative colitis by feeding with germinated barley foodstuff: first report of a multicenter open control trial.

BACKGROUND: Germinated barley foodstuff (GBF) is a prebiotic foodstuff that effectively increases luminal butyrate production by stimulating the growth of protective bacteria. In the first pilot study, GBF has been shown to reduce both clinical activity and mucosal inflammation in ulcerative colitis (UC). The aim of this study was to investigate the efficacy of GBF in the treatment of UC in a multicenter open control trial. METHODS: Eighteen patients with mildly to moderately active UC were divided into two groups using a random allocation protocol. The control group (n = 7) were given a baseline anti-inflammatory therapy for 4 weeks. In the GBF-treated group (n = 11), patients received 20-30 g GBF daily, together with the baseline treatment, for 4 weeks. The response to the treatments was evaluated clinically and endoscopically. Fecal microflora were also analyzed. RESULTS: After 4 weeks of observation, the GBF-treated group showed a significant decrease in clinical activity index scores compared with the control group (P < 0.05). No side effects related to GBF were observed. GBF therapy increased fecal concentrations of Bifidobacterium and Eubacterium limosum. CONCLUSIONS: Oral GBF therapy may have the potency to reduce clinical activity of UC. We believe that these results support the use of GBF administration as a new adjunct therapy for UC.

Adult↗
PubMed2002

IL18 polymorphism is associated with an increased risk of Crohn's disease.

BACKGROUND: The etiology of inflammatory bowel disease, which includes ulcerative colitis and Crohn's disease, has not yet been made clear. However, inflammatory bowel disease is recognized as a multifactorial disease, and innate genetic factors might contribute to the pathogenesis. Cytokine genes are thought to be important in inflammatory bowel disease. Recently, interleukin 18, cloned as a novel proinflammatory cytokine, has been implicated in inflammatory bowel disease, especially Crohn's disease. METHODS: To identify germline mutations in patients with inflammatory bowel disease, the entire coding region of IL18 was examined using a DNA sequencing procedure. RESULTS: No functional mutations were found, but a novel single nucleotide polymorphism (SNP) was identified as TCA/TCC at codon 35. In patients with Crohn's disease, the frequency of TCC allele carriers was significantly higher than in healthy controls (chi2 = 9.35, P = 0.002229, OR = 2.58, 95% CI = 1.39-4.80). Also, the magnitude of the association was more remarkable in females (chi2 = 16.36, P = 0.000052, OR = 8.17, 95% CI = 2.73-24.41). The TCC allele at codon 35 of IL18 may increase the risk for Crohn's disease, especially in females. CONCLUSIONS: IL18 is probably one of several genes that determine susceptibility to Crohn's disease.

Adolescent↗