Ulcerative Colitis: Uchida K

Tomomasa T, Kobayashi A, Ushijima K, Uchida K, Kagimoto S, Shimizu T, Tajiri H, Tahara T, Yoden A, Anonymous00348. · Department of Pediatrics, Gunma University Graduate School, Japan. · Pediatr Int. · Pubmed #15310325 No free full text.

Abstract: This paper introduces the guidelines for treatment of ulcerative colitis in children, created by the working group of the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (Chair: Yuichiro Yamashiro) and the Japanese Society for Pediatric Inflammatory Bowel Disease (IBD) (Chair: Akio Kobayashi). The ideas of the working group, with regard to the fundamental differences in medical treatment between children and adults, included: (1) for children, intensive medical treatment including appropriate systemic management is important during the acute phase of illness. (2) Treatment with steroids, which can cause growth disturbances, should not be continued for long periods of time. (3) Pulsed steroid therapy, selective removal of blood cells, and intravenous infusion of cyclosporin should be included in the therapeutic option for severe and fluminant cases.

Matsushita M, Uchida K, Okazaki K. · Third Department of Internal Medicine, Kansai Medical University, 2-3-1 Shinmachi, Hirakata, Osaka 573-1191, Japan. · Inflammopharmacology. · Pubmed #17701017 No free full text.

Abstract: Although human appendix has been considered as a vestigial remnant, recent observations have focused attention on the role of the appendix in the pathogenesis of ulcerative colitis (UC). Many case-control studies suggest that previous appendectomy is rare in UC patients. This inverse relation is limited to patients who undergo appendectomy before the age of 20 years. Moreover, several investigators reported the improvement of UC after appendectomy, especially in young patients. In the appendix of UC patients, the CD4/CD8 ratio is significantly increased, and the proportion of CD4+CD69+ (early activation antigen) T cells, but not of CD4+HLA-DR+ (mature activation antigen) T cells, is also significantly increased. These findings suggest that the appendix may be a priming site in the development of UC. Further studies including analysis of CD4+ and CD8+ T cells are necessary to clarify the role of the appendix in the pathogenesis of UC.

Adachi E, Okazaki K, Matsushima Y, Seno H, Uchida K, Nakase H, Kawanami C, Nakamura T, Chiba T. · Department of Gastroenterology and Hepatology, and Endoscopic Medicine, Kyoto University Hospital, Japan. · Int J Pancreatol. · Pubmed #10453423 No free full text.

Abstract: Therapy with oral 5-aminosalicylic acid (5-ASA) for ulcerative colitis has been reported to be effective and safe. We describe a case of biochemically proven mild acute pancreatitis occurring after 9 d of oral 5-ASA therapy for ulcerative colitis. A hypersensitivity mechanism seemed to be involved in the development of pancreatitis probably owing to erratic systemic absorption of the drug. We suggest clinical and biochemical monitoring for early diagnosis of pancreatitis in patients with ulcerative colitis receiving 5-ASA administration. This is the first report of acute pancreatitis developed by oral 5-ASA therapy for the treatment of ulcerative colitis in the literature of Japan.

Kayazawa M, Saitoh O, Kojima K, Nakagawa K, Tanaka S, Tabata K, Matsuse R, Uchida K, Hoshimoto M, Hirata I, Katsu K. · Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan. · Am J Gastroenterol. · Pubmed #11866274 No free full text.

Abstract: OBJECTIVES: We investigated which neutrophil-derived proteins in whole gut lavage fluid (WGLF) most accurately reflect disease activity in inflammatory bowel disease. METHODS: WGLF was obtained from patients undergoing whole gut lavage as a bowel preparation for colonoscopy. Twenty-seven patients with ulcerative colitis (UC), 23 patients with Crohn's disease (CD), and 35 control subjects were examined. The concentrations of lactoferrin, polymorphonuclear neutrophil elastase (PMN-E), myeloperoxidase, and lysozyme in WGLF were measured by ELISA. For the assessment of stability, WGLF samples were stored at 37 degrees C for various periods. RESULTS: In UC, the concentrations of lactoferrin, myeloperoxidase, and lysozyme in WGLF had good correlations with colonoscopic grading. Zero, 12, five, and 10 of 28 samples from active UC patients showed normal concentrations of lactoferrin, PMN-E, myeloperoxidase, and lysozyme, respectively. In CD, the concentrations of lactoferrin and myeloperoxidase had good correlations with the Crohn's disease activity index. Thirteen and seven of 36 samples from inactive CD patients (Crohn's disease activity index < or = 150) showed high concentrations of lactoferrin and myeloperoxidase, respectively. Most of them (11/13, 6/7) were found to have ulceration by colonoscopy or small bowel x-ray. The ratio of the lactoferrin concentration in the WGLF supernatant to that in total WGLF was highest among these proteins in all disease groups and control subjects. Lactoferrin and myeloperoxidase showed good stability in WGLF, whereas PMN-E and lysozyme did not. CONCLUSION: Lactoferrin is the most suitable of these proteins for use as a neutrophil-derived WGLF marker of intestinal inflammation.

Saitoh O, Kojima K, Kayazawa M, Sugi K, Tanaka S, Nakagawa K, Teranishi T, Matsuse R, Uchida K, Morikawa H, Hirata I, Katsu K. · Second Department of Internal Medicine, Osaka Medical College, Takatsuki. · Intern Med. · Pubmed #11030199 links to  free full text

Abstract: OBJECTIVE: This prospective pilot study was conducted to compare the usefulness of measuring fecal lactoferrin (Lf) to that of fecal occult blood (FOB) test for detection of colorectal diseases. PATIENTS AND METHODS: The subjects were 351 patients who underwent colonoscopy. A fecal sample was obtained on the day before colonoscopy. Fecal Lf was measured by enzyme-linked immunosorbent assay. The FOB test was performed by combined assay (latex agglutination) of hemoglobin and transferrin. RESULTS: The specificities of the fecal Lf and FOB tests were the same (88.7%). For patients with colorectal cancer (13), colorectal polyp (69), ulcerative colitis (18), Crohn's disease (13), non-specific colitis (8), internal hemorrhoids (60), colon diverticulum (27), and miscellaneous diseases of the colon (10), the rates of positivity for fecal Lf were 7/13, 14/69, 12/18, 7/13, 4/8, 22/60, 8/27, and 6/10, respectively. The corresponding rates for FOB were 8/13, 12/69, 11/18, 4/13, 4/8, 9/60, 2/27, and 1/10. For patients with internal hemorrhoids, the rate of positivity for fecal Lf was significantly higher than that for FOB. In other disease groups, there was no significant difference in the rate of positivity between fecal Lf and FOB. CONCLUSION: These findings suggest that measurement of fecal Lf is as useful as FOB in detecting colorectal diseases.

Okita Y, Miki C, Araki T, Inoue M, Otake K, Uchida K, Kusunoki M. · Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan. · J Pediatr Surg. · Pubmed #19159709 No free full text.

Abstract: Extension of the inflammatory process to the terminal portion of the ileum in patients with ulcerative colitis is commonly known as backwash ileitis (BWI). To the best of our knowledge, few studies of severe BWI have been reported in the English literature, and surgical strategies for this disease have not been discussed. We report 2 patients with ulcerative colitis and severe BWI, with concomitant ileal bleeding and perforation. In both cases, staged operation without sacrificing the involved area of the terminal ileum led to ileal pouch-anal anastomosis, with a favorable postoperative outcome. Our cases suggest that the underlying pathophysiologic conditions in BWI may be reversible, and the involved lesion can be salvaged in some cases.

Yoshiyama S, Miki C, Okita Y, Araki T, Uchida K, Kusunoki M. · Department of Gastrointestinal Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan. · J Gastroenterol. · Pubmed #18958548 No free full text.

Abstract: BACKGROUND: There is some evidence that large preoperative doses of steroids are a causative factor for postoperative higher morbidity in ulcerative colitis (UC) patients. This study aimed to assess steroid-related changes in functional profiles of neutrophils in UC patients to estimate the immunological changes under surgical stress. METHODS: Neutrophils were extracted from peripheral blood of 30 UC patients and 30 healthy controls. UC patients whose neutrophils were isolated were divided into two subgroups according to their total preoperative dosage of prednisolone: group H, > or =10,000 mg; group L, <10,000 mg. Expression of neutrophil surface antigens was analyzed and neutrophil phagocytosis was evaluated. Patterns of cell death of neutrophils were evaluated by co-culturing with Escherichia coli. Production of inflammatory mediators in cultured neutrophils was assessed. RESULTS: There were no significant differences in the expression rates of TLR4, CD11b, and CD16b on neutrophils (CD15(+) cells) between the two patient groups and controls. There was also no significant difference in neutrophil phagocytosis between the two patient groups and controls. The neutrophil necrosis rate in group H was higher than that in group L and the controls 3 h after exposure to E. coli. Neutrophils from group H released the highest levels of proinflammatory cytokines following interleukin-1beta or lipopolysaccharide stimulation. Neutrophils from group H also released the highest levels of proteolytic enzymes. CONCLUSIONS: Steroid-overdosed UC patients may have a functional deficit in neutrophils, which may cause a postsurgical systemic "storm" of inflammatory mediators.

Miki C, Ohmori Y, Yoshiyama S, Toiyama Y, Araki T, Uchida K, Kusunoki M. · Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Edobashi 2-174, 514-8507, Tsu, Mie, Japan. · World J Surg. · Pubmed #17334865 No free full text.

Abstract: BACKGROUND: Positive outcomes after restorative proctocolectomy are compromised by a number of specific septic complications. However, there is no useful perioperative marker predicting postoperative infectious complications (PICs) in steroid overdosed patients with ulcerative colitis (UC). METHODS: To determine factors associated with PICs and their relation to circulating levels of pro- and anti-inflammatory cytokines and neutrophil elastase (NE), we obtained perioperative blood samples from 60 UC patients. RESULTS: Postoperative infectious complications were identified in 47% of cases. Patients who developed PICs had significantly longer disease duration, had been administered a greater total preoperative dosage of prednisolone, and had a higher body mass index. Logistic regression analysis showed that the total preoperative dosage of prednisolone was independently associated with the development of PICs. These patients showed suppressed systemic inflammation and pro- and anti-inflammatory cytokine induction. An early increase in the NE level was found to be predictive of PICs in the high-dose group, whereas there was no significant difference in neutrophil counts between the high- and low-dose groups. CONCLUSIONS: Circulating NE levels in the early postoperative period might be a useful predictor of PICs in immune-controlled UC patients who received high doses of steroids.

Miki C, Yoshiyama S, Okita Y, Araki T, Uchida K, Yanagi H, Kusunoki M. · Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan. · Dig Surg. · Pubmed #16837796 No free full text.

Abstract: AIMS: The present study was designed to assess whether preoperative neutrophil priming under surgical stress has causal effects on the postoperative clinical outcomes of ulcerative colitis (UC) patients. PATIENTS AND METHODS: In 63 consecutive UC patients, perioperative changes in cytokines and neutrophil elastase (NE) were quantified and their relationships to postoperative infectious complications (PICs) were evaluated. RESULTS: A preoperative increase in NE (high group: Group H) was associated with longer disease duration and greater preoperative total amount of steroids administered. Patients in Group H developed more PICs than those in the low NE group when they underwent surgery >240 min. In Group H, the NE level remained high after longer duration surgery, but decreased rapidly after shorter duration surgery. Multivariate analyses revealed that the total amount of steroids used and preoperative NE level were independent risk factors for predicting PICs in the longer operation group. CONCLUSION: Preoperative neutrophil activation may become a risk factor for postoperative morbidity when the patients undergo intense surgical stress. The most important procedures for preventing postoperative morbidity in high-risk UC patients may be reducing surgical stress and/or controlling neutrophil activation perioperatively.

Uchida K, Araki T, Toiyama Y, Yoshiyama S, Inoue M, Ikeuchi H, Yanagi H, Miki C, Yamamura T, Kusunoki M. · Second Department of Surgery, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie, 514-8507, Japan. · Dis Colon Rectum. · Pubmed #16283565 No free full text.

Abstract: PURPOSE: This study was designed to clarify a limit for steroid therapy in patients with ulcerative colitis through analyzing the preoperative major steroid-related complications and to define when alternative therapies, including surgery, should be performed in pediatric ulcerative colitis patients. METHODS: The medical records of 28 pediatric and 57 adult patients with ulcerative colitis who underwent total proctocolectomy and ileal J-pouch-anal anastomosis were reviewed. The relationship between the preoperative dose of glucocorticoids and major steroid-related complications, as well as the surgery variables, was evaluated. RESULTS: Significantly higher incidences of growth retardation, osteoporosis, glaucoma, and cataracts were noted in pediatric patients than in adult patients. In pediatric patients, major steroid-related complications occurred at a significantly lower preoperative total dosage of glucocorticoids/body weight (mg/kg) or preoperative total dosage of glucocorticoids/body surface area (mg/m2) than in adult patients. A similar surgical procedure was performed in both pediatric and adult patients. The presence of major steroid-related complications can lower a patient's long-term quality of life. CONCLUSIONS: Evidence-based guidelines for the recommended dose of glucocorticoids according to body weight or body surface area are needed. To allow patients to feel well and maintain a good quality of life, early introduction of alternative treatments, including surgery, should be considered.

Akazawa A, Sakaida I, Higaki S, Kubo Y, Uchida K, Okita K. · Department of Gastroenterology and Hepatology, Yamaguchi University, School of Medicine, Ube, Japan. · J Gastroenterol. · Pubmed #12051533 No free full text.

Abstract: BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha), may be involved in the pathogenesis of inflammatory bowel diseases (IBDs). The aim of this study was to evaluate the effect of TNF-alpha on the inflammatory activity of IBD. METHODS: TNF-alpha mRNA expression in intestinal mucosal biopsy specimens from IBD patients [ulcerative colitis (UC), n = 54; and Crohn's disease (CD), n = 11] was analyzed using a competitive polymerase chain reaction. The degree of macrophage infiltration was analyzed by immunohistochemistry, using an antihuman CD68 antibody. RESULTS: TNF-alpha mRNA expression was increased in UC patients, corresponding to the inflammatory activity. However, in CD, TNF-alpha mRNA expression was not correlated with the endoscopic findings. CONCLUSIONS: We clarified that TNF-alpha mRNA expression was responsible for the inflammatory activity in UC. However, TNF-alpha mRNA expression was not correlated with the mucosal injury in CD.

Saitoh O, Kojima K, Sugi K, Matsuse R, Uchida K, Tabata K, Nakagawa K, Kayazawa M, Hirata I, Katsu K. · Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan. · Am J Gastroenterol. · Pubmed #10606313 No free full text.

Abstract: OBJECTIVES: The aims of this study were: 1) to examine whether the fecal levels of eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease (IBD); and 2) to examine the extracellular release of these proteins from eosinophils and their stability in feces by an in vitro study. METHODS: We investigated 42 patients with ulcerative colitis (UC), 37 patients with Crohn's disease (CD), and 29 control subjects. The stool samples were collected at 4 degrees C over 48 h and were homogenized. The fecal levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured by radioimmunoassay. Fecal Hb (Hb), alpha1-antitrypsin (AT), and lactoferrin (Lf) were also measured by ELISA. RESULTS: Fecal ECP and EPX concentrations were significantly increased in both active UC and active CD compared to inactive UC and inactive CD, respectively. Fecal EPX concentration correlated with the fecal Hb, AT, and Lf concentrations more closely than fecal ECP concentration. Even in the inactive stage, CD patients who relapsed within the following 3 months showed higher fecal ECP and EPX concentrations compared to the patients who did not. EPX was released extracellularly more efficiently than ECP (18.6% vs 6.3%, after incubation for 15 min at 25 degrees C). EPX was more stable in the feces than ECP. CONCLUSIONS: The measurement of eosinophil granule-derived proteins in feces is useful for evaluating disease activity and predicting relapse in patients with IBD. EPX may be more suitable than ECP as a fecal eosinophil marker.

Nakanishi M, Yoh K, Uchida K, Maruo S, Rai SK, Matsuoka A. · Department of Clinical Pathology, Hyogo College of Medicine, Nishinomiya, Japan. · J Bone Miner Metab. · Pubmed #10340640 No free full text.

Abstract: This study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase (TrFsACP) activity using 2,6-dichloro-4-acetylphenyl phosphate as substrate at pH 6.2 in metabolic bone diseases. The mean Z-scores of TrFsACP activity in patients on hemodialysis were higher than in healthy subjects (male: 2.04+/-1.98, n = 49, P < .05; female: 1.49+/-2.43, n = 39, P < .05) and increased with duration of hemodialysis (r = .516, P < .01). Bone alkaline phosphatase also was found to be significantly higher in hemodialysis patients (male: 0.93+/-1.49, P < .05; female: 1.66+/-2.42, P < .05) compared with normal subjects: but had lower correlation with duration of hemodialysis than TrFsACP (r = .277, P < .05). Ulcerative colitis (1.37+/-2.21, n = 15) in males showed a significantly higher Z-score of TrFsACP compared with control subjects (P < .05). The relationship of TrFsACP activity and ultrasound findings (stiffness; speed of sound [SOS]; broadband ultra sound attenuation [BUA]) in healthy women aged 30-75 years (n = 95) were inversely and significantly correlated with stiffness (r = -.465, P < .01 ), SOS (r = -.484, P < .01), and BUA (r = -.366, P < .01), but were age dependent. TrFsACP activity significantly correlated with stiffness (r = -.521, P < .05) and SOS (r = -.527, P < .05) only in the age group of 46-55 years. BUA (r = -.313, P > .05) did not correlate significantly in any subject in the present study. We conclude that serum TrFsACP activity is useful in the diagnosis and monitoring of bone turnover.

Sugi K, Saitoh O, Matsuse R, Tabata K, Uchida K, Kojima K, Nakagawa K, Tanaka S, Teranishi T, Hirata I, Katsu K. · Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan. · Am J Gastroenterol. · Pubmed #10235211 No free full text.

Abstract: OBJECTIVE: Our aim was to investigate the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in Japanese patients with ulcerative colitis (UC) and Crohn's disease (CD), and the putative antigens recognized by perinuclear staining pattern ANCA (p-ANCA)-positive sera. METHODS: Sera from UC (n = 52) and CD (n = 43) patients, and from healthy controls (n = 74) were studied. The indirect immunofluorescence (IIF) method was used for the detection of ANCA and its binding pattern. p-ANCA-positive sera were studied further for putative antigens. ELISAs using lactoferrin (Lf), myeloperoxidase (MPO), and cathepsin G (Cat G) as antigens were performed. RESULTS: ANCA was positive in 40 of the 52 (76.9%) UC (p-ANCA in 33) and in 32 of the 43 (74.4%) CD (p-ANCA in 31) patients. UC and CD patients showed significantly higher titers of p-ANCA than controls; however, no significant difference was observed between UC and CD. In UC, 23, 17, and nine of the 33 patients with p-ANCA-positive sera showed reactivity with Lf, MPO, and Cat-G, respectively. In CD, 21, 20, and 11 of the 31 patients with p-ANCA-positive sera showed reactivity with Lf, MPO, and Cat-G, respectively. Fourteen of the UC and six of the CD patients showed reactivity with two different antigens, and seven of the UC and 11 of the CD patients showed reactivity with all three antigens. The presence of anti-Lf and anti-MPO antibodies was further confirmed by Western blotting. CONCLUSIONS: ANCA is useful in distinguishing patients with IBD from normal subjects but is not sufficient for the differential diagnosis of CD and UC. p-ANCA reactivity might be derived from the recognition of heterogeneous neutrophil-associated antigens.

Miki C, Okita Y, Yoshiyama S, Araki T, Uchida K, Kusunoki M. · No affiliation provided · J Gastroenterol. · Pubmed #17671769 No free full text.

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