1.Infliximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naive Patients with Crohn's Disease.
Kyoichi KATO ; Ken FUKUNAGA ; Koji KAMIKOZURU ; Shinichiro KASHIWAMURA ; Nobuyuki HIDA ; Yoshio OHDA ; Naohisa TAKEDA ; Koji YOSHIDA ; Masaki IIMURO ; Yoko YOKOYAMA ; Risa KIKUYAMA ; Hiroto MIWA ; Takayuki MATSUMOTO
Gut and Liver 2011;5(1):37-45
BACKGROUND/AIMS: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-alpha has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles is lacking. The purpose of this study was to reveal the immunological effects of IFX. METHODS: Twenty-two patients with a CD activity index (CDAI) of 194.2+/-92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their first IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. RESULTS: CDAI significantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-beta1 (p<0.01), and 'regulated on activation, normal T cell expressed and secreted' (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-alpha (p<0.04), IL-6 (p<0.03), interferon (IFN)-gamma (p<0.04), IFN-gamma-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage inflammatory protein-1beta (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-gamma)/Th2 (IL-4) ratio (p<0.03). CONCLUSIONS: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naive Th0 lymphocytes to Treg. This knowledge should have clinical relevance.
Antibodies
;
Antibodies, Monoclonal
;
Chemokine CCL2
;
Chemokine CCL5
;
Chemokines
;
Crohn Disease
;
Cytokines
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Humans
;
Immune System
;
Interferons
;
Interleukin-10
;
Interleukin-13
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Interleukin-6
;
Interleukin-8
;
Interleukins
;
Lymphocytes
;
Macrophages
;
Mesalamine
;
Remission Induction
;
T-Lymphocytes, Regulatory
;
Tumor Necrosis Factor-alpha
;
Infliximab
2.Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals.
Takahisa YAMASAKI ; Toshihiko TOMITA ; Mayu TAKIMOTO ; Takashi KONDO ; Katsuyuki TOZAWA ; Yoshio OHDA ; Tadayuki OSHIMA ; Hirokazu FUKUI ; Jiro WATARI ; Hiroto MIWA
Journal of Neurogastroenterology and Motility 2017;23(4):526-532
BACKGROUND/AIMS: When a person is experiencing stress, corticotropin-releasing hormone (CRH) can modulate gut physiologies, such as visceral sensation or gastrointestinal motility, and its intravenous administration mimics stress-induced physiological changes. However, the influence of CRH on the esophagus is yet unknown. Accordingly, we investigated whether intravenous CRH administration increases esophageal sensitivity to electrical stimulation in healthy Japanese subjects. METHODS: Twenty healthy subjects were recruited. We quantified the initial perception threshold (IPT) every 15 minutes after CRH injection. Venous blood was collected with a cannula, and both plasma adrenocorticotropic hormone (ACTH) and cortisol were measured at pre-stimulation, 0, 30, 60, 90, and 120 minutes. The results from each time point were compared against a baseline IPT obtained before electrical stimulation was initiated. RESULTS: When compared to the baseline IPT value (16.9 ± 4.5), CRH significantly decreased electrical threshold of the esophagus at 30, 45, 60, 75 minutes (14.1 ± 4.2, 13.1 ± 5.0, 12.1 ± 5.7, 14.0 ± 5.8 minutes, P < 0.01, respectively) after CRH injection, suggesting that CRH increased esophageal sensitivity to the electrical stimulus. CRH also significantly increased plasma ACTH levels at 30 minutes (50.3 ± 17.7, P < 0.01), and cortisol levels at 30 minutes (22.0 ± 6.7 minutes, P < 0.01) and 60 minutes (20.3 ± 6.7 minutes, P < 0.01) after CRH injection, when compared to the pre-stimulation ACTH and cortisol values. CONCLUSION: Intravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity.
Administration, Intravenous
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Adrenocorticotropic Hormone
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Asian Continental Ancestry Group
;
Catheters
;
Corticotropin-Releasing Hormone*
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Electric Stimulation
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Esophagus
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Gastrointestinal Motility
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Healthy Volunteers
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Humans
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Hydrocortisone
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Plasma
;
Sensation
3.Cytapheresis in Patients with Severe Ulcerative Colitis after Failure of Intravenous Corticosteroid: A Long-Term Retrospective Cohort Study.
Ken FUKUNAGA ; Kazuko NAGASE ; Takeshi KUSAKA ; Nobuyuki HIDA ; Yoshio OHDA ; Koji YOSHIDA ; Katsuyuki TOZAWA ; Koji KAMIKOZURU ; M IIMURO ; Shiro NAKAMURA ; Hiroto MIWA ; Takayuki MATSUMOTO
Gut and Liver 2009;3(1):41-47
BACKGROUND/AIMS: Cytapheresis (CAP) is a novel strategy for ulcerative colitis (UC). However, there is insufficient data on the long-term outcome of UC patients who achieve remission by CAP. This study involved patients with severe UC who refracted to intravenous (iv) corticosteroid. METHODS: Forty-seven UC patients who had received CAP therapy for the first time within 1 year after UC diagnosis were followed for 36 months. One of the inclusion criteria was a clinical activity index (CAI) of > or =7 points at the end of a 2-week iv course of corticosteroid therapy. CAP therapy consisted of ten sessions over 10 weeks. RESULTS: CAP induced clinical remission (CAI< or =4) in 70.2% patients (33/47). The number of submissions for colectomy was higher for severe UC at entry (CAI> or =12, n=25) than for moderately severe UC at entry (7< or =CAI<12, p=15; p<0.02). The cumulative rates of avoiding surgery and relapse were 54.5% and 24.2%, respectively, at 36 months in patients who responded to CAP therapy. This was similar to that of iv cyclosporine reported recently. CONCLUSIONS: This study suggest that CAP is an effective therapy in patients who are refractory to conventional medications including iv corticosteroid. Increased remission rates should be expected in refractory patients with moderately severe UC.
Cohort Studies
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Colectomy
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Colitis, Ulcerative
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Cyclosporine
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Cytapheresis
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Humans
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Inflammatory Bowel Diseases
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Leukapheresis
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Recurrence
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Retrospective Studies
;
Ulcer
4.Prevalence and Self-recognition of Chronic Constipation: Results of an Internet Survey.
Akio TAMURA ; Toshihiko TOMITA ; Tadayuki OSHIMA ; Fumihiko TOYOSHIMA ; Takahisa YAMASAKI ; Takuya OKUGAWA ; Takashi KONDO ; Tomoaki KONO ; Katsuyuki TOZAWA ; Hisatomo IKEHARA ; Yoshio OHDA ; Hirokazu FUKUI ; Jiro WATARI ; Hiroto MIWA
Journal of Neurogastroenterology and Motility 2016;22(4):677-685
BACKGROUND/AIMS: Although chronic constipation is a common symptom, to date no international consensus has been reached regarding its definition. The aims of this study were (1) to investigate defecation habits and (2) to examine the prevalence of constipation using the Japanese Society of Internal Medicine (JSIM) and the Rome III criteria using an online survey. METHODS: An online questionnaire composed of items on the frequency, interval, form of defecation, the management, and self-recognition of constipation (reference standard of constipation) was created. A total of 5155 valid responses were received. In addition, constipation symptoms were evaluated through a survey using the JSIM and the Rome III criteria. RESULTS: In the internet survey, 28.4% of the respondents considered themselves to be constipated. Stratified by sex, significantly more females (37.5%) than males (19.1%) considered themselves to be constipated (P < 0.001). The prevalence of constipation among the respondents was 28.0% using the Rome III, but only 10.1% using the JSIM. The diagnostic accuracy was 73.2% for the Rome III and 78.1% for the JSIM, while the diagnostic specificity was 81.1% for the Rome III and 97.5% for the JSIM. However, the diagnostic sensitivities for both measures were low, at 52.2% and 29.2% for the Rome III and the JSIM, respectively. CONCLUSIONS: The online survey developed for this study was able to provide clarification regarding defecation patterns. The results also suggest a discrepancy between the self-recognized prevalence of constipation in Japan and prevalence of constipation based on the JSIM criteria.
Asian Continental Ancestry Group
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Consensus
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Constipation*
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Defecation
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Female
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Humans
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Internal Medicine
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Internet*
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Japan
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Male
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Prevalence*
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Sensitivity and Specificity
;
Surveys and Questionnaires
5.Prevalence of Gastric Motility Disorders in Patients with Functional Dyspepsia.
Haruki ASANO ; Toshihiko TOMITA ; Kumiko NAKAMURA ; Takahisa YAMASAKI ; Takuya OKUGAWA ; Takashi KONDO ; Tomoaki KONO ; Katsuyuki TOZAWA ; Yoshio OHDA ; Tadayuki OSHIMA ; Hirokazu FUKUI ; Kazuhito FUKUSHIMA ; Shozo HIROTA ; Jiro WATARI ; Hiroto MIWA
Journal of Neurogastroenterology and Motility 2017;23(3):392-399
BACKGROUND/AIMS: Gastric motility abnormalities have been considered to be pathophysiological features of functional dyspepsia (FD) that are closely related to dyspepsia symptoms, especially postprandial distress syndrome (PDS). The aims of this study are to (1) investigate the prevalence of gastric motility disorders and (2) evaluate the association between gastric motility abnormalities and dyspeptic symptoms using gastric scintigraphy in the PDS type of FD. METHODS: Forty healthy subjects and 94 PDS type FD patients were enrolled in the study. The volunteers and patients ingested a radiolabeled (technetium-99m) solid test meal, and scintigraphic images were recorded. Gastric accommodation and emptying were assessed by scintigraphic imaging. The patients’ dyspeptic symptoms were also explored using self-completed symptom questionnaires with 10 variables (4 scales, 0–3 points) at the same time. RESULTS: In 94 Japanese FD patients, the prevalence of impaired gastric accommodation and delayed emptying were 14.9% (14/94) and 10.6% (10/94), respectively. Gastric motility abnormalities were seen in 25.5% (24/94) of FD patients. There was no association between gastric motility abnormalities and dyspeptic symptoms. CONCLUSIONS: Gastric motility abnormalities were seen in 25.5% of Japanese PDS type FD patients. However, there was no association between gastric motility abnormalities and dyspeptic symptoms on gastric scintigraphy.
Asian Continental Ancestry Group
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Dyspepsia*
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Healthy Volunteers
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Humans
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Meals
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Prevalence*
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Radionuclide Imaging
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Stomach
;
Volunteers
;
Weights and Measures
6.Prevalence of Irritable Bowel Syndrome–like Symptoms in Japanese Patients with Inactive Inflammatory Bowel Disease.
Toshihiko TOMITA ; Yu KATO ; Mayu TAKIMOTO ; Takahisa YAMASAKI ; Takashi KONDO ; Tomoaki KONO ; Katsuyuki TOZAWA ; Yoko YOKOYAMA ; Hisatomo IKEHARA ; Yoshio OHDA ; Tadayuki OSHIMA ; Hirokazu FUKUI ; Shigemi TANAKA ; Masayuki SHIMA ; Jiro WATARI ; Hiroto MIWA
Journal of Neurogastroenterology and Motility 2016;22(4):661-669
BACKGROUND/AIMS: Few studies are available that have investigated the risk factors for overlapping irritable bowel syndrome (IBS)-like symptoms in patients with inactive inflammatory bowel disease (IBD). The present study has 3 objectives: (1) to assess the prevalence of IBS-like symptoms in Japanese patients with inactive IBD using Rome III criteria, (2) to examine the relationship of IBS-like symptoms to health related quality of life (HR-QOL), and (3) to investigate associations for developing IBS-like symptoms in patients with inactive IBD. METHODS: IBS-like symptoms were evaluated using the Rome III questionnaire for functional gastrointestinal disorders. HR-QOL and hospital anxiety and depression scale were evaluated. RESULTS: IBS-like symptoms were found in 17.5% (7/40) of patients with inactive ulcerative colitis, 27.1% (29/107) of patients with inactive Crohn’s disease (CD), and 5.3% (23/438) of healthy control subjects. The QOL level was significantly lower and anxiety score was significantly higher in inactive CD patients with IBS-like symptoms than in those without such symptoms (P = 0.003, P = 0.009). Use of anti-anxiety drugs was associated with the presence of IBS symptoms (P = 0.045). HR-QOL score was lower and anxiety score was higher in patients with inactive ulcerative colitis, but the difference was not statistically significant. CONCLUSIONS: The prevalence of IBS-like symptoms in inactive IBD patients was significantly higher than in healthy controls. Inactive CD patients with IBS-like symptoms has low QOL and anxiety; suggesting that anxiety may be associated with symptom development in such patients.
Anti-Anxiety Agents
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Anxiety
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Asian Continental Ancestry Group*
;
Colitis, Ulcerative
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Depression
;
Gastrointestinal Diseases
;
Humans
;
Inflammatory Bowel Diseases*
;
Irritable Bowel Syndrome
;
Prevalence*
;
Quality of Life
;
Risk Factors