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Takashi Nonaka,
Takaomi Kessoku,
Yuji Ogawa,
Shogo Yanagisawa,
Tadahiko Shiba,
Takashi Sakaguchi, Kazuhiro Atsukawa,
Hisao Takahashi,
Yusuke Sekino,
Hiroshi Iida,
Hiroki Endo,
Yasunari Sakamoto,
Tomoko Koide,
Hirokazu Takahashi,
Masato Yoneda,
Shin Maeda,
Atsushi Nakajima,
Eiji Gotoh,
Masahiko Inamori
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to examine the convenience of the quality of life and utility evaluation survey technology (QUEST) questionnaire and the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire as self-assessment diagnostic instrument.
This was a two-way crossover study conducted over 6 weeks from September 2010 to November 2010. The subjects were 60 consecutive patients admitted to the Hiratsuka city hospital with a gastrointestinal condition, regardless of the coexistence of heartburn. They were assigned to fill in both the QUEST and FSSG questionnaires in random order. We analyzed the time taken to complete the questionnaires, whether subjects asked any questions as they filled in the questionnaire, and the questionnaire scores.
Comparison of the QUEST and the FSSG revealed significant differences in the completion time (196.5 vs. 97.5 seconds, respectively; P < 0.0001) and in whether subjects asked any questions (37 vs. 15 subjects, respectively; P < 0.0001). Completion time in QUEST scores of ≥ 4 was lower than < 4 (170.5 vs. 214.0 seconds, respectively; P = 0.022), and the QUEST score was significantly higher without questions than with question (3 vs. 1 points, respectively; P = 0.025).
This study revealed that the FSSG questionnaire may be easier for Japanese subjects to complete than the QUEST questionnaire.
Journal of neurogastroenterology and motility 01/2013; 19(1):54-60.
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Tatehiro Kagawa,
Sei-Ichiro Kojima,
Koichi Shiraishi,
Shunji Hirose,
Yoshitaka Arase,
Shinji Takashimizu,
Norihito Watanabe,
Naruhiko Nagata,
Makoto Numata,
Hirokazu Shiozawa,
Yasuhiro Nishizaki,
Mayu Toki,
Teruji Sugita,
Kijuro Nomura,
Takashi Sakaguchi, Kazuhiro Atsukawa,
Hiroto Tajima,
Yoshihiro Tei,
Tsutomu Inomoto,
Tetsuya Mine
[show abstract]
[hide abstract]
ABSTRACT: AIM: In this multicenter, randomized trial, we evaluated the effectiveness of meloxicam - a non-steroidal anti-inflammatory drug - as an adjuvant for enhancing antiviral efficacy and preventing neutropenia during the treatment of patients with genotype 1 chronic hepatitis C using peginterferon and ribavirin. METHODS: A total of 60 patients were randomly assigned, in a 1:1 ratio, to either the meloxicam or the control group after stratification by neutrophil count. Both groups received weekly peginterferon-α-2a (180 μg) and a weight-based dose of ribavirin for 48 weeks. The meloxicam group received meloxicam (10 mg/day) for the first 8 weeks after initiation of treatment. RESULTS: Through intent-to-treat analysis, we found that the sustained virological response rate in the meloxicam group (19/30, 63.3%) was significantly higher than in the control group (11/30, 36.7%, P < 0.05). The relapse rate was more than twice as high (45%) in the control group than in the meloxicam group (19.0%); however, this difference was not statistically significant. The rate of neutrophil decrease, calculated by dividing the lowest value observed during the first 8 weeks by pretreatment count, was significantly smaller in the meloxicam group (55.1 ± 14.3%) than in the control group (62.3 ± 9.6%, P < 0.05). CONCLUSION: Meloxicam enhanced antiviral efficacy and reduced the decline in neutrophil counts for the peginterferon and ribavirin treatment of genotype 1 chronic hepatitis C. This drug could be a reasonable adjuvant for the treatment of patients with chronic hepatitis C. The present study including a small number of patients warrants larger clinical trials.
Hepatology Research 12/2012; · 2.20 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Human E-cadherin is a homophilic cell adhesion molecule and its expression is well preserved in normal human hepatocytes;
a decrease in its expression has been observed in poorly differentiated hepatocellular carcinoma cells. We examined the alteration
of E-cadherin and catenin expressions caused by differentiation inducers in human hepatocellular carcinoma cells. Hepatocellular
carcinoma cell lines, HCC-T and HCC-M, were cultured with all-trans retinoic acid (ATRA), dexamethasone (DEX), sodium butyrate, and interferon-α. E-cadherin expression was only up-regulated
by butyrate and interferon-α (IFN-α) in both cell lines, studied by means of fluorescence immunostaining and flow cytometry.
The localization of E-cadherin staining was shown at their cell membrane. According to the increase in E-cadherin expression,
β-catenin expression appeared at the cell membrane of both cell lines when treated with butyrate and IFN-α. Such an appearance
was not observed when cells were treated with ATRA and DEX. Western blotting showed that α-and γ-catenin expression was not
changed, while only the expression of β-catenin increased. β-Catenin oncogenic activation as a result of amino acid substitutions
or interstitial deletions within or including parts of exon 3, which has been demonstrated recently, was not detected in these
cell lines by direct deoxyribonucleic acid sequencing. These results suggest that the expression and interaction between E-cadherin
and wild-type β-catenin are potentially modulated by butyrate and IFN-α, and that these two agents are potent inhibitors of
hepatocellular carcinoma cell invasion and metastasis.
In Vitro Cellular & Developmental Biology - Animal 04/2012; 36(6):387-394. · 1.31 Impact Factor
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Tatehiro Kagawa,
Sei-Ichiro Kojima,
Koichi Shiraishi,
Shinji Takashimizu,
Naruhiko Nagata,
Hirokazu Shiozawa,
Yasuhiro Nishizaki,
Akihiko Ikeda,
Yoshihiro Tei, Kazuhiro Atsukawa,
Jun-Ichiro Kamochi,
Mitsuru Wasada,
Makoto Numata,
Yoshitaka Arase,
Shunji Hirose,
Takuji Yamada,
Yasuo Hata,
Norihito Watanabe,
Toshio Morizane,
Tetsuya Mine
[show abstract]
[hide abstract]
ABSTRACT: Aim: The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. Methods: We compared the efficacy and tolerability of the 24-week peginterferon α-2b (1.5 µg/kg/week) therapy in combination with a weight-based higher dose (600-1000 mg) and lower dose (400-800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. Results: A total of 120 patients were randomized to a higher-dose or a lower-dose group. Sustained virological response (SVR) by intention-to-treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6-89.5) patients in the higher-dose group and 41/60 (68.3%, 90% CI: 58.5-78.2) patients in the lower-dose group (difference, -12.7%; 90% CI, -25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher-dose and the lower-dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs <9.5 mg/kg per day; odds ratio = 3.34; 95% CI, 1.41-7.92; P = 0.006). Twenty-one (36.2%) in the higher-dose group required ribavirin dose reduction because of anemia, whereas seven patients (11.7%) did in the lower-dose group (P < 0.01). Three of the higher-dose group and two of the lower-dose group required premature termination of therapy. Conclusions: Weight-based lower-dose ribavirin regimen was not equivalent to the higher-dose counterpart in the treatment of HCV genotype 2. We discourage treating these patients with low-dose ribavirin regimens. The peginterferon therapy in combination with ribavirin at a weight-based higher dose (600-1000 mg) remains the standard-of-care treatment for this genotype.
Hepatology Research 12/2011; 42(4):351-358. · 2.20 Impact Factor
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Hirotoshi Ebinuma,
Hidetsugu Saito,
Shinichiro Tada,
Nobuhiro Nakamoto,
Tazuko Ohishi,
Satoshi Tsunematsu,
Naoki Kumagai,
Kanji Tsuchimoto,
Nobuhiro Tsukada,
Yasutaka Inagaki,
Yoshinori Horie,
Masahiko Takahashi, Kazuhiro Atsukawa,
Yukishige Okamura,
Takanori Kanai,
Toshifumi Hibi
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: Peginterferon (PEG-IFN) and ribavirin (RBV) combination treatment for patients with chronic hepatitis C (CHC), infected by genotype-1 hepatitis C virus with high viral loads, results in a sustained viral response (SVR) in ~50%. However, a trend of decreasing SVR in the older patients has been reported. In the present study, we verified this trend of treatment efficacy in older patients using the propensity score (PS). METHODS: We conducted a survey of 327 patients with CHC (genotype 1 and high viral loads) who were treated with PEG-IFN and RBV for 48 weeks. The SVR rate was compared between patients =60 and <60 years of age. Because backgrounds of these patients differed considerably, we verified this efficacy between the older (n = 102) and younger (n = 102) patients matched for gender, body weight, platelets (PLT), and red blood cell (RBC) counts using PS. RESULTS: The total SVR rate was 42.9% (161/327); this rate decreased with increasing age and was lower in the older patients (≥60 years: 41.5%, <60 years: 54.3%, P = 0.0245). Moreover, younger age was a significant factor for SVR. After correction by PS, the SVR in older patients remained significantly lower (≥60 years: 43.1%, <60 years: 57.8%, P = 0.0497). In addition, RBC counts and hemoglobin (Hgb) concentrations, as well as RBV adherence in the older patients, decreased with this treatment, although there were no significant differences in pretreatment RBC and Hgb levels. CONCLUSIONS: The analysis using PS indicated that RBV adherence in the older patients decreased even if they did not have lower pretreatment RBC and Hgb levels.
Hepatology International 09/2011; · 2.64 Impact Factor
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Takashi Nonaka,
Takaomi Kessoku,
Yuji Ogawa,
Kento Imajyo,
Shogo Yanagisawa,
Tadahiko Shiba,
Takashi Sakaguchi, Kazuhiro Atsukawa,
Hisao Takahashi,
Yusuke Sekino, [......],
Koji Fujita,
Masato Yoneda,
Tomoko Koide,
Hirokazu Takahashi,
Chikako Tokoro,
Yasunobu Abe,
Eiji Gotoh,
Shin Maeda,
Atsushi Nakajima,
Masahiko Inamori
[show abstract]
[hide abstract]
ABSTRACT: The effects of Histamine-2 receptor antagonists and proton pump inhibitors on the gastrointestinal motility have not yet been sufficiently investigated. The aim of this study was to determine the effects of intravenous bolus administration of famotidine and omeprazole on the rate of gastric emptying using the continuous (13)C breath test (BreathID system, Exalenz Bioscience Ltd, Israel).
Twelve healthy male volunteers participated in this randomized, 3-way crossover study. After fasting overnight, the subjects were randomly assigned to receive 20 mg of famotidine, 20 mg of omeprazole or 20 mL of saline alone by intravenous bolus injection before a test meal (200 kcal per 200 mL, containing 100 mg of (13)C-acetate). Gastric emptying was monitored for 4 hours after the ingestion of test meal by the (13)C-acetic acid breath test performed using the BreathID system.
No significant differences in the calculated parameters, namely, the T(1/2), T(lag), GEC, β and κ, were observed among the 3 test conditions.
The study revealed that intravenous administration of gastric acid suppressant drugs had no significant influence on the rate of gastric emptying in comparison with that of saline alone as a placebo. Our results indicating the absence of any effect of either famotidine or omeprazole on accelerating the rate of gastric emptying suggest that both medications can be administered safely to patients suffering from hemorrhagic peptic ulcers who need to be kept nil by mouth from the viewpoint of possible acceleration of gastrointestinal motility in the clinical setting.
Journal of neurogastroenterology and motility 07/2011; 17(3):287-93.
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Takashi Nonaka,
Masahiko Inamori,
Tadaomi Kessoku,
Yuji Ogawa,
Shogo Yanagisawa,
Tadahiko Shiba,
Takashi Sakaguchi,
Eiji Gotoh,
Shin Maeda,
Atsushi Nakajima, Kazuhiro Atsukawa,
Hisao Takahasi,
Yoshikiyo Akasaka
[show abstract]
[hide abstract]
ABSTRACT: Mucosal prolapse syndrome (MPS) has been recognized as a chronic benign inflammatory disorder, characterized mainly by rectal mucosal prolapse. Disorders representing this condition include solitary rectal ulcer syndrome (SRUS), rectal prolapse, proctitis cystica profunda, and inflammatory cap polyps. The gross appearance of rectal MPS can be occasionally misinterpreted as rectal cancer. In contrast, there have been a few reports of colorectal cancer originating from prolapsed mucosa. Herein, we report a case of MPS associated with two independent rectal cancers extending into the submucosal layer. We speculate that long-standing MPS may increase the risk of malignant transformation.
Internal Medicine 01/2011; 50(21):2569-73. · 0.94 Impact Factor
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Takeshi Nagase,
Toshio Kanai,
Motohito Nakagawa,
Yusuke Kumamoto,
Syun Imai,
Osamu Wada,
Tomo Honda,
Go Hoshino, Kazuhiro Atsukawa,
Takashi Sakaguchi,
Tadahiko Shiba,
Takashi Nonaka,
Kento Imajyo,
Yuji Ogawa
[show abstract]
[hide abstract]
ABSTRACT: We analyzed the clinical efficacy of pre-operative combination chemotherapy using docetaxel, cisplatin and S-1 for advanced gastric cancer. Four patients were enrolled and staging laparoscopy was performed. Patients received intravenous docetaxel and cisplatin (35 mg/m2) on day 1 and 15, and oral S-1 80 mg/m2 on day 1-14 every 4 weeks. Two patients received two courses of chemotherapy and two patients received three courses of chemotherapy. Neutropenia of more than grade 3 was found in 3 cases. All cases were PR on preoperative imaging. Curative operation was performed on three cases. Histological anti-tumor effect was judged to be grade 2 in 1 case and grade 1a in 3 cases. In the postoperative period, all patients received S-1-based adjuvant chemotherapy. The combination chemotherapy using docetaxel, cisplatin and S-1 plus operation was a candidate for the standard treatment strategy for advanced gastric cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(11):2177-9.
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Makoto Numata,
Tatehiro Kagawa,
Sei-Ichiro Kojima,
Shunji Hirose,
Naruhiko Nagata,
Koichi Shiraishi,
Norihito Watanabe,
Hirokazu Shiozawa,
Yasuhiro Nishizaki,
Shigeyuki Motegi,
Shinji Takashimizu,
Jun-Ichiro Kamochi,
Mitsuru Wasada,
Takashi Ohno,
Yoshihiro Tei,
Atsushi Nakano,
Takuji Yamada, Kazuhiro Atsukawa,
Tetsu Watanabe,
Tetsuya Mine
[show abstract]
[hide abstract]
ABSTRACT: To clarify the impact of adherence, we treated 122 genotype 1 high viral titer chronic hepatitis C patients with pegylated interferon (peg-IFN) and ribavirin for 48 weeks at nine referral hospitals, and evaluated the prognostic factors with a focus on the adherence to the treatment. This study included 68 (55.7%) treatment-naïve patients and 54 (44.3%) patients who did not respond to the previous treatment. Multivariate analysis revealed adherence to peg-IFN and ribavirin as the only significant predictor. Sustained virological response (SVR) rate was 72.2%, 19.0%, and 27.3% in patients given ≥80%, 60%-80%, and <60% dose peg-IFN, respectively, and was 68.6%, 41.2%, and 5.3% in those given ≥80%, 60%-80%, and <60% dose ribavirin, respectively. SVR rate sharply fell when exposure to peg-IFN was below 80% whereas it decreased in a stepwise manner as for ribavirin. Therefore, ≥80% of peg-IFN and as much as possible dose of ribavirin are desired to achieve SVR in the treatment of genotype 1 high viral titer chronic hepatitis C.
Hepatitis research and treatment 01/2010; 2010:702748.
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Hiroyuki Kirikoshi,
Satoru Saito,
Masato Yoneda,
Koji Fujita,
Hironori Mawatari,
Takashi Uchiyama,
Takuma Higurashi,
Kento Imajo,
Takashi Sakaguchi, Kazuhiro Atsukawa,
Aya Sawabe,
Akira Kanesaki,
Hirokazu Takahashi,
Yasunobu Abe,
Masahiko Inamori,
Noritoshi Kobayashi,
Kensuke Kubota,
Norio Ueno,
Atsushi Nakajima
[show abstract]
[hide abstract]
ABSTRACT: Spontaneous rupture is rare complication of hepatocellular carcinoma (HCC) with high mortality rate in cirrhotic cases. The aim of this study was to determine the factors influencing prognosis in cases of spontaneously ruptured HCC and to investigate the outcomes of the treatments employed, especially transcatheter arterial embolization (TAE).
A retrospective multicenter study was conducted in 48 cirrhotic patients with spontaneous rupture of HCC. Conservative treatment was employed in 32 patients (ConT group) and TAE was performed in 16 patients (TAE group).
The median survival time (MST) in the ConT group was only 13.1 days and the survival rate was extremely poor: 59.4% at 7 days, 37.5% at 14 days, and 6.3% at 30 days. On the other hand, the MST in the TAE group was 244.8 days and the survival rate was 87.5% at 1 month, 56.3% at 3 months, 23.4% at 12 months, and 15.6% at 24 months. According to the results of univariate analyses, factors associated with poor hepatic function and poor suitability for TAE was important determinants of short-term death (less than 3 weeks) among the patients (p < 0.05). On the other hand, among the patients in whom initial TAE was successfully performed (n = 15), a multivariate analysis showed that a maximum tumor size not exceeding 7 cm was the only independent factor determining long-term survival (p = 0.0130).
Despite the inherent limitations of this retrospective study, TAE appears to be a useful treatment strategy for cirrhotic patients with spontaneous HCC rupture, as it yielded a longer survival period compared with conservative treatment in patients with ruptured HCC. Among the patients with ruptured HCC in whom initial TAE was successfully performed, the maximum tumor size was an important factor influencing survival.
BMC Gastroenterology 01/2009; 9:29. · 2.42 Impact Factor
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Atsuya Takeda,
Masahiko Takahashi,
Etsuo Kunieda,
Toshiaki Takeda,
Naoko Sanuki,
Yuji Koike, Kazuhiro Atsukawa,
Toshio Ohashi,
Hidetsugu Saito,
Naoyuki Shigematsu,
Atsushi Kubo
[show abstract]
[hide abstract]
ABSTRACT: Aim: To investigate the efficacy and toxicity of hypofractionated stereotactic radiotherapy for the treatment of patients presenting with hepatocellular carcinoma (HCC) in a single institutional setting. Methods: Sixteen patients who presented with solitary HCC, including two patients with a tumor thrombus of the portal veins, were treated with stereotactic radiotherapy with or without transarterial chemoembolization. The criteria for stereotactic radiotherapy were existence of technical difficulties for other ablation therapies, inoperable disease or refusal to undergo surgery, tumor staged as Grade A or B according to the Child-Pugh classification, and solitary tumor distant from the gastrointestinal tract and kidney with a tumor volume <100 cm(3). In 14 of 16 patients, a total dose of 35- 50 Gy was delivered in 5-7 fractions over 5-9 days. Results: At the end of a mean follow-up of 612 days (median 611 days; range 244-994 days), all patients were alive. Eight of 16 patients had complete responses and seven others were judged as stable with lipiodol accumulation. In one patient, local recurrence developed after 489 days. Intrahepatic recurrences developed outside the treated volume in six patients and no extrahepatic metastases developed during follow-up. No serious treatment-related toxic manifestations developed. Conclusions: Stereotactic radiotherapy for HCC with or without transarterial chemoembolization is feasible therapy and provides good local control with a short treatment period. Stereotactic radiotherapy may be of clinical benefit in patients who are inoperable or for whom there are difficulties in other ablation therapies.
Hepatology Research 01/2008; 38(1):60-9. · 2.20 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity = 100%, specificity = 85.0%, accuracy = 86.4%), whereas RNA negativity could predict SVR on day 7 (sensitivity = 100%, specificity = 87.2%, accuracy = 88.6%). None of the patients who had detectable serum core Ag or RNA on day 14 achieved SVR (specificity = 100%). The predictive accuracy on day 14 was higher by RNA negativity (93.2%) than that by core Ag negativity (75.0%). The combined predictive criterion of both viral load decline during the first 24 h and basal viral load was also predictive for SVR; the sensitivities of Lumipulse-Ag and Amplicor-M were 45.5 and 47.6%, respectively, and the specificity was 100%. Amplicor-M had better predictive accuracy than Lumipulse-Ag in 2-week disappearance tests because it had better sensitivity. On the other hand, estimates of kinetic parameters were similar regardless of the detection method. Although the correlations between Lumipulse-Ag and Amplicor-M were good both before and 24 h after IFN administration, HCV core Ag seemed to be relatively lower 24 h after IFN administration than before administration. Lumipulse-Ag seems to be useful for detecting the HCV concentration during IFN therapy; however, we still need to understand the characteristics of the assay.
Journal of Clinical Microbiology 02/2005; 43(1):186-91. · 4.15 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: We have isolated two stable human bcl-2 transfected cell lines, HCC-T-bcl and PLC-bcl, that were derived from the transfection of two human hepatocellular carcinoma cell lines (HCC-T and PLC/PRF/5, respectively) with a plasmid vector containing recombinant bcl-2 (pCAGGS-bcl).) Cell lines transfected with the plasmid alone (pCAGGS-neo) were also established as controls (HCC-T-neo and PLC-neo). HCC-T-neo and PLC-neo were sensitive to doxorubicin-induced apoptosis, as defined by morphological observation. Although HCC-T-neo expressed endogenous Bcl-2, the sensitivity of HCC-T-neo to doxorubicin-induced cytotoxicity was similar to that of PLC-neo, which does not express endogenous Bcl-2. In contrast, both HCC-T-bcl and PLC-bcl were more resistant to doxorubicin-induced cytotoxicity. Although these bcl-2 transfectants were resistant to the drug-induced apoptosis, Bcl-2 overexpression did not affect doxorubicin-induced growth suppression. These results suggest that the overexpression of Bcl-2 renders human HCC cells resistant to doxorubicin-induced cytotoxicity.
Hepatology Research 03/2003; 25(2):192-201. · 2.20 Impact Factor
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Hepatology Research 05/2002; 22(4):322. · 2.20 Impact Factor
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Hepatology Research 05/2002; 22(4):323-324. · 2.20 Impact Factor
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Kyoko Toda,
Naoki Kumagai,
Kanji Tsuchimoto,
Hiroyuki Inagaki,
Tatsuo Suzuki,
Tazuko Oishi, Kazuhiro Atsukawa,
Hidetsugu Saito,
Toshio Morizane,
Toshifumi Hibi,
Hiromasa Ishii
[show abstract]
[hide abstract]
ABSTRACT: We studied hepatic stellate cell proliferation in vitro. Peripheral blood mononuclear cells (PBMC) from patients with chronic
active hepatitis C (CAH) and liver cirrhosis (LC) were cultured for 24 h in the presence or absence of Escherichia coli lipopolysaccharides (LPS). Hepatic stellate cell proliferation induced by the culture supernatants was measured, and interleukin-1
(IL-1) and IL-6 levels in the culture supernatants were quantified. Culture supernatants of LPS-stimulated PBMC from LC patients
induced rat hepatic stellate cell proliferation by almost 2.8-fold (stimulation index, 2.83 ± 1.41) compared with when the
cells were cultured without addition of PBMC culture supernatants. Production of IL-1β was significantly higher in the culture
supernatants of both CAH and LC patients than in those of ten healthy controls (P < 0.01 and P < 0.05, respectively). But there was no significant correlation between IL-1 production and the induction of hepatic stellate
cell proliferation by the culture supernatants. Although there were no significant differences in IL-6 production by LPS-stimulated
PBMC among healthy controls and CAH and LC patients, we observed a significant correlation between IL-6 production and the
induction of hepatic stellate cell proliferation in the culture supernatants of LC patients. Rat hepatic stellate cells themselves
produced IL-6, and treatment with IL-6 antisense oligodeoxynucleotides suppressed the cell proliferation, suggesting that
IL-6 is an autocrine growth factor for hepatic stellate cells. The addition of human recombinant IL-6 (hrIL-6) augmented rat
hepatic stellate cell proliferation, indicating that excessive IL-6 may further facilitate cell proliferation. These findings
suggest that a cytokine cascade including IL-6 may participate in hepatic stellate cell proliferation in LC patients when
they are exposed to endotoxin.
Journal of Gastroenterology 02/2000; 35(3):214-220. · 4.16 Impact Factor
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Nobutaka Fujisawa,
Masahiko Inamori,
Hiroki Endo,
Takashi Uchiyama,
Kunihiro Hosono,
Tomoyuki Akiyama,
Ayako Tomimoto,
Sigeru Koyama,
Aya Sawabe,
Emiko Tanida, [......],
Yasuo Hata,
Kazuhisa Okada, Kazuhiro Atsukawa,
Seitaro Watanabe,
Harunobu Kawamura,
Takuma Higurashi,
Hajime Nagase,
Keiko Akimoto,
Nobuyuki Matsuhashi,
Atsushi Nakajima
[show abstract]
[hide abstract]
ABSTRACT: Low-dose aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases. However, administration of low-dose aspirin is associated with an increased risk of upper gastrointestinal complications, such as upper gastrointestinal erosions, ulcers and bleeding. The aim of this study was to clarify the prevalence and various clinical factors of upper gastrointestinal complications associated with low-dose aspirin treatment.
A total of 1213 patients taking low-dose aspirin were evaluated with upper endoscopic examinations. We studied retrospectively the incidence of and risk factors for upper gastrointestinal complications associated with low-dose aspirin use.
Of the 1213 patients taking low-dose aspirin, 598 patients and 72 patients were found to have gastroduodenal erosions (57.3%) and peptic ulcers (5.9%), respectively. Of these 72 peptic ulcers, 27 were diagnosed as hemorrhagic ulcers. Previous ulcer history was identified as a risk factor for peptic ulcer and upper gastrointestinal bleeding during low-dose aspirin therapy. Upper gastrointestinal symptoms and no use of gastroprotective agents were also identified as risk factors for peptic ulcers. In this study, the use of a histamine-2 receptor antagonist was indicated as a protective factor for peptic ulcers.
Low-dose aspirin therapy is associated with an increased risk of developing upper gastrointestinal complications. Administration of a histamine-2 receptor antagonist was effective for the prevention of low-dose aspirin induced peptic ulcers.
Hepato-gastroenterology 58(105):229-34. · 0.66 Impact Factor
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Takashi Nonaka,
Takaomi Kessoku,
Yuji Ogawa,
Shogo Yanagisawa,
Tadahiko Shiba,
Takashi Sahaguchi, Kazuhiro Atsukawa,
Hisao Takahashi,
Yusuke Sekino,
Hiroshi Iida,
Kunihiro Hosono,
Hiroki Endo,
Yasunari Sakamoto,
Tomoko Koide,
Hirokazu Takahashi,
Chikako Tokoro,
Yasunobu Abe,
Shin Maeda,
Atsushi Nakajima,
Masahiko Inamori
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to determine whether oral Itopride hydrochloride (itopride) intake might have any effect on the rate of gastric emptying, using a novel non-invasive technique for measuring the rate of gastric emptying, namely, the continuous real time 13C breath test (BreathID system: Exalenz Bioscience Ltd., Israel).
Eight healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted overnight and were randomly assigned to receive 50mg itopride following a test meal (200 kcal per 200mL, containing 100mg 13C acetate), or the test meal alone. Under both conditions, gastric emptying was monitored for 4 hours after administration of the test meal by the 13C-acetic acid breath test performed continually using the BreathID system. Using Oridion Research Software (beta version), the time required for emptying of 50% of the labeled meal (T 1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (T lag), the gastric emptying coefficient (GEC), and the regression-estimated constants (beta and kappa) were calculated. The parameters measured under the two conditions were compared using the Wilcoxon's signed-rank test.
No significant differences in the calculated parameters, namely, the T 1/2, T lag, GEC, beta or kappa, were observed between the two test conditions, namely, administration of a test meal+itopride and administration of the test meal alone.
The present study revealed that postprandial itopride intake had no significant influence on the rate of gastric emptying. Recently, several studies have shown that itopride may be effective in the treatment of patients with functional dyspepsia. Our results suggest that the efficacy of itopride in patients with functional dyspepsia may be based on its effect of improving functions other than the rate of gastric emptying, such as the activities at neuronal sites, brain-gut correlation, visceral hypersensitivity, gastric accommodation and distension-induced adaptation.
Hepato-gastroenterology 58(105):224-8. · 0.66 Impact Factor
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Kazuhisa Okada,
Masahiko Inamori,
Kento Imajo,
Hideyuki Chiba,
Takashi Nonaka,
Tadahiko Shiba,
Takashi Sakaguchi, Kazuhiro Atsukawa,
Hisao Takahashi,
Etsuo Hoshino,
Atsushi Nakajima
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to clarify the prevalence and various clinical factors of upper gastrointestinal bleeding (UGIB) associated with low-dose aspirin (LDA) treatment.
There were 6,807 patients who were under treatment with LDA at our hospital between January 2003 and November 2007. They had kept taking the LDA or started treatment in the study period and kept taking the whole period of observation. Esophagogastroduodenoscopy (EGD) was performed 453 patients of these patients, and 71 were diagnosed as LDA-associated UGIB. We examined the prevalence and various clinical factors of UGIB associated with LDA treatment.
The occurrence rate of UGIB was 0.209 UGIB per 100 patient-years at least. The multivariate odds ratio of LDA-associated UGIB was 3.318 (95% confidence interval (CI) 1.650-6.671, p = 0.0008) for a history of peptic ulcer, 0.086 (95% CI: 0.011-0.652, p = 0.0176) for the use of a proton pump inhibitor (PPI) with LDA, and 0.253 (95% CI: 0.113-0.569, p = 0.0009) for the use of a histamine type 2 receptor antagonist (H2RA) with LDA.
Our results suggest that a history of peptic ulcer significantly increases the risk of LDA-associated UGIB. Regular use of a PPI or a H2RA effectively decreases the risk.
Hepato-gastroenterology 56(96):1665-9. · 0.66 Impact Factor
