T Kamada

Osaka City University, Ōsaka, Ōsaka, Japan

Are you T Kamada?

Claim your profile

Publications (832)3663.18 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The heterogeneity of the hepatitis C virus (HCV) genome has been reported to be associated with the effectiveness of interferon therapy. We investigated the correlation of the viral and host factors, including the degree of sequence complexity of the HCV genome for responses to interferon-α in patients with chronic hepatitis C. Methods: Ninety-seven patients received a 26-week course of recombinant interferon-α2a therapy. The sequence complexity of the envelope 1–2 region was evaluated by polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis. Results: Of the 85 patients who completed the treatment, 31 (36%) achieved a sustained response, and 28 (33%) showed a sustained loss of HCV RNA. A low HCV RNA level, determined by the branched DNA probe assay, and serotype group 2 HCV correlated with a sustained response. In patients with serotype group 1 HCV of more than the threshold of the branched DNA probe assay, a band number on PCR-SSCP analysis of more than 2 could be associated with inefficacy of interferon therapy. Multivariate analysis in the 50 patients whose sera were available for all the virologic tests showed that only the HCV RNA level is independently predictive of a sustained response. Conclusions: Determination of the HCV RNA level is most important for predicting the response before interferon therapy. PCR-SSCP analysis may be useful as an additional test for patients with a high HCV RNA level of serotype group 1 HCV.
    07/2009; 31(10):1021-1026.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ischaemic preconditioning (IP) protects the myocardium against irreversible ischaemic injury by activating protein kinase C (PKC). The mechanism by which PKC protects the myocardium is unknown. We have shown that PKC increases the activity of ecto-5′-nucleotidase (ecto-5′-N) and thereby the production of adenosine in cardiomyocytes which may protect the myocardium against ischaemia-reperfusion injury in vivo.The objective of this study was to elucidate the possible role of PKC-induced activation of ecto-5′-N in the cardioprotection associated with IP in the canine heart.IP increased the activities of both ecto-5′-N and PKC, and minimized ischaemic damage (infarct size: 7.5±1.8 vs. 42.3±2.8%, P<0.01 vs. the control group). Treatment with the PKC activator (4β-phorbol 12-myristate-13-acetate) also reduced infarct size (13.5±2.9%, P<0.01 vs. the control group). 8-Sulfophenyltheophylline (an antagonist of adenosine receptors) or α,β-methyleneadenosine 5′-diphosphate (an inhibitor of ecto-5′-N) eliminated the cardioprotective effect of the PKC activator (infarct size: 36.6±3.9 and 34.7±4.2%, respectively), suggesting that PMA limits infarct size by increasing the activity of ecto-5′-N and the adenosine level.The PMA-induced cardioprotection was blunted by GF109203X (an inhibitor of PKC, infarct size: 36.2±3.1%), but not by pretreatment with dexamethasone (infarct size, 14.2±2.6%).We conclude that the PMA- and IP-induced cardioprotection is attributable to phosphorylation and activation of ecto-5′-N.British Journal of Pharmacology (1997) 120, 273–281; doi:10.1038/sj.bjp.0700890
    British Journal of Pharmacology 02/2009; 120(2):273 - 281. · 5.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The distribution of immunoreactive glucagon, substance P (SP) and vasoactive intestinal polypeptide (VIP)-like structures was investigated in the rat liver, with special reference to the hepatic vasculature by means of the indirect immunofluorescence method. Immunoreactive structures of glucagon were seen in the walls of the portal vein, hepatic artery and hepatic vein, but not in the central vein. Immunoreactive glucagon was localized in the smooth muscle cells of these blood vessels. SP and VIP-like immunoreactive (SPI and VIPI) structures were seen in the neuronal elements. In the porta hepatis, thick, compact SPI and VIPI fibers, which were dissociated from their fiber bundles, reached the tunica adventitia where they were distributed. No SPI and VIPI structures were seen in the tunica media or the tunica interna. No SPI- and VIPI-containing cell bodies could be detected in the liver. These observations suggest that these peptides may have an important role in the neural regulation of hepatic hemodynamics.
    Hepatology 07/2008; 4(6):1184 - 1189. · 12.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the astrocyte response to hypoxia/reoxygenation, as a model relevant to the pathogenesis of ischemic injury, cultured rat astrocytes were exposed to hypoxia. On restoration of astrocytes to normoxia, there was a dramatic increase in protein synthesis within 3 h, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of metabolically labeled astrocyte lysates showed multiple induced bands on fluorograms. Levels of cellular ATP declined during the first 3 h of reoxygenation and the concentration of AMP increased to ± 3.6 nmol/mg of protein within 1 h of reoxygenation. Reoxygenated astrocytes generated oxygen free radicals early after replacement into ambient air, and addition of diphenyliodonium, an NADPH oxidase inhibitor, diminished the generation of free radicals as well as the induction of several bands on fluorogram. Although addition of cycloheximide on reoxygenation resulted in inhibition of both astrocyte protein synthesis and accumulation of cellular AMP, it caused cell death within 6 h, suggesting the importance of protein synthesis in adaptation of hypoxic astrocytes to reoxygenation. Potential physiologic significance of biosynthetic products of astrocytes in hypoxia/reoxygenation was suggested by the recovery of glutamate uptake. These results indicate that the astrocyte response to hypoxia/reoxygenation includes generation of oxygen free radicals and de novo synthesis of products that influence cell viability and function in ischemia.
    Journal of Neurochemistry 06/2008; 62(4):1489 - 1495. · 3.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although interleukin (IL)-8 is well known as a chemotactic agent for neutrophil migration in vitro, the relationship between IL-8 activity and the degree of neutrophil infiltration in gastric mucosa is still unclear. In the present study, we investigated IL-8 and myeloperoxidase activity, a marker of neutrophil infiltration, in gastric antral mucosa using biopsy samples in 23 patients with no gastric lesions. The results indicate that there is a good correlation between IL-8 and myeloperoxidase activity (y = 0.173x + 13.9; r = 0.49, P<0.01). Furthermore, IL-8 and myeloperoxidase activity are significantly higher in Helicobacter pylori-positive patients than in H. pylori-negative patients. In conclusion, an increase of IL-8 activity in the gastric mucosa causes increased neutrophil infiltration in human gastric mucosa and H. pylori infection acclerates these reactions in the mucosa.
    Journal of Gastroenterology and Hepatology 06/2008; 12(2):104 - 108. · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Kupffer cells (KC) become activated in response to lipopolysaccharide (LPS) and produce a variety of mediators. Among them, TNFα is known to injure the liver. Here we report that TNFα mediates apoptosis in KC and sinusoidal endothelial cells. After stimulation for 24 h with LPS (0-10 μg/mL), apoptosis in KC detected by TUNEL TdT-mediated dUTP-biotin nick end labelling (TUNEL) increased in a concentration-dependent manner (0 μg/mL, 12 ± 4%; 0.1 μg/mL, 36 ± 11%; 1.0 μg/mL, 65 ± 9%; 10 μg/mL, 78 ± 15%). In contrast, co-incubation of endothelial cells with LPS-stimulated KC resulted in a marked increase in TUNEL-positive endothelial cells. TNFα antibody blocked apoptosis in both KC and endothelial cells. Apoptosis was observed in cells adjacent to or in contact with KC. Reducing transmembrane TNFα expressed on KC also led to a decrease in endothelial cell apoptosis, suggesting that transmembrane TNFα is implicated in the cell-to-cell contact mechanism of induction of apoptosis. Thus, TNFα mediates apoptosis in KC and endothelial cells.
    Journal of Gastroenterology and Hepatology 06/2008; 10(S1):S65 - S67. · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biopsy samples from patients with liver cirrhosis were investigated for changes in gastric mucosal energy metabolism and intracellular mucin content using high performance liquid chromatography and an image analysing system. The test group consisted of eight non-cirrhotic patients with endoscopically normal mucosa (controls) and eight cirrhotic patients with oesophageal varices. The amount of ATP, energy charge level and intracellular mucin content were all significantly decreased in cirrhotic patients when compared with those of the controls. The decrease in energy charge also correlated well with the decrease in intracellular mucin content in the gastric mucosa. The results indicate that gastric mucosal energy metabolism is impaired in cirrhotic patients concomitantly with a decrease in the intracellular mucin content in the gastric mucosa. These changes may weaken defensive mechanisms against acid and NSAID, resulting in gastric mucosal injury in cirrhotic patients.
    Journal of Gastroenterology and Hepatology 06/2008; 11(4):380 - 384. · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A double-blind placebo-controlled parallel design study was conducted in 12 healthy male volunteers to examine the effects of misoprostol, a newly synthesized prostaglandin E1 analogue, on gastric mucosal haemodynamics in human. The indices of mucosal blood volume (expressed as ΔEr) and mucosal blood haemoglobin oxygenation (Hb-SO2) were measured at 20 locations in the stomach prior to and after administration of misoprostol or its placebo using reflectance spectrophotometry during endoscopy. It was found that after misoprostol administration, mucosal blood volume was increased by approximately 10–25% throughout the stomach without any significant change in mucosal blood Hb-SO2. Administration of placebo produced no significant change in these parameters. The results suggest that misoprostol has the potential to accelerate healing of gastric ulcers by increasing the gastric mucosal blood volume and oxygenation in addition to its gastric acid antisecretory activity.
    Journal of Gastroenterology and Hepatology 03/2008; 2(6):499 - 505. · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Changes in gastric mucosal haemoglobin concentration (mucosal blood volume), mucosal haemoglobin oxygenation, mucosal blood flow and gastric arterial blood flow caused by indomethacin, an ulcerogenic agent, and anti-ulcer agents were investigated in the stomach flap of anesthetized dogs. Indices of mucosal haemoglobin concentration and haemoglobin oxygenation, mucosal blood flow and arterial blood flow to the stomach flap were measured simultaneously. The intravenous injection of indomethacin (10 mg/kg) caused an immediate decrease in mucosal haemoglobin concentration with a gradual decrease in mucosal and arterial blood flow, and a slight decrease in mucosal haemoglobin oxygenation. The topical application of prostaglandin E2 (10 μg/ml) and spizofurone (a new anti-ulcer agent, 1 mg/ml) to the mucosa significantly increased these parameters, and remedied the decreases of these parameters caused by indomethacin. Cimetidine (20 mg/ml), pirenzepine (10 mg/ml) and proglumide (40 mg/ml) given topically did not significantly increase these parameters in the resting state or the indomethacin-induced ischaemic state. This study indicates that: indomethacin decreases gastric haemodynamics, and that improvement occurred with application of mucosal protective agents (i.e. prostaglandin E2 and spizofurone) and changes in mucosal blood concentration were closely correlated with those in mucosal blood flow and arterial blood flow, but correlated less well with those in the case of haemoglobin oxygenation.
    Journal of Gastroenterology and Hepatology 03/2008; 1(2):87 - 96. · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: For studying microcirculation of intact tissues or organs, a new noninvasive, heat-transient method using laser photoexcitation is described. As a heating source an argon ion laser or R6G dye laser was used via a quartz fiber optic guide. Infrared radiation from heated tissue was detected by a thermography apparatus. After switching the laser irradiation on and off, a thermal transient curve of a model tissue, the skin, was biphasic: a component with a fast time constant and the other with a slow time constant. The temperature increases of both phases following laser irradiation were linear to the applied power from the laser onto the tissue. The temperature rises as a function of the wavelength of irradiated light have shown that the absorption of the light by tissue hemoglobin is a main heat-generation source. Furthermore, the temperature rises as a function of tissue blood volume and flow have shown that the component with a slow time constant is more related to the tissue hemoglobin concentration and tissue blood flow and heat conductivity. Thus, the analysis of heat-transient curves following laser irradiation gives information as to regional tissue blood volume, blood flow, and tissue heat conductivity.
    Lasers in Surgery and Medicine 12/2005; 2(3):275 - 280. · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effects of tumor necrosis factor-a and/or interferon-γ on the replication of hepatitis B virus were examined using HB611 cells. These cells were derived from human hepatoblastoma cells, Huh6, by integrating hepatitis B virus DNA, and produce hepatitis B virus continuously. Each of the cytokines inhibited hepatitis B virus replication in the cells assessed as the amount of episomal hepatitis B virus DNA, without a decrease in cell viability. When the two cytokines were administered together, the inhibitory effect became greater. Incubation of the cells with 1, 000 U/ml tumor necrosis factor-α decreased HBV DNA replicative intermediates by 55%, and that with 1, 000 U/ml interferon-γ decreased these by 51%. Furthermore, incubation with 1, 000 U/ml tumor necrosis factor-α and 1, 000 U/ml interferon-γ in combination decreased HBV DNA replicative intermediates by 71%. In contrast, the amount of hepatitis B virus RNA and secretion of hepatitis B e antigen were not apparently reduced by the cytokines, and 2′, 5′-oligoadenylate synthetase activity was not detected in the supernatant. These results suggest that tumor necrosis factor-α and interferon-γ inhibit hepatitis B virus replication by blocking some step in reverse transcription and that the 2′, 5′-oligoadenylate synthetase is not involved in the mechanism underlying the inhibition by these two cytokines. © Wiley-Liss, Inc.
    Journal of Medical Virology 12/2005; 47(3):272 - 277. · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dual infection with hepatitis B and C viruses is often encountered in endemic areas of both viruses. However, understanding of the clinical and virological implications is limited. The aim of this study was to investigate the role of each virus in liver injury and the interaction between the two viruses in dual infection with hepatitis B and C viruses. Three patients who had chronic infection with both hepatitis B and C viruses were examined, and a longitudinal study of both serum hepatitis B virus DNA and hepatitis C virus RNA levels over 4 years was undertaken. The results were correlated with serum alanine aminotransferase levels. Serum alanine aminotransferase values showed a relationship with hepatitis B virus replicative levels, but not with hepatitis C virus replicative levels in all 3 patients. Serial changes of replicative levels of both viruses were studied, and it was found that hepatitis C virus replicative levels were enhanced after the decline of hepatitis B virus replication in 1 of the 3 patients. In the remaining 2 patients, a transient rise of hepatitis C virus replicative levels in association with a decrease of hepatitis B virus replication was also observed during part of the follow-up period. These findings indicate that hepatitis B virus may play a dominant etiological role in liver injury, and that a suppressive action between hepatitis B and C viruses may occur in dual infection with both viruses. © 1995 Wiley-Liss, Inc.
    Journal of Medical Virology 12/2005; 46(3):258 - 264. · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The distribution and origin of calcitonin gene-related peptide immunoreactive structures in hepatic and splanchnic vasculature of the rat were investigated by the immunofluorescent technique. Calcitonin gene-related peptide immunoreactive fibers were dissociated from compact thick calcitonin gene-related peptide immunoreactive fiber bundles located around the hepatic and splanchnic vasculature, and reached the tunica adventitia of the vasculature. Some fibers penetrated further into the tunica media of the vasculature. In the tunica adventitia of the vasculature, calcitonin generelated peptide immunoreactive fibers formed a fine meshwork which could be traced to the branches and arterioles. In the liver, calcitonin gene-related peptide immunoreactive innervation extended from porta hepatis to portal triads, running with branches of the hepatic artery and portal vein. Some calcitonin generelated peptide immunoreactive fibers separated from thinner calcitonin gene-related peptide immunoreactive fiber bundles in portal triads and coursed into the immediately adjacent parenchyma. In the doral spinal ganglia (T8–10, L1), calcitonin gene-related peptide immunoreactive cells accounted for about 60% of the total number of ganglion cells. Bilateral vagotomy just below the diaphragm or bilateral transection of the greater splanchnic nerve resulted in a marked decrease of the number of calcitonin gene-related peptide immunoreactive fibers in the vasculature, whereas a combined operation was followed by the complete depletion of calcitonin gene-related peptide immunoreactive fibers. These results indicate that calcitonin gene-related peptide immunoreactive innervation in hepatic and splanchnic vasculature may have a dual origin.In conclusion, the widespread distribution of calcitonin gene-related peptide immunoreactive fibers in the hepatic and splanchnic vasculature suggest that calcitonin gene-related peptide innervation may be involved in sensory transmission.
    Hepatology 12/2005; 6(4):676 - 681. · 12.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genotyping of 179 consecutive Japanese chronic hepatitis C patients was carried out based on the variation in the hepatitis C virus (HCV) core gene. The results were correlated with clinical features and antibody responses toward specific HCV proteins deduced from the nucleotide sequence of genotype I/1 a. Genotypes II/1 b, III/2a, and IV/2b were identified in 138 (77%), 24 (13%), and 12 (7%) patients, respectively. Five patients had double infections. Genotype dependence was observed only for antibody response toward the NS4 (5–1–1) protein, which was infrequent in genotype III/2a patients (33%) compared with genotype II/1 b (81%; P < 0.01) and genotype IV/2b (75%; P < 0.05). Following interferon-α therapy, sustained aminotransferase normalisation was achieved by 89% (eight of nine) patients without antibody to the 5–1–1 protein and 33% (17 of 51) with it (P < 0.01). These findings indicate that absence of antibody response to the 5–1–1 protein is frequent in genotype III/2a HCV carriers and may serve to predict responses to interferon therapy. © 1995 Wiley-Liss, Inc.
    Journal of Medical Virology 12/2005; 45(2):162 - 167. · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The X protein can act on the enhancer of hepatitis B virus in an in vitro system and elevate the transcriptional level of hepatitis B virus. However, because no relationship had been reported between X protein expression and hepatitis B virus replication in patients with chronic hepatitis B, we focused on its expression in the liver in comparison with markers of hepatitis B virus replication. Liver biopsy samples and sera from 59 carriers with HBsAg were examined immunohistochemically for X protein using rabbit IgG against recombinant X protein. There was a significant difference in the serum hepatitis B virus DNA level between X protein–positive and –negative patients (p < 0.001). Serum pre-S1 and pre-S2 antigens were also measured quantitatively by enzyme immunoassay using monoclonal antibodies specific against each antigen. The titers of pre-S1 antigen in patients positive for X protein were significantly higher (p < 0.001) than those of the X protein–negative patients (3.02 ± 0.99 vs. 2.00 ± 0.59, respectively). Similarly, the titers of pre-S2 antigen were 2.98 ± 0.91 vs. 1.94 ± 0.54, respectively (p < 0.001). The rate of positivity of the X protein was higher (38 of 49; 77.6%) in the replicative group (serum HBeAg, serum hepatitis B virus DNA or HBcAg in liver positive) compared with that observed in the nonreplicative group (3 of 10; 30% – serum HBeAg, serum hepatitis B virus DNA and HBcAg in liver negative) (p < 0.01). Our findings indicate that the X protein is closely correlated with hepatitis B virus replication and may have an important role in viral replication in chronic hepatitis B virus infection. (HEPATOLOGY 1991;13:417–421.)
    Hepatology 12/2005; 13(3):417 - 421. · 12.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We describe a method for quantifying hepatitis C virus RNA in serum. This competitive assay combines reverse transcription and polymerase chain reaction and is based on coamplification of the target RNA with known amounts of synthetic mutated RNA. We tested serum samples from 104 hepatitis C virus carriers (9 asymptomatic blood donors and 95 patients with type C chronic liver disease) to determine the relationship between the replicative level of hepatitis C virus and various stages of the carrier states. The amount of circulating hepatitis C virus RNA ranged from 104 to 109.5 genomes/ml serum. The titer of hepatitis C virus RNA (logarithmic transformed copy numbers of RNA per milliliter of serum) was lower in asymptomatic blood donors (5.4 ± 2.0) and in patients with chronic persistent hepatitis (7.3 ± 1.1) than in patients with chronic active hepatitis (7.9 ± 0.8), cirrhosis (7.8 ± 0.7) or hepatocellular carcinoma (7.9 ± 0.7). The titer of hepatitis C virus RNA was significantly lower in carriers younger than 40 yr old and correlated positively with the logarithmic transformed serum ALT level. Logistic regression showed that age and titer of hepatitis C virus RNA correlated independently with the stages of liver disease. These results showed that the replicative level of hepatitis C virus is higher in advanced liver disease and that elevation of viral replication may play an important role in liver injury and progression of liver disease. This competitive assay is useful in evaluating the state of viral replication in hepatitis C virus infection. (HEPATOLOGY 1993;17:545–550.)
    Hepatology 12/2005; 17(4):545 - 550. · 12.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We quantified IgG antibodies to structural (core) and nonstructural (C100-3) hepatitis C virus proteins in 42 patients with chronic hepatitis C treated with a 6-mo course of interferon-α Sera were drawn before and at the end of therapy and also 6 mo after therapy withdrawal; they were stored for later analysis of antibodies and serum hepatitis C virus RNA. Sustained virus clearance was observed at the end of therapy and 6 mo after therapy withdrawal in nine cases; it was accompanied with sustained reductions of antibody to hepatitis C virus core protein and antibody to C 100-3 protein. A sustained reduction of antibody to hepatitis C virus core protein was specific to sustained virus clearance, although that of antibody to C 100-3 protein was not. None of the patients who did not show reductions of levels of both antibodies at the end of therapy displayed sustained virus clearance. Five patients showed hepatitis C virus RNA negativity and normal aminotransferase levels at the end of therapy without reduction of antibody to hepatitis C virus core protein levels. Of these five patients, relapse of hepatitis occurred in four, and viremia was present 6 mo after therapy withdrawal in all cases. These results demonstrate that testing for antibody titers may add information for evaluating virus clearance after interferon therapy. (HEPATOLOGY 1993;17:960–965.)
    Hepatology 12/2005; 17(6):960 - 965. · 12.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis C virus (HCV) has been reported to conform to a quasispecies nature, which is most evident in hypervariable regions of the putative envelope 2 domain. The aim of this study was to determine the relationship between the nucleotide complexity and diversity of hypervariable region 1 and various stages of the carrier states. The subjects studied were 20 HCV carriers with normal alanine aminotransferase (ALT) levels, 50 patients with chronic hepatitis who showed elevated ALT levels, 22 with cirrhosis, and 24 with hepatocellular carcinoma. The quasispecies complexity was analyzed by means of polymerase chain reaction-mediated single strand conformation polymorphism (PCR-SSCP). The value of nucleotide diversity was calculated by PCR cloning and sequencing. The number of SSCP bands ranged from 1 to 7, with no significant differences in the mean numbers among the stages of HCV infection. There was no correlation between the amounts of serum HCV RNA and the numbers of SSCP bands. No significant difference was found in the values of nucleotide diversity between carriers with normal ALT levels (mean, 6.6 × 10−2 per site) and patients with chronic hepatitis (7.7 × 10 −2). These findings suggest that the quasispecies complexity of hypervariable region 1 is independent of the stage of chronic HCV infection. (Hepatology 1995; 22:407–412.)
    Hepatology 12/2005; 22(2):407 - 412. · 12.00 Impact Factor
  • Nippon rinsho. Japanese journal of clinical medicine 12/2005; 63 Suppl 11:512-5.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Little is known about the clinical efficacy of co-therapy of enprostil, a prostaglandin E2 analogue, with a histamine H2-receptor antagonist. We aimed to assess the additive benefit of enprostil in combination with cimetidine for treating gastric ulcer in a prospective multicenter randomized controlled trial. In 43 hospitals 171 intention-to-treat (ITT) patients, diagnosed as having gastric ulcer by endoscopy, were randomly allocated to receive either enprostil 25microg b.i.d. and cimetidine 400mg b.i.d. (Group E=85), or cimetidine 400mg b.i.d. alone (Group C=86) for 8 weeks. Healing was examined by endoscopy at 4 and 8 weeks. Per protocol (PP) analysis comprised 166 patients (E=82, C=84). Despite no significant advantage at 4 weeks (E=55.3%, C=42.2%), the combination yielded higher healing rates at 8 weeks by ITT (E=89.4%, C=68.6%; p<0.001) and PP analysis (E=92.7%, C=70.2%; p<0.001). Symptom relief rates [E, C] at 2, 4, and 8 weeks were [80.2%, 68.3%] (not significant), [97.4%, 88.3%] (p<0.05), and [95.6%, 87.0%] (p<0.05), respectively. Significant advantage was observed in the patients aged 40 or older, with solitary ulcer (>5mm in diameter), and without smoking or drinking habits. No adverse effects were critical. Enprostil safely and significantly augmented gastric ulcer healing and symptom relief by cimetidine.
    Hepato-gastroenterology 01/2005; 52(66):1925-9. · 0.77 Impact Factor

Publication Stats

13k Citations
3,663.18 Total Impact Points

Institutions

  • 1969–2008
    • Osaka City University
      • • Graduate School of Medicine
      • • First Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
  • 1993–2003
    • Osaka Rosai Hospital
      Ōsaka, Ōsaka, Japan
    • Xi'an Medical University
      Ch’ang-an, Shaanxi, China
    • Kansai Rosai Hospital
      Itan, Hyōgo, Japan
  • 2000
    • Osaka Medical Center for Cancer and Cardiovascular Diseases
      Ōsaka, Ōsaka, Japan
  • 1994–1997
    • Osaka Kosei Nenkin Hospital
      Ōsaka, Ōsaka, Japan
    • Osaka Red Cross Hospital
      Ōsaka, Ōsaka, Japan
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany
  • 1992–1997
    • Juntendo University
      • • Division of Metabolism and Endocrinology
      • • Department of Medicine
      • • Division of Gastroenterology
      Edo, Tōkyō, Japan
    • Osaka Central Hospital
      Ōsaka, Ōsaka, Japan
    • Izumi City Hospital
      Ōsaka, Ōsaka, Japan
  • 1996
    • Emory University
      • Department of Internal Medicine
      Atlanta, GA, United States
  • 1995
    • Hyogo College of Medicine
      • Department of Internal Medicine
      Nishinomiya, Hyogo-ken, Japan
  • 1987–1995
    • Osaka National Hospital
      Ōsaka, Ōsaka, Japan
  • 1987–1993
    • Osaka University
      • • School of Medicine
      • • Department of Internal Medicine
      Suika, Ōsaka, Japan
  • 1981–1993
    • Kagoshima University
      • • Department of Laboratory Medicine
      • • Faculty of Medicine
      • • Department of Anatomy II
      Kagosima, Kagoshima, Japan
  • 1988–1992
    • Osaka Police Hospital
      Ōsaka, Ōsaka, Japan
    • Kanazawa Medical University
      Kanazawa, Ishikawa, Japan
  • 1987–1992
    • Fukushima Medical University
      • Division of Medicine
      Hukusima, Fukushima, Japan
  • 1988–1991
    • Sakurabashi Watanabe Hospital
      Ōsaka, Ōsaka, Japan