bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycophenolate mofetil for Crohn's disease: short‐term efficacy and long‐term outcome
Authors: Wenzl H. H. , Hinterleitner T. A. , Aichbichler B. W. , Fickert P. , Petritsch W. 
Published: December 2004

SummaryAim : To assess the long‐term efficacy of the antimetabolite agent mycophenolate mofetil in patients with Crohn's disease.Methods : Twenty patients with complicated Crohn's disease were treated with mycophenolate mofetil, 1 g b.d., for up to 7 years. Twelve patients were intolerant to azathioprine, seven were resistant to azathioprine and one had a history of mesalazine‐induced pancreatitis. The response to mycophenolate mofetil was determined by calculation of the Harvey–Bradshaw index, the ability to taper steroids and the grading of fistula activity.Results : After 6 months, 11 of the 20 patients had responded. Seven of the 11 responders relapsed after a median of 18 months, three have an ongoing response at month 17, 19 and 82, and one discontinued mycophenolate mofetil owing to toxicity. After initial treatment failure, mycophenolate mofetil was continued in 12 of 17 patients for a further 2–41 months without inducing a stable remission. Mycophenolate mofetil was of benefit in nine of the 12 patients intolerant to azathioprine and in two of the seven patients resistant to azathioprine. Perianal fistulas improved in seven of eight patients; five of the seven subsequently deteriorated, but only one due to reactivated perianal disease.Conclusions : Mycophenolate mofetil was initially effective in a sizeable fraction of patients with complicated Crohn's disease, but relapse within 18 months was common. Nevertheless, mycophenolate mofetil could be a useful alternative in patients intolerant to azathioprine.
Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics
Authors: Tonini M. , Cipollina L. , Poluzzi E. , Crema F. , Corazza G. R. , De Ponti F. 
Published: December 2004

SummaryAntidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D2 receptors, ability to interact with other receptor systems [5‐hydroxytryptamine‐3 (5‐HT3) and 5‐HT4 receptors for metoclopramide; 5‐HT4 receptors for levosulpiride) and ability to permeate the blood–brain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5‐HT4) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D2 receptors may lead to both therapeutic (e.g. anti‐emetic effect due to D2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood–brain barrier, hyperprolactinaemia is a side‐effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood–brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D2 receptor (i.e. compounds that bind loosely to D2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D2 receptor pharmacology can help the clinician to choose between the antidopaminergic prokinetics to obtain a more favourable risk/benefit ratio.
Cost‐effectiveness of hepatic venous pressure gradient measurements for prophylaxis of variceal re‐bleeding
Authors: Raines D. L. , Dupont A. W. , Arguedas M. R. 
Published: December 2004

SummaryBackground: Measurement of the hepatic venous pressure gradient may identify a sub‐optimal response to drug prophylaxis in patients with a history of variceal bleeding. However, the cost‐effectiveness of routine hepatic venous pressure gradient measurements to guide secondary prophylaxis has not been examined.Methods: A Markov model was constructed using specialized software (DATA 3.5, Williamstown, MA, USA). Three strategies involved secondary prophylaxis without haemodynamic monitoring using beta‐blockers alone, beta‐blockers plus isosorbide mononitrate or endoscopic variceal ligation alone. Four strategies involved secondary prophylaxis with beta‐blockers plus isosorbide mononitrate or beta‐blockers alone, accompanied by one or two hepatic venous pressure gradient measurements to identify haemodynamic non‐responders, who underwent endoscopic variceal ligation as an alternative. The total expected costs, variceal bleeding episodes and total deaths were calculated for each strategy over 3 years.Results: The two most effective strategies were combination therapy alone and combination therapy with two hepatic venous pressure gradient measurements. The incremental cost‐effectiveness ratio of the latter strategy was $136 700 per year of life saved compared with combination therapy alone. The ratio improved as the time horizon was extended or the rates of variceal re‐bleeding were increased.Conclusions: The cost‐effectiveness of haemodynamic monitoring to guide secondary prophylaxis of recurrent variceal bleeding is highly dependent on local hepatic venous pressure gradient measurement costs, life expectancy and re‐bleeding rates.
Correlation of percutaneous liver biopsy fragmentation with the degree of fibrosis
Authors: Malik A. H. , Kumar K. S. , Malet P. F. , Jain R. , Prasad P. , Ostapowicz G. 
Published: December 2004

SummaryBackground : Although fragmentation of a liver biopsy specimen has been considered to be suggestive of cirrhosis, the evidence for this is difficult to find in the published literature.Aim : To determine whether fragmentation of percutaneous liver biopsy specimens correlates with the degree of fibrosis.Methods : One hundred and eighty‐six patients underwent percutaneous liver biopsy prospectively. The specimens were measured for the length and number of fragments. The extent of fibrosis was scored by a pathologist blind to the clinical data. Length and fragmentation data were compared between the different stages.Results : The overall median fragment length was 1.85 cm and the median fragment number was four. Specimens with advanced fibrosis (stages III–IV) had more fragments than those with no or mild fibrosis (stages 0–II) (P < 0.0001). The aggregate fragment length decreased with increasing stage of fibrosis (P < 0.0001). Specimens with greater than 12 fragments were seen only with advanced fibrosis.Conclusions : Fragmentation of percutaneous liver biopsy specimens is common and increases with progression from early to advanced fibrosis. Fibrotic specimens fragment more often and more extensively.
Improvement in serum pepsinogens and gastrin in long‐term monitoring after eradication of Helicobacter pylori: comparison with H. pylori‐negative patients
Authors: Ohkusa T. , Miwa H. , Nomura T. , Asaoka D. , Kurosawa A. , Sakamoto N. , Abe S. , Hojo M. , Terai T. , Ogihara T. , Sato N. 
Published: December 2004

SummaryBackground : A decrease in pepsinogen and gastrin levels 1–3 months after Helicobacter pylori eradication is well known. However, few data are available on the long‐term progression of these decreases beyond 1 year after eradication, and there has been no investigation into whether pepsinogen and gastrin levels return to normal levels as defined by data from H. pylori‐negative patients with dyspepsia.Aim : We studied the effect of H. pylori eradication on pepsinogen and gastrin levels for more than 1 year, and compared levels to those in H. pylori‐negative patients with dyspepsia. We also investigated the effect of H. pylori eradication on the course of atrophic corpus gastritis as reflected by histology, and on PGI levels and PG I/II ratio.Methods : We enrolled 172 H. pylori‐positive patients with dyspepsia who had undergone successful eradication therapy of more than 1 year's duration and 101 non‐treated H. pylori‐negative patients with dyspepsia. H. pylori status was assessed at entry and at each endoscopy after eradication by culture, histological results, the rapid urease test and the urea breath test. In both groups, patients were evaluated for fasting serum pepsinogen I and II and gastrin using a radioimmunoassay technique, and underwent detailed histological assessment according to the updated Sydney System.Results : In the H. pylori‐negative patients, mean serum pepsinogen I and II, I/II ratio and gastrin levels were 52.6 ± 20.8 ng/mL, 9.2 ± 4.2 ng/mL, 6.0 ± 1.7 and 53.5 ± 29.2 pg/mL, respectively. In H. pylori‐positive patients with long‐term eradication, pepsinogen I and II, I/II ratio and gastrin levels were 81.3 ± 46.6 ng/mL, 25.9 ± 17.1 ng/mL, 3.4 ± 1.3 and 131.9 ± 130.8 pg/mL, respectively, before treatment. At 1–3 months after eradication, serum pepsinogen I and II levels in the H. pylori‐positive patients decreased to levels similar to those in the negative patients, whereas pepsinogen I/II ratio and gastrin levels remained lower and higher, respectively, than in the negative patients. Serum pepsinogen I/II ratio and gastrin levels then became similar between the groups at 12–15 months after eradication. In histological findings, inflammation and neutrophil activity decreased by 1–3 months, and atrophy in the corpus and metaplasia in the antrum decreased by 12–15 months.Conclusion : The results suggest that atrophic corpus gastritis and superficial gastritis are reversible, as indicated by both histological and serological findings in a long‐term follow‐up study.
Helicobacter pylori infection in two areas in Japan with different risks for gastric cancer
Authors: Nobuta A. , Asaka M. , Sugiyama T. , Kato M. , Hige S. , Takeda H. , Kato T. , Ogoshi K. , Keida Y. , Shinomura J. 
Published: December 2004

SummaryBackground : We evaluated the relationship between Helicobacter pylori and various factors associated with gastric cancer in two areas in Japan with different risks for mortality due to gastric cancer.Methods : A total of 250 sera from Niigata and 209 from Okinawa were used. H. pylori antibody and CagA antibody were measured by antigen‐specific ELISAs. Serum gastrin and pepsinogen levels were determined by RIA.Results : Although there was no significant difference in H. pylori prevalence among the persons in Niigata (50%) and Okinawa (42%), CagA prevalence in these populations was significantly different, at 41% and 26%, respectively (OR = 1.98, 95%CI: 1.33–2.95, P < 0.01). Serum gastrin levels in Niigata were significantly lower than those in Okinawa in H. pylori‐negative persons (P < 0.01). The serum pepsinogen I/II ratio in Niigata was significantly lower than that in Okinawa in H. pylori positive persons (P < 0.01), whereas there was no significant difference in H. pylori‐negative persons. Among those positive for H. pylori, serum pepsinogen I/II ratio in Niigata was significantly lower than that in Okinawa in CagA‐negative persons (P < 0.01), whereas no significant difference was observed in CagA‐positive persons.Conclusions : These results suggest that the difference in the mortality ratio of gastric cancer between Niigata and Okinawa is mainly associated with the difference between areas in the prevalence of cagA‐positive strains rather than that of H. pylori itself.
Helicobacter pylori‐positive patients with pruritic skin diseases are at increased risk for gastric cancer
Authors: Shiotani A. , Sakurane M. , Furukawa F. 
Published: December 2004

SummaryBackground : Helicobacter pylori infection has been implicated as a possible cause of extraintestinal disorders such as skin diseases. A number of case reports describe patients with skin diseases, such as prurigo nodularis, that are associated with gastric cancer.Aim : The aim of this study was to examine the prevalence of H. pylori infection and the incidence of gastric cancer in patients with pruritic skin diseases.Methods : The patients were examined for circulating specific IgG antibodies against H. pylori in sera using ELISA. H. pylori‐positive patients who were more than 40 years old underwent endoscopic screening for gastric cancer.Results : We examined 134 patients with pruritic skin diseases, including 55 cases of cutaneous pruritus, 21 cases of prurigo chronica multiforme, 15 cases of nummular dermatitis and 43 cases of chronic urticaria. Early gastric cancer was detected in 2/36 (5.6%) patients with cutaneous pruritus and 3/16 (18.8%) with prurigo chronica multiforme. The prevalence of early gastric cancer was 5.6%, which was much higher than that among patients undergoing general endoscopic screening for gastric cancer.Conclusions : These results suggest that H. pylori‐positive patients with pruritic skin diseases may be at increased risk for development of gastric cancer, and endoscopic screening in such patients is recommended.
Hypoacidity combined with high gastric juice nitrite induced by Helicobacter pylori infection is associated with gastric cancer
Authors: Shiotani A. , Iishi H. , Uedo N. , Higashino K. , Kumamoto M. , Nakae Y. , Tatsuta M. 
Published: December 2004

SummaryBackground : In patients with Helicobacter pylori infection, the concentration of nitrite in gastric juice is elevated. The degree of elevation correlates with that of inflammation and H. pylori density.Aim : The aim of this study was to examine hypoacidity and high nitrite levels related to H. pylori infection in patients with gastric cancer.Methods : We studied 88 patients with more than one history of endoscopic mucosal resection (EMR) for early gastric cancer and 88 age‐matched controls. Concentration of nitrite in gastric juice was measured by Griess reaction, and serum pepsinogen levels were measured by RIA.Results : Multiple malignant lesions were found in 20 of the 88 patients. Serum gastrin, gastric juice pH and nitrite levels in patients with gastric cancer were significantly higher and pepsinogen I and pepsinogen I/II significantly lower than in control subjects. Pepsinogen I level and I/II ratio were lower and gastric juice pH was higher in the protruded‐type group than in the depressed‐type group. Pepsinogen I and pepsinogen I/II were lower and gastric juice pH was higher in multiple than in single cases.Conclusions : Hypoacidity combined with high gastric juice nitrite induced by H. pylori infection is associated with the intestinal type of gastric cancer, especially protruded lesions.
Expression of leptin in two‐layered culture of gastric mucous cells and fibroblasts: effect of Helicobacter pylori attachment
Authors: Nakamura M. , Takahashi T. , Matsumoto T. , Akiba Y. , Matsui H. , Tsuchimoto K. , Ishii H. , Yamada H. 
Published: December 2004

SummaryBackground : Our recent histochemical studies have revealed an increase in myofibroblasts and in leptin and its receptor in endothelial cells, and myofibroblasts in Helicobacter pylori‐infected human and Mongolian gerbil fundic mucosa.Aim : The present study was undertaken to clarify the H. pylori–induced interaction between leptin in cultured gastric surface mucous cells and fibroblasts.Methods : GSM06 cells were incubated with an air− liquid interface on a collagen gel layer containing mouse fibroblast cell line L929. Medium containing H. pylori bacilli (ATCC43504) at 10–100 times higher concentration than the GSM06 cells was added from the luminal side and the localization of leptin was observed by immunohistochemistry. The transformation of L929 cells to myofibroblasts was detected by electron microscopy and PR 2D3 immunoreactivity.Results : L929 cells in the control group showed a spindle shape with scarce cytoplasm. In the H. pylori‐treated group, L929 cells showed features characteristic of myofibroblasts, and most GSM06 and L929 cells showed leptin immunoreactivity. In contrast, L929 cells incubated with H. pylori alone did not undergo this differentiation.Conclusions : Attachment of H. pylori to surface epithelial cells caused conversion of fibroblasts to myofibroblasts. We suggest that leptin plays a role in this transformation.
Analysis of the cag pathogenicity island and IS605 of Helicobacter pylori strains isolated from patients with gastric cancer in Japan
Authors: Deguchi R. , Igarashi M. , Watanabe K. , Takagi A. 
Published: December 2004

SummaryBackground : CagA protein is encoded by the cagA gene, which is part of the cag pathogenicity island (PAI) in Helicobacter pylori. Insertion sequence (IS) elements are a diverse set of specialized DNA segments that can move to new sites in bacterial genomes.Aim : To determine the role of cagPAI and IS605 in the development of gastric cancer, we analysed cagPAI from patients with gastric cancer and compared the results with the host's CagA antibody status.Methods : H. pylori strains were isolated from 29 gastric cancer patients, and CagA status was determined by measuring serum antibody against CagA. The cagPAI region and IS605 were determined by PCR.Results : CagA seropositivity tended to be higher in the IS605/PAI+ group (5/7, 71.4%) than in the IS605/PAI– group (9/22, 40.9%). Association with cag13 was more frequent in the IS605+ group (92.3%; 12/13) than in the IS605– group (25.0%; 4/16; P = 0.0005).Conclusions : cag13 may be associated with the presence of IS605 in gastric cancer patients.
Correlation of MAP kinases with COX‐2 induction differs between MKN45 and HT29 cells
Authors: Tominaga K. , Higuchi K. , Sasaki E. , Suto R. , Watanabe T. , Fujiwara Y. , Oshitani N. , Matsumoto T. , Kim S. , Iwao H. , Arakawa T. 
Published: December 2004

SummaryBackground : Mitogen‐activated protein (MAP) kinases, including extracellular signal‐regulated kinases (ERK),c‐Jun NH2‐terminal kinases (JNK) and p38 MAP kinase (p38 MAPK) are important intermediates of the signal‐transduction pathway from the cell surface to the nucleus. Expression of cyclooxygenase (COX)‐2, associated with proliferation, apoptosis or both of gastrointestinal cancer cells, is mediated through MAP kinase families. However, the correlation between respective MAP kinase signals and COX‐2 in the proliferation of gastric and colon cancer cells has not been well elucidated.Aim : We examined the effect of selective inhibitors of MAP kinases and COX‐2 on serum‐induced proliferation of gastric (MKN45) and colon (HT29) cancer cells.Methods : After 24‐h serum starvation, cancer cells were stimulated with 2% serum and COX‐2 inhibitors (NS398 10 µmol/L, or etodolac 100 µmol/L) or 1 h after preincubation with inhibitors for ERK (PD98059 20 µmol/L) or p38 MAPK (SB203580 10 µmol/L). Phosphorylated MAP kinases and COX‐2 protein were evaluated by Western blotting, and the proliferation of cancer cells was estimated by 3H‐thymidine incorporation. Transcription factors nuclear factor‐κB and CREB were assayed by an electorophoretic mobility shift assay.Results : Serum increased the proliferation of MKN45 and HT29 cells by 280% and 200%, respectively, compared with the control levels (100%). In both cancer cells, phosphorylated MAP kinases were increased within 30 min after stimulation. PD98059 and SB203580 inhibited the serum‐induced proliferation of MKN45 by 21% and 51% and of HT29 by 81% and 69%, respectively. NS398 and etodolac inhibited the proliferation of HT29 by 21% and 41%, respectively, but not that of MKN45. PD98059 and SB203580 also suppressed serum‐induced expression of COX‐2 protein in HT29 cells. In addition to the activation of MAP kinases and COX‐2, activities of nuclear factor‐κB and CREB were also increased during HT29 cell proliferation.Conclusions : These results suggest that the correlation of MAP kinases with COX‐2 induction for cell proliferation differs between MKN45 and HT29 cells.
Indometacin up‐regulates TFF2 expression in gastric epithelial cells
Authors: Koitabashi A. , Shimada T. , Fujii Y. , Hashimoto T. , Hosaka K. , Tabei K. , Namatame T. , Yoneda M. , Hiraishi H. , Terano A. 
Published: December 2004

SummaryBackground : Trefoil factor family peptides are expressed in gastrointestinal epithelial cells and play a critical role in maintaining mucosal integrity. Although non‐steroidal anti‐inflammatory drugs (NSAIDs) are important causative agents of gastric mucosal lesions, few data are available about the effect of NSAIDs on trefoil family peptides in gastric mucosa.Aim : To examine whether indometacin, a widely used NSAID, affects trefoil factor family expression in gastric epithelial cells.Methods : MKN45, a cell line derived from human gastric cancer, was used. TFF1, TFF2, and TFF3 mRNA expression was assessed by real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). TFF2 gene transcription was also examined by luciferase reporter gene assay.Results : Relative expression level of TFF1, TFF2, TFF3 mRNA was 616: 12: 1 in unstimulated MKN45 cells. Although indometacin (1–250 µmol/L) had no significant effect on the expression of TFF1 and TFF3 mRNA, it up‐regulated TFF2 mRNA expression in a dose‐ and time‐dependent manner. Luciferase reporter gene assay confirmed the up‐regulation of TFF2 gene transcription by indometacin. Indometacin‐induced up‐regulation of TFF2 expression was not antagonized by externally applied prostaglandin E2.Conclusion : These results suggest that indometacin up‐regulates gastric epithelial cell TFF2 expression through a COX‐independent mechanism. Since TFF peptides play an important role in gastric mucosal protection, indometacin‐induced TFF2 may reduce the degree of gastric mucosal damage induced by indometacin.
High prevalence rate of Helicobacter pylori resistance to clarithromycin during long‐term multiple antibiotic therapy for chronic respiratory disease caused by non‐tuberculous mycobacteria
Authors: Kaneko F. , Suzuki H. , Hasegawa N. , Kurabayshi K. , Saito H. , Otani S. , Nakamizo H. , Kawata K. , Miyairi M. , Ishii K. , Ishii H. 
Published: December 2004

SummaryBackground : Helicobacter pylori resistance to clarithromycin, probably due to the frequent use of this antibiotic for the treatment of other diseases, is the greatest obstacle against its eradication.Aim : To clarify the prevalence of clarithromycin‐resistant H. pylori in patients with non‐tuberculous mycobacterial lung disease receiving multiple antibiotic treatment, including clarithromycin.Methods : We enrolled 88 patients with non‐tuberculous mycobacterial lung disease; 29 underwent upper gastrointestinal endoscopy for the diagnosis of H. pylori infection prior to treatment, and 60 underwent it during treatment. The diagnosis of H. pylori infection was confirmed by histological examination, urease test and microaerobic bacterial culture. The minimum inhibitory concentration of clarithromycin was determined and the DNA was analysed for each of the isolated H. pylori strains.Results : Patients during the treatment had a high prevalence rate of clarithromycin‐resistant H. pylori (100%). Analysis of DNA of the clarithromycin‐resistant H. pylori isolates revealed point mutations at A2142G or A2143G. Moreover, a linear correlation was found between the total cumulative dose of clarithromycin and the minimum inhibitory concentration.Conclusion : All patients with non‐tuberculous mycobacterial lung disease being treated long‐term with multiple antibiotics, including clarithromycin, harboured clarithromycin‐resistant H. pylori in the stomach. Therefore, eradication of H. pylori before commencement of long‐term therapy including clarithromycin should be recommended.