Effect of rebamipide in treatment of Helicobacter pylori-associated duodenal ulcer: attenuation of chemokine expression and nitrosative damage.

Production of cytokines along with increased activity of nitric oxide synthase has been implicated as one of the contributing mechanisms of Helicobacter pylori-mediated gastroduodenal diseases. We aimed to evaluate the effect of rebamipide in treating Helicobacter pylori-associated duodenal ulcers in terms of cytokine production and nitrosative damage of the gastric mucosa. In patients with duodenal ulcers, rebamipide or placebo were given randomly after eradication. Mucosal cytokine production was measured by enzyme linked immunoassay, and nitrotyrosine immunoexpression was measured by immunohistochemistry. The inflammatory activity and degree of neutrophil infiltration were graded accordingly. The mucosal production of RANTES, interleukin-8, and TNF-alpha showed a significant decrease after eradication in patients with rebamipide after-treatment. The nitrotyrosine immunoreactivity of gastric epithelium was significantly decreased in the rebamipide group. Rebamipide treatment after eradication resulted in a significant reduction in chemokine production along with nitrotyrosine immunoexpression in Helicobacter pylori-associated duodenal ulcers.

Seroepidemiological study of Helicobacter pylori infection in asymptomatic people in South Korea.

BACKGROUND: Helicobacter pylori infection occurs throughout the world and causes gastroduodenal diseases in all age groups. The prevalence of H. pylori infection varies between countries and races. The aim of this study was to evaluate the seroprevalence of H. pylori infection in asymptomatic healthy people in South Korea. METHODS: From March 1998 to October 1998, 5732 asymptomatic subjects who responded to the self-assessment questionnaires from 54 hospitals in South Korea were enrolled in this study. The serum levels of antibodies for H. pylori immunoglobulinG were measured by using an ELISA test. RESULTS: The overall seroprevalence of H. pylori infection was 46.6% and there was no statistical difference between males (47.2%) and females (45.9%). In adults, a significant difference was observed between genders. According to the geographic areas, the high prevalent provinces were Kangwon (53.4%), Cheju (52.9%) and Cholla province (50.6%); Seoul (41.9%) was the lowest prevalent area. The seroprevalence increased with age and was highest when patients were aged in their 40s (78.5%). The characteristic feature of our study was that the infection rate was steeply increased in three age groups (10-12 year olds, 16-19 year olds and those aged in their 20s). In Seoul, there was no difference in the prevalence rate among the districts studied. CONCLUSIONS: This nation-wide seroprevalence of H. pylori infection in South Korea was 46.6%, which showed the transition from a developing country to a developed country. More studies on the epidemiological factors and the route of transmission of H. pylori infection should be warranted.

Topographic expression of p21WAF1/SDI1/CIP1, bcl2, and p53 is altered at the early stage of colorectal carcinogenesis.

We analyzed the expression of p21, bcl2, and p53 in normal and different pathologic mucosa of the human colorectum using immunohistochemistry and cold polymerase chain reaction-single strand conformation polymorphism. The topography of normal mucosa showed; bcl2 and p53 expression restricted to basal epithelial cells and p21 expressed only in superficial epithelial cells. This topographic expression was altered in hyperplastic polyps and adenomas. Hyperplastic polyps revealed absence of or weak bcl2 expression and strong p21 expression without topography. In adenomas, whereas bcl2 expression increased and extended to parabasal and superficial dysplastic epithelium, the increase of p21 expression was limited to surface dysplastic epithelium. p53 was weakly expressed throughout the full thickness of dysplastic epithelium. Bcl2 expression in adenomas was stronger than in carcinomas; p53 expression was converse and p21 expression was variable. In carcinomas, this topographic expression was largely abrogated but p53 mutation (36%) was more frequent than in adenomas (2%). In carcinomas, p21 and p53 expression correlated inversely, but there was no relationship with bcl2. These results suggest that there is precisely ordered topographic pattern of p21, bcl2, and wild p53 expression in normal colorectal cells, but this becomes disordered during the early stage of colorectal carcinogenesis.

Epidemiological study on Korean gallstone disease: a nationwide cooperative study.

To clarify the epidemiological characteristics of gallstone disease in Korea and to evaluate the chronological changes in gallstone disease, the authors performed this first prospective nationwide cooperative study. The subjects were 1263 gallstone patients who were admitted at 19 hospitals in Korea from February to July 1997. Questionnaires were recorded on 1263 patients and gallstones were harvested from 1133 patients. The proportion of patients with gallbladder (GB), common bile duct (CBD), and intrahepatic duct (IHD) stones among total gallstone patients was 64.0%, 21.9%, and 14.1%, respectively. GB stones were categorized as cholesterol (58.1%), black pigment (25.2%), and brown pigment (12.1%) stones. CBD stones were classified as brown pigment (76.1%), cholesterol (18.4%), and black pigment (3.5%) stones. IHD stones were classified as brown pigment (61.4%) and mixed (35.6%) stones. Intrahepatic mixed stones had mean cholesterol and bilirubin contents of 63.4 +/- 20.8% and 23.1 +/- 9.9%, respectively. In contrast, IHD brown pigment stones had mean cholesterol and bilirubin contents of 35.1 +/- 20.5% and 39.6 +/- 17.4%, respectively. Our study showed that the type and composition of gallstones in Korea was somewhat different compared with those in the West. This study also demonstrated that there have been chronological changes in the type and composition of gallstones when compared with previous domestic data. Another nationwide cooperative study may be needed to elucidate and confirm the changing pattern of gallstone disease.

Diagnostic p53 expression in gastric endoscopic mucosal resection.

Endoscopic mucosal resection (EMR) has been standardized for the treatment of intestinal type of intramucosal gastric carcinomas, and careful histological examination of the resected specimen is important for further treatment. To evaluate the diagnostic utility of p53 expression in gastric EMR samples, using immunohistochemical staining, we examined 24 gastric carcinomas (22 intestinal types and two diffuse types) and 20 adenomas removed by EMR. Intestinal type of adenocarcinomas revealed strong p53 expression in 13 cases (59%), weak in four cases (18%), and negative in five cases (23%). Resection margins of 11 carcinomas were involved in the carcinoma cells, which showed the same p53 expression pattern with main carcinoma cells. Squeezed carcinoma cells, remaining in resection margins, were definitely identified by strong p53 expression in seven cases of which the main tumor strongly expressed p53. Microscopic in situ carcinoma could be easily detected in p53 immunostaining. Multifocal involvement and submucosal invasion of carcinomas could be demarcated easily and definitely by strong p53 expression of carcinoma cells. All adenomas showed diffuse weak p53 expression. The difference of p53 expression (p< 0.001) could be used as a differential diagnosis between adenomas and carcinomas. According to these results, we propose that for careful histological examination in hospital diagnosis, both histological evaluation and p53 immunostaining are important diagnostic parameters in EMR samples of the intestinal type of gastric carcinomas.

Detection of Helicobacter DNA in bile from bile duct diseases.

Several species of Helicobacter colonize the hepatobiliary tract of animals and cause hepatobiliary diseases. The aim of this study is to investigate Helicobacter found in the biliary tract diseases of humans. Thirty-two bile samples (15 from bile duct cancer, 6 from pancreatic head cancer, and 11 from intrahepatic duct stone) were obtained by percutaneous transhepatic biliary drainage. Polymerase chain reaction analysis using Helicobacter specific urease A gene and 16S rRNA primers, bile pH measurement, and Helicobacter culture were performed. Helicobacter DNA was detected in 37.5%, and 31.3% by PCR with ureA gene, and 16S rRNA, respectively. The bile pH was not related to the presence of Helicobacter. The cultures were not successful. In conclusion, Helicobacter can be detected in the bile of patients with bile duct diseases. The possibility of pathogenesis of biliary tract diseases in humans by these organisms will be further investigated.

Changes in the evolution of the antigenic profiles and morphology during coccoid conversion of Helicobacter pylori.

OBJECTIVES: The significance of the coccoid forms of H. pylori is still controversial and the questions of whether these forms are viable and infective or degenerative are still open. We induced conversion from rod to coccoid forms and studied morphological changes and antigenic evolutions during this conversion and, thereby, elucidated the viability of coccoid forms. METHODS: The H. pylori strain (C001) used for Western blotting was isolated from the patient with gastric cancer. The antigenic evolution during coccoid conversion of H. pylori was studied by Western blotting, using different sera from thirty patients known to be culture positive. These sera were used to reveal the total antigens of the strain cultured for 2 days (100% rod) and 15 days (> 99% coccoid). After SDS-PAGE, with 10% separating gel of total antigens (rod and coccoid), transblotting (Trans-Blot electrophoretic cell, Bio-Rad) was taken onto a nitrocellulose membrane (Bio-Rad). Then, the blots, with human sera diluted at 1/100, were developed with color reaction by goat serum anti-human IgG with alkaline phosphatase and BCIP. RESULTS: The antigenic profiles were not changed in 46.7% (14/30 cases) and were changed in 53.3% (16/30 cases) during coccoid conversion. Antigenic fractions changed during coccoid conversion were protein band at 120 kDa and band at 35 kDa, and were not detected in coccus forms. The rest of the profiles were identical between rod and coccoid forms. The protein which disappeared include CagA (120 kDa) and porin, or adhesin (35 kDa). The morphological changes during coccoid conversion were U shaped at day 7, doughnut shaped at day 9 and full coccoid at day 15. CONCLUSIONS: The results showed that coccoid forms of H. pylori retain cellular structures similar to rod form, and some of the antigens (CagA and porin) disappeared during coccoid conversion. Therefore, coccoid form might be viable and represent one of the stages of H. pylori biological cycle.

Variant angina complicating ergot therapy of migraine.

A 55-year-old man demonstrated typical reflux esophagitis, not esophageal spasm, by esophageal manometry, although he demonstrated classic migraine, positive Raynaud's scan, and proven coronary artery spasm. He suffered from severe chest pain by medication of ergotamine tartrate. Ergot alkaloids should be avoided in patients with symptomatic coronary artery spasm.