A clinico-epidemiological analysis ofHelicobacter pylori (H. pylori) by Southern blotting with A urease gene probe

Helicobacter pylori (H. pylori) is a gramnegative bacillus thought to be involved in such diseases of the upper gastrointestinal tract as gastritis, peptic ulcers, and gastric cancer. Urease is regarded as the factor responsible for the pathogenic nature of this bacterium. Therefore, in our examination of the genetic polymorphism ofH. pylori, by means of Southern blotting, we used the urease gene as a probe. The Southern blot patterns ofH. pylori isolated from different patients differed greatly, the inter-individual variation being so marked that it allowed approximate distinction between individual patients. The Southern blot patterns of individual strains ofH. pylori did not change, even when they were stored and passed from generation to generation in our laboratory. These results suggest that DNA fingerprints with a urease gene probe will be useful in epidemiologically tracingH. pylori infection. Almost all strains ofH. pylori isolated from different sites in the stomach of a patient on different occasions showed the same pattern, allowing us to confirm that only one strain ofH. pylori was responsible forH. pylori infection in individual patients.     

Detection ofHelicobacter pylori by polymerase chain reaction assay using gastric biopsy specimens taken for CLOtest

The concordance rate between a rapid urease test (CLOtest) and polymerase chain reaction (PCR) assay for the detection ofHelicobacter pylori in gastric biopsy samples was investigated. To avoid the bias produced by patchy distribution of the organism in the stomach, the samples used for these two tests were not obtained from two different sites of the antrum. Instead, the PCR assay was performed with the the same biopsy sample that was taken for the CLOtest. Among 82 biopsy samples included for this study, 56 were positive and 26 were negative by CLOtest. Of the 56 CLOtest-positive samples, 52 (93%) were also positive by PCR assay, and of the 26 CLOtest-negative samples, 20 (78%) were negative by PCR assay. The total concordance rate of these two tests was 87.6%. Of the 4 cases with CLOtest-positive and PCR-negative results, 3 had been treated with long-term H₂ blockers. Of the 6 patients with CLOtest-negative and PCR-positive results, 4 suffered from recurrent or poorly healing duodenal ulcers. Interestingly, a significantly lower density of the PCR products was observed during electrophoresis analysis for all the 6 cases, presumably due to a small number ofH. pylori in these samples. These results indicated that PCR might be used as a complementary assay for CLOtest. False negative results by CLOtest might occur when only a small amount ofH. pylori was present in the samples, which could be detected by subsequent PCR assays using the same biopsy specimens. The clinical significance of such CLOtest-negative and PCR-positive cases requires further study.     

Recurrence of Gastric Ulcer Dependent Upon Strain Differences of Helicobacter pylori in Urease B Gene

To evaluate the role of different strains of Helicobacter pylori on the recurrence of gastric ulcer, we divided H. pylori into four types (I, II, III, and IV) according to the urease B gene using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). The relationship between the recurrence of gastric ulcer and the prevalence of H. pylori types was studied in 32 patients with benign open gastric ulcers using upper gastrointestinal endoscopy. The rate of recurrence was significantly lower in patients with type II than in patients with types I, III, and IV (P < 0.05). Using Mongolian gerbils, an animal model of H. pylori infection, we also showed that the occurrence of gastric ulceration following restraint water-immersion stress was significantly lower in type II compared with types I and III. These data indicate that in the context of ulcer recurrence, it is not necessary to eradicate H. pylori during infection with type II.     

Detection and partial sequence analysis ofHelicobacter pylori DNA in the bile samples

The existence ofhelicobacter pylori in the biliary tract was investigated. Seven bile samples were included in this study. Among them, six bile samples were collected by percutaneous transhepatic cholangiodrainage and the other by needle aspiration during cholecystectomy. Using nested PCR with two sets of primers homologous to the urease A gene,Helicobacter pylori DNA was detected. Three samples, one from a patient with advanced gastric cancer involving the pancreatic head and two from patients with pancreatic head tumor, were found to be positive forHelicobacter pylori DNA. On the other hand, three samples from patients with cholangiocarcinoma and one from a patient with chronic cholecystitis were all negative. To further verify the specificity of our PCR analysis, partial sequences of the PCR products from the three positive samples were analyzed by direct sequencing. Several silent mutations and a missense mutation (AAA to AGA; Lys-164 to Arg-164) were identified in the urease A gene. We conclude thatHelicobacter pylori DNA can be easily detected in the bile samples. The possibility of asymptomatic cholangitis caused by this organism requires further investigation.This study was supported in part by grants from Chang Gung Medical Center (CMRPs) and also by a grant from the Prosperous Foundation, Taipei, Taiwan.     

Role ofHelicobacter pylori serology in evaluating treatment success

Duodenal ulcer recurrence and gastritis are reduced with successfulHelicobacter pylori treatment. Serology is accurate in the diagnosis ofH. pylori, but its value in determining eradication is unproved. To evaluate the usefulness of serology in monitoring treatment, we measured serial serum antibodies in three patient groups: eradication success (N=57), eradication failure (N=19), and untreated patients (N=24). Eradication was determined by Warthin Starry staining of antral biopsies and repeat¹³C breath tests at six weeks. Subsequent¹³C breath tests were then performed at three-month intervals to monitor eradication. IgG antibody concentrations toH. pylori were determined by a commercially available ELISA kit. Serology concentrations remained constant throughout the study period in the untreated patients. IgG concentrations decreased slightly in the treatment failure group at six weeks but thereafter remained at baseline values. In the eradicated group, serum IgG concentrations decreased 26% by three months, 43% by six months and 55% at nine and 12 months (P<0.001). A 20% reduction in IgG concentrations by six months was associated with successful treatment (sensitivity 86% and specificity 88%). We conclude that serology is a potentially useful way to monitorH. pylori treatment success.This work was presented in part in a poster at the May 1992 meeting of the American Gastroenterology Association.[¹³C]urea was kindly provided by Cambridge Isotope Laboratories, Boston, Massachusetts. Reagents and equipment to perform ELISA supplied by Bio Whittaker, Inc., Walkersville, Maryland.     

Detection of genotypic clarithromycin-resistant Helicobacter pylori by string tests

AIM:To evaluate the utility of the string test to detect genotypic clarithromycin-resistant Helicobacter pylori (H.pylori)by polymerase chain reaction(PCR)-restriction fragment length polymorphism.METHODS:Patients undergoing endoscopic examinations were enrolled in the present study.String tests were done on the next day of endoscopy.Segments of 23S rRNA were amplified from DNA obtained from string tests.PCR-restriction fragment length polymorphism was accomplished by restriction enzymes BbsI and BsaI recognizing the mutation site A to G at 2143or at 2142 of 23S rRNA domain V,respectively.RESULTS:One hundred and thirty-four patients with H.pylori infection underwent string tests.To compare phenotypic resistance,43 isolates were successfully cultured in 79 patients in whom 23S rRNA was successfully amplified.Of five patients with clarithromycinresistant H.pylori,23S rRNA of H.pylori isolates from four patients could be digested by BsaI.In 38 susceptible isolates,23S rRNA of H.pylori isolates from 36 patients could not be digested by either BsaI or BbsI.The sensitivity and specificity of the string test to detect genotypic clarithromycin resistance were 66.7%and97.3%,respectively.Positive and negative predictive values were 80%and 94.7%,respectively.CONCLUSION:String test with molecular analysis is a less invasive method to detect genotypic resistance before treatment.Further large-scale investigations are necessary to confirm our results.     

Profound increase ofHelicobacter pylori urease activity in gastric antral mucosa at low pH

The effect of pH onH. pylori urease activity in its ecological niche was studied in gastric antral biopsy specimens. Specimens were incubated in 10 mmol/liter urea solutions at pH range 3.3–8.2. Activity of urease was studied by measuring production of ammonia and change in pH of the solutions. Urease activity was reduced at pH 8.2 (1424 ± 218 µmol/liter) but decreasing initial pH to neutral and acidic values resulted in significant maximal 6.5-fold increase in ammonia production (9491 ± 1073 µmol/liter,P<0.0005), which considerably raised the pH of the test solutions. Peak urease activity was between pH 5.0 and 7.0. In contrast to specimens incubated initially at pH 8.0, reincubation of washed specimens from solutions with initial pH 7.0 showed eightfold decreased urease activity. It is concluded that urease activity is markedly pH dependent with pH optima below the physiological mucosal surface pH. Furthermore, availability of urease is limited. Thus, an impaired gastric mucosal integrity allowing back diffusion of hydrogen ions may release urease activity, which might further weaken the mucus barrier and damage the gastric epithelium.This study was supported by the Deutsche Forschungsgemeinschaft (Mi 190/3).     

Role ofHelicobacter pylori in cirrhotic patients with peptic ulcer

Helicobacter pylori was found to be a promoter factor of peptic ulcer that has an incidence higher in patients with hepatic cirrhosis. To clarify the role betweenH. pylori and peptic ulcer in patients with hepatic cirrhosis, a serological test (ELISA test, HEL-p, AMRAD, Australia), was used to measure the presence ofH. pylori of patients with hepatic cirrhosis. Within two years, 108 cirrhotic patients who had received a panendoscopic examination were enrolled in this study. There were 79 males and 27 females with a mean age of 53.2 years. Sixty-four cases had positive serum HBsAg and 44 had negative serum. The results showed that the prevalence ofHelicobacter pylori in cirrhosis was 43.5% (47/108). There was no difference of HEL-p-positive rate between peptic ulcer and normal gastroduodenal mucosa (45.2% vs 46.1%,P>0.05). According to this study, there appears to be no relation between peptic ulcer andH. pylori in patients with hepatic cirrhosis. The etiology of peptic ulcer in cirrhotic patients need further study.     

Pathogenetic role ofHelicobacter pylori in duodenal ulcer disease

The pathogenesis of duodenal ulcer disease is multifactorial and the contribution ofHelicobacter pylori in relation to the other factors to the release of duodenal ulcer is unknown. To investigate this, we studied 147 patients with endoscopically proven healed ulcers. These patients were randomized to receive either placebo, misoprostol 200 g or misoprostol 300 g four times daily, and clinical, personal, physiological and endoscopic characteristics were obtained prospectively. Endoscopy was performed at the active phase of the ulcer and when the ulcer healed. Biopsies were taken from the antrum to assess histologically for: (1) the activity of gastritis as assessed by the degree of polymorph infiltration, (2) the degree of chronic inflammation by the degree of chronic inflammatory cells infiltration and degree of mucosal degeneration, and (3) bacteriologically for the presence ofH. pylori. The severity of the gastritis and the bacterial density were graded independently by two pathologists. The patients were assessed at two-month intervals for 12 months or until the ulcer relapsed. The results demonstrated that the relapse rates of duodenal ulcer were similar in the three treatment groups. The relapse rate was higher in the group with higher density of the bacteria (P<0.05). The degree of gastritis did not affect the relapse rate of duodenal ulcer in either the placebo or misoprostol group or in all patients combined. Stepwise logistic regression analysis identified that increased duodenal inflammation, male sex, early-onset disease, andH. pylori adversely affected relapse of the ulcer. We conclude that multiple factors affect the relapse of duodenal ulcer andH. pylori is one of them.     

High seroprevalence ofHelicobacter pylori in diabetes mellitus patients

To assess the prevalence ofHelicobacter pylori in diabetes mellitus, a serological test was used to detect antibodies toH. pylori in patients with diabetes mellitus. Within six months, 45 insulin-dependent, 98 non-insulin-dependent, and a control group of 159 outpatients were enrolled in this study. The age adjusted seroprevalence rates ofHelicobacter pylori were determined using a commercial anti-Helicobacter pylori IgG and IgA ELISA (Bio-Rad). The prevalence rates increased with age in all age groups until 60–70 years. In diabetic patients, the frequency ofHelicobacter pylori infection was higher than in control subjects in nearly all age groups, reaching significance in three age categories for NIDDM patients and in one age category in IDDM patients. This higher seroprevalence could not be explained by differences in socioeconomic status or use of antibiotics.This work was supported by Glaxo BV, The Netherlands.Address for reprint requests: University Hospital Utrecht, Department of Gastroenterology, Room F2.618, PO Box 85500, 3508 GA Utrecht, The Netherlands.     

Unique features ofHelicobacter pylori disease in children

In a six-year period, 41 children had endoscopically documented duodenal ulcer disease or primaryH. pylori antral gastritis without duodenal ulcer. Of 37 children withH. pylori gastritis, group 1 comprised 23 patients with duodenal ulcer disease and group 2 had 14 patients without ulcers (primaryH. pylori gastritis). Group 3 comprised four children with duodenal ulcer disease andH. pylori-negative antral biopsies. During the study period, all primary chronic ulcer disease was duodenal; no primary chronic gastric ulcer was present. Two distinct types of duodenal ulcer disease were identified; the majority (85%) was always associated with significant activeH. pylori antral gastritis (group 1). The minority (15%) had virtually absent gastritis and noH. pylori (group 3). Native Indian children were represented in group 1 quite out of proportion to the referral population and had the most severe disease. While it is established that a higher prevalence of asymptomaticH. pylori infection exists in non-Caucasians, this appears to be the first demonstration of a higher prevalence of symptomatic ulcer disease in non-Caucasian children or adults. Caucasian children tended to have primaryH. pylori gastritis (group 2) or duodenal ulcer withoutH. pylori (group 3). Antral nodularity was found to be an important specific endoscopic sign, unique to those children withH. pylori disease. It has not been described in adultH. pylori disease. Non-Caucasian children, especially Native Indians, in British Columbia have more prevalent and more severeH. pylori disease than Caucasians. Endoscopy with gastric antral biopsies is necessary to distinguish different types of duodenal ulcer disease and to diagnose primaryH. pylori gastritis.     

Long-term prospective study ofHelicobacter pylori in nonulcer dyspepsia

Helicobacter pylori is present in up to 87% of patients with nonulcer dyspepsia. This study assessed the effect of eradicatingHelicobacter pylori infection on the symptoms of nonulcer dyspepsia at four weeks and one year after treatment. Dyspepsia was assessed on the frequency and severity of six symptoms [epigastric pain (night and day), nausea and vomiting, upper abdominal discomfort, and regurgitation] where each symptom was scored from 0 to 4.Helicobacter pylori status was assessed before treatment and four weeks after treatment with histology and microbiology, and at one year with a carbon-13 urea breath test. Eighty-three patients (23 males, 60 females; mean age 56.3 years; mean symptom duration 3.6 months) with nonulcer dyspepsia andHelicobacter pylori infection entered the study. Seventy-five were available at one year follow-up. Four weeks after treatment, the mean symptom score improved in those with eradication (6.95–2.3,P=0.01,N=41) or persistent infection (6.69–3.0,P=0.015,N=42). At one year, those with persistentHelicobacter pylori infection (N=38, score 5.24) had a higher score than those remaining clear of infection (N=24, score 1.4,P<0.0001) and those with reinfection (N=13, score 2.2,P<0.0001). In addition, persistentHelicobacter pylori infection was associated with more additional treatments than those with eradication (34/38 versus 4/37,P<0.001). These results suggest thatHelicobacter pylori plays an important role in the symptoms of nonulcer dyspepsia.     

Seroepidemiology ofHelicobacter pylori infection in India

Helicobacter pylori (previouslyCampylobacter pylori) is now accepted as the major cause of type B gastritis and thus what is known about the epidemiology of type B gastritis can reasonably be transferred toH. pylori. We used a specific ELISA for anti-H. pylori IgG to study the prevalence ofH. pylori infection in a population of lower socioeconomic class from Hyderabad, India. The results from India were compared to studies from other parts of the world. Two hundred thirty-eight individuals ages 3 to 70 participated. The frequency ofH. pylori infection increased with age (P<0.01) and was >80% by age 20.H. pylori infection was present in 79% of the population studied; there was no gender-related difference in prevalence ofH. pylori infection. IgG antibody against hepatitis A (HAV) was rapidly acquired in Hyderabad; in a subset of 58 children between the ages of 3 and 21 tested, the frequency of anti-HAV was 98.2%. The prevalenc ofH. pylori infection increases with age in both developed and developing countries. The high age-specific prevalence ofH. pylori infection in developing countries is probably a reflection of the lower socioeconomic level of those areas.This work was supported by the research funds from the Department of Veterans Affairs; by grant DK 39919 from the National Institute of Diabetes and Digestive and Kidney Diseases, and by the generous support of Hilda Schwartz.     

Validity of various diagnostic tests to evaluate cure ofHelicobacter pylori infection

Many diagnostic methods have been developed and used for detectingHelicobacter pylori to evaluate the success of treatment ofH. pylori infection. We investigated and compared the suitability of the rapid urease test (RUT), polymerase chain reaction (PCR),¹³C-urea breath test (¹³C-UBT), and serology with culture for evaluating cure ofH. pylori infection. Forty-sevenH. pylori-positive gastric ulcer patients received dual therapy of lansoprazole (30 mg u.i.d.) and clarithromycin (200 mg b.i.d.). Four weeks after the completion of treatment, RUT, PCR,¹³C-UBT, and culture were performed and the negative rates of these tests were compared. Anti-H. pylori IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA) before and 4 weeks after completion of the treatment to evaluate changes of titers during the treatment. The negative rate of RUT (55%) was significantly greater than that of culture (27%). Significant declines in titers were seen in the patients who had negative culture results, while the decline in the titer was not significant in the patients who had positive results. PCR assay and¹³C-UBT were suitable for the evaluation ofH. pylori eradication, but RUT was not suitable, because of its sensitivity. By monitoring anti-H. pylori IgG antibody titers, therapeutic failure can be detected early after completion of treatment.     

Prevalence ofHelicobacter pylori in specific forms of gastritis

Helicobacter pylori colonization of the gastric mucosa is strongly associated with chronic nonspecific gastritis; moreover, there is evidence to suggest thatH. pylori may cause this form of gastritis. However, there is little or no information on the prevalence ofH. pylori in specific forms of gastritis. Our hypothesis was that ifH. pylori was pathogenic in chronic nonspecific gastritis, organisms would be found frequently in this type of gastritis but infrequently in specific forms of gastritis. Prevalence rates ofH. pylori were determined independently in patients with eosinophilic and Crohn's gastritis, Menetrier's disease, and chronic nonspecific gastritis. The prevalence ofH. pylori in patients with chronic nonspecific gastritis was 71%, whereas the organism was not identified in patients with any form of specific gastritis. This finding further supports the accumulating evidence thatH. pylori is a primary pathogenic factor in chronic nonspecific gastritis.This work was supported in part by the Mayo Digestive Diseases Center Grant (DK34988) from the National Institutes of Health, United States Public Health Service.This work was presented in part at the American College of Gastroenterology Annual Meeting, New Orleans, October 1989, and published as an abstract in theAmerican Journal of Gastroenterology (84:1166, 1989).     

Detection ofHelicobacter pylori DNA in gastric juice by the polymerase chain reaction: Comparison with findings in bacterial culture and the detection of tissue IgA and serum IgG antibodies againstHelicobacter pylori

The detection ofHelicobacter pylori in gastric juice by the polymerase chain reaction (PCR) was undertaken in 124 patients with peptic ulcer or chronic gastritis. PCR products were evaluated by agarose gel electrophoresis and Southern hybridization ofH. pylori-specific DNA sequences. Positive and negative results of the PCR analysis in 72 examinations were compared with those from bacterial culture, and with the detection of tissue IgA antibody againstH. pylori by enzyme-linked immunosorbent assay ELISA; Serion, Wuerzburg, Germany, and detection of serum IgG antibody againstH. pylori by ELISA; Radim Pomezia, Italy. Thirty-four PCR-positive samples evaluated by electrophoresis and hybridization coincided with positive samples in 56% of bacterial cultures, 59% of tissue IgA antibody identifications, and 94% of serum IgG antibody evaluations; 26 PCR-negative samples coincided with negative samples in 96% of bacterial cultures, 81% of tissue IgA antibody evaluations, and 38% of serum IgG assessments. We compared the detection achieved with theH. pylori PCR assay in gastric juice with that in biopsies taken from the antrum and upper corpus in 90 examinations, and found them to be both positive in 34 (38%) and 36 (40%) of specimens, both negative in 37 (41%) and 30 (33%) specimens, gastric juice-positive but biopsynegative in 10 (11%) and 12 (13%) specimens, and vice versa in 9 (10%) and 12 (13%) specimens, when detected by electrophoresis and hybridization, respectively, showing equivalent detection rates. In relation to the type of disease, the positive PCR assay results with gastric juice, evaluated by electrophoresis and hybridization, respectively, were: gastric ulcer 34/53 (64%) and 39/53 (74%), duodenal ulcer 23/38 (61%) and 25/38 (66%), and chronic gastritis 20/33 (61%) and 23/33 (70%), showing no significant difference in positive rates between peptic ulcer and chronic gastritis. Of the samples of 16 patients withH. pylori-positive gastric juice by the PCR assay, 7 were negative by PCR assay analyzed by electrophoresis and hybridization after the completion of treatmentH. pylori. However, after treatment, 3 were negative on electrophoresis but still had positive results with hybridization, indicating that a minimal number of bacilli may have still remained. Detection ofH. pylori in gastric juice has potential advantages for examiningH. pylori infection in the entire stomach and for follow up after treatment for the eradication ofH. pylori. This study was supported by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare, Japan.     

Regression of atypical lymphoid hyperplasia after eradication ofHelicobacter pylori

A rare case of endescopic and histological regression of a gastric lymphoid mucosal lesion after eradication ofHelicobacter pylori is reported. A 72-year-old man was suspected of having a low-grade B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma by endoscopic and histological findings. Histology of biopsy specimens showed massive infiltration of atypical lymphocytes and lymphoepithelial lesions. Immunohistochemical staining revealed kappa light chain expression in the infiltrated atypical lymphocytes to be twofold that of lambda light chain. The above diagnosis was thus highly suspected but not confirmed. Antibiotic therapy was given on the basis of evidence ofH. pylori infection. Successful eradication ofH. pylori resulted in remarkable improvement of endoscopic and histological findings. Follow-up studies were carried out 8 months after eradication, with no evidence of relapse. The eradication ofH. pylori appears to be an effective alternative therapy for B-cell lymphoproliferative disease, although longer follow-up and further studies are needed before this treatment can be establisted.     

Noninvasive detection ofHelicobacter pylori colonization in stomach using [11C]urea

Summary Helicobacter pylori is associated with chronic type B gastritis. Diagnosis can be made on gastric biopsy specimens and noninvasively using [¹³C]-or [¹⁴C]urea breath tests. Both breath tests require meticulous breath collection, and false positive results are possible from urease producing oral-pharyngeal flora. We used [¹¹C]urea, a positronemitting radionuclide allowing dynamic imaging, to measure metabolism of urea in the stomach of biopsy documentedH. pylori-positive patients. [¹¹C]urea was synthesized from¹¹CO₂ produced using a Van de Graaff accelerator and administered with [^99mTc]DTPA to control for loss of radioactivity via gastric emptying. Images were obtained externally by gamma camera every minute and¹¹CO₂ was monitored in the breath continuously for 30 min. AnH. pylori-positive patient exhibited a^99mTc/¹¹C activity ratio of 2.1 in the stomach 10–20 min following administration, compared to a 11 ratio in a negative control, indicating metabolism of urea to¹¹CO₂ with subsequent diffusion of¹¹C activity out of the stomach. The¹¹C activity in the breath peaked at 10–20 min in theH. pylori-positive patients. The short half-life of carbon-11 (20.4 min) alleviates radiation safety concerns and results in low absorbed radiation doses to patients.This work was supported in part by the National Science Foundation (grant R11-8110671), the Commonwealth of Kentucky through the Kentucky EPSCoR program, a grant from the University of Kentucky Association for Medical Research, and the Veterans Administration.     

Medium- and high-dose omeprazole plus amoxicillin for eradication ofHelicobacter pylori in duodenal ulcer disease

The purpose of the present study was to investigate theHelicobacter pylori eradication potency of combined amoxicillin-omeprazole treatment in patients with duodenal ulcer disease and to compare the efficacy of two omeprazole and amoxicillin doses concerningH. pylori eradication, ulcer healing, pain relief, and safety. Ninety patients with activeH. pylori-positive (culture and/or histology) duodenal ulcer disease were randomly treated with either omeprazole 20 mg twice a day plus amoxicillin 1 g twice a day (group I,N=30), omeprazole 40 mg twice a day plus amoxicillin 1 g twice a day (group II,N=30), or omeprazole 40 mg twice a day plus amoxicillin 1 g three times a day (group III,N=30) over two weeks, followed by ranitidine at bedtime for another four weeks. The overall proportion ofH. pylori eradication was 83% and of ulcer healing 92% without statistically significant differences between the study groups. Complete pain relief occurred after a median of one day in all groups. Six patients complained of side effects during the therapy phase, which led to therapy discontinuation in one female patient. In conclusion, omeprazole plus amoxicillin is a highly effective and well-tolerated therapy regimen to eradicateH. pylori in duodenal ulcer disease. In addition, the results suggest that there is no clear dose-response relation between the dosages of omeprazole and amoxicillin used in this study on the one hand and theH. pylori eradication rates on the other.     

Effect of eradication ofHelicobacter pylori infection on gastric epithelial cell proliferation

Helicobacter pylori infection has been linked with gastric carcinoma. Epithelial cell proliferation is an indicator of cancer risk. The aim of this study was to assess gastric epithelial cell proliferation before and after eradication therapy and to assess the efficacy of treatment ofH. pylori infection using lanzoprazole and clarithromycin. Twenty-three patients withH. pylori-associated gastritis were treated with lanzoprazole 30 mg daily for four weeks and clarithromycin 500 mg three times a day for two weeks. Antral mucosal biopsies were taken for gastric epithelial cell proliferation analysis using thein vitro bromodeoxyuridine (BrdU) immunohistochemical technique before and four weeks after eradication therapy. Labeling index percent (LI%) was calculated as the percent ratio of proliferating cells to the total number of cells in the gastric pit. Efficacy of treatment was assessed in 16 subjects. Eight were negative forH. pylori infection 28 days after therapy and in eight patientsH. pylori infection was not eradicated. The eradication rate for the regimen was 50%. Cell kinetics were assessed in 19 subjects who completed treatment. Patients withH. pylori infection had a significantly higher LI% compared to normal (N=19, LI%: 5.01±0.3 vs 3.2±0.2,N=29). Eradication ofH. pylori infection significantly reduced epithelial cell proliferation (N=9, LI%:5.2±0.4 to 3.2 ±0.8,P<0.001), whereas it was unaltered in those whose infection was not eradicated (N=10, LI%: 4.8±0.4 to 5.5±0.5,P=0.18). Eradication ofH. pylori reduces gastric epithelial cell proliferation to normal levels and may reduce the long-term the risk of gastric carcinoma.We wish to thankLederle for their support with this trial.