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Background: Gastrin G cells and somatostatin D cells are important regulators of gastric acid secretion and alterations in their relative numbers may play a key role in gastroduodenal disease., Aim: To investigate the effect of Helicobacter pylori infection on the density of immunoreactive G and D cells in gastric antral and corpus biopsies from patients with dyspeptic complaints., Methods: One hundred and twenty two patients with dyspeptic complaints had two antrum and two corpus biopsies taken during upper endoscopy. The severity of inflammation and the density of H pylori were evaluated semiquantitatively. In addition, the density and distribution of neuroendocrine cells, especially G and D cells, were examined using immunohistochemistry. Patients were divided into three groups, those with H pylori positive gastritis, H pylori negative gastritis, and histologically normal gastric mucosa., Results: The number of immunoreactive G cells was significantly higher and the number of immunoreactive D cells lower in patients with H pylori positive gastritis compared with H pylori negative gastritis or histological normal gastric mucosa. The percentage of G cells as a percentage of mucosal endocrine cells was also raised and that of D cells was decreased., Conclusions: Helicobacter pylori infection produces alterations in the number of endocrine cells responsible for regulating acid secretion in relation to intragastric pH and feeding. The alterations correlate best with the severity of inflammation and not with H pylori density.

Background: Current noninvasive tests to confirm the eradication of Helicobacter pylori must be performed 4 weeks or more after eradication therapy is completed., Objective: To determine whether the stool antigen test, a relatively new noninvasive test for H. pylori, administered at various times after eradication therapy correctly identifies persons with persistent H. pylori infection., Design: Prospective blinded study., Setting: Six clinical centers in the United States and Europe., Patients: 84 H. pylori --infected patients undergoing endoscopy for upper abdominal symptoms., Measurements: At baseline and on day 35 after the completion of triple eradication therapy, all patients underwent endoscopy with histologic examination, rapid urease test and culture, urea breath test, and a stool antigen test. The stool antigen test was also performed on days 3, 7, 15, 21, 28, and 35 after completion of therapy., Results: Compared with the gold-standard endoscopic tests on day 35 after antimicrobial therapy, the urea breath test had a sensitivity of 94% (95% CI, 71% to 100%) and a specificity of 100% (CI, 94% to 100%). The stool antigen test had a sensitivity of 94% (CI, 71% to 100%) and a specificity of 97% (CI, 89% to 100%). On day 7 after treatment, the stool antigen test was predictive of eradication (positive predictive value, 100% [CI, 69% to 100%]; negative predictive value, 91% [CI, 82% to 97%])., Conclusion: A positive result on the stool antigen test 7 days after completion of therapy identifies patients in whom eradication of H. pylori was unsuccessful.

AIM-Atrophy and intestinal metaplasia (IM) as precancerous conditions consistently begin in the antrum and are most severe along the lesser curvature. The aim of this study was to investigate discrepancies in the prevalence, the severity of atrophy, and IM in antral mucosa of Helicobacter pylori infected gastritis and difference in age of onset among Chinese and Dutch patients. METHODS-Two hundred and sixty five Chinese patients and 261 Dutch patients with H pylori infection were enrolled. The degrees of atrophy and IM were graded according to the updated Sydney system. RESULTS-The overall prevalences of atrophy and IM were lower in Dutch patients (42% and 26%, respectively) than in Chinese patients (52% and 32%, respectively). Only the difference in atrophy reached significance (p = 0.028). However, in both Chinese and Dutch patients, the degrees of atrophy and IM were low and severe degrees were rare. The mean ages of Chinese and Dutch patients with atrophy and IM were higher than those without atrophy and IM (with atrophy (Chinese patients): mean, 42.12; SD, 9.80; with IM (Chinese patients): mean, 42.56; SD, 9.96; with atrophy (Dutch patients): mean, 55.16; SD, 12.20; with IM (Dutch patients): mean, 57.79; SD, 11.13; without atrophy (Chinese patients): mean, 39.71; SD, 10.16; without IM (Chinese patients): mean, 40.19; SD, 9.99; without atrophy (Dutch patients): mean, 45.70; SD, 12.44; without IM (Dutch patients): mean, 46.89; SD, 12.68). Atrophy and IM occurred earlier and were more severe in Chinese patients, with both reaching a peak value in patients over 60 years. CONCLUSIONS-There are geographical differences in the prevalence and severity of H pylori infected gastritis, in particular with respect to atrophy and IM, which suggests that infection with H pylori occurs earlier in life and has a higher prevalence in CHINA:

Objective: In a recently published multicenter study involving 501 patients undergoing esophagogastroduodenoscopy (EGD) throughout Europe, we showed the high accuracy of a recently developed simple test (HpSA) to detect Helicobacter pylori (H. pylori) antigens in stools of untreated patients. The aim of this study was to assess the diagnostic usefulness of HpSA compared with 13C UBT shortly after H. pylori eradication treatment., Methods: Of the 501 patients enrolled in the validation study, 279 were found to be H. pylori-positive. These patients were given H. pylori eradicating regimen and asked to return for follow-up EGD with biopsies, 13C UBT and HpSA testing 4 wk after therapy. Follow-up results were available for 235 patients. Of these, 162 consented to all testing and 73 consented only to 13C UBT and HpSA testing. We assessed sensitivity and specificity of both HpSA and 13C UBT compared with biopsy-based methods in the 162 patients, who accepted follow-up EGD. We also assessed sensitivity and specificity of HpSA compared with 13C UBT, arbitrarily chosen as the gold standard, in the whole population of 235 patients., Results: Sensitivity and specificity in 162 patients who consented to a second EGD were 93.8% (CI: 85.4-100%) and 96.9% (CI: 93.9-99.9%) for HpSA, and 90.6% (CI: 80.5-100%) and 99.2% (CI: 97.7-100%) for UBT. Using EGD-based methods as the gold standard, 130 of the 162 treated patients' H. pylori infection were eradicated (125 HpSA-negative, one borderline, and four false-positive; 129 13C UBT-negative, one false-positive), and 32 remained H. pylori-infected (30 HpSA-positive, two false-negative, 29 13C UBT-positive, three false negative). The overall eradication rate was 80.2%. The sensitivity and specificity of HpSA relative to UBT as the gold standard in the overall population (n = 235) were 95.6% (CI: 89.6-100%) and 94.7% (CI: 91.5-97.9%), respectively., Conclusions: HpSA has proven to be a useful method in posttreatment eradication testing for H. pylori. Its ease of use, speed, and noninvasive nature make HpSA testing an ideal method for post-treatment monitoring where a second EGD may not be justified.

Objective: In this pilot study we investigated the efficacy and tolerability of a new monocapsule that contains a bismuth compound, tetracycline, and metronidazole. If proven to be effective, this monotherapy would turn the well-accepted multidrug regimen of standard bismuth-based triple therapy into an easy and more patient-friendly regimen. It can be used in patients allergic to penicillin., Methods: A total of 53 consecutive H. pylori-infected patients (30 with proven ulcer disease, 23 with gastritis only) from a single center were prescribed two monocapsules q.i.d. after the three meals and after an evening snack during 10 days. Each capsule contained 60 mg colloidal bismuth subcitrate (as Bi2O3 equivalent), 125 mg tetracycline, and 125 mg metronidazole. Repeat endoscopy with biopsies for urease test, Giemsa stain, and culture was carried out > or =5 wk later. Side effect data were collected., Results: One patient was lost to follow-up, two failed to respond, and 50 were cured. The intention-to-treat cure rate was 50 of 53 (94.4%, 95% CI 88.1-100%). Antibiotic sensitivity was available from 51 isolates. The cure rate in the metronidazole sensitive strains was 44 of 45 (97.8%, 95% CI: 93.5-100%), whereas it was four of five in the resistant strains. The regimen was well tolerated, with only two drop-outs (4%) because of side effects., Conclusions: The new monocapsule is an inexpensive, well tolerated, and patient-friendly formulation of a bismuth based triple therapy. A 10-day course with this multidrug capsule reached a very high cure rate in metronidazole-sensitive strains. The number of cases with resistant strains was insufficient to allow firm conclusions about its efficacy in case of resistance. The results are in agreement with previous data with bismuth triple therapy using separate drugs. From the high cure rate, we can conclude that the new capsule dissolves adequately, with proper delivery of its ingredients at the site of action.

Once again this year, developments in the field of ulcers and gastritis have been entirely dominated by findings relating to Helicobacter pylori. However, interest in H. pylori can be expected to decline, since the prevalence of the infection is rapidly decreasing in the developing world - to the point that many gastroduodenal ulcers are now unrelated to H. pylori A further reason for declining interest is disappointment regarding the role of H. pylori in dyspepsia. The expected reduction in the endoscopic workload produced by screening for H. pylori or cagA positivity has so far not occurred. The exact role of the damage caused by nonsteroidal anti-inflammatory drugs in H. pylori-infected stomachs remains controversial. Equally controversial is the magnitude of the increased reflux symptomatology and reflux disease observed after H. pylori infection has been cured in patients with ulcer disease. Eradication therapy is largely dominated by proton-pump inhibitor triple therapies, although the efficacy of these is declining. Bismuth triple therapy and quadruple therapy continue to be valid alternatives.

Aim: To test the reproducibility between two histopathologists of features of Helicobacter pylori gastritis, using the updated Sydney classification., Methods: 290 dyspeptic Dutch patients with biopsy proven H pylori infection were enrolled in the study. Gastric antral mucosal biopsy specimens were analysed before and after H pylori eradication treatment. The biopsies were scored semi-quantitatively by two histopathologists, according to the updated Sydney classification system. Variables analysed included the density of H pylori infection, the degree of chronic inflammation, inflammatory activity, atrophy, intestinal metaplasia, and surface epithelial damage. Before grading biopsy specimens, both pathologists reached a consensus on the scoring of gastritis through interactive sessions using a multiheaded microscope. Subsequently all biopsy specimens were graded. Interobserver variability was also analysed using weighted kappa scores., Results: For interobserver agreement on scoring the various gastritis features a high degree of reproducibility was reached overall. Agreement on grading of atrophy was the lowest; however, moderate to good reproducibility was achieved, with weighted kappa values of 0.49 in the pretreatment biopsies and 0.52 in the post-treatment biopsies. Disagreement was most common in biopsy specimens with lesser degrees of atrophy. A high degree of agreement was obtained for intestinal metaplasia, with weighted kappa values of 0.72 in the pretreatment biopsies and 0.73 in the post-treatment biopsies. The best agreement was reached in the assessment of the density of H pylori both before and after H pylori eradication treatment, with excellent weighted kappa values of 0.76 and 0.95, respectively. The grade of reproducibility of inflammatory activity, superficial epithelial damage, and chronic inflammation was high, with weighted kappa values varying from 0.60 to 0.76 and 0.62 to 0.83 before and after eradication, respectively., Conclusions: Reproducibility of grading H pylori related gastritis is high using the updated Sydney system. Despite the novel criteria for scoring atrophy, there was imperfect agreement on this feature between two independent histopathologists.

Background: Helicobacter pylori is a common human pathogen implicated in certain gastrointestinal diseases. In the search for new non-invasive techniques to diagnose H. pylori infection, we evaluated an EIA for H. pylori antigen in stool (HpSA)., Methods: In a prospective multicentre study, stool specimens from 501 patients (276 men, 225 women; age range 17-88 years, mean 52) undergoing gastroscopy in 11 centres throughout Europe were tested with HpSA and the carbon-13-urea breath test. At endoscopy, four biopsy samples were taken for histology (haematoxylin and eosin) and H. pylori detection (giemsa in both antrum and corpus, culture and rapid urease test). Patients were defined as positive for H. pylori if histology (antrum, corpus, or both) and urease test were positive, or if culture was positive. Patients classified as having H. pylori infection received an eradication regimen; 107 were reassessed 4 weeks after therapy., Findings: Of 272 patients with H. pylori infection by the predefined criteria, 256 were positive by HpSA (sensitivity 94.1% [95% CI 90.6-96.6]). Of 219 patients without infection, 201 were negative by HpSA (specificity 91.8% [87.3-95.1])., Interpretation: The stool assay was a reliable and easy-to-use tool for diagnosis of H. pylori infection. The test was accurate even shortly after treatment.

Helicobacter pylori is the causative factor of chronic gastritis and ulcers of duodenum and stomach and relates to mucosa-associated lymphoid tissue (MALT) lymphomas. Host factors, bacterial factors and dietary habits conceivably play a part in the more severe mucosal lesions induced by H. pylori. H. pylori is a heterogeneous bacterial species, the various types differing in possession of a locus with genes coding for products that may intensify the inflammatory reaction. The cytotoxin-associated gene (cagA) protein is a marker for this locus; this protein and the vacuolating-associated cytotoxin A are clearly related to the ulcerative disease. Patients may be colonized by a mixed population of H. pylori consisting of cagA-positive and cagA-negative H. pylori. Also, a patient may be infected by a mixed population of H. pylori sensitive and resistant to metronidazole. Accordingly, a substantial part of the H. pylori population in a patient should be examined to arrive at an adequate conclusion concerning the production of H. pylori factors that may relate to a particular clinical picture and to the sensitivity to antibiotics of the H. pylori.

Objective: To investigate the magnitude of long-term prescription of acid secretion suppressant therapy in general practice, the frequency and methods of objectivation of the primary working diagnosis and the clinical grounds for the first prescription., Design: Retrospective., Method: Patients on long-term acid suppressant therapy were identified in a population of 46,813 patients in 24 general practices in the Amsterdam region by extraction from computerized medication databases of the pharmacists. The indications for the prescription and the investigations performed to confirm the working diagnosis were extracted from the patients' files in the GP practices. Long-term acid suppressant therapy was defined as prescription for at least 12 weeks in the period September 1994-August 1995., Results: 922/46,813 patients (2%) were on long-term acid suppressant therapy. Mean duration of prescription was 33 weeks. The duration of prescription varied from 12 weeks in 8% of the patients to > 52 weeks in 23%. In 25% of the patients no objectivating investigations were performed, in 75% endoscopy or radiology was done; the predominant diagnoses were ulcerative disease (39%) and/or gastroesophageal reflux disease (49%) and functional dyspepsia (gastritis, or normal aspect) (18%). The Helicobacter pylori status had been established in 29% of the patients with ulcerative disease. Eradication therapy was reported in 44% of these patients., Conclusion: Long-term acid suppressant therapy is frequently administered without a confirmed working diagnosis. An important part of the patients need H. pylori diagnostics, H. pylori eradication therapy and if possible tapering off of their medication.

Objective: To assess the laser assisted ratio analyser (LARA) system for detection of Helicobacter pylori infection in breath samples., Design: Descriptive., Method: Diagnostic gastroscopy with biopsies for histopathology and culture was performed in consecutive dyspeptic patients in the Department of Gastroenterology of the Academic Medical Centre of Amsterdam in January-May 1996. Subsequently, a LARA test was carried out, which measures the degradation by H. pylori of 13C urea using the ratio of 12CO2/13CO2 in the exhaled air. The combination of the results of the examination of gastric biopsies was regarded as the golden standard for the demonstration of H. pylori infection. After this comparison, the cut-off level above which the LARA system demonstrated H. pylori infection was established in the basis of a receiver operator characteristics (ROC) analysis. An area was defined round this value within which the results were inconclusive and outside of which the reliability increased., Results: 208 patients were included in the study; the data of nine of them could not be analysed (CO2 level in the exhaled air too low: 8; withdrawal: 1). The remaining 199 patients were 105 males and 94 females with a mean age of 48 years (range 19-75). Ninety-three of them (47%) were H. pylori positive according to the golden standard. With the breath analysis infection was detected in 86 of them, while in 97 patients breath analysis was correctly negative; it was false-negative in four, false-positive in three and unreliable in nine patients. The sensitivity was 96%, the specificity 97%. The positive and negative predictive values were 97% and 96%, respectively.

Aims: Conflicting data on c-erbB-2 overexpression in gastric carcinomas can be found in the literature with regard to overall prevalence, prognostic significance and the histological type according to Lauren. The majority of these studies have focused on advanced gastric carcinomas whereas data on c-erbB-2 overexpression in early gastric carcinomas, especially of Caucasian origin, are relatively sparse. We therefore examined a series of Caucasian early gastric carcinomas to assess overall c-erbB-2 overexpression and to correlate c-erbB-2 overexpression, if any, with the type of growth pattern and the Lauren type., Methods and Results: Forty-five paraffin-embedded gastrectomy specimens from early carcinomas were examined for the presence of chronic active gastritis, chronic atrophic gastritis, subtypes of intestinal metaplasia and dysplasia. The Lauren type and the type of growth pattern were reassessed for all early carcinomas. c-erbB-2 overexpression was assessed with monoclonal antibody 3B5 and polyclonal antibody A485. Complete absence of c-erbB-2 overexpression was observed in chronic active gastritis, chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. Moreover, c-erbB-2 overexpression was found absent in both intestinal-type (n = 20) and diffuse-type early gastric carcinomas (n = 25), irrespective of growth type., Conclusions: c-erbB-2 overexpression does not play a role in the progression from normal to neoplastic gastric mucosa and should be considered as a late event in gastric carcinogenesis. Moreover, c-erbB-2 overexpression does not discriminate between intestinal and diffuse type early gastric carcinomas of Caucasian origin. Finally, it appears that mechanisms other than c-erbB-2 overexpression underlie the reported differences in biological behaviour of early gastric carcinomas with different types of growth pattern.

The discovery of Helicobacter pylori as a dominant cause of gastritis is at least revolutionary both with respect to its clinical consequences as to its contribution to fundamental basic science. The velocity with which basic and clinical experience was accumulated in the H. pylori field has been unsurpassed in medicine. The organism is highly complex and can be divided in two subclasses, a more virulent strain containing the socalled 'pathogenicity island' in addition to vacA and IceA1 antigen and an almost commensal-like subtype. The virulent type in particular is associated with severe inflammation and various clinical disease states. The pathogenesis of duodenal ulcer is well understood. The infection is essentially limited to the antrum causing disturbance of the gastrin homeostasis which is one of the mechanisms leading to enhanced acid production. This constant hyperacidity in the duodenal bulb ultimately leads to development of gastric metaplasia with production of neutral mucus. The latter is essential to allow colonisation with the organism, leading to inflammation, erosion and ultimately ulcer. Curing the infection leads to permanent cure of the ulcer diathesis. The mechanisms that ultimately lead to gastric cancer or gastric Malt lymphoma are less clear. Curing the infection turns out to be more difficult than initially anticipated. Currently the triple therapy (a combination of a proton pump inhibitor with clarithromycin and either amoxycillin or metronidazole), or bismuth triple therapy or bismuth quadruple therapy (a combination of a proton pump inhibitor, bismuth, tetracyclin and metronidazole) are most commonly used. Sadly there is a rising frequency of resistance throughout the world against metronidazole and clarithromycin. Finally increasingly H. pylori infection is considered a model for study of fundamental biological problems such as interaction between organism and host, intracellular signalling in case of infection, evolution of inflammation towards atrophy and cancer etc. Equally interesting is the discovery of novel Helicobacters, such as Helicobacter resistance to bile or Helicobacters responsible for intestinal inflammation.

Approximately 60% of Helicobacter pylori isolates in the Western world possess the cytotoxin-associated gene A (cagA). cagA-positive H. pylori is found to be associated with peptic ulcer disease (PUD) and gastric adenocarcinoma. To investigate the cagA status of H. pylori isolates from Chinese patients with PUD and chronic gastritis (CG), H. pylori populations from 83 patients, 48 with PUD and 35 with CG, were assessed by two different cagA-specific PCRs, Southern blotting, and colony hybridization. The combined results from PCR, Southern blotting, and colony hybridization indicate a prevalence of cagA-positive H. pylori isolates of 98% (47 of 48) among Chinese PUD patients and 100% (35 of 35) among Chinese CG patients. Amplification with primer sets 1 and 2 yielded 52 and 95% of the 82 cagA-positive Chinese H. pylori, respectively. In contrast, the sensitivity of cagA-specific PCR for cagA-positive H. pylori isolates from Dutch patients with primer set 1 was 92% (112 of 122) and that with primer set 2 was 91% (50 of 55). The prevalence of cagA-positive H. pylori populations in Chinese patients with PUD and CG is almost universally high. Therefore, cagA cannot be used as a marker for the presence of PUD in Chinese patients. Our data further suggest that allelic variation in cagA may exist and that distinct H. pylori genotypes may circulate in China and Western Europe.

Combination therapies that include metronidazole (MTZ) are the most successful therapies used in eradicating Helicobacter pylori. In this study, the prevalence and the relevance of heterogeneity in susceptibility to MTZ among H. pylori populations of 156 patients were evaluated. The results of this study show that 37 patients (24%) were infected with MTZ-resistant H. pylori (MIC > or = 8 micrograms/ml). Furthermore, 33% (52 of 156) of the patients were found to be infected with H. pylori populations heterogeneous for their susceptibility to MTZ. The reassessment of the MICs of MTZ for these 52 H. pylori populations revealed MTZ resistance in 28 of them, increasing the number of MTZ-resistant H. pylori populations among the 156 patients to 65 (42%). Out of 20 isolates, 2 (10%) heterogeneous in their susceptibility to MTZ also appeared to be heterogeneous at the genome level as determined by randomly amplified polymorphic DNA fingerprinting. In conclusion, the results show the limitations and risk of possible misinterpretations when only a single colony, picked from the primary H. pylori populations isolated from patients, is analyzed for its susceptibility to MTZ.

Background: None of the currently used anti-Helicobacter pylori drug regimens cures the infection 100%, and cure results still vary considerably. The present article reviews the effectiveness of currently used antimicrobial regimens, aimed to cure H. pylori infection., Methods: Data collection started from the beginning of the anti-H. pylori-therapy era until May 1995. No attempt at formal metanalysis has been made, because many studies have been published only in abstract form. Attempts were made to exclude duplicates of studies by comparison to previously reported ones; the authors of suspected duplicates were contacted. After amalgamation of the number of included patients and the number of successfully treated patients, the mean values of eradication rates and the 95% confidence intervals were calculated., Results: A total of 237 treatment arms were analyzed. Bismuth triple therapy continues to reach high eradication rates worldwide (78-89%). Side effects leading to diminished patient compliance and the marked decline of eradication efficacy in cases of metronidazole resistance are considered to be the major drawbacks of this therapy. Proton pump inhibitor (PPI) dual therapy is better tolerated with fewer side effects than is bismuth triple therapy. The mean eradication rates vary from 55 to 75%, and the extremes lie between 24 and 93%. PPI triple therapies have been shown to be very effective against H. pylori (eradication rates, 80-89%). Quadruple therapy leads to a mean eradication rate of 96%., Conclusion: Based on efficacy, PPI triple or bismuth triple therapy are recommended as first-line treatment for H. pylori infection. Quadruple therapy could serve as second-line treatment for eradication of initial failures and in case of metronidazole resistance.

Aims: To investigate the effect of eradication of Helicobacter pylori infection on gastric epithelial damage and gastritis, scored according to the Sydney system., Methods: Gastritis scores and epithelial damage were assessed in gastric biopsy specimens before, and five weeks and one year after anti-H pylori therapy in 66 patients with H pylori related gastritis., Results: The mean initial levels of activity, inflammation, atrophy, intestinal metaplasia, and H pylori scores were higher in the antrum than in the corpus or fundus. Eradication of H pylori resulted in an improvement in the mean inflammatory score in antral biopsy specimens from 2.23 before treatment to 1.32 and 1.06, respectively, five weeks and one year after treatment. Corresponding values for fundic biopsy specimens were 1.30, 0.36 and 0.35. Activity scores improved from 1.41 before treatment to 0.13 and zero, respectively, five weeks and one year after treatment in antral biopsy specimens and from 0.60 before treatment to zero in fundic biopsy specimens. Before treatment, epithelial damage was present in 51% of biopsy specimens taken from the antrum and 23% of those from the corpus. Five weeks after eradication of H pylori none of the biopsy specimens revealed evidence of epithelial damage., Conclusion: Eradication of H pylori is followed by a rapid, significant improvement in the gastritis score and resolution of epithelial damage in antral and fundic mucosa.

Long-term infection with Helicobacter pylori could potentially lead to asymptomatic chronic gastritis, chronic dyspepsia, duodenal ulcer disease, gastric ulcer disease, or gastric malignancy, including both adenocarcinoma and B-cell lymphoma. Currently, the two most important indications for eradication of this bacterium are proven H. pylori-associated duodenal or gastric ulcer disease. Many studies have shown that successful eradication of H. pylori dramatically reduces the rate of duodenal ulcer relapse, and long-term follow-up data appear to support the claim 'no H. pylori, no gastritis; no gastritis, no ulcer', which follows on from the old, but certainly valid, dictum 'no acid, no ulcer'. Furthermore, absence of relapse parallels the marked improvement in gastric histology (e.g. regression of gastritis). Whether there is concomitant regression of gastric metaplasia in the duodenal bulb is, however, controversial. Despite the rather limited data for H. pylori-associated gastric ulcer, successful eradication of the organism has been equated with cure of peptic ulcer disease. Again, eradication parallels a substantial improvement in gastric histology. Although eradication of H. pylori is not currently recommended in asymptomatic individuals or dyspeptics, it has been well documented in previous studies that successful eradication improves the gastric histology in patients with H. pylori-associated dyspepsia. From these studies, it appears that the disappearance of polymorphs from the inflammatory infiltrate occurs rather rapidly after eradication, although regression of the mononuclear component of the inflammatory reaction is more prolonged.

Thirty-three dyspeptic patients with colonization of Helicobacter pylori in the gastric antrum were treated with tripotassium dicitrate bismuthate 120 mg q.d.s. for 28 days and metronidazole 250 mg q.d.s. for 10 days starting on day 19. Five weeks after cessation of this treatment regimen H. pylori was eradicated in 23 patients. In 8 of the remaining 10 patients, H. pylori had become resistant to metronidazole. In this study resistance was significantly associated with smoking habits, but not with age, bacterial load, gastritis score or alcohol consumption.

To shed some light on the question of gastric adaptation to Helicobacter pylori infection, an overview is given of the various histopathological and clinical consequences of H. pylori infection in man. H. pylori infection can be considered as a chronic bacterial infection. For many individuals there is a balance between a low degree of infection and a low degree of inflammation. The microbial or host factors in adaptation of this balance are largely unknown. If and how 'downregulation' of the inflammatory/immune response does occur need further study.

Helicobacter pylori is a unique pathogen and the leading cause of chronic gastric inflammation. For many individuals the organism is of low virulence, causing only mild inflammation and generating few, if any, dyspeptic symptoms. For those with more severe inflammation, H. pylori infection may be causal in the generation of dyspeptic symptoms. H. pylori infection appears to be the dominant factor in peptic ulcer disease. Events considered to be of importance are a disturbed gastrin homeostasis and the development of gastric metaplasia in the bulb. The most important argument in support of the dominant role of H. pylori in duodenal ulcer disease is the markedly reduced ulcer relapse after successful eradication. Eradication proves to be difficult, presumably because of the peculiar habitat of the organism. Currently the best pharmacologic approach is triple therapy, combining a bismuth salt, metronidazole, and amoxycillin or tetracycline.

The role of Helicobacter pylori infection in causing chronic dyspepsia is in need of further clarification. More well-designed prospective studies are necessary to ascertain whether and to what extent H. pylori-related chronic inflammation in the stomach and the duodenum causes dyspeptic symptoms; whether and to what extent there is a symptom cluster characteristic for H. pylori-related gastroduodenitis; whether and to what extent H. pylori infection is demonstrable in the chronic dyspeptic population; and whether and to what extent H. pylori infection interferes with gastrin homoeostasis and acid secretion or induces motor disturbances. Well-designed prospective H. pylori-eradication studies may further contribute in unravelling its role in chronic dyspepsia, especially in patients with active polymorphonuclear gastroduodenitis and hyperacidity.

In almost all patients with genuine nondrug-induced duodenal or gastric ulcer there is evidence of gastric Campylobacter pylori colonization and concomitant inflammation. C. pylori is only demonstrable in the duodenal cap when there is "gastric mucus metaplasia." Suppression or eradication of C. pylori with antibiotic therapy may accelerate duodenal ulcer healing. The relapse rate of duodenal ulcer is less after temporary clearing or permanent eradication of C. pylori. As eradication of C. pylori reduces or eliminates gastric (and duodenal) inflammation, this renders the gastroduodenal mucosa less susceptible to reulceration. Interference with C. pylori status presumably explains the retardation of relapse of duodenal ulcer healing with colloidal bismuth subcitrate.

A patient is presented with Zollinger-Ellison syndrome, in whom spontaneous disappearance of gastric hypersecretion and peptic ulcer disease occurred subsequent to an intercurrent illness causing acute nonspecific inflammation of the gastric mucosal lining. The dramatic clinical improvement after subsiding of the intercurrent illness was obviously linked to pronounced failure of the parietal cell mass for acid secretion and not to infarction of the gastrinoma because gastrin secretion by the tumor was unchanged.

To determine the clinical importance of Campylobacter pyloridis infection, its association with gastric inflammation, and the response to drug therapy, patients with a duodenal or gastric ulcer (n = 63), patients with nonulcer dyspepsia (n = 240), and asymptomatic volunteers (n = 34) were studied. In a prospective longitudinal study, the type, intensity, and distribution of inflammation in antral biopsy specimens were correlated with the presence of C. pyloridis. Campylobacter pyloridis was cultured from antral biopsy specimens in 98% of the ulcer patients, 70% of the nonulcer dyspepsia patients, and 20% of the asymptomatic volunteers. The dependency of chronic active gastritis on the presence of C. pyloridis was shown by an association of gastritis with positive culture and healing of gastritis with negative culture after various therapeutic regimens. Spontaneous disappearance of C. pyloridis never occurred. Colloidal bismuth subcitrate, amoxicillin, and the combination of colloidal bismuth subcitrate and amoxicillin were effective therapies in eradicating C. pyloridis. Recolonization with the same bacterial subtype and recurrence of gastritis frequently occurred within 1 mo after initial eradication. In this study we demonstrate ultimate normalization of gastric mucosa after successful eradication of C. pyloridis. Especially complete normalization of gastric mucosa after amoxicillin monotherapy provides additional strong evidence for a true cause-effect relationship between C. pyloridis colonization and gastritis.

Postgastrectomy biliary reflux gastritis is quite common. Several drugs have been used in its treatment, including the bile acid-binding resin cholestyramine, which seemed ineffective, possibly because of its rapid disappearance from the gastric remnant. It was suggested that by using alginates, which form a raft floating on the gastric contents, cholestyramine would be retained in the stomach for a longer period. 32 patients received either placebo or cholestyramine/alginates/bicarbonate (CAB). Gastroscopy with biopsies, laboratory studies and physical examination were performed before and after the trial. A two week intervals patients were interviewed about the effect on symptoms. A detailed Y-ray study was made of 5 patients, in which a series of pictures was taken after ingestion either of placebo or CAB together with a novel contrast medium. There was no statistical difference between treatment groups with respect to symptoms, gastroscopy or histological findings, nor did the X-ray study show any difference in retention time between placebo and CAB.

The pathophysiology of gastric ulcer and gastritis has been related to an increase in damaging factors such as duodeno-gastric reflux and anti-inflammatory drugs. A decreased capacity for mucosal prostaglandin generation is highly likely. Acid secretion is usually normal or even reduced. Colloidal bismuth subcitrate (CBS) has been shown to increase gastric mucosal defence. In controlled trials a clear superiority over placebo has been demonstrated. Amalgamation of the data shows an average healing rate of about 70% in gastric ulcer, which is statistically significantly higher than that for cimetidine in comparative trials. The therapeutic gain (the difference between the healing rate of drug and placebo in a direct comparison) of CBS is high compared with other anti-ulcer agents. In campylobacter gastritis we have shown that the microorganism is very sensitive to CBS, and its eradication results in histological improvement.

Worldwide Campylobacter pylori is a major cause of active chronic gastritis in man. This curved spiraled microorganism can readily be detected within the mucusgel especially in the antrum, in particular in patients suffering from peptic ulcer disease or non-ulcer dyspepsia, rarely in individuals with normal gastroduodenal mucosa. Increasingly arguments are being presented in support of a pathogenetic role of C. pylori in non-ulcer dyspepsia and in peptic ulcer disease. There is a striking discordance between in vitro antibiotic sensitivity, and in vivo efficacy with respect to suppression or eradication of the organism. At present the combination of colloidal bismuth subcitrate and amoxicilline or tinidazole appears to be encouraging with respect to longterm eradication of this peculiar microorganism. Eradication by antibacterial treatment ultimately may result in histologic normalization of the gastric mucosa. To what extent peptic ulcer disease. There is a striking discordance between in vitro antibiotic sensitivity, and in.

14C-urea breath test was used to detect Campylobacter pylori colonisation in 129 consecutive non-ulcer dyspepsia patients. Fasting patients were given 3 microCi (110 kBq) of 14C-labelled urea after a test meal. Breath samples were collected at 10 minute intervals for 90 minutes and the C-14 activity was counted on a liquid scintillation analyser. Urea derived 14CO2 appears in the exhaled breath of Campylobacter pylori culture positive individuals within 20-30 minutes. Likelihood analysis revealed a most favourable cut off level of [0.07% dose 14C-urea/mmol CO2] multiplied by body weight at t = 40 minutes, to separate culture positive from culture negative subjects. Using this upper limit of normal, a positive likelihood ratio of 50 and a negative likelihood ratio of 0.05 was calculated. Sensitivity of the test was 95% and specificity 98%. The 14C-urea breath test is a simple, sensitive and non-invasive test, that detects viable C pylori microorganism and semiquantitatively assesses the bacterial load of C pylori colonisation. Administration of a single dose of colloidal bismuth subcitrate resulted in a rapid decrease in 14CO2 excretion, so this test can be used to confirm eradication of the bacterium in therapeutic trials without endoscopy, or need for culture.

Campylobacter pylori may cause type B gastritis. C. pylori produces urease, and the presence of this enzyme in gastric mucosal biopsies is a marker for colonization with the microorganism. The value of a breath test to detect C. pylori colonization in non-ulcer dyspepsia patients was investigated. We compared the 14C-urea breath test with the culture results obtained from antral mucosal biopsies. The 14C-urea breath test is comparable to culture results in detecting C. pylori colonization.

Excessive Enterogastric reflux following partial gastrectomy is believed to be responsible for bilious regurgitation, vomiting, nausea, and epigastric pain. At endoscopy, striking erythema and inflammatory changes of the gastric mucosa may be seen. The nonsurgical treatment for this syndrome is unsatisfactory. Because of the potential pathogenetic role of regurgitating bile acids, lysolecithin, and pancreatic secretions, it seemed relevant to find out whether prostaglandin E2 (PGE2) in a dose of 0.5 mg qid could protect the gastric mucosa from further damage and thereby lead to symptomatic improvement. The results of this controlled doubled-blind crossover trial, comparing PGE2 and placebo, in the treatment of postgastrectomy reflux gastritis reveal no significant differences between PGE2 and placebo with regard to symptoms, endoscopic features, and histologic evidence of inflammatory changes. Thus, prostaglandin E2 in the dose used appears incapable of improving postgastrectomy reflux gastritis in patients with mild to moderate degrees of this entity.