Molecular characterization of bacterial colonization in the preterm and term infant's intestine.

OBJECTIVE: To further define patterns of colonising intestinal microflora in newborn infants utilising molecular methods. METHODS: Ten term and 5 preterm (<32 wk) infants born at the Royal Hospital for Women, Sydney, Australia were enrolled in the present study and followed for 6 mo post partum. Serial stools were collected, DNA was extracted and subjected to PCR-Denaturing Gradient Gel Electrophoresis using a range of primers and sequencing. The effect of gestational length, feeding and delivery method was compared to the pattern of bacterial acquisition. RESULTS: Intestinal bacterial diversity was lower in preterm compared with term infants. For term infants, bacterial DNA detection rates were not associated with feeding or delivery method, although Enterobacteria and Clostridia were commonly identified. The detection rate of Bifidobacteria was lower in preterm infants than term infants. Potential pathogens were detected in preterm infant samples. CONCLUSIONS: Preterm infants frequently have aberrant bacterial colonization of the intestine. Further research is now required to determine if this may contribute to adverse health outcomes.

Sustained modulation of intestinal bacteria by exclusive enteral nutrition used to treat children with Crohn's disease.

BACKGROUND: The use of exclusive enteral nutrition to treat paediatric Crohn's disease (CD) is widely accepted, although the precise mechanism(s) of action remains speculative. AIM: To investigate the changes to key intestinal bacterial groups of Eubacteria, Bacteroides, Clostridium coccoides, Clostridium leptum and Bifidobacteria, during and after exclusive enteral nutrition treatment for CD in paediatric patients and correlate these changes to disease activity and intestinal inflammation. METHODS: Stool was collected from six children at diagnosis of CD, during exclusive enteral nutrition and 4 months post-therapy, and from seven healthy control children. The diversity of bacteria was assessed by polymerase chain reaction-denaturing gradient gel electrophoresis with changes to bacterial diversity measured by Bray-Curtis similarity, intestinal inflammation assessed by faecal S100A12 and the disease activity assessed by PCDAI. RESULTS: A significantly greater change in intestinal bacterial composition was seen with exclusive enteral nutrition treatment compared with controls. Further, the intestinal bacteria remained altered 4 months following exclusive enteral nutrition completion. Changes in the composition of Bacteroides were associated with reduced disease activity and inflammation. CONCLUSIONS: Exclusive enteral nutrition reduces bacterial diversity and initiates a sustained modulation of all predominant intestinal bacterial groups. Exclusive enteral nutrition may reduce inflammation through modulating intestinal Bacteroides species. The implications of these results for exclusive enteral nutrition therapy and CD pathogenesis should now be the subject of further investigation.

Management guidelines for Helicobacter pylori infection: utilization by paediatric gastroenterologists in Australasia.

OBJECTIVE: Although there are published guidelines representing the consensus of several large groups, it is unclear whether these are used by practitioners in the management of Helicobacter pylori infection in children and if the guidelines are relevant to particular regions of the world. The aim of this study was to answer these questions in regard to the Australasian region. METHODS: An email-based questionnaire was circulated to Australasian paediatric gastroenterologists to ascertain aspects of practice related to H. pylori infection in children and to review practitioner awareness and use of the guidelines. RESULTS: Twenty-five (78%) of 32 questionnaires were completed. Current practice reported by the respondents followed the principles of the published guidelines. However, only 15 gastroenterologists were aware of the guidelines: a number of these practitioners were uncomfortable adapting the published guidelines to their local situation. CONCLUSIONS: Although widely distributed in the paediatric gastroenterology literature, guidelines for management of H. pylori infection may not be utilized fully by individual practitioners. As these guidelines are updated, based upon current developments in the understanding of H. pylori disease, attempts should be made to ensure that such documents are widely distributed to practitioners and that they reflect regional variations in disease patterns.

Clinical and pathological implications of IgG antibody responses to Helicobacter pylori and its virulence factors in non-ulcer dyspepsia.

AIM: To determine whether pre-treatment antibody response to Helicobacter pylori virulence factors predicts eradication success and symptom relief 12 months after triple therapy in non-ulcer dyspepsia. METHODS: H. pylori-positive patients with non-ulcer dyspepsia received 1-week omeprazole-based triple therapy, or omeprazole plus placebos. Symptoms were assessed using a validated Likert scale. Gastric biopsies taken before and 12 months after treatment were used for histological examination. Pre-treatment blood samples were used for the detection of anti-H. pylori immunoglobulin G (IgG) antibodies, and specific IgG antibodies to 19.5-, 26.5-, 30-, 35-, 89- (VacA) and 116-kDa (CagA) antigens of H. pylori. RESULTS: IgG antibodies to the six antigens were detected in 62%, 96%, 88%, 47%, 54% and 78% of patients, respectively. The presence of antibody to 19.5-, 26.5- or 30-kDa antigen was associated with an increased anti-H. pylori IgG absorbance index. IgG absorbance indices were greater in those with H. pylori eradication (vs. persistent infection). The prevalence of antibodies to the six antigens was not significantly different between those with symptom relief vs. those without. The 19.5-kDa antigen (P = 0.018) and VacA (P = 0.001) were independent risk factors for body gastritis. CONCLUSIONS: An increased pre-treatment anti-H. pylori IgG absorbance index may be a useful predictor of the success of eradication therapy. Although the 19.5-kDa antigen and VacA were associated with body gastritis, none of the six antigens tested predicted symptom relief after triple therapy.

Major differences in the IgG subclass response to Helicobacter pylori in the first and third worlds.

BACKGROUND: Studies in developed countries would suggest that the immune response to Helicobacter pylori infection is a T helper cell I predominant response. Unlike subjects from developed countries, those resident in developing countries are subject to infection with a myriad of gastrointestinal pathogens from early in life. Given that H. pylori is acquired early in life, such infections may alter the immune response to H. pylori. The aim of this study was to compare the immune response to H. pylori in subjects from developed and developing countries. METHODS: Using a previously validated IgG subclass ELISA, the H. pylori specific IgG I/IgG2 subclass ratio (a marker of the T helper cell response) in 58 adult and 21 paediatric symptomatic H. pylori positive Sowetan subjects was compared with that in 64 Australian and 45 German symptomatic H. pylori positive subjects. RESULTS: An IgGI predominant response (IgG1/IgG2 ratio >1) was observed in 81% of Sowetan adults and 90% of children compared with 4.7% of Australians and 4.4% of Germans. The IgG1/IgG2 ratio was significantly higher in Sowetans compared with Australians and Germans (P < 0.001). In Australian and German subjects the IgG1/IgG2 ratio was significantly higher in NUD compared with DU. No significant difference was observed between NUD and other disease states in Sowetans. CONCLUSIONS: This study is the first to provide evidence that the host immune response to H. pylori infection in an African population differs to that observed in subjects from developed countries. Further studies are required to determine if this occurs in other developing countries.

Association between the IgG subclass response, inflammation and disease status in Helicobacter pylori infection.

BACKGROUND: In many viral, bacterial and parasitic infections the Immunoglobulin G (IgG) subclass response has been shown to correlate with severity of inflammation and disease outcome. The aim of the present study was to investigate the association between the IgG subclass response to Helicobacter pylori infection and disease and inflammation. METHODS: Eighty-three symptomatic patients undergoing endoscopic examination were included in the study. Upon endoscopic examination, the presence of ulceration was noted and biopsy specimens were collected from the gastric antrum, body and transitional zone. Blood was also collected from each patient. Gastric biopsy sections were graded using the Sydney system. H. pylori specific IgG, IgG1, IgG2, IgG3 and IgG4 were measured by ELISA. The IgG subclass was also examined retrospectively in sera collected from 20 patients previously proven to have duodenal ulcer (DU). RESULTS: The results of histological examination and IgG serology showed 35 subjects to be H. pylori negative and 48 to be H. pylori positive. Of the 48 H. pylori positive subjects, 25 were diagnosed with functional dyspepsia (FD), 14 with current DU and 9 with evidence of past DU. Significantly higher levels of IgG2 antibodies were found in patients with DU as compared with patients with FD (P < 0.01). In addition, significantly higher IgG3 subclass antibody levels were associated with chronic inflammatory cells in the body (P < 0.05) and active inflammatory cells in the transitional zone (P < 0.01). A significantly increased level of IgG1 antibodies was associated with lower levels of colonization in the gastric antrum. CONCLUSION: The results of this study suggest that the IgG subclass response in subjects infected with H. pylori may be a marker of DU disease as well as increased levels of inflammation.

Can helicobacter pylori serology still be applied as a surrogate marker to identify peptic ulcer disease in dyspepsia?

BACKGROUND: Helicobacter pylori infection and associated peptic ulcer disease (PUD) has become less common in some countries. AIM: To determine if H. pylori serology alone or combined with a history of ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) and an age threshold can be used as an indirect ulcer test. METHODS: Two hundred and fifty-two consecutive Australian patients (121 males, mean age 52 years) referred for endoscopy were enrolled. Blood was tested by a validated ELISA. At endoscopy, eight biopsies were taken for CLO-testing, culture and histology. NSAID use over the prior 3 months was recorded. RESULTS: One hundred and six (42%) patients were seropositive for H. pylori, 48 (19%) patients had PUD and 30 (12%) used NSAIDs. Serology alone had a sensitivity of 52% and a specificity of 60% for identifying PUD; the sensitivity and specificity were 60% and 55%, respectively, when combined with a history of NSAID use. Serology, regardless of NSAID use, would have saved 23% in endoscopy workload but would have missed 17% of PUD cases if an age threshold of < 45 years was chosen for omitting endoscopy. CONCLUSIONS: Serology was a poor ulcer test despite an excellent performance for detecting H. pylori. A strategy combining serology and an age threshold with a history of NSAID use to reduce endoscopy workloads may not always be appropriate.

Antral-type mucosa in the gastric incisura, body, and fundus (antralization): a link between Helicobacter pylori infection and intestinal metaplasia?

OBJECTIVES: Helicobacter pylori is a carcinogen; gastric carcinoma involves a multistep process from chronic gastritis to atrophy, intestinal metaplasia, and dysplasia. The aims of this study were to determine the types of mucosa at different gastric sites in H. pylori-infected and uninfected patients, and whether the presence of antral-type mucosa in the incisura, body, and fundus is associated with gastric atrophy and intestinal metaplasia. METHODS: Two hundred and sixty-eight patients with dyspepsia were enrolled. Eight biopsies (i.e., antrum x3, body x2, fundus x2, and incisura x1) were obtained. One antral biopsy was used for the CLO-test. Three (each from the antrum, body, and fundus) were cultured. The remaining biopsies were examined histologically according to the updated Sydney System after staining with hematoxylin and eosin and Giemsa. A validated serological test was also applied. RESULTS: Overall, 113 (42%) patients were infected with H. pylori. At the incisura, antral-type mucosa was more prevalent in infected than in uninfected patients (84% vs. 18%; odds ratio [OR] = 23.9, 95% confidence interval [CI] 12.5-45.8; p<0.001). Atrophic gastritis and intestinal metaplasia at the incisura was present in 19.5% and 13.3%, respectively, of infected, and 4.5% and 3.2%, respectively, of uninfected patients (both p<0.01). Moreover, atrophic gastritis at the incisura was associated with the presence of antral-type mucosa at the site (termed antralization); the prevalence of atrophic gastritis was 19.5% (24/123) in the presence of antralization, whereas the rate was 2.1% (3/145) without antralization (OR = 11.4, 95% CI 3.4-39.2; p<0.001). Similarly, at the incisura, 16.3% (20/123) of "antralized" cases and 1.4% (2/145) of "unantralized" cases had intestinal metaplasia (OR = 13.8, 95% CI, 3.2-60.7; p<0.001). The association between antralization at gastric body and fundus also appeared to be associated with atrophic gastritis and intestinal metaplasia at these sites. CONCLUSIONS: Atrophic gastritis and intestinal metaplasia occurs predominantly at the gastric antrum and incisura with H. pylori infection. Antralization of the gastric incisura is a common event in H. pylori-infected patients, and appears to be associated with an increased risk of atrophic gastritis and intestinal metaplasia.

The prevalence of antibody to CagA in children is not a marker for specific disease.

BACKGROUND: In adults, a high prevalence of antibody to the cytotoxin-associated antigen (CagA) of Helicobacter pylori has been linked to the development of more serious gastroduodenal disease. Few investigators have examined this association in children. The purpose of this study was to investigate the seroprevalence of antibody to the CagA antigen as well as other specific H. pylori antigens in children. METHODS: By use of an immunoblot analysis kit, the immune response to specific H. pylori antigens in serum collected from 21 H. pylori-positive symptomatic Australian children, 5 with peptic ulcer disease and 16 with nonulcer dyspepsia, and 33 H. pylori-positive asymptomatic Chinese children. Sera from 20 H. pylori-negative symptomatic Australian children were used as control subjects. RESULTS: Antibody responses to the 26.5-kDa, 30-kDa, and 116-kDa (CagA) antigens were found to be the most prevalent, with 81.5%, 79.6%, and 76% of children, respectively, mounting a response. In contrast, antibody responses to the 19.5-kDa, 35-kDa, 45-kDa, 60-kDa, 89 kDa (VacA), and 180-kDa antigens occurred in 55.5%, 24%, 16.7%, 63%, 37%, and 7.4% of children, respectively. A higher prevalence of antibody response to CagA was found in the symptomatic Australian children with peptic ulcer disease (100%) compared with prevalence in those with nonulcer dyspepsia (56.3%), but the difference did not reach statistical significance. No significant difference was found between the prevalence of antibody to CagA in the Australian peptic ulcer disease group (100%) and that in the asymptomatic Chinese children (81.8%). CONCLUSION: These results suggest that in children CagA is not a marker of specific disease development.

A low rate of reinfection following effective therapy against Helicobacter pylori in a developing nation (China).

BACKGROUND & AIMS: In developed countries, reinfection after successful eradication of Helicobacter pylori appears unusual. High prevalences of H. pylori in developing countries may result in high reinfection rates. The aim of this study was to determine the rate of reinfection and ulcer recurrence in Chinese patients cured of H. pylori and duodenal ulcer disease. METHODS: One hundred eighty-four patients with duodenal ulcer disease shown by endoscopic examination (1 month) and 14C-urea breath test (3 months) after termination of treatment to have cleared their H. pylori were investigated. Patients were followed up by endoscopy (12 and 24 months) and breath test (6, 9, 12, 18, and 24 months). H. pylori status at endoscopic examination was determined by rapid urease, histology, and culture. In reinfected patients, random amplification of polymorphic DNA fingerprinting was used to compare isolates before and after therapy. RESULTS: Four patients were reinfected with H. pylori over 24 months (3 within 6 months and 1 at 24 months; average annual recurrence rate, 1.08%). Fingerprinting of isolates from 3 patients showed 1 patient (6 months) to have identical strains and the remainder to have nonidentical strains before and after treatment. Ulcer relapse occurred in 6 patients (4 H. pylori positive). CONCLUSIONS: Reinfection with H. pylori is rare in developing countries where treatment is effective.

Influence of a proton pump inhibitor-based therapy on Helicobacter pylori strain selection.

The influence of the proton pump inhibitor lansoprazole on strain diversity in Helicobacter pylori infected patients was investigated. Multiple isolates of Helicobacter pylori obtained pre- and post-therapy from gastric antral and body biopsies in 22 patients were compared using the random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) for analysis. Post-therapy strains exhibiting novel RAPD-profiles were found in 5 of 22 patients (4 of 11 patients treated with lansoprazole alone and 1 of 11 patients treated with lansoprazole plus amoxicillin). Proton pump inhibition may affect the microecology of the stomach by influencing the colonisation patterns of specific strains.

Genetic relationship among isolates of Helicobacter pylori: evidence for the existence of a Helicobacter pylori species-complex.

We investigated the population genetics of 23 isolates of H. pylori by allozyme electrophoresis using 16 enzyme loci. Isolates were obtained from adult patients of whom 48% were of Greek extraction. Eight patients (35%) had an active duodenal ulcer. Allelic variation per loci ranged from 2 to 11 alleles. Four major genetic clusters were apparent, having > 75% fixed genetic differences. There was no distinct clustering (clonal structure) on the basis of the geographical origin of the persons from whom isolates were obtained, indicating that this bacterium has not recently jumped a species barrier into humans. Isolates associated with ulcer disease were not monophyletic, with isolates from ulcer patients being found in phylogenetically diverse branches of the dendogram derived from the data. Based on the genetic diversity of H. pylori isolates, we propose that isolates should be classified as belonging not to a single species but to a 'Helicobacter pylori species-complex'.

Lansoprazole and amoxycillin: observations on the treatment of Helicobacter pylori infection.

Symptomatic patients (n = 101) with Helicobacter pylori infection were enrolled into a double-blind, double-dummy study to assess the efficacy of lansoprazole plus amoxycillin in the treatment of H. pylori infection. Patients were randomized to either lansoprazole 30 mg once daily (days 0-28) together with placebo (matched to amoxycillin) three times a day (days 0-14) followed by either placebo or amoxycillin 500 mg three times daily (days 15-28). Biopsy specimens for culture and histology were collected on days 0 and 56 or upon symptomatic relapse. Blood for serology was collected at days 0, 56 and 168. A [14C]-urea breath test was performed on day 168. Eighty-one (80.2%) patients completed the 56 day assessment. Of patients treated with lansoprazole plus amoxycillin, 35.1% (13/37) were cured of infection as assessed at day 56 (26.5% on an intention-to-treat basis), compared with 4.8% (2/42) of the placebo group (4% on an intention-to-treat basis). Recrudescence/re-infection occurred in one patient upon re-evaluation at day 168. Analysis of prognostic factors indicated that smoking and alcohol intake had little impact on the treatment outcome. Inflammation (both acute and chronic) improved in patients treated with lansoprazole plus amoxycillin. The relatively low efficacy of the treatment may relate to a single daily dose of lansoprazole (30 mg) being prescribed, treatment with amoxycillin being commenced 2 weeks after the initiation of lansoprazole or accurate assessment of treatment efficacy (both antral and body biopsy specimens taken).

Serological response to specific Helicobacter pylori antigens: antibody against CagA antigen is not predictive of gastric cancer in a developing country.

OBJECTIVES: In symptomatic patients resident in developed countries, a high prevalence of antibody to the cytotoxin-associated antigen (CagA) of Helicobacter pylori has been linked to the development of peptic ulcer disease and gastric cancer. This association has not been examined in developing countries, nor in asymptomatic subjects resident in either developed or developing countries. The aim of this study was to examine the seroprevalence of antibody to the CagA antigen; as well as other specific H. pylori antigens in symptomatic and asymptomatic individuals resident in Australia and China. METHODS: The Helico-blot 2.0 Western blot system was used for the detection of antibodies to specific antigens of H. pylori in sera obtained from the following H. pylori-positive groups: 19 Australian blood donors, 96 Australian nonulcer dyspepsia patients, 29 Australian duodenal ulcer patients, 35 asymptomatic Chinese subjects, and 48 Chinese gastric cancer patients. RESULTS: Nine antigens were commonly recognized by sera from Australian and Chinese subjects. These antigens were of molecular mass 19.5 kDa, 26.5 kDa, 35 kDa, 45 kDa, 60 kDa, 89 kDa (VacA), 116 kDa (CagA), and 180 kDA. A significant association between the prevalence of antibody to the CagA antigen and duodenal ulcer disease was observed in Australian subjects; however, no association between the prevalence of antibody to the CagA antigen and gastric cancer was found in Chinese subjects. In subjects from both countries, a significant association was found between antibody to the 30-kDa and 45-kDa antigens and more serious gastroduodenal disease. CONCLUSION: The results of this study suggest that the cagA gene is not associated with the development of more serious gastroduodenal disease; however, it cannot be ruled out that this gene may be an important but insufficient factor in some disease processes.

Multiple strain colonization and metronidazole resistance in Helicobacter pylori-infected patients: identification from sequential and multiple biopsy specimens.

Helicobacter pylori strain diversity was investigated in infected persons by collection of multiple biopsies before and after therapy failure. It was demonstrated by random amplification of polymorphic DNA polymerase chain reaction that patients may be infected with a mixed population of H. pylori strains. Most patients were colonized with a predominant strain accompanied by up to 5 variant strains. The use of antimicrobials resulted in an altered distribution of the strains present, but the predominant strain usually remained. Patients may be infected with a mixed population of metronidazole-sensitive and -resistant strains at one time, with metronidazole-based therapy selectively enriching for a resistant population.

Antigen recognition during progression from acute to chronic infection with a cagA-positive strain of Helicobacter pylori.

We have previously published two reports on acute infection with Helicobacter pylori, one of an adult male and one of a family of four. In the present study, we have isolated H.pylori from each of twin boys in the family and compared these by use of random amplified polymorphic DNA PCR. In addition, we have monitored the antibody response over time of the family and the adult male by Western blotting (immunoblotting) with two different strains of H. pylori as the antigen and by use of a commercial kit. The acutely infected twin boys were infected by an identical strain of H. pylori. The twin boys responded to antigens of 19, 26.5, and 29 kDa 30 days after the initial diagnosis, with recognition of 43-to 49-, 66-, 69-, and 87-kDa antigens by day 63. One twin responded to the CagA antigen on day 63, whereas the other responded on day 857. Antibody to the CagA antigen was not detected by use of the infecting strain, UNSW-RU1. Investigation of UNSW-RU1 revealed the presence of cagA. In two acutely infected adults (one, the father of the boys), the initial response to a 45-kDA antigen was later followed by responses to 19-, 29-, 49-, 60-, 77-, and 84-kDa antigens. Sera from the twins' younger sister, born 17 months after the twins acute episode, indicated that she also had become infected. This report supports intrafamilial transmission of H. pylori. Initial antibody responses in the children were to small-molecular-size antigens; in the adults, the initial responses were to larger-molecular-size antigens. The pattern of the serological response differs according to the antigen used. This has implications in regard to international data comparisons.

Gastric atrophy and regional variation in upper gastrointestinal disease.

OBJECTIVE: To compare the upper gastrointestinal disease profiles of Helicobacter pylori-infected patients drawn from two distinct regions of China, one with a low incidence of gastric cancer (Guangzhou) and the other with a high incidence of gastric cancer (Lanzhou). The age-standardized prevalence of H. pylori within the populations of these two cities was similar (approximately 56%). In these patient groups, the prevalence of different gastrointestinal disease states and the occurrence and severity of gastritis, gastric atrophy, and intestinal metaplasia were compared. METHODS: This study was based on consecutive patients: 265 from Guangzhou and 275 from Lanzhou. The grading of gastritis and the detection of H. pylori was determined by histology using the "Sydney System". RESULTS: The ratio of cases of duodenal to gastric ulceration for the two cities was: Guangzhou 14:1 and Lanzhou 3:1. Gastric cancer was more prevalent in the patients from Lanzhou (9.8%) than from Guangzhou (3%). In nonulcer dyspepsia patients from Guangzhou, gastritis was predominantly antral, whereas, in Lanzhou, gastritis was predominantly uniform. The amount and severity of atrophy was significantly greater in Lanzhou compared with Guangzhou. CONCLUSIONS: The prevalence of atrophy, rather than age of acquisition and prevalence of H. pylori infection, appears to be a marker of the major upper gastrointestinal disease profiles of a region. Development of atrophy, although apparently related to H. pylori infection, may be a multifactorial condition. Differences in diet, as seen between Guangzhou and Lanzhou, may be important in this regard. Understanding the factors leading to the development of atrophy may enhance our understanding of processes leading to gastric malignancy.

Helicobacter pylori associated with a high prevalence of duodenal ulcer disease and a low prevalence of gastric cancer in a developing nation.

This study examines the relationship between Helicobacter pylori infection and peptic ulcer disease and gastric cancer--in particular, the presence or absence of bacteria, the grading of gastritis, and the degree of inflammation in the antral and oxyntic mucosae. The grading of gastritis and the detection of H pylori were determined by histology using the Sydney system. Of the 1006 patients examined, 34.5% had duodenal ulcer disease, 3.5% gastric ulcer disease, and 2% with coexistent ulceration. Most patients (50.2%) were classified as having non-ulcer dyspepsia. Altogether 2.4% of patients had gastric cancer and two further patients had carcinoma in the gastric stump. Of the ulcer disease patients, 87.2% had histological evidence of H pylori infection. After patients who had taken antibiotics or bismuth compounds in the preceding four weeks were excluded, 98.9% of the duodenal ulcer disease, 100% of the gastric ulcer disease, and 100% of the coexistent ulcer disease patients had evidence of H pylori infection. In patients with gastric cancer who had not taken antimicrobial agents in the four weeks before endoscopy, 83.3% had evidence of H pylori infection. Thus, there was a high rate of duodenal ulcer disease and a low rate of gastric ulcer disease in southern China, an area of low gastric cancer mortality. There was a specific topographical relationship between H pylori, the histological response, and gastroduodenal disease. Our data suggest that the status of a nation as either 'developed' or 'developing' can not be used to predict the upper gastrointestinal disease profile of its population.