Review article: Helicobacter pylori and gastric adenocarcinoma.

Gastric adenocarcinoma is still the second most common cause of death from cancer, even though it is on the decline in developed countries. Although H. pylori gastritis appears to be a necessary antecedent to the development of gastric adenocarcinoma, it is not a sufficient factor in and of itself. Other required factors for the progression of this disease are poorly understood. Patients with antral predominant gastritis seem protected from the disease, while patients with pangastritis are predisposed to both diffuse- and intestinal-type adenocarcinoma. Development of a vaccine against H. pylori might yield promising results in decreasing the incidence of gastric adenocarcinoma.

Acute gastritis with hypochlorhydria: report of 35 cases with long term follow up.

BACKGROUND: Between 1976 and 1987, 35 cases of acute gastritis with hypochlorhydria (AGH) were seen in our research laboratory. The aims of this study were to determine the natural history of AGH and the role of Helicobacter pylori in its pathogenesis. METHODS: Archived serum and gastric biopsy samples obtained from AGH subjects were examined for evidence of H pylori colonisation. Twenty eight of 33 (85%) surviving AGH subjects returned a mean of 12 years after AGH for follow up studies, including determination of H pylori antibodies, basal and peak acid output, endoscopy, and gastric biopsies. A matched control group underwent the same studies. RESULTS: Archived material provided strong evidence of new H pylori acquisition in a total of 14 subjects within two months, in 18 within four months, and in 22 within 12 months of recognition of AGH. Prevalence of H pylori colonisation at follow up was 82% (23 of 28) in AGH subjects, significantly (p<0.05) higher than in matched controls (29%). Basal and peak acid output returned to pre-AGH levels in all but two subjects. CONCLUSIONS: One of several possible initial manifestations of H pylori acquisition in adults may be AGH. While H pylori colonisation usually persists, hypochlorhydria resolves in most subjects.

Helicobacter pylori-related disease: guidelines for testing and treatment.

OBJECTIVE: To develop practical guidelines for the treatment of patients with suspected and documented Helicobacter pylori-related gastroduodenal diseases. METHODS: A panel of physicians with expertise in H. pylori reviewed, critically appraised, and synthesized the literature on assigned topics and presented their overviews to the panel. Consensus was obtained in controversial areas through discussion. RESULTS AND CONCLUSIONS: The panel recommended testing for H. pylori in patients with active ulcers, a history of ulcers, or gastric mucosa-associated lymphoid tissue lymphomas. Young, otherwise healthy patients with ulcerlike dyspepsia and those with a family history or fear of gastric cancer may also undergo H pylori testing. Non-endoscopic methods are preferred for H. pylori diagnosis. Dual medication regimens should not be used for therapy; twice-daily triple therapy with a proton pump inhibitor or ranitidine bismuth citrate, clarithromycin, and amoxicillin for 10 to 14 days is an appropriate therapy. Posttreatment assessment of H. pylori status using urea breath testing should be considered in patients with a documented history of ulcer disease or with persistent symptoms.

"Familial hyperpepsinogenemia" and Helicobacter pylori infection.

OBJECTIVE: Pepsinogen 1 (PG1) is a proenzyme precursor to pepsin, a protease secreted by the gastric chief cell. PG1 levels correlate with maximal gastric acid output. In 1979, Rotter et al. reported two pedigrees in which elevated PG1 levels and duodenal ulcers were prevalent. They proposed autosomal dominant inheritance of elevated PG1 and suggested that it was a risk factor for duodenal ulcer disease. In 1982, Helicobacter pylori (Hp) was discovered and was shown to be an important factor in peptic ulcer disease. Hp infection is also associated with increased PGI levels. We tested serum from one of the original pedigrees for Hp antibodies to determine whether Hp infection could explain the ulcers and elevated PG1 levels. METHODS: ELISA tests were performed using the urease fraction of a crushed Hp extract. Banked serum from one of the original families was thawed and tested. RESULTS: Of the subjects, 90% (nine of 10) with elevated PG1 were seropositive for Hp, compared to only 31% (17 of 55) of those with normal PG1 levels (p < 0.001). The mean PG1 level was higher in the seropositive (94.1+/-13.3 ng/ml) than the seronegative subjects (54.8+/-3.6, p < 0.05). Three of the four subjects with ulcers were Hp-seropositive. The prevalence of Hp-seropositivity and elevated PG1 declined in parallel in each successive generation. When neither parent was seropositive, children were seronegative. CONCLUSIONS: The etiology of elevated PG1 levels in this pedigree is more likely due to Helicobacter pylori infection than to a genetic predisposition.

Review article: the management of Giardiasis.

Giardiasis is the intestinal infection resulting from infestation with the human parasite Giardia intestinalis, also called Giardia lamblia. The infection may be asymptomatic or present with a variety of symptoms such as diarrhoea, weight loss, abdominal cramps, and failure to thrive. Giardiasis is most often diagnosed after recent travel or in day care centres. The organism has two stages in its life cycle. It is usually ingested as a cyst with as few as 10-25 cysts being sufficient to cause infection. After excystation, the organism is a replicative trophozoite which may attach to the small bowel wall. Giardia intestinalis does not invade the bowel wall. Trophozoites may encyst and be shed in faeces for future ingestion by another host. Diagnosis of infection is by stool examination which may also eliminate other possible infectious agents. Small bowel biopsy may be necessary in difficult individual cases or to rule out non-infectious illnesses, and stool ELISA may serve for large population screening examinations. The mainstay of treatment is metronidazole 250-400 mg three times per day by mouth for 5 days.

Eradication of Helicobacter pylori infection after ranitidine bismuth citrate, metronidazole and tetracycline for 7 or 10 days.

BACKGROUND: We assessed the efficacy, tolerance, and compliance of twice-daily triple therapy for Helicobacter pylori with ranitidine bismuth citrate, metronidazole and tetracycline for 7 or 10 days. METHODS: 105 subjects with H. pylori infection documented by the 13C-urea breath test were randomly assigned to a 7 or 10-day course of ranitidine bismuth citrate 400 mg b.d., metronidazole 500 mg b.d. and tetracycline 500 mg b.d. Subjects returned at the end of therapy for assessment of side-effects and pill count. A repeat 13C-urea breath test was obtained 4 or more weeks after completion of therapy and cure of infection was defined as a negative test result. RESULTS: Poor compliance (< 80% of medications) was seen in 2% of subjects randomized to 7 days of therapy and in 10% randomized to 10 days of therapy (P = N.S.). Intention-to-treat eradication rates were 56% for 7-day and 60% for 10-day therapy (P = N.S.). Per protocol eradication rates were 58% for 7-day and 61% for 10-day therapy (P = N.S.). The 10-day intention-to-treat eradication rate for males was 78% and 32% for females (P < 0.01) and per protocol eradication rates were 79% and 31%, respectively (P < 0.01). CONCLUSIONS: Despite excellent compliance and tolerance, neither 7 nor 10 days of therapy with twice-daily ranitidine bismuth citrate, metronidazole and tetracycline are adequate as a treatment of H. pylori infection.

Reduction of pain-related behaviors with either cold or heat treatment in an animal model of acute arthritis.

OBJECTIVE: To assess the effects of heat and cold on quantifiable pain behaviors in an animal model of arthritis that minimizes the motivational-affective component of pain. DESIGN: The effects of superficial heat (40 degrees C) and cold (4 degrees C) on pain behaviors in rats with knee joint inflammation were tested before and after induction of inflammation and after treatment with heat or cold. SUBJECTS: Joint inflammation was induced in male Sprague-Dawley rats by intra-articular injection of the knee joint with 3% kaolin and 3% carrageenan. MAIN OUTCOME MEASURES: Withdrawal latency to heat applied to the paw (PWL) assessed secondary hyperalgesia; spontaneous pain behaviors assessed degree of weight bearing/ guarding; and joint circumference assessed joint swelling. RESULTS: Cold treatment of the inflamed knee joint significantly reversed the PWL immediately after treatment (p = .003) without affecting spontaneous pain behaviors orjoint circumference. In contrast, heat treatment produced a small but significant decrease in spontaneous pain behaviors (p = .03) without affecting PWL or joint circumference. CONCLUSION: Acute arthritic pain can be treated with either superficial heat for reducing guarding or with cold for reducing pain or hyperalgesia outside the injury site.

Role of seroconversion in confirming cure of Helicobacter pylori infection.

CONTEXT: The role of serologic testing to confirm cure of Helicobacter pylori infection after antimicrobial therapy is not completely defined. OBJECTIVE: To determine the utility of serologic testing in confirming cure of H pylori infection more than 1 year after therapy. DESIGN: A prospective, before-after interventional trial. SETTING: An outpatient clinical research laboratory in an academic, urban Veterans Affairs medical center. PARTICIPANTS: Twenty-three otherwise healthy men and women with active H pylori infection demonstrated by gastric biopsy and with positive H pylori serologic findings. INTERVENTION: A 14-day course of bismuth, tetracycline, and metronidazole. MAIN OUTCOME MEASURES: Determination of IgG serum antibodies to H pylori at baseline, 1 month, 3 months, and approximately 18 months after completion of therapy compared with serial gastric mucosal biopsy specimens with stains for H pylori and for histologic examination as the criterion standard. RESULTS: Fifteen (65%) of 23 subjects were cured of their H pylori infection as assessed by gastric biopsy, with elimination of gastritis; median antibody levels declined from 92.5 U/mL at baseline to undetectable levels at 18 months. The other 8 subjects (35%) were not cured and had persistent gastritis at 18 months; median antibody levels declined from 130.6 U/mL at baseline to 89.7 U/mL at 18 months. Sensitivity and specificity of seroconversion (from a positive to negative test result) in detecting cure of H pylori infection were 60% and 100%, respectively. CONCLUSION: Undetectable antibody levels beyond the first year of therapy accurately confirm cure of H pylori infection in initially seropositive healthy subjects, with reasonable sensitivity.

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study.

INTRODUCTION: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing. AIM: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole. PATIENTS AND METHODS: Patients whose active erosive reflux oesophagitis (grade > or = 2) had healed (grade 0 or 1) after 4-8 weeks of open-label omeprazole 40 mg daily (phase I) were eligible to join a multi-centre, 6-month double-blind, placebo-controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n = 138), 20 mg omeprazole for 3 consecutive days each week (n = 137), or placebo (n = 131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse. RESULTS: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P < 0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3-days-a-week (P < 0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells. CONCLUSIONS: These results show that after healing of erosive oesophagitis with 4-8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.

The role of antisecretory drugs in the treatment of Helicobacter pylori infection.

The efficacy of antibiotics against Helicobacter pylori is enhanced by the co-administration of antisecretory drugs. While proton pump inhibitors appear to have some direct effect on H. pylori and extreme hypochlorhydria has a deleterious effect on the organism, the most likely mechanism by which antisecretory drugs as a class provide this effect is by improving the efficacy of the antibiotics themselves. Although proton pump inhibitors are the most widely used antisecretory agents, H2 receptor antagonists also enhance antibiotic effects.

Ranitidine bismuth citrate plus clarithromycin is effective for healing duodenal ulcers, eradicating H. pylori and reducing ulcer recurrence. RBC H. pylori Study Group.

AIM: To compare the efficacy of the coadministration of ranitidine bismuth citrate plus the antibiotic clarithromycin, with ranitidine bismuth citrate alone or clarithromycin alone for the healing of duodenal ulcers, eradication of H. pylori and the reduction of ulcer recurrence. METHODS: This two-phase, randomized, double-blind, placebo-controlled, multicentre study consisted of a 4-week treatment phase followed by a 24-week post-treatment observation phase. Patients with an active duodenal ulcer were treated with either ranitidine bismuth citrate 400 mg b.d. for 4 weeks plus clarithromycin 500 mg t.d.s. for the first 2 weeks; ranitidine bismuth citrate 400 mg b.d. for 4 weeks plus placebo t.d.s. for first 2 weeks; placebo b.d. for 4 weeks plus clarithromycin 500 mg t.d.s. for the first 2 weeks; or placebo b.d. for 4 weeks plus placebo t.d.s. for the first 2 weeks. RESULTS: Ulcer healing rates after 4 weeks of treatment were highest with ranitidine bismuth citrate plus clarithromycin (82%) followed by ranitidine bismuth citrate alone (74%; P = 0.373), clarithromycin alone (73%; P = 0.33) and placebo (52%; P = 0.007). Ranitidine bismuth citrate plus clarithromycin provided significantly better ulcer symptom relief compared with clarithromycin alone or placebo (P < 0.05). The coadministration of ranitidine bismuth citrate plus clarithromycin resulted in significantly higher H. pylori eradication rates 4 weeks post-treatment (82%) than did treatment with either ranitidine bismuth citrate alone (0%; P < 0.001), clarithromycin alone (36%; P = 0.008) or placebo (0%; P < 0.001). Ulcer recurrence rates 24 weeks post-treatment were lower following treatment with ranitidine bismuth citrate plus clarithromycin (21%) compared with ranitidine bismuth citrate alone (86%; P < 0.001), clarithromycin alone (40%; P = 0.062) or placebo (88%; P = 0.006). All treatments were well tolerated. CONCLUSIONS: The coadministration of ranitidine bismuth citrate plus clarithromycin is a simple, well-tolerated and effective treatment for active H. pylori-associated duodenal ulcer disease. This treatment regimen effectively heals duodenal ulcers, provides effective symptom relief, eradicates H. pylori infection and reduces the rate of ulcer recurrence. The eradication of H. pylori infection in patients with recently healed duodenal ulcers is associated with a significant reduction in the rate of ulcer recurrence.

Gastrin and acid in relation to Helicobacter pylori.

H. pylori infection, both in normal healthy subjects and patients with duodenal ulcer, results in modest elevations of serum gastrin concentrations in the fasting state and quite substantial elevations after a meal or gastrin releasing peptide (GRP) stimulation. Cure of the infection leads to normalization of gastrin homeostasis. Acid secretion in response to a submaximal infusion of GRP is three-fold higher in H. pylori-infected normal subjects and six-fold higher in DU patients than in non-infected controls. These changes also normalize after cure of the infection. H. pylori infection appears to lead to increased basal acid output in some patients with duodenal ulcer while effects on peak acid output to pentagastrin remain under debate. With the possible exception of peak acid output, the abnormalities of gastrin and acid secretion reported for patients with duodenal ulcer are largely a result of infection with H. pylori.

The influence of food, beverages and NSAIDs on gastric acid secretion and mucosal integrity.

Gastric acid secretion is stimulated by all foods, especially proteins, and many beverages, the most potent beverages are milk and fermented substances such as beer and wine. The effects of food on mucosal integrity have been little studied, whereas non-steroidal anti-inflammatory drugs are well known to induce tissue injury.

The treatment of Helicobacter pylori infection in the management of peptic ulcer disease.

Antimicrobial therapy against H. pylori is indicated for all patients with documented peptic ulcer disease who have evidence of the infection. The regimen of first choice, selected on the basis of available studies, is triple therapy with bismuth, metronidazole, and tetracycline (Table 1). For patients who are known to have taken metronidazole previously, clarithromycin may be substituted for metronidazole. For patients with active, symptomatic peptic ulcers we also recommend an antisecretory drug to promote healing and relieve symptoms. Second-choice regimens consist of combinations of two antimicrobial drugs--metronidazole, amoxicillin, or clarithromycin--with an antisecretory agent, preferably an H+/K+-ATPase antagonist such as omeprazole. The combination of a single antimicrobial drug (especially amoxicillin) with omeprazole is less efficacious and cannot be recommended. Regardless of the antimicrobial regimen used, successful eradication of H. pylori infection markedly reduces the risk of recurrent peptic ulcers. If this therapeutic approach is taken with all patients with peptic ulcers, the recurrence of ulcers should become a rarity in medical practice.