Helicobacter pylori and peptic ulcer disease: evolution to revolution to resolution.
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Age Factors↗
Biomedical subjects
B J Marshall
Publications and source records attributed to B J Marshall.
Long-term follow-up of gastric histology after Helicobacter pylori eradication.
Helicobacter pylori causes chronic active gastritis and is thought to be associated with the development of gastric atrophy, intestinal metaplasia and carcinoma. As the effect of H. pylori eradication on this process is poorly understood, we sought to determine the long-term effects of H. pylori eradication on gastric histology. Fifty-four patients with duodenal ulceration associated with H. pylori infection received H. pylori eradication therapy in 1985/86 and either remained infected (n = 22) or had the infection eradicated (n = 32); patients were followed up by endoscopy with gastric antral biopsy for 7.1 years (mean). Histopathological analysis of gastric antral mucosa from patients rendered H. pylori-negative revealed a marked decrease in both inflammatory cells within the lamina propria and intraepithelial neutrophils and an increase in epithelial mucinogenesis. Gland atrophy remained unchanged in both H. pylori-positive and -negative patients. When examined for the presence and severity of intestinal metaplasia, there was neither a difference between the two patient groups nor a change with time. These data demonstrate that significant long-term improvements in gastric histology accompany H. pylori eradication when compared with histology in patients with persistent infection. Whether this confers a protective effect by reducing the risk of gastric carcinoma remains unknown.
Adult↗
Microdose 14C-urea breath test offers diagnosis of Helicobacter pylori in 10 minutes.
OBJECTIVES: The urea breath test diagnoses Helicobacter pylori infection of the stomach by identifying the urease enzyme activity of the bacterium. In this "microdose" version of the test, 1 microCi 14C-urea is given orally in a capsule. Our objectives were: 1) to evaluate a microdose 14C-urea breath test capsule in a gastroenterology outpatient setting, 2) to determine the diagnostic ranges of the 14C-urea breath test for HP-positive and HP-negative patients, 3) to define the sensitivity and specificity of the test, and 4) to see whether breath sample results changed when they were mailed to a remote site for analysis. METHODS: In a prospective blinded study, we breath-tested 200 fasted patients before elective outpatient endoscopy. At endoscopy, two gastric biopsy samples were taken and were examined for curved organisms; a third biopsy specimen was evaluated with a rapid urease test (CLOtest). Breath samples were mailed in aluminized balloons to a testing laboratory. RESULTS: Using a single breath sample collected at 10 min, with > or = 200 dpm as positive, the breath test correctly classified 63 of 65 HP-positive patients (sensitivity 97%, CI 89-99%), and 128 of 135 HP-negative patients (specificity 95%, CI 90-98%). Radiation exposure from the test equated to natural background received in 1 day. No adverse events were caused by the breath test. CONCLUSIONS: The 14C-urea capsule breath test (PYtest) is a convenient noninvasive test for the detection of gastric H. pylori infection. Accuracy is equivalent to invasive methods such as histology. Results can be obtained within 15 min if a counting instrument is nearby, or breath samples can be mailed to a testing laboratory for analysis.
Adolescent↗
Microdose 14C-urea breath test in detection of Helicobacter pylori.
Etiologic role for Helicobacter pylori (Hp) seems to be well established in gastric pathology. The high urease activity of Hp can be used to detect this bacterium by non-invasive urea breath tests (UBT). We validated the microdose version of the test in which 37 kBq 14C-urea is given orally in capsule. With the cut off value > 100 DPM as positive, UBT results correlated highly significant with combined results for invasive methods i.e. CLOtest + histology score. The reproducibility of the test was 100%. The results obtained for the breath test performed locally were almost identical with that read at remote laboratory. The data found for fasting and fed states of subjects agreed in 87%. When 14C-urea was confined in the mouth of both Hp positive and Hp negative patients UBT showed the presence of urease activity in the mouth cavity. 14C-urea capsule based breath test is highly reliable, safe, and reproducible for detection of Hp in the stomach. Results can be obtained within 15 min if a scintilation counter is nearby, or breath samples can be mailed to a testing laboratory for analysis.
Breath Tests↗
The 1995 Albert Lasker Medical Research Award. Helicobacter pylori. The etiologic agent for peptic ulcer.
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Awards and Prizes↗
Helicobacter pylori in peptic ulcer: have Koch's postulates been fulfilled?
This brief review considers whether or not Koch's postulates have been fulfilled for Helicobacter pylori and peptic ulceration. The histological features of peptic ulcer disease in man are active chronic gastritis with antral predominance, duodenal gastric metaplasia and active duodenitis. Other features are hyperpepsinogenaemia, relative postprandial hypergastrinaemia and basal acid hypersecretion. The macroscopic features are duodenal bulb ulceration or lesser curve and antral gastric ulceration. At present, gastric colonization with H. pylori has been produced in small animal species (rats and mice), but the infection is difficult to establish in immunocompetent animals, and histological gastritis is unconvincing. In larger animals the germ-free pig has been the most reliable model but the gastritis tends to be chronic with little activity. The best examples of acute infection are in three 'self-administration' experiments in humans. In these cases acute gastritis with hypochlorhydria developed which, when it converted to active chronic gastritis, tended to be asymptomatic. Either the circumstances were incompatible with ulceration, or the experiments were not continued for the many years necessary to develop peptic ulceration. It is concluded that only one of the many steps required for the development of peptic ulceration has so far been fulfilled, i.e. the ability of H. pylori to produce histological gastritis in a susceptible host.
Animals↗
Managing acid peptic disease in the Helicobacter pylori era.
The advent of new diagnostic and therapeutic modalities for Helicobacter pylori allows any physician to offer curative antibiotic regimens to patients with peptic ulcer disease and gastritis. This article describes new management strategies and discusses the advantages of each. In the old strategy, endoscopy was performed on patients with dyspepsia, in the hope of detecting a treatable peptic ulcer. In the new strategy, patients with dyspepsia are investigated with serology to detect those with H. pylori and potentially curable peptic ulcers. Patients with persistent symptoms require a urea breath test and only those who are now H. pylori-negative undergo endoscopy. The cost-effectiveness of these strategies will depend on the expense of each diagnostic test, particularly endoscopy. Whether a noninvasive strategy can be implemented safely may depend also on the incidence of gastric carcinoma in a particular population and the effectiveness of antibacterial therapy at reducing cancer risk.
Anti-Bacterial Agents↗
Duodenal ulcer treated with Helicobacter pylori eradication: seven-year follow-up.
The long-term benefits of Helicobacter pylori-eradication treatment (HET) in H pylori-associated duodenal ulcer are unclear. We followed up patients with duodenal ulcers from a trial of H pylori eradication in 1985-86. 63 of 78 patients (81%) were reviewed clinically and had upper gastrointestinal endoscopy with gastric antral biopsy. Of 35 patients previously rendered H pylori negative, 32 (92%) remained H pylori negative after 7.1 years (mean). All patients initially H pylori positive remained infected, unless HET was given in the interim. Duodenal ulceration was found in 20% (5 out of 25) of patients remaining H pylori-positive, compared with 3% (1 of 38) of H pylori-negative patients (p < 0.05). The reduction of duodenal ulcer relapse obtained from H pylori eradication in H pylori-associated duodenal ulcer extends to at least 7 years after treatment, and is likely to be due to freedom from H pylori infection. However, duodenal ulcer may recur in patients rendered H pylori negative, due to factors other than reinfection with H pylori.
Adult↗
[Management of the peptic ulcer patient in the Helicobacter pylori age].
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Algorithms↗
Occupational exposure to Helicobacter pylori for the endoscopy professional: a sera epidemiological study.
OBJECTIVES: The purpose of this prospective study was to determine if medical and nursing staff in the United States who are regularly involved in endoscopic procedures are at an increased risk of acquiring Helicobacter pylori infection. METHODS: One hundred and twenty-two gastroendoscopists and endoscopy nurses attending an advanced gastroendoscopy course (17 women, 105 men) completed a questionnaire consisting of past medical and professional history. Serum from each subject was collected and tested using a validated ELISA assay (sensitivity 99%, specificity 96%). H. pylori prevalence in the experimental group was compared to that of 510 blood donors. RESULTS: In all age groups, H. pylori positivity was significantly higher among the study subjects compared with controls. Caucasian subjects, when matched to controls for age, race, and level of education, had significantly higher rates of H. pylori positivity. Foreign-born subjects, when compared to US-born subjects, also had higher rates of H. pylori positivity. There was no statistical difference of H. pylori positivity with respect to gender, years involved in endoscopy, or number of endoscopies performed monthly. CONCLUSION: H. pylori infection is more common in gastroendoscopists and endoscopy nurses than the general population and should be viewed as an occupational hazard.
Adult↗
Helicobacter pylori.
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Helicobacter Infections↗
Bismuth subsalicylate suppression of Helicobacter pylori in nonulcer dyspepsia: a double-blind placebo-controlled trial.
Gastritis caused by Helicobacter pylori (HP) is common in patients with nonulcer dyspepsia (NUD), but an etiologic relationship between the histologic lesion and clinical symptoms is unproven. HP is inhibited by bismuth subsalicylate (BSS), a traditional remedy for dyspeptic complaints. The aim of this study was to assess the short- and long-term effects of BSS on HP, gastritis, and symptoms in patients with NUD. One hundred twenty-six patients with NUD who were shown to be infected with H. pylori (HP+) were enrolled. There was a two-week placebo run-in period to eliminate placebo responders. Fifty patients remained symptomatic and were randomly assigned to therapy with either BSS liquid or a matching placebo. EGD, biopsy, and clinical evaluations were performed at entry, at week 5 (end of therapy), at week 9 (four weeks after therapy), or at time of symptomatic relapse. Twenty-seven patients received placebo and 23 patients received BSS. BSS suppressed H. pylori in 15/23 patients (65%) and eradicated it in one patient, whereas the placebo had no effect on H. pylori. Gastritis improved during therapy with BSS but relapsed by week 9. There was no significant change in level of dyspeptic symptoms during or after treatment, although one month after the end of treatment, the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured. The study confirms that BSS given for three weeks suppresses but does not usually eradicate H. pylori. Such short-term suppression of H. pylori heals gastritis but does not result in clinical improvement.
Adult↗
The role of Helicobacter pylori in acid-peptic disease.
Acid peptic disease is common, and its management is costly. Less than a decade ago, the traditional theories regarding the etiology and pathogenesis of acid peptic disease were upset by the discovery of Helicobacter pylori infection in association with chronic active gastritis. A substantial body of investigation after that discovery has established this infection as the major cause of human chronic active gastritis and has defined a critical role for H. pylori in the etiology, pathophysiology, and treatment of duodenal ulcer disease. Furthermore, evidence is accumulating to link H. pylori to gastric ulcers, non-ulcer dyspepsia, and even gastric carcinoma. Research has clarified some unique features of the organism that have been put to advantage in the development of diagnostic tests, and it has also clarified some features of the infection that make it difficult to treat. Although treatment is decidedly beneficial for certain patient subsets, simpler and more effective therapy is needed.
Helicobacter Infections↗
Metronidazole susceptibility testing for Helicobacter pylori: comparison of disk, broth, and agar dilution methods and their clinical relevance.
Since the methods for metronidazole susceptibility testing of Helicobacter pylori have not been standardized or validated, we compared three methods that are used to test the metronidazole susceptibilities of 25 isolates of H. pylori. Specifically, we examined the methods of Steer's replicator agar dilution, tube broth microdilution, and modified Kirby-Bauer disk diffusion. The metronidazole disk zone sizes obtained by the disk diffusion method correlated well (r = 0.74) with the MICs obtained by the agar dilution method. Afterward, the disk diffusion method was used to characterize the metronidazole susceptibilities of 44 isolates of H. pylori. Dual therapy (bismuth and metronidazole) proved to be highly effective against metronidazole-susceptible strains (81.6% eradication rate) but fared poorly against resistant strains (16.7% eradication rate; P < 0.01). Using agar dilution testing, we validated the modified Kirby-Bauer disk diffusion method for metronidazole susceptibility testing of H. pylori and conclude that it is practical, accurate, and clinically applicable.
Drug Resistance, Microbial↗
Helicobacter pylori: a primer for 1994.
Ten years after the original isolation of Helicobacter pylori, we know that this interesting new bacterium infects half of the world's population and at least 25% of people in the United States. The mode of transmission is probably fecal-oral, and its prevalence increases in lower socioeconomic groups or older people. Fortunately, the organism can now be diagnosed using serology, breath testing, biopsy, and culture. We also have effective means of therapy in the United States giving 80 to 95% cure rates in 14 days. In the past four years at least five well-controlled, double-blind studies have shown that curing Helicobacter pylori usually results in curing duodenal ulcer disease. Increasing data confirm that this also holds true for gastric-ulcer and ulcer complications. The role of Helicobacter pylori in non-ulcer dyspepsia is still controversial, and its association with increased gastric-cancer risk offers an exciting opportunity for further research.
Adenocarcinoma↗
The Automatic Patient Symptom Monitor (APSM): a voice mail system for clinical research.
Double-blind clinical trials become very tedious when symptoms are measured rather than objective laboratory and physical parameters. The standard "diary card" method is labor intensive for patients and impractical to use for more than a few weeks. In chronic relapsing disorders it would be far better for patients to record symptoms one or more times per day, at defined times, for weeks, months or even years. The Automatic Patient Symptom Monitor (APSM) is a voice processing system designed to achieve this goal. APSM calls patients at home every night, addresses each patient by name and then asks a set of questions which patients answer by pressing the touch tone keys on their telephone. APSM enters data into a computer database file which can be easily retrieved by investigators, even by modem. In a pilot study, patients with telephones easily learned how to use APSM. They were given therapy for a gastric infection (H.pylori) and were monitored by APSM until follow-up one month after completing treatment. Eight of nine patients recorded valid data on > 80% of study days. In all cases, APSM data matched the patient's own impression of whether they were better, the same, or worse. With one exception, APSM assessment correlated with microbiologic data obtained post therapy i.e. when the gastric infection had been eradicated, patients felt better (p < 0.047). Long term clinical monitoring with APSM may decrease clinical trial time and improve the statistical power of double blind studies.
Anti-Bacterial Agents↗
Treatment strategies for Helicobacter pylori infection.
Helicobacter pylori can be eradicated easily in most patients with a 14-day triple-therapy regimen. In patients in whom this treatment fails or who cannot take a full course, other antimicrobial combinations must be considered. This article discusses the various alternatives and explains why various agents should or should not be used. It also includes many new therapies developed in 1992 that allow the physician to treat virtually all H. pylori infections.
Anti-Bacterial Agents↗
Radiation dose estimates for the carbon-14-labeled urea breath test.
The use of the 14C-urea breath test for diagnosis of Helicobacter pylori infection in gastric mucosa has gained widespread acceptance and utilization. In order to obtain regulatory approval for this procedure, new dose estimates were required. Previous radiation dose equivalent estimates for males only were based upon data published in 1975 for bicarbonate metabolism. Since that time, calculational techniques for dose estimation have been significantly improved and the organ masses of Reference Man updated. We have calculated dose estimates for males and females who test positive (HP+) and negative (HP-) for gastric H. pylori infection. Our results indicate that the urinary bladder wall receives the highest absorbed dose in all four of the above subject populations (HP- males = 0.14 mGy/MBq; HP- females = 0.19 mGy/MBq; HP+ males = 0.10 mGy/MBq; HP+ females = 0.14 mGy/MBq). Gonadal absorbed doses were similar to those previously estimated (testes < 0.065 mGy/MBq and ovaries < 0.084 mGy/MBq, respectively).
Breath Tests↗