Scandinavian Journal of Gastroenterology
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Helicobacter pylori: Fact or Fiction? M. G. Korman To cite this article: M. G. Korman (1990) Helicobacter pylori: Fact or Fiction?, Scandinavian Journal of Gastroenterology, 25:sup175, 159-165, DOI: 10.3109/00365529009093139 To link to this article: http://dx.doi.org/10.3109/00365529009093139
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 3
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [137.189.171.235]
Date: 08 May 2016, At: 09:55
Helicobacter pylori: Fact or Fiction? M. G. KORMAN Gastroenterology Unit, Prince Henry’s Hospital, Melbourne, Victoria, Australia
Korman MG. Helicobacter pylori: fact or fiction? Scand J Gastroenterol 1990, 25(suppl 175), 159-165 The recent isolation and classification of the spiral gastric bacteria Helicobacterpylori has led to an’explosion of worldwide research. The data strongly suggest that H . pylori is the causative agent for type-B active chronic gastritis. The role of H . pylori in duodenal ulcer awaits clarification, and, more importantly, potential treatment regimens need clear documentation and further detailed research. The past decade has revealed many intriguing facts about H . pylori infection. If, during the 1990s, eradication of H . pylori by means of appropriate and safe medication can lead to the control and prevention of gastroduodenal disease, then major clinical and economic benefits can be anticipated.
Downloaded by [] at 09:55 08 May 2016
Key words: Duodenal ulcer; gastritis; Helicobacter pylori Melvyn G . Korman, M . D . , Gastroenterology Unit, Prince Henry’s Hospital, S I . Kilda ’s Road, Melbourne, Victoria, Ausiralia 3004
Bizzozero in 1893 first demonstrated bacterial THE ORGANISM colonization of mammalian stomachs with spiral organisms (1). For decades, the clinical sig- H . pylori is a curved, S-shaped, gram-negative nificance of these bacteria has been vigorously rod, 2.5 pm long and 0.5 pm wide (9, 10). These debated and, until recently, they were dismissed bacteria were first referred to simply as ‘Campas probable contaminants. The reports by Warren ylobacter-like organisms’ (5,8). Subsequently, ( 2 ) and Marshall (3) from Perth, describing their the species was named Campylobacter pyloridis observation of a high prevalence of campylo- (11). It was then brought into line with other gut bacter-like bacteria in biopsy specimens taken pathogens such as C . jejuni and Escherichia coli, from patients with gastritis and peptic ulcer, and renamed Campylobacter pylori (12). Howstimulated worldwide interest in this organism. ever, there are some significant differences from Culture soon became the ‘gold standard’ for other campylobacters: i) four sheathed flagellae detection of the organism (4). Several groups arising from one pole (13), ii) production of large in the United Kingdom (5-7) and one in the amounts of urease (8), and iii) unique protein Netherlands (8) confirmed the findings of a high profile (14), different fatty acid composition ( l j ) , prevalence of campylobacter-like spiral organ- and different RNA sequences (16). Thus, it is not isms in patients with histologic gastritis and peptic an authentic campylobacter and was classified as a new genus, now named Helicobacter (1618). ulcer. The important question of whether bacteria The name Helicobacter pylori ( H . pylori) refers play a significant role in peptic ulcer and dyspepsia to the morphology of the organisms, which are awaits clarification. An alternative interpretation helical in vivo but often rod-like in vitro; also the of current data is that the organism is simply a name Helicobacter is euphonious and has the secondary invader of damaged gastric-like epi- advantage that it is similar to the name Camthelium. This paper examines the last decade of p y lobacter. Despite extensive investigation H . pylori has hectic research into the possible clinical relevance of Helicobacter pylori. been isolated from only the stomach and the
Downloaded by [] at 09:55 08 May 2016
160
M. G.Kormnn
duodenal bulb. In the stomach it may be detected DETECTION throughout the fundus, body, and antrum, lying By means of careful culture techniques, H. underneath the mucus layer in close apposition pylori can be isolated from 80% to 90% of persons to the surface mucous cells (9,14). Indeed, the subsequently proven by other methods to be organism seems to have very specifically adapted infected. Because the distribution of infection to living in the microenvironment closely related may be patchy, one should culture material from to this particular cell type. When the organism is at least two areas of the gastric mucosa (antrum present in the duodenum, it is always located and body) to maximize the likelihood of detecabove islands of metaplastic gastric surface tion. Histologic identification of Helicobacter mucous cells (19). Such metaplastic islands are organisms on the gastric epithelial surface corknown to be common in patients with duodenal relates well with culture results. The organisms ulcer (20). Organisms are rarely seen intracan usually be detected on haematoxylin-andcellularly, suggesting that H. pylori is nonineosin- or Giemsa-stained tissue. Warthin-Starry vasive. The mucus layer may insulate H. pylori and acridine orange stains facilitate detection of from gastric acid. Alternatively, bacterial hydrobacteria, especially if they are present in small lysis of urea to ammonium ion may produce an numbers. Gram stain of biopsy touch prepalkaline microclimate that allows it to survive in arations is a rapid and inexpensive method of an otherwise potentially hostile environment. diagnosing H. pylori, and its results correlate well with those of culture and other staining methods (23). The high urease activity exhibited by H. pylori has led to the development of diagnostic tests that MECHANISMS OF INJURY detect the presence of products of urea hydrolysis If H. pylori is a human pathogen, how does it and, by inference, the presence of H. pylori. cause damage? The precise mechanism(s) by Urease tests that detect high concentrations of which H. pylori induces mucosal injury is not this enzyme in mucosal biopsy specimens are easy known (9,21). Despite the lack of evidence of to perform, give a quick answer, and possess direct cellular invasion, cellular damage and reasonable sensitivity and specificity in cominflammation are prominent findings in infected parison with culture or histopathology. Breath persons. Gastric mucus is depleted, spotty epitests are also based on the high activity of urease thelial necrosis is seen, and polymorphonuclear produced by H. pylori and measure the excretion leukocytes infiltrate the epithelial layer in associof labelled C 0 2 in the expired air after the oral ation with acute and chronic inflammation in the administration of labelled urea. Both methods lamina propria. Ultrastructurally, surface epiare noninvasive, well-tolerated by the subjects, thelial cells are oedematous, degenerating, and and have good sensitivity and specificity. depleted of mucous granules. Surface microvilli Immunologic techniques using the enzymeare absent or sparse. The organism may interfere linked immunosorbent assay (ELISA) method with gastric mucous production directly or have reasonable specificity and sensitivity when indirectly, thereby permitting injury by gastric compared with culture or histopathology. Immuacid. Ammonia production by the bacteria may nologic techniques seem more suited to prevadamage cells through direct toxic effects or by lence studies than to examination of the results increasing pericellular pH. Alternatively, H. of therapy. pylori may release a yet undescribed toxin or chemotactic factor that promotes injury and inflammation. Active investigation of the pathoPREVALENCE genesis of H. pylori-mediated injury is ongoing and should be enhanced by further work in animal Helicobacter pylori in the normal population The worldwide prevalence and persistence of models, such as the gnotobiotic piglet (22).
Downloaded by [] at 09:55 08 May 2016
Helicobacter pylori
H . pylori suggest that it may be the commonest known human bacterial infection (9,24). Most current information documenting the prevalence of H. pylori comes from populations undergoing routine upper gastrointestinal endoscopy. Most such individuals have complained of dyspepsia. The overall isolation rate for H. pylori ranges from 32% to 62%, with a mean of 56% (5,14,25). Information about prevalence rates in either asymptomatic individuals or in a random cross-section of the population has proved more difficult to obtain. Prevalence in 34 asymptomatic volunteers was assessed endoscopically in Amsterdam, and 20% were found to be infected (26). Some of the volunteers were followed up prospectively for 2 years; during this period none exhibited spontaneous disappearance of the organism. In the United States the prevalence in healthy asymptomatic subjects is approximately 20%, but age and ethnic variations occur. For instance, H. pylori is rare is asymptomatic children but is present in 50% of SO-year-old persons and in 75% of those aged 65 years. Lambert (27) noted a similar age dependance in an Australian endoscopic series. Differences in population prevalence must be considered in attempts to establish the relationship between H. pylori and specific disease processes. Helicobacter pylori in disease states Active chronic gastritis (type B ) . The evidence is overwhelming that H. pylori is the cause of chronic type B gastritis (9,21). Active (neutrophilic infiltration) chronic gastric inflammation is virtually always found in association with H. pylori infection. Antral mucosa is involved most often. Autoimmune (type A) and secondary (Crohn’s disease, bile reflux) gastric inflammation are not often associated with H. pylori infection (28,29). Elimination of the organisms is usually associated with improvement in the gastric histologic picture. McNulty et al. (30) successfully cleared the organism from 78% of bismuth-treated patients compared with only 7% of those given erythromycin and none of those receiving placebo (30). Twelve of 13 whose organisms were cleared also had resolution of the gastritis, compared
161
with only 4 of 32 not cleared of the organism. Subsequent reports seem to confirm these findings (26,31). The definition of causation of disease by a microorganism requires that all of Henle-Koch’s postulates be satisfied. In attempts to fulfil Koch’s third postulate, two investigators have ingested H. pylori and developed an acute illness plus histologic gastritis (32,33). Further, it seems likely that inoculation with this organism led to an epidemic of hypochlorhydria and gastritis in a group of volunteers who took part in a study of acid secretion (34). Gastric juice had been removed for measurement of pH and, using the same glass electrode, then returned to each individual’s stomach. It is probable that an infectious agent contaminated the electrode. Recently, stored sera from these individuals were assessed for H. pylori antibodies, with a rise in titre dernonstrated in 9 of 12 subjects (35). Duodenal ulcer disease. The postulate that H. pylori is the sole cause of duodenal ulcer is far from established. Although prevalence of the bacteria in duodenal ulcer patients approaches loo%, this may merely reflect the close association between duodenal ulcer and antral inflammation. The prevalence of H. pylori infection increases with age, but dudoenal ulcer is not predominantly a disease of the elderly. Duodenal ulcer is a malepredominant disease, but H . pylori infection shows no gender predilection. Ulcer craters heal even though bacteria persist (36). Acid hypersecretion (for example, Zollinger-Ellison syndrome) leads to duodenal ulcer with no organisms present. Many persons infected with H. pylori never have ulcers, suggesting that important host factors or bacterial virulence factors determine the occurrence of disease. The strongest evidence that H. pylori infection is important in duodenal ulcer comes from antibiotic treatment trials. Antibiotics and bismuth produce healing of duodenal ulcers at the same rate as conventional H2 blocker therapy. However, once such acute therapy is stopped, the ulcers predictably return. On the other hand, when infection is eliminated and antimicrobial therapy is stopped, disease recurs less frequently. Those ulcers that do return after antibiotics
Downloaded by [] at 09:55 08 May 2016
162
M. G . Korman
usually do so in the setting of recurrent H. pylori infection (37). It is important to consider how an organism that colonizes gastric epithelium could cause duodenal ulcer (21,38). One theory is that a combination of bacteria and acid acts synergistically. Increased duodenal exposure to acid presumably leads to the formation of metaplastic gastric epithelium, which subsequently can become colonized, inflamed, and, with further acid contact, susceptible to ulceration. Thus, elimination of either acid by H2 receptor antagonists or bacteria by antibiotics would heal ulcers, but only antibiotic therapy would remove infection and lessen recurrence. Such a theory, which assigns an important role to both acid and bacteria, is supported by the high prevalence of gastric metaplastic epithelium in the duodenum of duodenal ulcer patients, but is far from proven. Family members, whether symptomatic or asymptomatic, of duodenal ulcer patients have a higher than expected prevalence of H. pylori infection. Bacterial analysis has revealed the similarity of organisms within families, suggesting the possibility of person-to-person spread or a common source of such infection. Such familial clustering of infection may stimulate re-evaluation of the genetic theories of ulcer disease. Recently, Levi et al. (39) have suggested that H. pylori in the gastric antrum may stimulate gastrin release in duodenal ulcer disease. Their study showed that pentagastrin-stimulated gastric acid secretion and postprandial plasma gastrin concentrations were significantly higher in H. pylori-positive than in H. pylori-negative patients with duodenal ulcer. This group also showed a fall in the integrated gastrin response to a meal in H.pylori-positive patients with duodenal ulcer after eradication of the organism, yet peak acid secretion did not fall (40). They proposed that the powerful urease produced by H. pylori splits urea, which is present in the stomach, to yield ammonia. The ammonia raises the pH of the mucus layer that overlies the gastric antrum, so that the expected normal inhibition of gastrin release by intraluminal acid is impaired. The increased gastrin release, which results from the absence of acid inhibition, stimulates gastric acid
secretion, both directly and by its trophic effect on the gastric secretory cell mass. Increased acid secretion may then cause duodenal ulcers by producing a low intraduodenal pH. However, their findings fail to offer an explanation for the presence of ulcers in H. pylorinegative patients or in those with normal gastric secretion. Presumably, ulcers in such patients could be due to other postulated abnormalities that have been reported in patients with duodenal ulcer disease. Obviously, much more data are required to clarify this intriguing area of research. Benign gastric ulcer. Currently, no studies have adequately evaluated the effects of eradication of bacteria on gastric ulcer healing or recurrence. Clearly, the organism is not the sole cause of gastric ulcer because the prevalence of infection is in the order of 6&80% (24). Because gastric ulcer patients tend to be older, this prevalence may not be significantly different from that seen in age-matched, non-disease groups. We must await further evidence. Non-ulcer dyspepsia. Non-ulcer dyspepsia (NUD) is potentially very important because of the high frequency with which this condition is diagnosed and the amount of time and valuable health resources it consumes. Patients with NUD have symptoms that suggest the presence of peptic ulcer, but no ulcer is found at endoscopy. The diagnosis of NUD is much more common than that of duodenal ulcer. The symptoms of NUD require the exclusion of gastro-oesophageal reflux, biliary tract disease, chronic pancreatitis, or the irritable bowel syndrome. This can only be achieved by careful history and thorough examination, followed by endoscopy to exclude the presence of peptic ulcer or oesophagitis. Further investigations may be needed, to exclude the presence of other conditions. NUD remains a clinical concept, characterized by the lack of objective features. Intentional ingestion of H. pylori definitely can cause transient dyspeptic symptoms (32,33). Whether this organism can lead to chronic abdominal symptoms is far from certain. The prevalence of infection in patients with NUD (40-60%) is similar to that in age-matched controls. Antibiotic therapy relieves NUD symptoms inconsistently, although
Helicobacter pylori
Downloaded by [] at 09:55 08 May 2016
it may reverse the gastric histologic change in infected persons (31). There are no convincing studies to support an aetiologic role of H . pylori in non-ulcer dyspepsia. Thus, there seems little justification for indiscriminate prescribing of bismuth compounds or antibiotics for NUD, even if H . pylori positivity is confirmed.
163
organism was cleared in only 57%, and no correlation was detected between ulcer healing and H . pylori eradication (36). Eradication of H . pylori is not necessary for ulcer healing, which is indirectly supported by the great efficacy demonstrated in peptic ulcer by histamine H2-receptor antagonists. These agents have no effect on the number of organisms, and ulcer healing has again been shown to be unreTREATMENT O F H . PYLORI INFECTION lated to the patient’s H . pylori status (42). LikeMany antibiotic regimens have proved effective wise, no change in H . pylori positivity occurred in suppressing bacterial growth but seem less in patients whose duodenal ulcers healed with effective in permanently eradicating the organ- misoprostol (43), and ranitidine maintenance ism. In vitro, H . pylori is usually sensitive to a therapy prevented ulcer relapse despite the perlarge number of antibiotics and moderately sen- sistence of organisms in most patients over a 12sitive to bismuth. However, in vitro sensitivities month period (44). These studies with powerful do not correlate well with in vivo efficacy for anti-secretory drugs do not imply that H . pylori eradicating H . pylori, perhaps because systemic is not an important initiating factor but only that antibiotics may not penetrate to the organism’s acid remains a major factor in the continuation habitat beneath the mucus gel layer. of an ulcer’s presence. Another important obserFurther complicating the selection of treatment vation has been the finding that bacteria persist is the inability to define successful eradication unchanged in 50% of patients whose ulcer heals of the bacteria. Whereas most culture-positive with placebo (42). This is further evidence against patients will become culture-negative immedi- an essential role for H . pylori, at least in ulcer ately after treatment with colloidal bismuth or persistence. amoxicillin singly or in combination, only 40% The success of bismuth in eliminating H . pylori remain culture-negative at 1 month, indicating has been suggested as an explanation for the lower that recurrence or recrudescence of infection is recurrence rate reported when ulcers heal with common (26). Recurrence appears to represent bismuth compared with cimetidine (45). More return of infection by the original bacterial strain recent studies have also found that those who rather than infection by a new organism. Possibly, relapsed in the year after their duodenal ulcers the use of higher doses, repeated or prolonged were healed with bismuth were much more likely courses of single antibiotics, or ‘triple therapy’ to be H . pylori-positive than those who did not (bismuth plus two antibiotics) may prove effective relapse (36,37). in eliminating H . pylori infection (41). However, These studies of duodenal ulcer relapse after such regimens undoubtedly will be associated with successful eradication of H . pylori may prove to significant side effects, including diarrhoea and be important links in establishing whether H . Clostridium dificile infection (26). Thus, one pylori plays a causal role in duodenal ulcer. Howmust carefully assess the possible risks versus ever, it must be remembered that colloidal bisthe potential benefits of a vigorous eradication muth has several effects other than those on H . program. pylori. It binds to the gastric mucosa and provides Colloidal bismuth subcitrate is moderately powerful protection against experimental injury inhibitory to H . pylori in vitro and renders many in acute animal models in which H . pylori has no patients H . pylori-negative (31,36). Whether role (46). Before we can confidently confirm that clearance of H . pylori by bismuth alone facilitates the lower relapse rate of duodenal ulcer after ulcer healing remains controversial. Lambert et successful bismuth therapy is directly related to al. (36) treated 45 patients with bismuth for 8 a marked reduction in the number of patients weeks; ulcers healed in 94%, even though the infected with H . pylori, it would be prudent to
164
M. G . Korman
wait for the results of studies using antibiotics that lack bismuth’s complex additional actions on the stomach and duodenum.
and economic impact on medical practise in the 1990s.
REFERENCES
Downloaded by [] at 09:55 08 May 2016
HELZCOBACTER INTO THE 1990s
1. Bizzozero G. Uber die Schlauchformigen Drusen
des Magendarkanals und die Bezienhungren ihres The many treatment trials being conducted in Epithels zu dem Oberflachenepithel der Schlemvarious research centres throughout the world haut. Arch Mikr Anat 1893, 42, 82-152 2. Warren JR. Unidentified curved bacilli on gastric will undoubtedly lead to clarification of the aetiepithelium in active chronic gastritis. Lancet 1983, ological role of H. pylori in digestive diseases. 1; 1273 The previous dictum of ‘no acid, no ulcer’ may 3. Marshall BJ. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983, now need to be supplemented with two further 1, 1273-1275 statements: ‘no H. pylori, no gastritis’ and ‘no H. 4. Marshall BJ, McGechie DB, Rogers PA, Glancy pylori, no ulcer’. Whether these dictums remain RJ. Pyloric campylobacter infection and gastrotrue will only be determined by future research. duodenal disease. Med J Aust 1985, 142, 439-444 5 . Jones DM, Lessells AM, Eldridge J. CampyloMuch work is required on the mechanisms by bacter-like organisms on the gastric mucosa: which H. pylori may cause gastrointestinal culture, histological and serological studies. J Clin disease. The determination of possible bacterial Pathol 1984, 37, 1002-1006 6. McNulty CAM, Watson DM. Spiral bacteria of the virulence factors or host susceptibility factors gastric antrum. Lancet 1984, 1, 1068-1069 requires careful study, particularly to explain why 7. Rollason TP, Stone J , Rhodes JM. Spiral organisms infected patients usually are free of clinical in endoscopic biopsies of the human stomach. J Clin Pathol 1984, 37, 23-26 disease. Possible environmental sources and 8. Langenberg ML, Tytgat GNJ, Schipper MEI, et al. modes of transmission of H . pylori should also be Campylobacter-like organisms in the stomach of patients and healthy individuals. Lancet 1984, I , elucidated; elimination of such sources or modes 1348 of transmission could lead to control or pre9. Goodwin CS, Armstrong JA, Marshall BJ. Camvention of clinical disease. The feasibility of vacpylobacter pyloridis, gastritis and peptic ulceration. cination requires further study, as this may prove J Clin Pathol 1986, 39, 353-365 to be a very important method of prevention. 10. Dooley CP, Cohen H. The clinical significance of campylobacter pylori. Ann Intern Med 1988, 108, Development of safe, convenient, effective ther70-79 apy for H . pylori will facilitate clinical inves- 11. Marshall BJ, Royce H, Annear DI, et al. Original isolation of Campylobacter pyloridis. Microbios tigations aimed at clarifying the role of this Letters 1984, 25, 83-88 bacteria in gastrointestinal disease. The issues of 12. Marshall BJ, Goodwin CS. Revised nomenclature how best to treat H . pylori, how long to treat, and of Campylobacter pyloridis. Int J Systemic Bacteriol 1987, 37, 68 whether to eradicate or reduce the microbiologic 13. Goodwin CS, McCulloch RK, Armstrong JA, Wee burden also remain to be resolved. Depending on SH. Unusual cellular fatty acids and distinctive the availability of appropriate therapy and further ultrastructure in a new spiral bacterium (Campylobacter pyloridis) from the human gastric clarification of the pathogenic role of H. pylori, it mucosa. J Med Microbiol 1985, 19, 257-267 would seem wise at present for those enthusiastic 14. Taylor DE, Hargreaves JA, Lai-King N , et al. supporters of Helicobacter infection to modify Isolation and characterization of Campylobacter pyloridis from gastric biopsies. Am J Clin Pathol their treatment decisions with good common 1987, 87, 49-54 sense and not needlessly subject patients to poss- 15. Goodwin CS, Armstrong JA, Marshall BJ. Camibly ineffective or potentially toxic therapeutic pylobacter pyloridis, gastritis and peptic ulceration. J Clin Pathol 1986, 39, 353-365 regimens. 16. Romaniuk PZ, Zoltowska B, Trust TJ, et al. CamWe await, with great interest, the data to conpylobacter pylori, the spiral organism associated with human gastritis is not a true Campylobacter firm that eradication of H . pylori leads to clinical sp. J Bacteriol 1987, 169, 2137-2141 improvement in infected symptomatic patients or, 17. Jones DM, Curry A. Ultrastructural study of gastric more importantly, prevention of gastrointestinal campylobacter-like organisms (GCLO) from man, baboon, pig and ferret. In Proceedings of the Fourth disease. Such findings would have a major clinical
Downloaded by [] at 09:55 08 May 2016
Helicobacter pylori International Workshop on Campylobacter Infections, Kungalv, Sweden, 1987, 73 18. Goodwin CS, Armstrong JA, Chilvers T, et al. Transfer of Campylobacter pylori and Campylobacter mustelae to Helicobacter gen. nov. as Helicobacter pylori comb. nov. and Helicobacter mustelae comb. nov., respectively. Int J Syst Bacteriol 1989, 39, 393-405 19. Steer HW. Surface morphology of the gastroduodenal mucosa in duodenal ulceration. Gut 1984, 25, 1203-1210 20. Fullman G , Van Deventer C, Schneidman D, et al. 'Healed' duodenal ulcers are histologically ill. Gastroenterology 1985, 88, 1390 21. Graham DY. Campylobacter pylori and peptic ulcer disease. Gastroenterology 1989, 96, 615-4562 22. Lambert JR, Borromeo M, Pinkard KJ, et al. Colonization of gnotobiotic piglets with Campylobacter pyloridis-an animal model? J Infect Dis 1987, 155, 1344 23. Montgomery EA, Martin DF, Peura DA. Rapid diagnosis of Campylobacter pylori by Gram's Stain. Am J Clin Pathol 1988, 56, 2896-2906 24. Graham DY, Klein PD, Opekun AR, Boutton TW. Effect of age on the frequency of active campylobacter pyloridis infection diagnosed by the ["C] urea breath test in normal subjects and patients with peptic ulcer disease. J Infect Dis 1988,157,777-780 25. Burnett RA, Forrest JAH, Girdwood RWA, Fricker CR. Campylobacter-like organisms in the stomach of patients and healthy individuals. Lancet 1984, 1 1349 26. Rauws EAJ, Langenberg W , Houthoff HJ, et al. Campylobacter-pyloridis-associatedchronic active antral gastritis: a prospective study of its prevalence and the effects of antibacterial and antiulcer treatment. Gastroenterology 1988, 94, 33-40 27. Lambert JR. Prevalence of C. pylori in diseases of GI tract and relationship to gastritis. In: Peterson WL, ed. Campylobacter pylori: a multi-disciplinary workshop, Colorado, 1987 28. O'Connor HJ, Axon ATR, Dixon MF. Campylobacter-like organisms unusual in type A (pernicious anaemia) gastritis. Lancet 1984, 2, 1091 29. Lambert JR, Dunn KL, Eaves ER, et al. Pyloric CLO in the human stomach. Med J Aust 1985, 143, 174 30. McNulty CAM, Gearty JC, Crump B, et al. Campylobacter pyloridis and associated gastritis: investigator blind, placebo controlled trial of bismuth salicylate and erythromycin ethylsucrinate. Br Med J 1986, 293, 645-649 31. Lambert JR, Borromeo M, Korman MG, Hansky J . Role of Campylobacter pyloridis in non-ulcer
165
dyspepsia: a randomized controlled trial. Gastroenterology 1987, 92, 1488 32. Morris A, Nicholson G. Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol 1987, 82, 192-199 33. Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ. Attempts to fulfil Koch's postulates for pyloric campylobacter. Med J Aust 1985, 142, 436439 34. Ramsey EJ, Carey KV, Peterson WL, et al. Epidemic gastritis with hypochlorhydria. Gastroenterology 1979, 76, 1449-1457 35. Peterson W, Lee E, Skoglund M. The role of Campylobacter pyloridis in epidemic gastritis and hypochlorhydria. Gastroenterology 1987, 92, 1489 36. Lambert JR, Borromeo M, Korman MG, et al. Effect of colloidal bismuth (De-Nol) on healing and relapse of duodenal ulcers: role of Campylobacter pyloridis. Gastroenterology 1987, 92, 1489 37. Coghlan JG, Gilligan D, Humphries H, et al. Campylobacter pylori and recurrence of duodenal ulcers-a 12 month follow-up study. Lancet 1987, 2, 1109-1111 38. Wyatt JI, Rathbone BJ, Dixon MF, Heatley RV. Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis. J Clin Path01 1987, 40, 841-848 39. Levi S, Beardshall K, Haddad G , et al. Campylobacter pylori and duodenal ulcers: the gastrin link. Lancet 1989 1 , 1167-1168 40. Levi S, Beardshall K, Swift I, et al. Antral Helicobacter pylori, hypergastrinaemia and duodenal ulcers: effect of eradicating the organism. Br Med J 1989, 299, 1504-1505 41. Borody TJ, Cole P, Noonan S, et al. Recurrence of duodenal ulcer and Campylobacter pylori infections after eradication. Med J Aust 1989, 151, 431-434 42. Humphries H, Dooley C, O'Leary D, et al. Effect of therapy on Campylobacter pyloridis: a randomized trial. Gut 1986, 27, A 611 43. Ho J , Lui I, Hui WM, et al. A study of the correlation of duodenal ulcer healing with campylobacter-like organisms. J Gastroenter Hepatol 1986, 1 , 69-74 44. Thomas JM, Poynter D, Gooding C, et al. Gastric spiral bacteria. Lancet 1984, 11, 100 45. Martin DF, Hollander SD, May SJ, et al. Differences of relapse rates of duodenal ulcer after healing with cimetidine or tripotassium citrato bismuthate. Lancet 1981, 1, 7-10 46. Wieriks J , Hespe W, Jaitley KO. Pharmacological properties of colloidal bismuth subcitrate (CBS DeNol). Scand J Gastroenterol 1982, 17(suppl 80), 1116
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Helicobacter pylori: Fact or Fiction? M. G. Korman To cite this article: M. G. Korman (1990) Helicobacter pylori: Fact or Fiction?, Scandinavian Journal of Gastroenterology, 25:sup175, 159-165, DOI: 10.3109/00365529009093139 To link to this article: http://dx.doi.org/10.3109/00365529009093139
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 3
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [137.189.171.235]
Date: 08 May 2016, At: 09:55
Helicobacter pylori: Fact or Fiction? M. G. KORMAN Gastroenterology Unit, Prince Henry’s Hospital, Melbourne, Victoria, Australia
Korman MG. Helicobacter pylori: fact or fiction? Scand J Gastroenterol 1990, 25(suppl 175), 159-165 The recent isolation and classification of the spiral gastric bacteria Helicobacterpylori has led to an’explosion of worldwide research. The data strongly suggest that H . pylori is the causative agent for type-B active chronic gastritis. The role of H . pylori in duodenal ulcer awaits clarification, and, more importantly, potential treatment regimens need clear documentation and further detailed research. The past decade has revealed many intriguing facts about H . pylori infection. If, during the 1990s, eradication of H . pylori by means of appropriate and safe medication can lead to the control and prevention of gastroduodenal disease, then major clinical and economic benefits can be anticipated.
Downloaded by [] at 09:55 08 May 2016
Key words: Duodenal ulcer; gastritis; Helicobacter pylori Melvyn G . Korman, M . D . , Gastroenterology Unit, Prince Henry’s Hospital, S I . Kilda ’s Road, Melbourne, Victoria, Ausiralia 3004
Bizzozero in 1893 first demonstrated bacterial THE ORGANISM colonization of mammalian stomachs with spiral organisms (1). For decades, the clinical sig- H . pylori is a curved, S-shaped, gram-negative nificance of these bacteria has been vigorously rod, 2.5 pm long and 0.5 pm wide (9, 10). These debated and, until recently, they were dismissed bacteria were first referred to simply as ‘Campas probable contaminants. The reports by Warren ylobacter-like organisms’ (5,8). Subsequently, ( 2 ) and Marshall (3) from Perth, describing their the species was named Campylobacter pyloridis observation of a high prevalence of campylo- (11). It was then brought into line with other gut bacter-like bacteria in biopsy specimens taken pathogens such as C . jejuni and Escherichia coli, from patients with gastritis and peptic ulcer, and renamed Campylobacter pylori (12). Howstimulated worldwide interest in this organism. ever, there are some significant differences from Culture soon became the ‘gold standard’ for other campylobacters: i) four sheathed flagellae detection of the organism (4). Several groups arising from one pole (13), ii) production of large in the United Kingdom (5-7) and one in the amounts of urease (8), and iii) unique protein Netherlands (8) confirmed the findings of a high profile (14), different fatty acid composition ( l j ) , prevalence of campylobacter-like spiral organ- and different RNA sequences (16). Thus, it is not isms in patients with histologic gastritis and peptic an authentic campylobacter and was classified as a new genus, now named Helicobacter (1618). ulcer. The important question of whether bacteria The name Helicobacter pylori ( H . pylori) refers play a significant role in peptic ulcer and dyspepsia to the morphology of the organisms, which are awaits clarification. An alternative interpretation helical in vivo but often rod-like in vitro; also the of current data is that the organism is simply a name Helicobacter is euphonious and has the secondary invader of damaged gastric-like epi- advantage that it is similar to the name Camthelium. This paper examines the last decade of p y lobacter. Despite extensive investigation H . pylori has hectic research into the possible clinical relevance of Helicobacter pylori. been isolated from only the stomach and the
Downloaded by [] at 09:55 08 May 2016
160
M. G.Kormnn
duodenal bulb. In the stomach it may be detected DETECTION throughout the fundus, body, and antrum, lying By means of careful culture techniques, H. underneath the mucus layer in close apposition pylori can be isolated from 80% to 90% of persons to the surface mucous cells (9,14). Indeed, the subsequently proven by other methods to be organism seems to have very specifically adapted infected. Because the distribution of infection to living in the microenvironment closely related may be patchy, one should culture material from to this particular cell type. When the organism is at least two areas of the gastric mucosa (antrum present in the duodenum, it is always located and body) to maximize the likelihood of detecabove islands of metaplastic gastric surface tion. Histologic identification of Helicobacter mucous cells (19). Such metaplastic islands are organisms on the gastric epithelial surface corknown to be common in patients with duodenal relates well with culture results. The organisms ulcer (20). Organisms are rarely seen intracan usually be detected on haematoxylin-andcellularly, suggesting that H. pylori is nonineosin- or Giemsa-stained tissue. Warthin-Starry vasive. The mucus layer may insulate H. pylori and acridine orange stains facilitate detection of from gastric acid. Alternatively, bacterial hydrobacteria, especially if they are present in small lysis of urea to ammonium ion may produce an numbers. Gram stain of biopsy touch prepalkaline microclimate that allows it to survive in arations is a rapid and inexpensive method of an otherwise potentially hostile environment. diagnosing H. pylori, and its results correlate well with those of culture and other staining methods (23). The high urease activity exhibited by H. pylori has led to the development of diagnostic tests that MECHANISMS OF INJURY detect the presence of products of urea hydrolysis If H. pylori is a human pathogen, how does it and, by inference, the presence of H. pylori. cause damage? The precise mechanism(s) by Urease tests that detect high concentrations of which H. pylori induces mucosal injury is not this enzyme in mucosal biopsy specimens are easy known (9,21). Despite the lack of evidence of to perform, give a quick answer, and possess direct cellular invasion, cellular damage and reasonable sensitivity and specificity in cominflammation are prominent findings in infected parison with culture or histopathology. Breath persons. Gastric mucus is depleted, spotty epitests are also based on the high activity of urease thelial necrosis is seen, and polymorphonuclear produced by H. pylori and measure the excretion leukocytes infiltrate the epithelial layer in associof labelled C 0 2 in the expired air after the oral ation with acute and chronic inflammation in the administration of labelled urea. Both methods lamina propria. Ultrastructurally, surface epiare noninvasive, well-tolerated by the subjects, thelial cells are oedematous, degenerating, and and have good sensitivity and specificity. depleted of mucous granules. Surface microvilli Immunologic techniques using the enzymeare absent or sparse. The organism may interfere linked immunosorbent assay (ELISA) method with gastric mucous production directly or have reasonable specificity and sensitivity when indirectly, thereby permitting injury by gastric compared with culture or histopathology. Immuacid. Ammonia production by the bacteria may nologic techniques seem more suited to prevadamage cells through direct toxic effects or by lence studies than to examination of the results increasing pericellular pH. Alternatively, H. of therapy. pylori may release a yet undescribed toxin or chemotactic factor that promotes injury and inflammation. Active investigation of the pathoPREVALENCE genesis of H. pylori-mediated injury is ongoing and should be enhanced by further work in animal Helicobacter pylori in the normal population The worldwide prevalence and persistence of models, such as the gnotobiotic piglet (22).
Downloaded by [] at 09:55 08 May 2016
Helicobacter pylori
H . pylori suggest that it may be the commonest known human bacterial infection (9,24). Most current information documenting the prevalence of H. pylori comes from populations undergoing routine upper gastrointestinal endoscopy. Most such individuals have complained of dyspepsia. The overall isolation rate for H. pylori ranges from 32% to 62%, with a mean of 56% (5,14,25). Information about prevalence rates in either asymptomatic individuals or in a random cross-section of the population has proved more difficult to obtain. Prevalence in 34 asymptomatic volunteers was assessed endoscopically in Amsterdam, and 20% were found to be infected (26). Some of the volunteers were followed up prospectively for 2 years; during this period none exhibited spontaneous disappearance of the organism. In the United States the prevalence in healthy asymptomatic subjects is approximately 20%, but age and ethnic variations occur. For instance, H. pylori is rare is asymptomatic children but is present in 50% of SO-year-old persons and in 75% of those aged 65 years. Lambert (27) noted a similar age dependance in an Australian endoscopic series. Differences in population prevalence must be considered in attempts to establish the relationship between H. pylori and specific disease processes. Helicobacter pylori in disease states Active chronic gastritis (type B ) . The evidence is overwhelming that H. pylori is the cause of chronic type B gastritis (9,21). Active (neutrophilic infiltration) chronic gastric inflammation is virtually always found in association with H. pylori infection. Antral mucosa is involved most often. Autoimmune (type A) and secondary (Crohn’s disease, bile reflux) gastric inflammation are not often associated with H. pylori infection (28,29). Elimination of the organisms is usually associated with improvement in the gastric histologic picture. McNulty et al. (30) successfully cleared the organism from 78% of bismuth-treated patients compared with only 7% of those given erythromycin and none of those receiving placebo (30). Twelve of 13 whose organisms were cleared also had resolution of the gastritis, compared
161
with only 4 of 32 not cleared of the organism. Subsequent reports seem to confirm these findings (26,31). The definition of causation of disease by a microorganism requires that all of Henle-Koch’s postulates be satisfied. In attempts to fulfil Koch’s third postulate, two investigators have ingested H. pylori and developed an acute illness plus histologic gastritis (32,33). Further, it seems likely that inoculation with this organism led to an epidemic of hypochlorhydria and gastritis in a group of volunteers who took part in a study of acid secretion (34). Gastric juice had been removed for measurement of pH and, using the same glass electrode, then returned to each individual’s stomach. It is probable that an infectious agent contaminated the electrode. Recently, stored sera from these individuals were assessed for H. pylori antibodies, with a rise in titre dernonstrated in 9 of 12 subjects (35). Duodenal ulcer disease. The postulate that H. pylori is the sole cause of duodenal ulcer is far from established. Although prevalence of the bacteria in duodenal ulcer patients approaches loo%, this may merely reflect the close association between duodenal ulcer and antral inflammation. The prevalence of H. pylori infection increases with age, but dudoenal ulcer is not predominantly a disease of the elderly. Duodenal ulcer is a malepredominant disease, but H . pylori infection shows no gender predilection. Ulcer craters heal even though bacteria persist (36). Acid hypersecretion (for example, Zollinger-Ellison syndrome) leads to duodenal ulcer with no organisms present. Many persons infected with H. pylori never have ulcers, suggesting that important host factors or bacterial virulence factors determine the occurrence of disease. The strongest evidence that H. pylori infection is important in duodenal ulcer comes from antibiotic treatment trials. Antibiotics and bismuth produce healing of duodenal ulcers at the same rate as conventional H2 blocker therapy. However, once such acute therapy is stopped, the ulcers predictably return. On the other hand, when infection is eliminated and antimicrobial therapy is stopped, disease recurs less frequently. Those ulcers that do return after antibiotics
Downloaded by [] at 09:55 08 May 2016
162
M. G . Korman
usually do so in the setting of recurrent H. pylori infection (37). It is important to consider how an organism that colonizes gastric epithelium could cause duodenal ulcer (21,38). One theory is that a combination of bacteria and acid acts synergistically. Increased duodenal exposure to acid presumably leads to the formation of metaplastic gastric epithelium, which subsequently can become colonized, inflamed, and, with further acid contact, susceptible to ulceration. Thus, elimination of either acid by H2 receptor antagonists or bacteria by antibiotics would heal ulcers, but only antibiotic therapy would remove infection and lessen recurrence. Such a theory, which assigns an important role to both acid and bacteria, is supported by the high prevalence of gastric metaplastic epithelium in the duodenum of duodenal ulcer patients, but is far from proven. Family members, whether symptomatic or asymptomatic, of duodenal ulcer patients have a higher than expected prevalence of H. pylori infection. Bacterial analysis has revealed the similarity of organisms within families, suggesting the possibility of person-to-person spread or a common source of such infection. Such familial clustering of infection may stimulate re-evaluation of the genetic theories of ulcer disease. Recently, Levi et al. (39) have suggested that H. pylori in the gastric antrum may stimulate gastrin release in duodenal ulcer disease. Their study showed that pentagastrin-stimulated gastric acid secretion and postprandial plasma gastrin concentrations were significantly higher in H. pylori-positive than in H. pylori-negative patients with duodenal ulcer. This group also showed a fall in the integrated gastrin response to a meal in H.pylori-positive patients with duodenal ulcer after eradication of the organism, yet peak acid secretion did not fall (40). They proposed that the powerful urease produced by H. pylori splits urea, which is present in the stomach, to yield ammonia. The ammonia raises the pH of the mucus layer that overlies the gastric antrum, so that the expected normal inhibition of gastrin release by intraluminal acid is impaired. The increased gastrin release, which results from the absence of acid inhibition, stimulates gastric acid
secretion, both directly and by its trophic effect on the gastric secretory cell mass. Increased acid secretion may then cause duodenal ulcers by producing a low intraduodenal pH. However, their findings fail to offer an explanation for the presence of ulcers in H. pylorinegative patients or in those with normal gastric secretion. Presumably, ulcers in such patients could be due to other postulated abnormalities that have been reported in patients with duodenal ulcer disease. Obviously, much more data are required to clarify this intriguing area of research. Benign gastric ulcer. Currently, no studies have adequately evaluated the effects of eradication of bacteria on gastric ulcer healing or recurrence. Clearly, the organism is not the sole cause of gastric ulcer because the prevalence of infection is in the order of 6&80% (24). Because gastric ulcer patients tend to be older, this prevalence may not be significantly different from that seen in age-matched, non-disease groups. We must await further evidence. Non-ulcer dyspepsia. Non-ulcer dyspepsia (NUD) is potentially very important because of the high frequency with which this condition is diagnosed and the amount of time and valuable health resources it consumes. Patients with NUD have symptoms that suggest the presence of peptic ulcer, but no ulcer is found at endoscopy. The diagnosis of NUD is much more common than that of duodenal ulcer. The symptoms of NUD require the exclusion of gastro-oesophageal reflux, biliary tract disease, chronic pancreatitis, or the irritable bowel syndrome. This can only be achieved by careful history and thorough examination, followed by endoscopy to exclude the presence of peptic ulcer or oesophagitis. Further investigations may be needed, to exclude the presence of other conditions. NUD remains a clinical concept, characterized by the lack of objective features. Intentional ingestion of H. pylori definitely can cause transient dyspeptic symptoms (32,33). Whether this organism can lead to chronic abdominal symptoms is far from certain. The prevalence of infection in patients with NUD (40-60%) is similar to that in age-matched controls. Antibiotic therapy relieves NUD symptoms inconsistently, although
Helicobacter pylori
Downloaded by [] at 09:55 08 May 2016
it may reverse the gastric histologic change in infected persons (31). There are no convincing studies to support an aetiologic role of H . pylori in non-ulcer dyspepsia. Thus, there seems little justification for indiscriminate prescribing of bismuth compounds or antibiotics for NUD, even if H . pylori positivity is confirmed.
163
organism was cleared in only 57%, and no correlation was detected between ulcer healing and H . pylori eradication (36). Eradication of H . pylori is not necessary for ulcer healing, which is indirectly supported by the great efficacy demonstrated in peptic ulcer by histamine H2-receptor antagonists. These agents have no effect on the number of organisms, and ulcer healing has again been shown to be unreTREATMENT O F H . PYLORI INFECTION lated to the patient’s H . pylori status (42). LikeMany antibiotic regimens have proved effective wise, no change in H . pylori positivity occurred in suppressing bacterial growth but seem less in patients whose duodenal ulcers healed with effective in permanently eradicating the organ- misoprostol (43), and ranitidine maintenance ism. In vitro, H . pylori is usually sensitive to a therapy prevented ulcer relapse despite the perlarge number of antibiotics and moderately sen- sistence of organisms in most patients over a 12sitive to bismuth. However, in vitro sensitivities month period (44). These studies with powerful do not correlate well with in vivo efficacy for anti-secretory drugs do not imply that H . pylori eradicating H . pylori, perhaps because systemic is not an important initiating factor but only that antibiotics may not penetrate to the organism’s acid remains a major factor in the continuation habitat beneath the mucus gel layer. of an ulcer’s presence. Another important obserFurther complicating the selection of treatment vation has been the finding that bacteria persist is the inability to define successful eradication unchanged in 50% of patients whose ulcer heals of the bacteria. Whereas most culture-positive with placebo (42). This is further evidence against patients will become culture-negative immedi- an essential role for H . pylori, at least in ulcer ately after treatment with colloidal bismuth or persistence. amoxicillin singly or in combination, only 40% The success of bismuth in eliminating H . pylori remain culture-negative at 1 month, indicating has been suggested as an explanation for the lower that recurrence or recrudescence of infection is recurrence rate reported when ulcers heal with common (26). Recurrence appears to represent bismuth compared with cimetidine (45). More return of infection by the original bacterial strain recent studies have also found that those who rather than infection by a new organism. Possibly, relapsed in the year after their duodenal ulcers the use of higher doses, repeated or prolonged were healed with bismuth were much more likely courses of single antibiotics, or ‘triple therapy’ to be H . pylori-positive than those who did not (bismuth plus two antibiotics) may prove effective relapse (36,37). in eliminating H . pylori infection (41). However, These studies of duodenal ulcer relapse after such regimens undoubtedly will be associated with successful eradication of H . pylori may prove to significant side effects, including diarrhoea and be important links in establishing whether H . Clostridium dificile infection (26). Thus, one pylori plays a causal role in duodenal ulcer. Howmust carefully assess the possible risks versus ever, it must be remembered that colloidal bisthe potential benefits of a vigorous eradication muth has several effects other than those on H . program. pylori. It binds to the gastric mucosa and provides Colloidal bismuth subcitrate is moderately powerful protection against experimental injury inhibitory to H . pylori in vitro and renders many in acute animal models in which H . pylori has no patients H . pylori-negative (31,36). Whether role (46). Before we can confidently confirm that clearance of H . pylori by bismuth alone facilitates the lower relapse rate of duodenal ulcer after ulcer healing remains controversial. Lambert et successful bismuth therapy is directly related to al. (36) treated 45 patients with bismuth for 8 a marked reduction in the number of patients weeks; ulcers healed in 94%, even though the infected with H . pylori, it would be prudent to
164
M. G . Korman
wait for the results of studies using antibiotics that lack bismuth’s complex additional actions on the stomach and duodenum.
and economic impact on medical practise in the 1990s.
REFERENCES
Downloaded by [] at 09:55 08 May 2016
HELZCOBACTER INTO THE 1990s
1. Bizzozero G. Uber die Schlauchformigen Drusen
des Magendarkanals und die Bezienhungren ihres The many treatment trials being conducted in Epithels zu dem Oberflachenepithel der Schlemvarious research centres throughout the world haut. Arch Mikr Anat 1893, 42, 82-152 2. Warren JR. Unidentified curved bacilli on gastric will undoubtedly lead to clarification of the aetiepithelium in active chronic gastritis. Lancet 1983, ological role of H. pylori in digestive diseases. 1; 1273 The previous dictum of ‘no acid, no ulcer’ may 3. Marshall BJ. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983, now need to be supplemented with two further 1, 1273-1275 statements: ‘no H. pylori, no gastritis’ and ‘no H. 4. Marshall BJ, McGechie DB, Rogers PA, Glancy pylori, no ulcer’. Whether these dictums remain RJ. Pyloric campylobacter infection and gastrotrue will only be determined by future research. duodenal disease. Med J Aust 1985, 142, 439-444 5 . Jones DM, Lessells AM, Eldridge J. CampyloMuch work is required on the mechanisms by bacter-like organisms on the gastric mucosa: which H. pylori may cause gastrointestinal culture, histological and serological studies. J Clin disease. The determination of possible bacterial Pathol 1984, 37, 1002-1006 6. McNulty CAM, Watson DM. Spiral bacteria of the virulence factors or host susceptibility factors gastric antrum. Lancet 1984, 1, 1068-1069 requires careful study, particularly to explain why 7. Rollason TP, Stone J , Rhodes JM. Spiral organisms infected patients usually are free of clinical in endoscopic biopsies of the human stomach. J Clin Pathol 1984, 37, 23-26 disease. Possible environmental sources and 8. Langenberg ML, Tytgat GNJ, Schipper MEI, et al. modes of transmission of H . pylori should also be Campylobacter-like organisms in the stomach of patients and healthy individuals. Lancet 1984, I , elucidated; elimination of such sources or modes 1348 of transmission could lead to control or pre9. Goodwin CS, Armstrong JA, Marshall BJ. Camvention of clinical disease. The feasibility of vacpylobacter pyloridis, gastritis and peptic ulceration. cination requires further study, as this may prove J Clin Pathol 1986, 39, 353-365 to be a very important method of prevention. 10. Dooley CP, Cohen H. The clinical significance of campylobacter pylori. Ann Intern Med 1988, 108, Development of safe, convenient, effective ther70-79 apy for H . pylori will facilitate clinical inves- 11. Marshall BJ, Royce H, Annear DI, et al. Original isolation of Campylobacter pyloridis. Microbios tigations aimed at clarifying the role of this Letters 1984, 25, 83-88 bacteria in gastrointestinal disease. The issues of 12. Marshall BJ, Goodwin CS. Revised nomenclature how best to treat H . pylori, how long to treat, and of Campylobacter pyloridis. Int J Systemic Bacteriol 1987, 37, 68 whether to eradicate or reduce the microbiologic 13. Goodwin CS, McCulloch RK, Armstrong JA, Wee burden also remain to be resolved. Depending on SH. Unusual cellular fatty acids and distinctive the availability of appropriate therapy and further ultrastructure in a new spiral bacterium (Campylobacter pyloridis) from the human gastric clarification of the pathogenic role of H. pylori, it mucosa. J Med Microbiol 1985, 19, 257-267 would seem wise at present for those enthusiastic 14. Taylor DE, Hargreaves JA, Lai-King N , et al. supporters of Helicobacter infection to modify Isolation and characterization of Campylobacter pyloridis from gastric biopsies. Am J Clin Pathol their treatment decisions with good common 1987, 87, 49-54 sense and not needlessly subject patients to poss- 15. Goodwin CS, Armstrong JA, Marshall BJ. Camibly ineffective or potentially toxic therapeutic pylobacter pyloridis, gastritis and peptic ulceration. J Clin Pathol 1986, 39, 353-365 regimens. 16. Romaniuk PZ, Zoltowska B, Trust TJ, et al. CamWe await, with great interest, the data to conpylobacter pylori, the spiral organism associated with human gastritis is not a true Campylobacter firm that eradication of H . pylori leads to clinical sp. J Bacteriol 1987, 169, 2137-2141 improvement in infected symptomatic patients or, 17. Jones DM, Curry A. Ultrastructural study of gastric more importantly, prevention of gastrointestinal campylobacter-like organisms (GCLO) from man, baboon, pig and ferret. In Proceedings of the Fourth disease. Such findings would have a major clinical
Downloaded by [] at 09:55 08 May 2016
Helicobacter pylori International Workshop on Campylobacter Infections, Kungalv, Sweden, 1987, 73 18. Goodwin CS, Armstrong JA, Chilvers T, et al. Transfer of Campylobacter pylori and Campylobacter mustelae to Helicobacter gen. nov. as Helicobacter pylori comb. nov. and Helicobacter mustelae comb. nov., respectively. Int J Syst Bacteriol 1989, 39, 393-405 19. Steer HW. Surface morphology of the gastroduodenal mucosa in duodenal ulceration. Gut 1984, 25, 1203-1210 20. Fullman G , Van Deventer C, Schneidman D, et al. 'Healed' duodenal ulcers are histologically ill. Gastroenterology 1985, 88, 1390 21. Graham DY. Campylobacter pylori and peptic ulcer disease. Gastroenterology 1989, 96, 615-4562 22. Lambert JR, Borromeo M, Pinkard KJ, et al. Colonization of gnotobiotic piglets with Campylobacter pyloridis-an animal model? J Infect Dis 1987, 155, 1344 23. Montgomery EA, Martin DF, Peura DA. Rapid diagnosis of Campylobacter pylori by Gram's Stain. Am J Clin Pathol 1988, 56, 2896-2906 24. Graham DY, Klein PD, Opekun AR, Boutton TW. Effect of age on the frequency of active campylobacter pyloridis infection diagnosed by the ["C] urea breath test in normal subjects and patients with peptic ulcer disease. J Infect Dis 1988,157,777-780 25. Burnett RA, Forrest JAH, Girdwood RWA, Fricker CR. Campylobacter-like organisms in the stomach of patients and healthy individuals. Lancet 1984, 1 1349 26. Rauws EAJ, Langenberg W , Houthoff HJ, et al. Campylobacter-pyloridis-associatedchronic active antral gastritis: a prospective study of its prevalence and the effects of antibacterial and antiulcer treatment. Gastroenterology 1988, 94, 33-40 27. Lambert JR. Prevalence of C. pylori in diseases of GI tract and relationship to gastritis. In: Peterson WL, ed. Campylobacter pylori: a multi-disciplinary workshop, Colorado, 1987 28. O'Connor HJ, Axon ATR, Dixon MF. Campylobacter-like organisms unusual in type A (pernicious anaemia) gastritis. Lancet 1984, 2, 1091 29. Lambert JR, Dunn KL, Eaves ER, et al. Pyloric CLO in the human stomach. Med J Aust 1985, 143, 174 30. McNulty CAM, Gearty JC, Crump B, et al. Campylobacter pyloridis and associated gastritis: investigator blind, placebo controlled trial of bismuth salicylate and erythromycin ethylsucrinate. Br Med J 1986, 293, 645-649 31. Lambert JR, Borromeo M, Korman MG, Hansky J . Role of Campylobacter pyloridis in non-ulcer
165
dyspepsia: a randomized controlled trial. Gastroenterology 1987, 92, 1488 32. Morris A, Nicholson G. Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol 1987, 82, 192-199 33. Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ. Attempts to fulfil Koch's postulates for pyloric campylobacter. Med J Aust 1985, 142, 436439 34. Ramsey EJ, Carey KV, Peterson WL, et al. Epidemic gastritis with hypochlorhydria. Gastroenterology 1979, 76, 1449-1457 35. Peterson W, Lee E, Skoglund M. The role of Campylobacter pyloridis in epidemic gastritis and hypochlorhydria. Gastroenterology 1987, 92, 1489 36. Lambert JR, Borromeo M, Korman MG, et al. Effect of colloidal bismuth (De-Nol) on healing and relapse of duodenal ulcers: role of Campylobacter pyloridis. Gastroenterology 1987, 92, 1489 37. Coghlan JG, Gilligan D, Humphries H, et al. Campylobacter pylori and recurrence of duodenal ulcers-a 12 month follow-up study. Lancet 1987, 2, 1109-1111 38. Wyatt JI, Rathbone BJ, Dixon MF, Heatley RV. Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis. J Clin Path01 1987, 40, 841-848 39. Levi S, Beardshall K, Haddad G , et al. Campylobacter pylori and duodenal ulcers: the gastrin link. Lancet 1989 1 , 1167-1168 40. Levi S, Beardshall K, Swift I, et al. Antral Helicobacter pylori, hypergastrinaemia and duodenal ulcers: effect of eradicating the organism. Br Med J 1989, 299, 1504-1505 41. Borody TJ, Cole P, Noonan S, et al. Recurrence of duodenal ulcer and Campylobacter pylori infections after eradication. Med J Aust 1989, 151, 431-434 42. Humphries H, Dooley C, O'Leary D, et al. Effect of therapy on Campylobacter pyloridis: a randomized trial. Gut 1986, 27, A 611 43. Ho J , Lui I, Hui WM, et al. A study of the correlation of duodenal ulcer healing with campylobacter-like organisms. J Gastroenter Hepatol 1986, 1 , 69-74 44. Thomas JM, Poynter D, Gooding C, et al. Gastric spiral bacteria. Lancet 1984, 11, 100 45. Martin DF, Hollander SD, May SJ, et al. Differences of relapse rates of duodenal ulcer after healing with cimetidine or tripotassium citrato bismuthate. Lancet 1981, 1, 7-10 46. Wieriks J , Hespe W, Jaitley KO. Pharmacological properties of colloidal bismuth subcitrate (CBS DeNol). Scand J Gastroenterol 1982, 17(suppl 80), 1116
