Helicobacter pylori virulence factors in duodenal ulceration: A primary cause or a secondary infection causing chronicity.

Reports from countries with a high prevalence of Helicobacter pylori (H pylori) infection do not show a proportionately high prevalence of duodenal ulceration, suggesting the possibility that H pylori cannot be a primary cause of duodenal ulceration. It has been mooted that this discrepancy might be explained by variations in the prevalence of virulence factors in different populations. The aim of this paper is to determine whether the published literature gives support to this possibility. The relevant literature was reviewed and analyzed separately for countries with a high and low prevalence of H pylori infection and virulence factors. Although virulent strains of H pylori were significantly more often present in patients with duodenal ulcer than without the disease in countries with a low prevalence of H pylori infection in the population, there was no difference in the prevalence of virulence factors between duodenal ulcer, non - ulcer dyspepsia or normal subjects in many countries, where the prevalence of both H pylori infection and of virulence factors was high. In these countries, the presence of virulence factors was not predictive the clinical outcome. To explain the association between virulence factors and duodenal ulcer in countries where H pylori prevalence is low, only two papers were found that give little support to the usual model proposed, namely that organisms with the virulence factors are more likely than those without them to initiate a duodenal ulcer. We offer an alternative hypothesis that suggests virulence factors are more likely to interfere with the healing of a previously produced ulcer. The presence of virulence factors only correlates with the prevalence of duodenal ulcer in countries where the prevalence of H pylori is low. There is very little evidence that virulence factors initiate duodenal ulceration, but they may be related to failure of the ulcer to heal.

Precise role of H pylori in duodenal ulceration.

The facts that H pylori infection is commoner in duodenal ulcer (DU) patients than in the normal population, and that eradication results in most cases being cured, have led to the belief that it causes DU. However, early cases of DU are less likely than established ones to be infected. H pylori-negative cases are usually ascribed to specific associated factors such as non-steroidal anti-inflammatory drugs (NSAIDs), Crohn's disease, and hypergastrinaemia, but even after excluding these, several H pylori-negative cases remain and are particularly common in areas of low prevalence of H pylori infection. Moreover, this incidence of H pylori negative DU is not associated with a fall in overall DU prevalence when compared with countries with a higher H pylori prevalence. In countries with a high H pylori prevalence there are regional differences in DU prevalence, but no evidence of an overall higher prevalence of DU than in countries with a low H pylori prevalence. There is no evidence that virulence factors are predictive of clinical outcome. After healing following eradication of H pylori infection DU can still recur. Medical or surgical measures to reduce acid output can lead to long-term healing despite persistence of H pylori infection. Up to half of cases of acute DU perforation are H pylori negative. These findings lead to the conclusion that H pylori infection does not itself cause DU, but leads to resistance to healing, i.e., chronicity. This conclusion is shown not to be incompatible with the universally high prevalence of DU compared with controls.

Dietary Phytosterols Protective Against Peptic Ulceration.

BACKGROUND: In developing countries the prevalence of duodenal ulceration is related to the staple diet and not to the prevalence of Helicobacter pylori. Experiments using animal peptic ulcer models show that the lipid fraction in foods from the staple diets of low prevalence areas gives protection against ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs), and also promotes healing of ulceration. The lipid from the pulse Dolichos biflorus (Horse gram) was highly active and used for further investigations. Further experiments showed the phospholipids, sterol esters and sterols present in Horse gram lipid were gastroprotective. Dietary phospholipids are known to be protective, but the nature of protective sterols in staple diets is not known. The present research investigates the nature of the protective phytosterols. METHODS: Sterol fractions were extracted from the lipid in Dolichos biflorus and tested for gastroprotection using the rat ethanol model. The fractions showing protective activity were isolated and identification of the components was investigated by Gas Chromatography-Mass Spectrometry (GC-MS). RESULTS: The protective phytosterol fraction was shown to consist of stigmasterol, ß-sitosterol and a third as yet unidentified sterol, isomeric with ß-sitosterol. CONCLUSIONS: Dietary changes, affecting the intake of protective phospholipids and phytosterols, may reduce the prevalence of duodenal ulceration in areas of high prevalence and may reduce the incidence of recurrent duodenal ulceration after healing and elimination of Helicobacter pylori infection. A combination of phospholipids and phytosterols, such as found in the lipid fraction of ulceroprotecive foods, may be of value in giving protection against the ulcerogenic effect of NSAIDs.

Controversies in the Helicobacter pylori/duodenal ulcer story.

In patients with Helicobacter pylori-positive duodenal ulcer (DU), the organism must be eradicated to achieve rapid, stable healing. However, evidence is against much else that is commonly accepted. (1) Does H. pylori cause the ulcer? Evidence against includes archaeopathology, geographical prevalence, temporal relationships and H. pylori-negative DU patients. DU can recur after eradication of H. pylori infection, and DUs may remain healed after reduction of acid secretion despite persistent infection. The faster healing of ulcers when H. pylori has been eradicated is due to the organism's interference with neoangiogenesis and the healing of wounded epithelial cells. (2) Does H. pylori infection persist until pharmacologically eradicated? Studies based on current infection show that H. pylori infection is a labile state that can change in 3 months. High rates of gastric acid secretion result in spontaneous cure, whereas low rates permit re-infection. Hydrochloric acid, necessary for producing a DU, is strongly associated with the likelihood of an ulcer. At the start, patients owe their ulcer to gastric hypersecretion of hydrochloric acid; approximately 60% may be H. pylori-negative. If acid is suppressed, the less acid milieu encourages invasion by H. pylori, especially if the strain is virulent.

Duodenal ulcer in South Africa: home-pounded versus milled maize.

BACKGROUND: In South Africa there is suggestive evidence that home-pounded maize protects against duodenal ulceration. Therefore the purpose of the present paper was to test, in an animal model, whether oil from home-pounded maize gives protection against ulceration and whether this effect is present in commercially prepared maize oil. METHODS: Gastric ulceration was induced in rats with topical ethanol 1 h after giving oil prepared either from fresh-pounded or from commercially treated maize. The lengths of the linear ulcers produced were measured with a planimeter and summed in each rat. Control observations were made using arachis oil (which is known not to be ulceroprotective) and horse gram lipid (which is known to be strongly ulceroprotective). Statistical comparisons were performed mainly with the Mann-Whitney U-test, but also with reference to the normal distribution. Thin-layer chromatography (TLC) was performed on the oil from fresh maize, and the fractions similarly investigated for ulceroprotective activity. RESULTS: Fresh maize oil was strongly ulceroprotective (P = 0.0039), commercial maize oil was not (P = 0.2864). The active ingredient in the fresh maize oil was located in the fraction near the solvent front. CONCLUSION: These findings support the hypothesis that home-pounded maize protects against duodenal ulceration.

Post-gastrectomy patients need to be followed up for 20-30 years.

AIM:To investigate the incidence and management of nutritional deficiencies following a gastrectomy.METHODS:A gastrectomy population of 227 patients in London was followed up for 30 years after operation to detect and treat nutritional deficiencies.RESULTS:By the end of the first decade iron deficiency was the commonest problem. Vitamin B(12) deficiency became more important in the second decade. During the third decade both reached equal prevalence, being found in some 90% of the female and 70% of the male residual population. Vitamin D deficiency was a lesser problem, reaching its climax in the second decade. Overall, all women fared worse than men.CONCLUSION:The importance of long-term follow-up of gastrectomy patients for iron, Vitamin B(12) and Vitamin D deficiencies is emphasised.

Duodenal ulcer prevalence: research into the nature of possible protective dietary lipids.

The varying geographical prevalence of duodenal ulceration has suggested a relationship to staple diet. Previous experiments on animal peptic ulcer models showed that certain foods, particularly the lipid fraction, are ulceroprotective. This paper reports experiments on animal models further to investigate the nature of the protective substances in the most active lipid, that of horse gram. The free fatty acids and triglycerides, sterols, sterol esters and phospholipids from horse gram were extracted and tested for protective activity on rat peptic ulcer models: the pyloric ligation model which is chronic, involving 14 days pre-feeding, and two acute models using ethanol or cysteamine to induce ulceration. The results showed that sterol esters, but not sterols, were protective in the pyloric ligation model. Sterols were protective in the acute models using ethanol-induced and cysteamine-induced ulceration. Phospholipids were protective in both types of model. The free fatty acids and triglycerides gave no protection using the pyloric ligation model. The presence of sterols, sterol esters and phospholipids in the lipid fraction of foods in staple diets may account for the low prevalence of duodenal ulcer in certain geographical areas, despite a uniformly high prevalence of Helicobacter pylori infection.

Duodenal gastric metaplasia and Helicobacter pylori infection in high and low duodenal ulcer-prevalent areas in India.

BACKGROUND: Previous reports, based on surgery, showed duodenal ulcer (DU) to be more common in the rice-eating areas of southern India than in the northern wheat-eating areas. AIMS: Does this difference persist? Can it be explained by risk factors other than diet? METHODS: A total of 20 053 records from patients undergoing endoscopy for dyspepsia, and 590 endoscopy patients from two northern and two southern centers in India were studied prospectively. Records were scrutinized to determine the relative incidence of DU and non-ulcer dyspepsia in wheat- and rice-eating areas. Age, sex, length of history, smoking and medication were recorded. Three antral biopsies and one from each duodenal quadrant were taken. A rapid urease test was carried out on one of the antral biopsies; the others were examined for Helicobacter pylori, gastritis, duodenitis and duodenal gastric metaplasia. RESULTS: The difference in diet-associated prevalence persisted. No differences in smoking, Helicobacter pylori infection or duodenal gastric metaplasia were found between the two regions, but all three were more common in DU than in non-ulcer dyspeptic patients from both dietary areas. CONCLUSIONS: The dietary differences between the regions remain the only factor to account for the differences in DU prevalence. A strong interrelationship between duodenal gastric metaplasia and cigarette smoking is demonstrated.