Is Helicobacter pylori the cause of dyspepsia?

OBJECTIVE--To determine the association between infection with Helicobacter pylori and dyspepsia. DESIGN--Cross sectional study of dyspeptic subjects and age and sex matched controls identified by a questionnaire survey of all inhabitants aged 20-69. (Endoscopy, histological examination, and microbiological examinations of biopsies from the gastric mucosa were performed blind.) SETTING--Population based survey in Sørreisa, Norway. SUBJECTS--All 782 dyspeptic subjects (excluding those with a previous history of peptic ulcer, gall stones or kidney stones, and coronary heart disease) and controls were offered an endoscopy, of whom 309 dyspeptic subjects and 310 controls attended. MAIN OUTCOME MEASURES--Prevalences of endoscopic and histological diagnoses and of cultures positive for H pylori. RESULTS--A high prevalence of positive cultures, increasing with age, was found in both dyspeptic subjects (48%) and non-dyspeptic controls (36%) (p = 0.004). Positive cultures in both dyspeptic subjects and controls were strongly associated with histological gastritis (70%, 95% confidence interval 65.5 to 85.3; 60%, 52.7 to 67.7, respectively) and peptic ulcer (92%, 61.5 to 99.8; 64.1, 9.4 to 99.2, respectively). Only 3% of subjects with a histologically non-inflamed gastric mucosa had this infection (dyspeptic subjects 2%, 0.2 to 7.0; controls 4%; 1.2 to 8.8). CONCLUSIONS--The relation between dyspeptic symptoms and H pylori is dubious; H pylori seems to have a pathogenetic role in gastritis and may be a contributing factor but not a cause of peptic ulcer.     

Helicobacter pylori vaccines and mechanisms of effective immunity: is mucus the key?

In this theoretical article, the hypothesis is proposed that immunization against gastric helicobacter infection is mediated by CD4+ T-cell induced changes in mucus production. Vaccine development for the gastric pathogen Helicobacter pylori has encountered several problems. Resolving these problems is impeded by our lack of understanding of the mechanisms by which the immune response influences bacterial colonization. Protective immunity requires CD4+ T cells, but the majority of helicobacters are located in the mucus of the gastric lumen, away from the epithelial surface. Evidence suggests that this mechanism functions independently of antibodies, so how this is achieved is unknown. Clues to this mechanism may be provided by immune clearance of nematode infection. Similar to H. pylori, expulsion of the intestinal nematode, Nippostrongylus brasiliensis, in rodents is mediated by CD4+ T-cell changes in the numbers of goblet cells and the type of mucins secreted into the gut. Immune-mediated changes in secretion of gastric mucins could similarly be responsible for the reductions in helicobacter colonization seen in immunized animals. Helicobacter pylori are highly motile bacteria that have evolved to inhabit their specialized niche. Alterations in their mucus environment could influence their motility, such that the bacteria cannot remain efficiently within the mucus and are flushed away.     

Will cardiac surgery improve my quality of life?

Background. The intention of this study is to analyse the correlation between a visual analogue scale (VAS) and the most common preoperative comorbidity and cardiac variables in patients undergoing elective cardiac surgery. This VAS is simple, easy to register and can be used as a global measurement of quality of life (QOL). Methods. Preoperative assessment of QOL in 1351 patients, 979 men and 372 women, with a mean age of 64.5±10.5 (18-88), undergoing elective cardiac surgery between January 2003 and December 2005. QOL was measured by the EuroQol questionnaire. Results. The mean VAS was 58.7±20.9, range 3 to 100. Univariate analysis showed a difference for sex (p=0.000), and NYHA (p=0.009) between patients with an isolated CABG and those with a combined revascularisation (p=0.05). Stepwise logistic regression analysis identified female gender (p=0.00), NYHA (p=0.00) and valve disease (p=0.03) as independent variables for a low QOL. The correlation between NYHA and QOL was low (r=-0.09, p=0.003). Conclusion. The clinical consequence is that using this simple VAS we can identify patients with a good QOL. If these patients present for high-risk surgery, with a better quality of life as primary indication, more extended counselling regarding their QOL is recommended. (Neth Heart J 2007; 15:51-4.)     

Is there seasonal periodicity in the prevalence of Helicobacter pylori?

The objective of the present study was to evaluate seasonal periodicity in the prevalence of Helicobacter pylori. A prospective study was performed on 1076 consecutive patients who were investigated in our hospital over a 3-year span because of epigastric complaints. Our findings indicate a significant accumulation of positive Helicobacter pylori tests in October. Gastric acidity, gender, and age did not influence Helicobacter pylori infection significantly. There was no significant correlation between potential seasonal influence on the diagnosis of ulcer disease and the seasonal fluctuation of Helicobacter pylori infection. The seasonality was confirmed by cosinor analysis for the absolute frequencies of H. pylori infections and also for the number of cases positive for H. pylori per number of presenting patients per month. A seasonal concept of a sensitivity threshold for positive Helicobacter pylori testing is introduced, taking into account such factors as immune system, nutrition, and medication status.     

Lipid peroxidation in chronic gastritis; any influence of Helicobacter pylori?

In an attempt to investigate the significance of lipid peroxidation in the pathogenesis of gastritis associated with or without Helicobacter pylori infection, malonodialdehyde (MDA) levels were measured by the thiobarbiturate assay in the gastric juice of 101 patients undergoing upper GI endoscopy and correlated with histopathological findings. Elevated MDA levels were found in all patients with gastritis compared with controls. MDA levels were significantly correlated with the extent of the mucosal inflammation and with disease activity in patients with reactive gastritis. In patients with H. pylori associated gastritis MDA levels were not correlated with disease activity but rather with the degree of atrophy. In this case, MDA levels were equal or even less than in patients with reactive gastritis. MDA levels were not affected by the history of consumption of PPIs, of H(2)-blockers or of NSAIDs over the last month before the endoscopy. It is concluded that lipid peroxidation is a mechanism involved in the pathogenesis of gastritis associated or not to H. pylori infection.     

Global estimate of gastric cancer in Helicobacter pylori–infected population: A systematic review and meta-analysis

There is information regarding the rates of gastric cancer (GC) in different populations and the important role of Helicobacter pylori in GC development; however, no comprehensive study has yet been performed to investigate the prevalence of GC in H. pylori–infected patients. PubMed, Embase, and Cochrane Library through January 1, 2000 were searched without language restrictions. Quality of included studies was assessed with a critical appraisal checklist recommended by the Joanna Briggs Institute. All of the analyses were conducted using Comprehensive Meta-Analysis Software Version 2.0 and Stata 14.0. Forty-four studies from 17 countries were included. The pooled frequency of GC was 17.4% (95% confidence interval: 16.4–18.5) in H. pylori–infected population. The frequency of GC among H. pylori–infected population varied markedly across countries. The highest rate of GC was observed in H. pylori–infected individuals from Asian countries. The frequency of GC was relatively high in H. pylori–infected population in the world. However, the eradication of H. pylori might be a promising strategy for GC prevention, especially in high-risk populations such as Asian countries.     

High eradication rates of Helicobacter pylori infection following sequential therapy: the Israeli experience treating naïve patients

Background: Helicobacter pylori eradication rates following triple therapy are decreasing. Cure rates as low as 57%, mainly to claritromycin resistance, have been reported in Israel. Studies performed in Italy have shown eradication rates of 93%, following sequential therapy. Our aim was to evaluate the effect of sequential therapy on eradication rates of H. pylori in naïve Israeli patients. Material and Methods: Consecutive patients referred for esophagogastroduodenoscopy with a positive rapid urease test and positive ¹³C urea breath test were included. Patients received omeprazole 20 mg bid and amoxicillin 1 g bid for 5 days followed by omeprazole 20 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for the subsequent 5 days. A second ¹³C urea breath test was performed at least 4 weeks after completion of therapy. Patients were asked to avoid antibiotics, bismuth compounds or proton pump inhibitor until after the second ¹³C urea breath test. Adverse effects were documented by a questionnaire. Results: One hundred and twenty‐four patients (mean age 56.1 ± 12.5 years, 55.6% women) were included; 120/124 (96.8%) completed treatment and performed the second ¹³C urea breath test. Two patients (1.6%) were lost to follow‐up; 2 (1.6%) were noncompliant with study regulations. One hundred and fifteen patients achieved eradication of H. pylori. The eradication rate was 95.8% by per protocol analysis and 92.7% by intention to treat analysis. Conclusion: The sequential regimen attained significantly higher eradication rates in naïve patients than usually reported for conventional triple therapy. Sequential therapy may be an alternative first‐line therapy in eradicating H. pylori in Israel.     

Is Antrum or Corpus the Best Site for Culture of Helicobacter pylori?

Background Isolating Helicobacter pylori on culture media and performing antibiotic susceptibility testing is potentially the most useful tool for guiding antibiotic therapy, especially when antimicrobial resistance is suspected. The aim of this study was to determine whether the yield of H. pylori culture was related to the site from which the gastric specimen was obtained either before or after therapy.
Methods. Gastric mucosal biopsies from the antrum and the corpus of the stomach were cultured. H. pylori status was determined by histological assessment using the Genta stain.
Results. Fifty-two patients with documented H. pylori infection were studied: Twenty-three were tested before antibiotic therapy and 29 after therapy had failed. In 47 patients (90%), both antral and corpus culture specimens were positive. In 5 patients (10%), only one site was positive, with three false-negative antral and two false negative corpus cultures. The overall sensitivity of culture in detecting H. pylori infection was 95% (95% confidence interval = 89–98%) and was not significantly different for the antrum or corpus, either before or after therapy.
Conclusion. Culture of gastric biopsies from either the antrum or the corpus has an excellent diagnostic yield even in patients who failed antimicrobial therapy.     

Helicobacter pylori and autoimmune pancreatitis: role of carbonic anhydrase via molecular mimicry?

Autoimmune pancreatitis is a recently defined nosological entity, which accounts for 4.6-6% of all forms of chronic pancreatitis and is often associated with other autoimmune diseases, particularly Sjogren's syndrome. Possession of the HLA DRB1*0405-DQB1*0401 genotype confers a risk for the development of autoimmune pancreatitis. Autoantibodies against carbonic anhydrase II and lactoferrin are frequently present in affected subjects and are suspected to have a pathogenic role. A link between gastric infection by Helicobacter pylori and autoimmune pancreatitis has been hypothesized. We used in silico protein analysis and search for HLA binding motifs to verify this hypothesis. We found a significant homology between human carbonic anhydrase II and alpha-carbonic anhydrase of Helicobacter pylori, an enzyme which is fundamental for the survival and proliferation of the bacterium in the gastric environment. Moreover, the homologous segments contain the binding motif of the HLA molecule DRB1*0405. Our data strengthen the hypothesis that gastric Helicobacter pylori infection can trigger autoimmune pancreatitis in genetically predisposed subjects.     

Acid survival of Helicobacter pylori: how does urease activity trigger cytoplasmic pH homeostasis?

Helicobacter pylori can survive for several hours at pH 1 in the presence of urea. Under these conditions, the organism maintains its cytoplasmic pH at a value close to neutral. The role of the cytoplasmically located urease enzyme in this process is a matter of debate. We propose that cytoplasmic ammonia generated by the action of urease is protonated by H(+) ions leaking in from the acidic medium and that the NH(4)(+) formed is extruded from the cytoplasm via an as-yet-unidentified transport system. This mechanism is compared with the general mechanism of cytoplasmic pH homeostasis in microorganisms.