Will eradication of Helicobacter pylori improve symptoms of non-ulcer dyspepsia? Meta-analysis included unreliable studies.
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Controlled Clinical Trials as Topic↗
Biomedical subjects
A L Blum
Publications and source records attributed to A L Blum.
The effects of omeprazole on healing and appearance of small gastric and duodenal lesions during dosing with diclofenac in healthy subjects.
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal mucosal damage. Omeprazole prevents the formation, and accelerates the healing, of NSAID-induced ulcers. AIM: To test whether omeprazole accelerates healing of standardized gastroduodenal lesions in the presence of diclofenac. METHODS: In a double-blind, double-dummy, placebo-controlled, crossover study, 12 healthy volunteers received consecutive, 2-week courses of omeprazole (40 mg o.d.) and placebo, in random order, with an intervening, 4-week washout period; diclofenac (50 mg t.d.s.), was given for the second week of each course. Five endoscopies were performed, one at the outset and the others before and after each course of diclofenac. Biopsies were taken from the endoscopically normal mucosa of the corpus, antrum and duodenum and also from any new mucosal lesion that developed after diclofenac. The sites of biopsies taken before each course of diclofenac were evaluated endoscopically after each course to assess the extent of healing according to a predetermined healing score scale. RESULTS: The healing scores observed after administration of placebo/diclofenac (median=0; range 0-6) and after omeprazole/diclofenac (median=0; range 0-6; P=0.17) did not differ. Small gastroduodenal lesions developed de novo in six subjects during placebo/diclofenac and in seven during omeprazole/diclofenac. Focal chemical gastropathy was observed only in close proximity to macroscopic lesions. CONCLUSIONS: In healthy subjects, omeprazole does not accelerate the healing of pre-existing mucosal lesions or prevent the development of small diclofenac-induced mucosal lesions.
Adult↗
Oral administration of antigens from intestinal flora anaerobic bacteria reduces the severity of experimental acute colitis in BALB/c mice.
Homeostasis between indigenous intestinal flora and host response may be broken in inflammatory bowel disease. The present study explores whether repeated oral administration of intestinal flora antigens can protect mice against dextran sodium sulphate (DSS)-induced colitis. Sonicates of Gram-positive, Gram-negative, or anaerobic resident bacteria isolated from mouse intestinal flora were fed to BALB/c mice by gastric gavage, with or without cholera toxin. After four weekly doses of 1 mg of these antigen preparations (or of PBS as control), DSS colitis was induced. One week later colitis was evaluated by clinical scores and histology. Mice fed a pool of the three sonicates had decreased inflammation scores (5 (1-14); median (range)) compared with PBS-fed control animals (15 (7-19); P < 0.05). Decreased inflammation was observed in mice fed anaerobic bacteria antigens (7 (6-11); P < 0.05 versus control), but not in mice fed a pool of Gram-positive and -negative sonicates (16 (12-16)). Inflammation scores of mice fed antigens with cholera toxin were similar to those of PBS-fed control animals. DSS-induced colitis can be suppressed by oral administration of normal intestinal flora antigens containing anaerobes.
Acute Disease↗
Quantitative analysis of intestinal motor patterns: spatiotemporal organization of nonneural pacemaker sites in the rat ileum.
BACKGROUND & AIMS: Intestinal contractions are triggered by electric activity of pacemaker cells within the smooth muscle. However, the precise spatial organization of the pacemaker system is unknown. We directly assessed the spatiotemporal organization of pacemakers by video image analysis combined with manometry and electromyography. METHODS: Isolated segments of rat ileum were perfused arterially with oxygenated fluorocarbon solution and luminally with saline. Luminal end pressures, extracellular electric activity, and images of the intestine were recorded simultaneously. Tetrodotoxin, N(G)-nitro-L-arginine methyl ester (L-NAME), L-arginine, and eserine were administered arterially. RESULTS: Myogenic contractions originated in discrete areas (dominant pacemakers) and propagated faster in aboral than in oral direction. Dominant pacemakers were distributed along the intestine at regular intervals. The preparations were mostly driven by 1 pacemaker at the time, but 2 or 3 pacemakers with different frequencies could be active simultaneously. Tetrodotoxin decreased aboral propagation velocity and revealed multiple regularly spaced pacemaker areas. Eserine increased, whereas L-arginine decreased, their frequency. After L-NAME, pacemaker activity increased and isolated pacemakers with higher frequency appeared. CONCLUSIONS: Nonneural pacemakers in rat ileum are functionally organized not as a continuous system but show a segmental arrangement, spatially and temporally modulated by neural activity.
Animals↗
The effect of intra-gastric acidity and flora on the concentration of N-nitroso compounds in the stomach.
BACKGROUND: Correa's hypothesis proposes that gastric carcinogenesis is due to atrophic gastritis and hypochlorhydria which permit gastric bacterial colonization, the reduction of dietary nitrates to nitrites and the formation of potentially carcinogenic N-nitroso compounds (NOCs). OBJECTIVE: To test the hypothesis that omeprazole-induced hypochlorhydria is associated with increased intra-gastric concentrations of nitrate-reducing bacteria (NRB), nitrites and NOCs. DESIGN: Single-blind study in healthy volunteers. PARTICIPANTS: Fourteen healthy subjects (seven female, mean age 24 years), free of Helicobacter pylori infection, received a one-week course of placebo followed by a two-week course of omeprazole, 20 mg daily. METHODS: Fasted gastric samples, aspirated using a sterile double-lumen nasogastric tube at the end of the 1 st week (placebo) and the 2nd and 3rd weeks (omeprazole), were cultured aerobically and anaerobically; gastric pH and intra-gastric concentrations of nitrates, nitrites and NOCs were also determined. RESULTS: After weeks 1, 2 and 3, the intra-gastric concentrations of nitrate-reducing bacteria exceeded 10(5) colony-forming units (c.f.u.)/ml in 3, 7 and 9 subjects, respectively (P > 0.05). A gastric pH greater than 4.0 was associated with increased NRB (P < 0.05); however, neither increased gastric pH nor increased NRB, alone or in combination, was associated with increased intra-gastric concentrations of nitrites or NOCs (P > 0.05). CONCLUSIONS: A two-week increase in gastric pH in healthy, H. pylori-negative subjects was associated with increased intra-gastric concentrations of nitrate-reducing bacteria but not of nitrites or N-nitroso compounds. These data suggest that reduced gastric acid secretion is not a necessary precursor to the formation of carcinogenic N-nitroso compounds and that other mechanisms should be invoked to explain gastric carcinogenesis.
Achlorhydria↗
The effect of ammonia on omeprazole-induced reduction of gastric acidity in subjects with Helicobacter pylori infection.
OBJECTIVE: Omeprazole produces a higher intragastric pH during Helicobacter pylori (H. pylori) infection than after cure. We tested the hypothesis that this difference is due to the production of ammonia by H. pylori. METHODS: Gastric acidity and acid output (AO) were measured overnight in 12 subjects, with and without omeprazole, before and 1 and 6 months after cure of H. pylori infection. Gastric ammonia ([NH3]), total bile acid ([TBA]) and protein concentrations and plasma omeprazole levels were measured. RESULTS: During omeprazole, median AO were 0.0 mmol/h before, 0.86 mmol/h (p = 0.003 vs before cure) at 1 month, and 0.34 mmol/h (p = 0.02) at 6 months after cure; median NH3 output was 0.17 mmol/h before, 0.03 mmol/h (p = 0.002) at 1 month, and 0.02 mmol/h (p = 0.005) at 6 months after cure. AO and NH3 output were similar 1 and 6 months after cure. When corrected for [NH3], AO and gastric pH curves were similar before and after cure. Omeprazole plasma levels increased after cure and gastric [TBA] were unchanged. CONCLUSIONS: The higher pH observed before cure of H. pylori during omeprazole administration is attributable, in large part, to ammonia production. Other acid-neutralizing substances and changes in acid secretion may also be important, but duodenogastric reflux and omeprazole pharmacokinetics are not involved.
Adult↗
Diagnostic accuracy and interobserver agreement of CT colonography (virtual colonoscopy).
BACKGROUND AND AIMS: Computed tomographic (CT) colonography or virtual colonoscopy (VC) is a non-invasive imaging method proposed for screening patients with colorectal neoplasias. Our aims were to study the diagnostic accuracy and interobserver agreement of VC for correct patient identification compared with conventional colonoscopy (CC). METHODS: This was a prospective study of 50 patients successively undergoing VC and CC. Multiplanar two dimensional CT images and three dimensional VC were constructed using surface rendering software and interpreted by two independent investigator teams. VC findings were compared with those of CC. Interobserver agreement was determined using kappa statistics. RESULTS: CC found 65 polyps in 24 patients. For identification of patients with polyps > or =10 mm, the sensitivity of VC was 38% and 63%, and specificity was 74% and 74% for teams 1 and team 2. Interobserver agreement was good (kappa 0.72). For patients with polyps of any size, the sensitivity of VC was 75% and 71%, and specificity was 62% and 69% for teams 1 and 2. Interobserver agreement was fair (kappa 0.56). Accuracy improved when comparing the results of the first 24 with the last 26 patients. CONCLUSIONS: In our experience, VC had a low diagnostic value for identification of patients with colorectal neoplasias. Interobserver agreement for VC interpretation was fair. These results may be explained by software imperfections and a learning curve effect.
Aged↗
Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults.
BACKGROUND & AIMS: Oral immunization with Helicobacter pylori urease can cure Helicobacter infection in animals. As a step toward therapeutic immunization in humans, the safety and immunogenicity of oral immunization with recombinant H. pylori urease were tested in H. pylori-infected adults. METHODS: Twenty-six H. pylori-infected volunteers were randomized in a double-blind study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 microg heat-labile enterotoxin of Escherichia coli (LT), LT alone, or placebo. Side effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for histology and quantitative cultures. RESULTS: Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study. Antiurease serum immunoglobulin A titers increased 1. 58-fold +/- 0.37-fold and 3.66-fold +/- 1.5-fold (mean +/- SEM) after immunization with 60 and 180 mg urease, respectively, whereas no change occurred in the placebo +/- LT groups (P = 0.005). Circulating antiurease immunoglobulin A-producing cells increased in volunteers exposed to urease compared with placebo (38.9 +/- 13. 6/10(6) vs. 5.4 +/- 3.1; P = 0.018). Eradication of H. pylori infection was not observed, but urease immunization induced a significant decrease in gastric H. pylori density. CONCLUSIONS: H. pylori urease with LT is well tolerated and immunogenic in H. pylori-infected individuals. An improved vaccine formulation may induce curative immunity.
Administration, Oral↗
Effects of pumaprazole (BY841), a novel reversible proton pump antagonist, and of omeprazole, on intragastric acidity before and after cure of Helicobacter pylori infection.
BACKGROUND: Omeprazole produces a higher intragastric pH in the presence of Helicobacter pylori infection than after cure. AIM: To investigate whether this effect also occurs with pumaprazole (BY841), a reversible proton pump antagonist which, in contrast to omeprazole, does not require activation in the acid compartment of the parietal cell. METHODS: In a randomized, crossover, double-blind study, 24-h intragastric pH was measured in 13 H. pylori-positive subjects before and after a 1-week course of omeprazole (20 mg o.d.) or of pumaprazole (100 mg b.d.). The studies were repeated after the infection was cured. RESULTS: In the absence of drug administration, the median 24-h pH values before cure (median 2.0, 90% CI: 1.2-3.2) did not differ from those after cure (median 1.5, 90% CI: 1.3-2.2; P = 0.115). The 24-h pH values were higher before cure of the infection than after during both pumaprazole (6.0, 4.8-6.7 vs. 4.3, 2.6-5.7; P = 0.002) and omeprazole (5.8, 4.0-6.2 vs. 3.6, 2.8-5; P = 0.004). Both before and after cure, there were no significant differences between the two drugs with respect to acid inhibition over the 24-h period. The median decrease in acid inhibition after cure of the infection (calculated as the difference in H+ activity in mmol/L) during pumaprazole (median 0.05, 90% CI: 6 x 10-4- 2.3) was no different from that during omeprazole (median 0.2, 90% CI: 3 x 10-3-1.5; P = 0.6). CONCLUSIONS: Both before and after cure of H. pylori infection, pumaprazole raised the intragastric pH over a 24-h period to a similar degree as omeprazole. H. pylori infection similarly augments the pH-increasing effect of both drugs. This effect is related to H. pylori infection and not to an increased activation of acid inhibitory agents in the parietal cell compartment.
Adult↗
Low prevalence of Helicobacter pylori infection in Swiss adolescents.
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Adolescent↗
Urease-based mucosal immunization against Helicobacter heilmannii infection induces corpus atrophy in mice.
Mucosal immunization with Helicobacter heilmannii urease B or Helicobacter pylori urease, given nasally with cholera toxin, protects BALB/c mice against H. heilmannii infection and significantly reduces a preexisting infection. However, immunization aggravates gastric corpus atrophy. Our results underline the necessity of defining immunization regimens that do not enhance mucosal damage.
Animals↗
Omeprazole: Helicobacter pylori makes thee greater yet.
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Anti-Ulcer Agents↗
Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification.
BACKGROUND: Endoscopic oesophageal changes are diagnostically helpful and identify patients exposed to the risk of disease chronicity. However, there is a serious lack of agreement about how to describe and classify the appearance of reflux oesophagitis AIMS: To examine the reliability of criteria that describe the circumferential extent of mucosal breaks and to evaluate the functional and clinical correlates of patients with reflux disease whose oesophagitis was graded according to the Los Angeles system. METHODS: Forty six endoscopists from different countries used a detailed worksheet to evaluate endoscopic video recordings from 22 patients with the full range of severity of reflux oesophagitis. In separate studies, Los Angeles system gradings were correlated with 24 hour oesophageal pH monitoring (178 patients), and with clinical trials of omeprazole treatment (277 patients). RESULTS: Evaluation of circumferential extent of oesophagitis by the criterion of whether mucosal breaks extended between the tops of mucosal folds, gave acceptable agreement (mean kappa value 0.4) among observers. This approach is used in the Los Angeles system. An alternative approach of grouping the circumferential extent of mucosal breaks as occupying 0-25%, 26-50%, 51-75%, 76-99%, or 100% of the oesophageal circumference, gave unacceptably high interobserver variation (mean kappa values 0-0.15) for all but the lowest category of extent (mean kappa value 0.4). Severity of oesophageal acid exposure was significantly (p<0.001) related to the severity grade of oesophagitis. Preteatment oesophagitis grades A-C were related to heartburn severity (p<0.01), outcomes of omeprazole (10 mg daily) treatment (p<0.01), and the risk for symptom relapse off therapy over six months (p<0.05). CONCLUSIONS: Results add further support to previous studies for the clinical utility of the Los Angeles system for endoscopic grading of oesophagitis.
Endoscopy, Digestive System↗
Helicobacter pylori in the oral cavity reflects handling of contaminants but not gastric infection.
Helicobacter pylori colonises the gastric mucosa, but can also be found within the oral cavity. The presence of H. pylori was monitored in the oral cavity of 22 patients with duodenal ulcer, before and after antibiotic treatment and of 24 hospital employees who were or were not professionally exposed to H. pylori. Gastric infection was determined by breath test. Bacteria in the oral cavity were detected by nested PCR of samples containing saliva and dental plaque, using primers specific for 16S rRNA and ureC genes. Before treatment, 9 out of 22 infected ulcer patients harbored H. pylori in their oral cavity. Bacteria disappeared from the oral cavity of 3 of 7 cured patients. Twelve of 17 exposed subjects harbored H. pylori in their oral cavity, while no bacteria could be detected in the mouths of the 7 nonexposed subjects. Presence of bacteria in the oral cavity reflects handling of contaminants; it does not correlate with gastric infection and does not seem to promote it.
Adolescent↗
Effect of whey-based culture supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori infection in humans.
BACKGROUND: Specific strains of Lactobacillus acidophilus are known to inhibit intestinal cell adhesion and invasion by enterovirulent bacteria. As L. acidophilus can survive transiently in the human stomach, it may downregulate Helicobacter pylori infection. METHODS: The ability of L. acidophilus (johnsonii) La1 supernatant to interfere with H. pylori bacterial growth, urease activity, and adhesion to epithelial cells was tested in vitro. Its effect on H. pylori infection in volunteers was monitored in a randomized, double-blind, controlled clinical trial, using a drinkable, whey-based, La1 culture supernatant. H. pylori infected volunteers were treated 14 days with 50 ml of La1 supernatant four times a day combined with either omeprazole 20 mg four times a day or with placebo. Infection was assessed by breath test, endoscopy, and biopsy sampling, performed at inclusion, immediately at the end of the treatment (breath test only), and 4 weeks after the end of the treatment. RESULTS: La1 supernatant inhibited H. pylori growth in vitro, regardless of previous binding of H. pylori to epithelial cells. In 20 subjects (8 females, 12 males, mean age 33.1 years) a marked decrease in breath test values was observed immediately after treatment with La1 supernatant, both in the omeprazole and in the placebo group (median 12.3 vs. 28.8 and 9.4 vs. 20.4, respectively; p < 0.03). In both treatment groups, breath test values remained low 6 weeks after treatment (omeprazole treated 19.2, placebo treated 8. 3; p < 0.03 vs. pretreatment), but the persistence of H. pylori infection was confirmed in gastric biopsies. CONCLUSION: La1 culture supernatant shown to be effective in vitro has a partial, acid-independent long-term suppressive effect on H. pylori in humans.
Adolescent↗
Lack of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. Omeprazole plus Clarithromycin and Amoxicillin Effect One Year after Treatment (OCAY) Study Group.
BACKGROUND: It is uncertain whether treatment of Helicobacter pylori infection relieves symptoms in patients with nonulcer, or functional, dyspepsia. METHODS: We conducted a double-blind, multicenter trial of patients with H. pylori infection and dyspeptic symptoms (moderate-to-very-severe pain and discomfort centered in the upper abdomen). Patients were excluded if they had a history of peptic ulcer disease or gastroesophageal reflux disease and had abnormal findings on upper endoscopy. Patients were randomly assigned to seven days of treatment with 20 mg of omeprazole twice daily, 1000 mg of amoxicillin twice daily, and 500 mg of clarithromycin twice daily or with omeprazole alone and then followed up for one year. Treatment success was defined as the absence of dyspeptic symptoms or the presence of minimal symptoms on any of the 7 days preceding the 12-month visit. RESULTS: Twenty of the 348 patients were excluded after randomization because they were not infected with H. pylori, were not treated, or had no data available. For the remaining 328 patients (164 in each group), treatment was successful for 27.4 percent of those assigned to receive omeprazole and antibiotics and 20.7 percent of those assigned to receive omeprazole alone (P=0.17; absolute difference between groups, 6.7 percent; 95 percent confidence interval, -2.6 to 16.0). After 12 months, gastritis had healed in 75.0 percent of the patients in the group given omeprazole and antibiotics and in 3.0 percent of the patients in the omeprazole group (P<0.001); the respective rates of H. pylori eradication were 79 percent and 2 percent. In the group given omeprazole and antibiotics, the rate of treatment success among patients with persistent H. pylori infection was similar to that among patients in whom the infection was eradicated (26 percent vs. 31 percent). There were no significant differences between the groups in the quality of life after treatment. CONCLUSIONS: In patients with nonulcer dyspepsia, the eradication of H. pylori infection is not likely to relieve symptoms.
Adolescent↗
Differential expression of laminin-5 subunits and integrin receptors in human colorectal neoplasia.
Cell-matrix interactions contribute to regulating the adhesion, growth, migration, and differentiation of epithelial intestinal cells. Alterations in matrix components and their cellular receptors have been found in tumours but their specific roles remain unclear. The tissue patterns of laminin-5 and alpha 3, beta 3 and gamma 2 subunits, as well as those of the alpha 3, alpha 6, beta 1, and beta 4 integrin chains, were determined by immunofluorescence on frozen sections of 12 colorectal mucosal samples from four patients, 15 adenomas, 29 adenocarcinomas, and eight metastases. Distinct patterns of laminin-5 and integrin expression were found along the mucosa-adenoma, and adenoma-carcinoma transitions. Expression of basement membrane laminin-5 and subunits was continuous and gradient-like in normal mucosa, enhanced at the periphery of adenomas, and discontinuous in places in carcinomas and metastases. Decrease of the alpha 3 integrin chain was found in adenomas, together with that of alpha 6 and beta 4 chains in carcinomas. A subpopulation of carcinoma cells dissociating (budding) from neoplastic tubules was found to accumulate the laminin-5 beta 3 gamma 2 heterodimer in the cytoplasm, with progressive loss of surface integrin expression. These results suggest that in colorectal cancer, an abnormal expression of laminin-5 subunits and integrin chains may identify a subset of carcinoma cells prone to invade focally and to contribute to disease aggressiveness.
Adenocarcinoma↗
[Helicobacter pylori infection and ulcer].
Our understanding of ulcer pathogenesis has dramatically changed since the discovery of Heliobacter pylori. Peptic ulcer is now recognized as a chronic gastric infectious disease. H. pylori can be considered the pacemaker, with other known risk factors ultimately contributing to the ulcer formation. Treatment of H. pylori in peptic ulcer disease cures the acute lesion and prevents relapse and complications. In clinical management a positive diagnosis of H. pylori is required and other potential causes for ulcer formation must be excluded before starting treatment. The standard treatment in H. pylori positive ulcer consists of PPI in standard dose and two antibiotics either clarithromycin 2 x 500 mg and amoxycillin 2 x 1 g or metronidazole 2 x 400 mg and clarithromycin 2 x 250 mg (or 500 mg) for 7 days. The simultaneous presence of H. pylori and NSAID intake requires distinct management. Following bleeding complication a PPI needs to be given beyond 7 days until ulcer healing is endoscopically confirmed.
Amoxicillin↗