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Does eradication of Helicobacter pylori infection reduce hypergastrinema during long term therapy with proton pump inhibitors?

BACKGROUND/AIMS: Proton pump inhibitors and Helicobacter pylori infection are the major cause of hypergastrinemia. In this study the effect of eradication therapy on blood gastrin levels in patients using long term proton pump inhibitors was evaluated. METHODS: Twenty-seven Helicobacter pylori (positive) patients were included in the study, of whom 20 were given eradication treatment for seven days consisting of ranitidine bismuth citrate, clarithromycin and amoxicillin (eradication therapy group) and seven were given symptomatic therapy (symptomatic therapy group). Four patients who remanied Helicobacter pylori (positive) after eradication therapy were later added to the symptomatic therapy group. Lansoprazole 30 mg/day was then given to both the eradication therapy (n: 16) and the symptomatic therapy groups (n: 11) for the following three months. Fasting and non-fasting blood gastrin levels were measured initially then at one and four months after treatment. RESULTS: Fasting gastrin levels were 49 % higher in the fourth month than in the first month (p<0.01) and 51 % higher than the initial level (p<0.01) in the symptomatic therapy group. There were no statistical differences between the initial, first month and fourth month non-fasting blood gastrin levels in the symptomatic therapy group (p>0.05). Fasting gastrin levels were 47 % higher in the fourth month than the first month (p<0.001) and 18 % lower than the initial level (p<0.05) in the eradication therapy group. Non-fasting gastrin levels were 4% higher in the fourth month than in the first month (p>0.05) and 34 % lower than the initial level (p< 0.05) in the eradication therapy group. CONCLUSIONS: It is suggested that patients receiving long term proton pump inhibitor treatment should be evaluated for Helicobacter pylori positivity and treatment of this infection would be an appropriate approach to avoid hypergastrinemia.

Journal Article↗

[Azithromycin versus amoxicillin in triple therapy for the treatment of Helicobacter pylori infection].

BACKGROUND: To establish if azithromycin, in association with omeprazole and metronidazole, is effective to eradicate Helicobacter pylori, compared to amoxicillin in triple therapy. METHODS: Two hundred consecutive patients with duodenal ulcer and Helicobacter pylori infection were enrolled in the study: group a) 100 patients (69 males, 31 females; mean age 47.61 years; range 23-75); group b) 100 patients (70 males, 30 females; mean age 45.56 years; range 22-72). Group a) omeprazole 20 mg od, azithromycin 500 mg od the first three and the last three days of association with metronidazole, this one 250 mg qid, for ten days; group b) omeprazole 20 mg od, amoxicillin 1 g bid, metronidazole 250 mg qid for ten days. Omeprazole was continued for other four weeks in each treatment with the same dosage. RESULTS: In group a ulcer healing was observed in 89 patients (89 %), while in group b in 93 patients (93%) (p=n.s.). Helicobacter pylori infection was eradicated in group a in 70 patients (70 %), while in group b in 78 patients (78 %) (p=n.s.). Side effects in 11 patients (5.5 %), in particular: group a 5 (5 %), group b 6 (6 %) (p=n.s.). CONCLUSIONS: Azithromycin could be proposed for treatment of Helicobacter pylori eradication.

English Abstract↗

Effects of sucralfate and sulglycotide treatment on active gastritis and Helicobacter pylori colonization of the gastric mucosa in non-ulcer dyspepsia patients.

We conducted a double-blind randomized treatment study on patients affects by non-ulcer dyspepsia in whom multiple biopsy specimens showed active gastritis. Patients were given either 3 g/day of sucralfate (n = 39) or 600 mg/day of sulglycotide (n = 50) for 6 wk, a glycopeptide isolated from pig duodenum constituents. Endoscopy was carried out at baseline and at the end of treatment. We took biopsies from the gastric body (twice) and antrum (six times) at each endoscopy in order to determine grade and extent of gastritis and Helicobacter pylori colonization. Both treatments induced a marked regression of active gastritis (sucralfate group: p less than 0.05 and p less than 0.0001, respectively, in body and in antrum; sulglycotide group: p less than 0.01 and p less than 0.001, respectively). Conversely, Helicobacter pylori colonization remained unchanged at the end of the treatments. At baseline, a close relationship was found between grade of active inflammation in each biopsy and Helicobacter pylori density. After therapy, the association was lost in each treatment group. These results suggest that there can be a remission of active gastritis in patients with non-ulcer dyspepsia even without changes in Helicobacter pylori colonization. This result can be achieved by enhancing the protective properties of the gastric mucosa.

Adult↗

[Detection of Helicobacter pylori in biopsy specimens, methodical studies].

Demonstration of Helicobacter pylori infection receives more and more importance in nowadays gastroenterological practice. The authors have compared culture and histology from 69 antral biopsy specimens for their ability to document Helicobacter pylori infection. Infection ratios in the context of clinical and histological diagnoses resulted in a distribution pattern similar to that described by others: 85-69% of duodenal ulcer patients, 67-67% of gastric ulcer patients, 62-54% of patients with gastritis and/or erosion(s) and 33-60% of endoscopically negative patients were found to be Helicobacter pylori positive with culture and histology respectively. Normal or atrophic mucosa showed no bacteria with either methods, but one must also consider the small number of such cases in this study. Chronic gastritis with no signs of activity proved to be infected only in a minority of cases, while chronic active gastritis cases were Helicobacter pylori positive in 72 and 61% histologically and with culture respectively. The modified Giemsa stain used in this study grave a relative specificity of 0.74 and sensitivity of 0.79 as compared with culture. There was a good association between the two methods tested, and this could be further improved by doing the two tests simultaneously. The association was weaker when the tests were done asynchronously, this is why it is not recommended to use such a diagnostic schedule. Comparison of the traditional haematoxylin-eosin stain with the modified Giemsa stain resulted in a very strong association between the two.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Helicobacter pylori--is it a novel causative agent in Vitamin B12 deficiency?

BACKGROUND: Evidence for vitamin B12 deficiency usually involves combinations of low serum vitamin B12 levels, clinical and metabolic abnormalities, and therapeutic response. Identification of the underlying cause is important in the diagnosis of vitamin B12 deficiency that is usually attributed to malabsorption. Helicobacter pylori is one of the most common causes of peptic ulcer disease worldwide and a major cause of chronic superficial gastritis leading to atrophy of gastric glands. It is suggested that there may be a casual relationship between H. pylori and food-cobalamin malabsorption. OBJECTIVES: To evaluate the H. pylori incidence in patients with vitamin B12 deficiency prospectively and to assess whether treatment for H pylori infection could correct this deficiency over time. PATIENTS AND METHODS: We performed a prospective cohort study involving 138 patients who had anemia and vitamin B12 deficiency. An upper gastrointestinal endoscopy was performed to assess the severity of atrophic gastritis and biopsy specimens for Campylobacter-like organisms tests and histological examination for H pylori were obtained at the time of diagnosis. The diagnosis of H. pylori prompted a combination treatment. RESULTS: Helicobacter pylori was detected in 77 (56%) of 138 patients with vitamin B12 deficiency and eradication of H pylori infection successfully improved anemia and serum vitamin B12 levels in 31 (40 %) of 77 infected patients. CONCLUSIONS: Helicobacter pylori seems to be a causative agent in the development of adult vitamin B12 deficiency. Eradication of H. pylori infection alone may correct vitamin B12 levels and improve anemia in this subgroup of patients.

Adult↗

Gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma in an animal model of 'Helicobacter heilmannii' infection.

While Helicobacter pylori is accepted as the dominant human gastric bacterial pathogen, a small percentage of human infections have been associated with another organism, commonly referred to as 'Helicobacter heilmannii', which is more prevalent in a range of animal species. This latter bacterium has been seen in association with the full spectrum of human gastric diseases including gastritis, peptic ulceration, and gastric carcinomas, including gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. This study describes an analysis of the pathogenic potential of a number of 'H heilmannii' isolates in an animal model of gastric MALT lymphoma. BALB/c mice were infected with ten different 'H heilmannii' isolates originating from both human and animal hosts. The animals were examined at various time points for up to 28 months after infection. The infected animals initially developed a chronic inflammatory response within 6 months. This histological response increased in severity with the length of infection, with the development of overt lymphoma in some animals 18 months after infection. MALT lymphomas were detected in up to 25% of the infected animals. The prevalence of lymphoma was dependent on the length of infection and the origin of the infecting isolates. A range of other histological features accompanied the lymphocytic infiltration, including invaginations of the gastric epithelium and associated hyperplastic tissue, mucus metaplasia, and a small number of diffuse large B-cell lymphomas. The ability to manipulate experientially the presence of the bacterium in the animal model will allow further studies examining the role of antigen drive in the development of Helicobacter-associated MALT lymphoma.

Animals↗

In vitro anti-Helicobacter pylori potential of methanol extract of Allium ascalonicum Linn. (Liliaceae) leaf: susceptibility and effect on urease activity.

The crude methanol extract of the leaf of Allium ascalonicum was screened in vitro against fi ve strains of Helicobacter pylori (Hp) (ATCC 24376, UCH 97001, UCH 97009, UCH 98026 and UCH 99039) for antibacterial activity by the agar diffusion method in Mueller-Hinton agar supplemented with de fi brinated horse blood. All the strains were inhibited by the extract to varying degrees. The minimum inhibitory concentrations (MICs) of the extract against all the tested strains ranged from 6.25 to 12.5 mg/mL. The effects of increasing concentrations of the extract on the urease activity of three of the Helicobacter pylori strains were investigated further. The results showed that increasing the concentration of the extract decreased the urease activity of all the strains tested. Phytochemical screening of the plant showed that it contains alkaloids, cardiac glycosides and saponins. The anti-Hp activity observed is discussed in relation to the chemical constituents reportedly isolated from these plants and their traditional uses. The result of this work suggests that Allium ascalonicum has some therapeutic potential against Helicobacter pylori infection, which could be explored for patients with gastroduodenal disorders.

Anti-Bacterial Agents↗

Helicobacter pylori infection, ABO blood group, and effect of misoprostol on gastroduodenal mucosa in NSAID-treated patients with rheumatoid arthritis.

Our aim was to investigate the effect of misoprostol on NSAID-induced gastroduodenal mucosal damage in patients with rheumatoid arthritis. The study included 40 patients, and it was designed as a double-blind, placebo-controlled trial. Misoprostol significantly reduced the gastroduodenal mucosal lesions found at endoscopy (P < 0.05) and prevented the development of ulcers. The cumulative incidence of ulcers at four weeks was 5% in the placebo group and 0% in the misoprostol group. The basal and pentagastrin-stimulated acid output as evaluated after 23 days of treatment with misoprostol was not significantly affected. Forty-one percent of the patients had signs of current Helicobacter pylori infection, 33% had positive serology only, and 26% had no evidence of infection. Most of the patients with current infection belonged to blood group O (P < 0.05). Misoprostol treatment did not affect the occurrence of Helicobacter pylori or the rheumatic disease activity. It is concluded that the protective actions of misoprostol on the gastroduodenal mucosa of NSAID-treated patients are largely mediated by mechanisms other than inhibition of acid secretion. The relationship among active Helicobacter pylori infection, blood group O, and peptic ulcer may be helpful to identify a subpopulation of patients taking NSAIDs at risk of developing peptic ulcers.

ABO Blood-Group System↗

A new histological procedure for re-evaluation of the serological test for Helicobacter pylori.

To re-evaluate the accuracy of the serological test for Helicobacter pylori, fixation of biopsy specimens with Carnoy's solution (preserving the mucous layer in tissue preparations) followed by immunohistochemical staining (a new histological procedure) was used as the reference histological method instead of 10% formalin fixation followed by hematoxylin-eosin staining (the conventional histological procedure). Biopsy specimens (antrum and body) from 114 patients with gastritis (including non-ulcer dyspepsia) or gastric and/or duodenal ulcers were obtained by endoscopy and used for both bacteriological culture and histological examination. Serum samples were taken from all patients at the time of endoscopy. The serum levels of specific IgG and IgA antibodies for Helicobacter pylori were measured by commercial enzyme immunoassay kits. The reliability of the IgG and IgA measurements was evaluated by analyzing receiver operating characteristic curves obtained using the two histological procedures. With the conventional histological procedure as the reference, the sensitivity and specificity levels of the serological test were 87.2% and 82.1%, respectively. With the new histological procedure as reference, sensitivity and specificity were 94% and 96.7%, respectively. The insufficient accuracy reported for the serological test could be due to false-positive or false-negative results obtained when the conventional histological procedure is used as the reference. The new histological procedure used here revealed that the serological test for Helicobacter pylori is more reliable than previously thought.

Antibodies, Bacterial↗

Evaluation of a serological test for diagnosis of Helicobacter pylori infection in children.

A serological test for the diagnosis of Helicobacter pylori infection (Cobas Core Roche, IgG, 2nd Generation; Roche, France) was compared with the examination of biopsy samples (culture and histology) obtained after endoscopy in 115 children to assess its value. In 94 children (42 positive and 52 negative), results were concordant. In 10 children a positive serological test was associated with an absence of Helicobacter pylori, while in 11 others a negative serological test was associated with a positive culture. Sensitivity of the test was 79.2% and specificity 83.9%. A relationship between IgG titers and age (r = 0.31, p < 0.05) was found. Serological tests could be useful for the diagnosis of Helicobacter pylori infection, but a negative test result does not rule out infection, particularly in children under 10 years of age.

Adolescent↗

Lack of correlation between vacuolating cytotoxin activity, cagA gene in Helicobacter pylori, and peptic ulcer disease in children.

To determine the prevalence of the cagA gene and vacuolating cytotoxin in Helicobacter pylori isolates obtained from children and to characterize the relationship between cagA, cytotoxin production, and ulcerogenesis, pediatric Helicobacter pylori isolates were tested for cagA by the polymerase chain reaction and for vacuolating cytotoxin by a cell culture assay. Helicobacter pylori isolates were obtained from 33 children referred for upper gastrointestinal endoscopy. Twenty-six of these isolates were tested for cagA by the polymerase chain reaction; all 26 (100%) were positive. Of the 26 children from whom these isolates were obtained, 26 (100%) had chronic gastritis and 12 (46%) had duodenal ulcers. Nine (30%) of 30 isolates tested showed expression of vacuolating cytotoxin, only three of which came from patients with duodenal ulceration (odds ratio 0.81, 95% confidence interval 0.1-5.3). Of the 23 cagA-positive isolates tested for cytotoxin, only nine (39%) were positive. There was no association between vacuolating cytotoxin and clinical symptoms, nor was cytotoxicity associated with ulcerogenesis. In summary, the findings suggest that cagA is not a marker of duodenal ulceration or of vacuolating cytotoxin production in children referred for endoscopy.

Adolescent↗

Evaluation of two commercial enzyme immunoassays for the diagnosis of Helicobacter pylori infection.

Sera from 65 patients with upper gastrointestinal tract symptoms and proven Helicobacter pylori infection, and from 42 negative controls were tested with two commercial EIAs (GAP test, BioRad; and ECP test, Biometra) and two non-commercial EIAs, one performed with whole sonicated cells and the other with acid extract of Helicobacter pylori as antigen. The GAP assay showed a sensitivity of 83.1% and a specificity of 47.6%. The ECP assay showed a sensitivity of 87.7% and a specificity of 61.9%. For both non-commercial EIAs these figures were 87.7% and 88.1%, respectively. Independent of the interpretive criteria established by the manufacturers, receiver operating characteristic curves were plotted for better evaluation of the four methods. Both commercial tests showed a lower probability of yielding a correct diagnosis than the non-commercial tests (p less than 0.05). Although commercial EIAs are convenient for the diagnosis of Helicobacter pylori infection, the accuracy of the two commercial tests evaluated in this study was lower compared to that of the two non-commercial EIAs.

Adult↗

Helicobacter pylori in a Costa Rican dyspeptic patient population.

Gastric biopsies from 65 Costa Rican dyspeptic patients were investigated for the presence of Helicobacter pylori DNA by polymerase chain reaction (PCR) amplification of 16S rRNA sequences. Both frozen and paraffin-embedded samples were used, and the results were compared with bacterial culture and histological examination. Helicobacter pylori DNA was detected by PCR in 60 (92%) of the patients, and Helicobacter pylori strains confirmed by PCR could be isolated from 37 of them. Altogether, 59 patients were shown to be infected using the combination of culture and histology as the reference method. The sensitivity of PCR analysis of frozen material was 98% (58/59). The PCR analysis of paraffin-embedded samples seemed less reliable than that of frozen biopsy material.

Adult↗

Evaluation of a commercial latex test for serological diagnosis of Helicobacter pylori infection in treated and untreated patients.

The value of a commercially available latex test (Pyloriset) for the diagnosis of Helicobacter pylori infection by demonstration of specific antibodies was compared with that of direct diagnostic methods such as culture, biopsy-urease test and microscopy of fuchsin-stained smears. The sera were from 136 patients who prior to this study either had or had not been treated for Helicobacter pylori-infection simultaneously with amoxicillin (3 x 750 mg/day) and metronidazole (3 x 500 mg/day) for 12 days. On average, the sensitivity of the test was 90%. The specificity with sera from untreated patients was 75.9%; with sera from treated patients specificity was 22.2%, 28% and 20% 1, 3 and 6 months respectively after start of treatment. Only as late as one year after the onset of chemotherapy did the specificity return to 67%. Because of its low specificity this test does not offer any advantage over other tests in the detection of Helicobacter pylori-infection or in monitoring the chemotherapeutic success.

Amoxicillin↗

Detection in an enzyme immunoassay of an immune response to a recombinant fragment of the 128 kilodalton protein (CagA) of Helicobacter pylori.

The possibility of using a recombinant fragment of the CagA (128 kDa protein) for the diagnosis of Helicobacter pylori infection was evaluated. Following cloning of the gene coding for the CagA, a recombinant fragment of it was expressed in Escherichia coli, purified and used in Western blot and an EIA to screen sera from 82 patients with gastroduodenal disease who underwent endoscopic examination. In Western blot, good correlation was found between the serological data obtained with the recombinant antigen and those obtained using non-purified extracts of Helicobacter pylori. The EIA using the antigen showed a sensitivity of 96.2% and a specificity of 96.6% compared with Western blot. These data indicate that the recombinant protein is a reliable antigen for detection of infections with Helicobacter pylori strains that are associated with disease. The EIA assay described may be used in follow-up of the progression of the illness and the results of therapy.

Adult↗

Use of a receiver operating characteristic in the evaluation of two commercial enzyme immunoassays for detection of Helicobacter pylori infection.

Two novel commercial IgG enzyme immunoassay (EIA) systems based on acid-glycine-extracted (Pyloriset IgG EIA, Orion Diagnostica) or fast protein liquid chromatography-purified (Cobas Core Anti-H. pylori EIA, Roche Diagnostic Systems) Helicobacter antigens were evaluated in a prospective study involving 127 patients. All patients underwent upper endoscopy with biopsy, and biopsies were examined for the presence of Helicobacter pylori by a rapid urease test, microscopy and culture. Of the 71 patients found to be infected with Helicobacter pylori, 69 (97.2%) and 65 (91.5%) tested positive with the Cobas Core and Pyloriset test, respectively. A detailed receiver operating characteristic analysis of the two tests showed that the Cobas Core assay was more sensitive and specific at every possible cut-off level; gave a better resolution of individual results, indicating a greater fine-sensitivity; and had no grey zone compared to a large grey zone encompassing 13.4% of the serum samples tested with the Pyloriset EIA. The Cobas Core assay appears to be a valuable tool for epidemiological purposes as well as for pre-endoscopic screening of dyspeptic patients.

Antigens, Bacterial↗

Trials of novel 13C-urea-containing capsule for more economic and sensitive diagnosis of Helicobacter pylori infection in human subjects.

To develop a 13C-urea-containing capsule for more economic and sensitive diagnosis of Helicobacter pylori infection, the 13C-urea-containing capsules were prepared with various additives such as polyethylene glycol, microcrystalline cellulose, sodium lauryl sulfate and citric acid. Their dissolution test and 13C-urea Breath Test in human volunteers were then performed. Polyethylene glycol increased the initial dissolution rates of urea and difference delta 13C values from 13C-urea, while microcrystalline cellulose and sodium lauryl sulfate decreased them. Irrespective of addition of citric acid, the compositions with polyethylene glycol showed higher values from 13C-urea compared to a commercial 76 mg 13C-urea-containing capsule due to higher initial dissolution rate. The capsules with 38 mg 13C-urea and 1.9 mg polyethylene glycol, which showed higher Helicobacter pylori-positive value of about 8 per thousand at 10 min, improved the sensitivity of 13C-urea in human volunteers. Thus, the 13C-urea-containing capsule with polyethylene glycol would be a more economical and sensitive preparation for diagnosis of Helicobacter pylori infection.

Adult↗

Helicobacter pylori prevalence in diabetic patients and its relationship with dyspepsia and autonomic neuropathy.

AIMS: We evaluated the prevalence of Helicobacter pylori (HP) in Type 2 diabetic patients and its relationship with dyspeptic symptoms and complications of diabetes. MATERIALS AND METHODS: Seventy-eight Type 2 diabetic patients (54 females, 24 males, mean age: 51.9 +/- 10.6 yr) and 71 non-diabetic control subjects were involved in the study. Patients were questioned for dyspeptic symptoms. Cardiovascular autonomic neuropathy, nephropathy and retinopathy were investigated in diabetic patients. Upper gastrointestinal tract endoscopy was performed for all patients and gastric biopsies were obtained and searched for HP. RESULTS: Helicobacter pylori prevalence was significantly higher in diabetic patients than in control subjects (75.6 vs 46%, p < 0.05). No differences were found between women and men with regard to HP infection status in diabetic patients. There was no relation between HP and diabetic complications, nephropathy and retinopathy. Helicobacter pylori prevalence was significantly higher in diabetic patients with cardiovascular autonomic neuropathy than in diabetic patients without cardiovascular autonomic neuropathy (90.6 vs 44.0%, p < 0.02). Forty-seven subjects with diabetes had symptoms of dyspepsia (60.3%) and the prevalence of HP was higher in these patients (p < 0.002). CONCLUSION: There is a high prevalence of HP infection in diabetic patients and it is correlated with dyspeptic symptoms. Diabetic subjects complicated with cardiovascular autonomic neuropathy and dyspepsia are at high risk of HP infection and should be carefully investigated and considered for eradication therapy.

Autonomic Nervous System Diseases↗