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Immunomodulation of helicobacter infection.

Helicobacter pylori leads to a chronic infection in humans that is associated with gastric inflammation and a vigorous immune response. Despite the humoral and cellular responses that can be detected in both human and animal models of helicobacter infection, the immune response fails to eliminate the organism. Eradication failure may be due to the niche in which H pylori confines itself, well away from direct contact with elements of the immune system. Alternatively, the general tendency of the intestinal immune response to down- regulate reactivity to noninvasive luminal bacteria also may contribute to the failure to eliminate helicobacter infection. Results of vaccine studies in mouse models indicate that modulating the helper T cell response from a T helper cell type 1 to a T helper cell type 2 response likely is required for the prevention and elimination of helicobacter infection. Understanding the mechanisms by which the immune response controls bacterial infections will allow for the design of novel strategies of immune modulation and the development of vaccines for both the treatment and prevention of H pylori.

Animals↗

Cholangiohepatitis and inflammatory bowel disease induced by a novel urease-negative Helicobacter species in A/J and Tac:ICR:HascidfRF mice.

Helicobacter bilis and H. hepaticus, both urease-positive intestinal helicobacters of mice, have been shown experimentally to induce proliferative typhlocolitis in scid mice. We recently isolated a urease-negative Helicobacter sp. (H. sp.) that also induced proliferative typhlocolitis in pilot studies in scid mice. To determine the pathogenic potential of H. sp. in immunocompromised and immunocompetent mice, 5-week old male A/J or Tac:Icr:Ha(ICR)-scidfRF mice were inoculated by intraperitoneal (IP) injection with approximately 3 x 10(7) colony-forming units (CFU) of H. sp. Mice were necropsied at various time points postinoculation (PI). Sham-inoculated mice had no clinical, gross, or histopathological lesions. In contrast, scid mice inoculated IP with H. sp. had severe hemorrhagic diarrhea and decreased weight gain at 2, 7, and 18 weeks postinoculation (PI), with severe proliferative typhlocolitis, phlebothrombosis, and hepatitis. A/J mice had no clinical signs, but had mild to moderate proliferative typhlocolitis and moderate to marked cholangiohepatitis at 7 and 24 weeks PI. A/J mice infected with H. sp. developed robust immune responses of a predominant Th1 type. This report demonstrates that infection with a urease-negative helicobacter can cause inflammatory bowel disease (IBD) and hepatitis in scid and immunocompetent A/J mice. These results provide a new model of IBD and cholangio-hepatitis associated with a specific urease-negative, novel H. species.

Animals↗

Low frequency of Helicobacter species in the stomachs of experimental rabbits.

The natural occurrence of established Helicobacter species was investigated in the stomachs of 65 laboratory rabbits, by means of polymerase chain reaction (PCR) (65/65) and histological analysis (51/65). The degree of inflammation in the different regions of the rabbits' stomach was evaluated on haematoxylin and eosin (HE)-stained histological slides. Four rabbits were found positive for Helicobacter species by PCR. Based on 16S ribosomal ribonucleic acid (rRNA) sequences, H. canadensis/H. pullorum organisms were identified in three animals. Bacteria were seen on merely one histological slide from one of these animals. H. felis was identified in one rabbit. Histological examination revealed no inflammation in the stomachs of 40 rabbits, while moderate gastric inflammation was seen in 11 animals, mainly in the antrum. In conclusion, the stomach of the laboratory rabbits included in the study was occasionally found positive for Helicobacter species, which were mostly identified as enterohepatic helicobacters, probably reflecting a mere passage of these bacteria through the stomach.

Animals↗

The relationship between Helicobacter pylori and oxygen-derived free radicals in the mechanism of duodenal ulceration.

This prospective randomized study investigated the possibility that duodenal ulcer relapse associated with Helicobacter Pylori infection is mediated by oxygen-derived free radicals. To this end, the radical scavengers allopurinol (50 mg 4 times daily) and dimethyl sulphoxide (DMSO, 500 mg 4 times daily) were administered orally. One hundred and forty-six consecutive patients with previous symptomatic endoscopy proven duodenal ulceration, which had been shown endoscopically to have healed in the presence of gastric mucosal infection with Helicobacter Pylori, were randomized to receive for the period of one year either placebo, or cimetidine 400 mg at bedtime, or allopurinol, or DMSO. In one hundred and twenty-six patients evaluable for efficacy, the cumulative relapse at one year was: placebo 47%, cimetidine 24%, allopurinol 6% and DMSO 6%. Cimetidine was significantly effective in preventing the relapse (p < 0.01), however allopurinol and DMSO were superior to cimetidine in this respect (p < 0.05). In the patients who relapsed, ulcer recurrence tended to occur early in those on placebo and cimetidine and to be evenly distributed over the year in those on free radical scavenging therapy. In all groups, ulcer recurrence throughout the maintenance year was more frequently symptomatic than silent. The incidence of infection with Helicobacter Pylori was not influenced by any of the regimens employed and the bacterium was detected with every relapse noted in this study and during the follow-up endoscopy which was carried out at 6 months and at 12 months during the maintenance year. The results suggest that oxygen-derived free radicals are involved in the relapse of duodenal ulceration in patients infected with Helicobacter Pylori.

Adult↗

Relevance of vacA genotypes of Helicobacter pylori to cagA status and its clinical outcome.

BACKGROUND: Determination of vacA mosaicism may be important because specific Helicobacter pylori vacA genotype can be used to predict different clinical outcome. The aim of this study was to assess the relationship of vacA genotypes of Helicobacter pylori to cagA status and its development of peptic ulcer diseases in Korean patients. METHODS: Gastric biopsy specimens were obtained from 53 patients with gastric ulcer(GU), 57 with duodenal ulcer (DU) and 26 with chronic gastritis(CG) patients; all patients were infected with Helicobacter pylori. Bacterial mRNAs in the gastric mucosa were amplified by RT-PCR, using synthetic oligonucleotide primers specific for the vacA and the cagA gene. Patients with vacA s1 subtype were further examined to determine whether they had s1a or s1b subtype. RESULTS: There was no correlation in frequency of vacA s1 and/or s1a genotype between CG and either GU or DU, as the vacA s1 and s1a/m1 were present in the majority of strains independent of clinical status(s1; 100.0% versus 94.3% or 93.0% and s1a/m1; 76.9% versus 62.3% or 64.9%, respectively). Likewise, there was no difference in the prevalence of the cagA gene between CG and either GU or DU patients (92.3% versus 90.6% or 98.2%, respectively). In addition, the cagA-negative status did not predict the presence of vacA s2 genotype. CONCLUSION: These results strongly suggest that either cagA or vacA s1 and/or s1a is not proved to be a useful marker to distinguish disease-specific Helicobacter pylori strains for the development of peptic ulcer diseases in Korean patients.

Adolescent↗

Effect of Helicobacter pylori eradication therapy in rosacea patients.

OBJECTIVE: The causal relation between rosacea and Helicobacter pylori infection is discussed. We evaluated the clinical evolution of rosacea after infection eradication. PATIENTS AND METHODS: We have prospectively studied 44 patients diagnosed with rosacea. Helicobacter pylori infection was determined, and infected patients were treated with eradication therapy. The evolution of dermatological symptoms in a subgroup of 29 infected patients in whom eradication had been achieved was followed during 16.8 (+/- 17.8) months. Median age was 50.6 (+/- 14.1) years for 22 women (75.9%) and 7 men (24.1%). Clinical response according to gender and clinical subtype of rosacea was evaluated. RESULTS: Complete improvement was observed in 10 patients (34.5%; 95% CI: 18.6-54.3%), relevant improvement in 9 (31.1%; 95% CI: 16-51%), poor improvement in 5 (17.2%; 95% CI: 6.5-36.4%), and absence of improvement in 5 cases (17.2%; 95% CI: 6.5-36.4%). No significant differences in dermatological evolution according to sex were observed. Regarding subtype of rosacea there was a relevant improvement in 83.3% (95% CI: 64.1-93.8%) of cases with papulopustular type as opposed to 36.5% (95% CI: 20-56.1%) of cases with erythematous predominance, p = 0.02. CONCLUSIONS: Based on these results, the relation between Helicobacter pylori and rosacea is supported, and infection should be investigated in these patients because an appreciable percentage of patients diagnosed with rosacea and Helicobacter pylori infection can benefit from eradication therapy, mainly in the papulopustular subtype.

Adult↗

Dyspepsia and gastroparesis in chronic renal failure: the role of Helicobacter pylori.

AIMS: Many patients with chronic renal failure have dyspeptic symptoms. In the present study, we assessed the Helicobacter pylori (Hp) status, dyspeptic symptoms and gastric emptying rates in uremic patients. The present study was undertaken to compare chronic renal failure patients not under dialysis therapy (predialysis), hemodialysis (HD) patients and peritoneal dialysis (PD) patients for these variables and to search for a possible causative role of Hp. METHODS: We used a standardized questionnaire to assess dyspeptic symptoms. Gastric emptying rates were determined by the 13C-octanoic acid breath test. HD patients were examined outside a dialysis session, PD patients were examined with a "full" abdomen. Specific Helicobacter pylori IgG was measured by a second-generation enzyme-linked immunosorbent assay. RESULTS: Sixty-six HD patients. 58 predialytic patients and 28 PD patients were included. Prevalences of Hp infection were highest in HD patients (46.2%) and predialysis patients (42.3%) compared to PD patients (28.6%) (p < 0.02). On the contrary, the prevalence of dysmotility-like dyspepsia was higher in PD patients (67.9%) when compared to HD patients (33.3%) (p < 0.01) and predialytic patients (53.6%) (difference not significant). Neither dyspepsia nor delayed gastric emptying were related to the presence of Helicobacter pylori IgG antibodies. CONCLUSION: A positive Helicobacter status based on serology was not related to the presence of dyspepsia or gastroparesis in uremic patients, whether on dialysis therapy or not. Dyspeptic complaints as well as gastroparesis are most prevalent in patients on peritoneal dialysis. The physiopathological mechanisms and clinical impact of these findings merit further investigation.

Adult↗

Occurrence of Helicobacter Infection in the gastric mucosa of free-living red foxes (Vulpes vulpes).

We studied gastric Helicobacter spp. in five red foxes (Vulpes vulpes). Samples of stomach from the cardia, corpus, pyloric antrum, and duodenum were subjected to histopathologic, immunohistochemical, and transmission electron microscopy (TEM) examination for the presence of Helicobacter and gastritis. All foxes had gastric Helicobacter-like organisms (GHLOs) on examination by light microscopy and TEM. Gastric Helicobacter-like organisms were present in all areas of the stomachs. Chronic mild or moderate gastric inflammation was associated with infection by GHLOs in one or more regions of the stomach, but there was no correlation between inflammation and infection. It is not clear whether the organisms were causing the minimal histologic lesions observed, but the gastric mucosa of free-living foxes appears to be commonly colonized with GHLOs. The frequent colonization of free-living foxes with distinct GHLOs possibly reflects their special characteristic in feeding and/or social behavior or the potential commensal nature of the bacteria in free-ranging foxes.

Animals↗

Therapeutic news on Helicobacter pylori from Budapest and Wien.

Helicobacter pylori is the most common infection in the world and is associated with some of the most prevalent gastroduodenal diseases. There is now considerable evidence that Helicobacter pylori eradication not only heals duodenal ulcer, but also prevents ulcer recurrences and probably ulcer complication. It is, therefore, universally accepted that, all patients with duodenal ulcer disease should receive eradication therapy. This review represents an attempt to summarize and analyse all the regimens proposed in September at the last International Meetings in Budapest and Wien in which different anti Helicobacter pylori regimens have been used. Despite the large number of clinical trials which had been performed, no significant advances have been made in relation to Helicobacter pylori therapy, so the "optimal" eradication treatment still remains a matter of debate. More than 10,000 patients were treated and most of them (around 5000) were found to have peptic ulcer disease which represents no more than 10-15% of our endoscopic findings. The proton pump inhibitor regimens are definitely the most representative drug policy appearing in the literature and despite several attempts (proton pump inhibitor given for less, one, or more than one week) the short one-week regimen (The Maastricht regimen) has been recognized as the most promising treatment.

Anti-Bacterial Agents↗

Experimental model of Helicobacter pylori infection.

Critical issues in the development of a vaccine against Helicobacter pylori are represented by the definition of molecules important in the pathogenesis of the infection, by the availability of an animal model reproducing several aspects of the human infection, and lastly by the availability of powerful adjuvants allowing strong protection after mucosal delivery of the antigens. A mouse model of Helicobacter pylori infection was established in our laboratories. Vaccination of these animals with Helicobacter pylori antigens, such as VacA, CagA, etc., induced protection, both prophylactic and therapeutic, when antigens were administered orally together with fully non toxic mutants of Escherichia coli heat-labile enterotoxin, as mucosal adjuvants. This experimental mouse model allows the study of the pathogenesis of Helicobacter pylori infection and the development of vaccines.

Animals↗

[Treatment with omeprazole, clarithromycin and amoxicillin over 6 days in patients with Helicobacter pylori-infected duodenal ulcer].

OBJECTIVE: To investigate the eradication rate of Helicobacter pylori with omeprazole, amoxicillin and clarithromycin during 6 days in patients with duodenal ulcer. To compare the reliability of the analysis of the eradication with urea-13C breath test performed one month and 3 months after therapy. To evaluate the one-year reinfection rate. PATIENTS AND METHODS: Prospective study including 99 patients with duodenal ulcer (65 with acute disease and 34 in maintenance treatment) infected by Helicobacter pylori (urease rapid test and urea-13C breath test positive). Patients were treated with omeprazole 20 mg, clarithromycin 500 mg and amoxicillin 1 g, b.i.d., during 6 days. The infection status was investigated 1 and 3 months after treatment by urea-13C breath test. The one-year reinfection rate was investigated using the same test. RESULTS: Per protocol eradication rates were 76% (95%-CI: 66-84) one month and 73% (95%-CI: 63-81) 3 months after treatment. In the intention to treat analysis, eradication rates were 74% (95%-CI: 64-82) and 70% (95%-CI: 60-79), respectively. Side effects were mild and uncommon. The rate of false negative urea-13C breath test results one month after therapy with respect to 3 months was 4.2% (95%-CI: 0.8-11.7). One-year reinfection rate determined in 56 patient was absent. CONCLUSIONS: The eradication of Helicobacter pylori with triple therapy for 6 days in patients with duodenal ulcer is not satisfactory. To investigate Helicobacter pylori infection with urea-13C breath test one month after treatment overestimates the results of the eradication. One-year reinfection rate is clinically irrelevant.

Adolescent↗

Rhesus monkey (Macaca mulatta) model of Helicobacter pylori: noninvasive detection and derivation of specific-pathogen-free monkeys.

BACKGROUND AND PURPOSE: Development of the rhesus monkey model of Helicobacter pylori has been hampered by problems with serodetection and by the difficulty of identifying specific-pathogen (Helicobacter)-free animals. Our purpose was to determine whether detection could be improved and to determine if pathogen-free monkeys could be derived by nursery rearing. METHODS: An enzyme-linked immunoabsorbent assay (ELISA) and a [14C]urea breath test were compared to endoscopy to determine H. pylori infection status in rhesus macaques; 18 animals were hand raised in the nursery to determine whether pathogen-free animals could be selected. RESULTS: Helicobacter pylori infection was common in colony-raised young rhesus monkeys and was nearly universal by adulthood. Serodetection, using antigen from rhesus-derived H. pylori strains, was 95% sensitive and 94% specific. The [14C]urea breath test was 96% sensitive and 88% specific for detection of chronic Helicobacter infection in rhesus monkeys. Segregation of newborn animals within the first 24 h of life was a reliable method to obtain pathogen-free rhesus monkeys. CONCLUSION: Isolation of specific-pathogen-free animals, together with better detection methods, may improve the value of the rhesus monkey model for the study of H. pylori pathogenesis, immune response, and vaccine development.

Animals↗

[Helicobacter pylori infection in diabetic patients].

The purpose of our research was to prove the occurrence of Helicobacter pylori infection in diabetic patients. Out of the 100 patients who were treated at the diabetological clinic, the antibody of Helicobacter pylori could be shown in 57 patients. Through histological tests carried out in the course of upper panendoscopia of the patients having positive results of serological test, Helicobacter pylori infection could be actually proved in 39 cases. On the basis of the evaluated material of diabetic patients, the occurrence of Helicobacter pylori infection was not higher than that in of the average population. No connection has been found between the frequency of the infection, and type of diabetes or its duration. The eradicational treatment was successful with 85% of the patients.

Adult↗

Relationship between enterogastric reflux estimated by scintigraphy and the presence of Helicobacter pylori.

The aim of the study is assessment of the relationship between enterogastric reflux and the presence of Helicobacter pylori infection as factors that cause gastritis, peptic ulcer and adenocarcinoma ventriculi. The study was performed in 52 patients with different digestive disorders, using gamma camera, during 90 min (1 frame/min) after intravenous injection of 185 MBq 99mTc-dietil IDA in the cubital vein. According to time/activity curves from the region of hepatobiliary system and stomach, index of enterogastric reflux (EGR) was assessed. There was no correlation between the presence of Helicobacter pylori and EGR (r = 0.181, df = 52, p > 0.05). However, Helicobacter pylori was present more frequently in the patients with positive EGR (p < 0.01), but there were no significant differences (p > 0.05) in reflux value in patients with either positive or negative findings of Helicobacter pylori.

Adult↗

Non-steroidal anti-inflammatory drug gastropathy and Helicobacter pylori infection.

The interest in the interaction between NSAIDs and Helicobacter pylori derives its importance from its potential to provide a different strategy to combat the common problem of NSAID-related peptic ulcers and their life threatening complications. Studies assessing this subject have differed in almost every aspect of their methodology, including the definition of a NSAID user as well as the types, doses, duration, and the indications for NSAID use. They also differed in their end points, the tests for the assessment of Helicobacter pylori, and the regimes used for its eradication. However, NSAIDs and Helicobacter pylori are known to share a number of important pathogenic mechanisms, and the prevalence of the infection is high in cohorts of ulcer patients taking NSAIDs. Eradication of Helicobacter pylori using bismuth-based regimes has also been more successful and beneficial in preventing the occurrence or relapse of NSAID-related ulcers than regimes using proton pump inhibitors.

Anti-Inflammatory Agents, Non-Steroidal↗

[Behavior of Helicobacter pylori in 3d and 4th age-bracket patients].

AIMS AND BACKGROUND: Helicobacter pylori is known to be the pathogenic agent of atrophic gastritis and above all ulcer disease. It is also thought to play a role, together with other factors, in the development of stomach cancer and is currently the focus of numerous studies. In industrialised countries, infection is relatively commonplace in children, whereas its incidence rises more steeply in patients aged over 35, reaching a mean prevalence of 50% in over 60 year olds. METHODS: During 1997 the authors carried out an epidemiological study to assay levels of anti-Helicobacter pylori (IgG anti-Hp) in a sample of 91 aged patients hospitalised in the S. Margherita Geriatric Hospital in Pavia. The patients had been admitted to hospital for various pathologies and the study also took into account gastric pathologies which usually, particularly in neoplastic forms, prefers the third and fourth ages. The assay for antibodies was performed using mouse monoclonal antibody, specific for Helicobacter pylori, absorbed on a polyester pad. A total of 5 ml of blood were collected from each patient. The blood samples were all centrifuged and the serum frozen at -20 degrees C until the tests were performed. RESULTS: In this study, 46 of the 91 patients tested were positive for anti-Helicobacter pylori antibodies, 35 were negative and 10 borderline. CONCLUSIONS: The high level of positive results found in these patients is in line with the findings reported by other authors.

Aged↗

Increased risk of infection with Helicobacter pylori in spouses of infected subjects: observations in a general population sample from the UK.

BACKGROUND/AIMS: To investigate risk factors for infection with Helicobacter pylori in a general population sample who accepted an invitation to be screened. In particular, to determine whether being the spouse of an infected subject is an independent risk factor for infection after adjustment for other risks. METHODOLOGY: A serological screening test for Helicobacter pylori was offered to 4015 randomly selected subjects registered at a single general practice in Market Harborough, UK. Those invited were also asked to complete a questionnaire if attending for screening; this included information relating to possible risk factors for infection. Results were analyzed in the overall sample of attenders and a subset of married couples, using univariate and multivariate analyses. RESULTS: Complete results were obtained for 1431 (36%) subjects. Age, childhood social class and household crowding in childhood were independent risk factors after adjustment for other variables. Positive status of spouse was an independent risk factor in a subset of 389 married couples (P = 0.005, Odds Ratio: 2.65, 95% Confidence Interval: 1.34-5.25). CONCLUSIONS: Our study confirmed the correlation between childhood living conditions and infection with Helicobacter pylori. In the study population, having a Helicobacter pylori-positive spouse was associated with a significant increased risk of being infected.

Adult↗

[The treatment of reflux esophagitis in patients with a Helicobacter infection of the gastric mucosa].

Among the pathogenetic mechanisms for the occurrence of gastroesophageal reflux disease, Helicobacter pylori infection is indicated. The conclusions are absolutely opposite. The object of our work was to assume ex juvantibus to what extent the eradication of the Helicobacter pylori infection would accelerate the healing of patients with reflux oesophagitis and would reduce the number of relapses. To investigation were submitted 42 patients with reflux oesophagitis with confirmed Helicobacter pylori infection, classified according to Savary-Miller. A group of 22 patients was treated 10 days with triple drug combination of omeprazole, amoxillin and metronidazol with the purpose of eradication of the infection, after which they continued with ranitidin up to 30 days, and a second group of 20 patients treated only with ranitidine for 30 days. The subjective complaints, endoscopic finding and present infection were followed up. A considerably higher number of recovered patients after eradication of the Helicobacter infection was established and the number of relapses for the six-month period of observation was considerably reduced.

Adolescent↗