Incidence of gastrointestinal malignancies increases in persons received eradication therapy for Helicobacter pylori: A cohort study.

BACKGROUND: Long-term Helicobacter pylori infection increases the risk of gastric malignancies. Since the symptoms for H. pylori gastritis, as well as for several malignancies, may be nonexisting or highly unspecific, even H. pylori-positive subjects with underlying malignancies may receive eradication therapy. The aim was to assess the incidence of gastrointestinal and various other malignancies in individuals after eradication therapy for H. pylori infection. MATERIALS AND METHODS: A cohort of 217,554 subjects (120,344 women and 97,210 men), who had purchased specific combinations of drugs for H. pylori eradication therapy in 1994-2004, was identified by the Finnish National Prescription Registry and followed for cancer incidence until the end of 2008 (1.89 million person-years at risk). RESULTS: A total of 22,398 malignancies were identified in the cohort. In both genders, for the first 6 months after drug prescription, the standardized incidence ratios (SIRs) were between 5 and 32 for gastric, colorectal, and pancreatic cancers, and 2 and 3 for several other malignancies. Although later on the SIRs of most malignancies fell rapidly, those of gastric noncardia and lung cancers remained elevated up to 5 years of follow-up. The only SIRs below unity were seen in men for gastric cancers (cardia 0.61, 95% CI: 0.37-0.95; intestinal noncardia 0.74, 95% CI: 0.56-0.97) during the post-therapy period covering years 5-15. CONCLUSION: Incidence levels significantly above the population rates were detected for many malignancies. Although eradication of H. pylori may have a long-lasting protective effect against gastric cancer, H. pylori therapy may postpone the detection of malignancies possibly underlying unspecific gastrointestinal symptoms. Therefore, it should be emphasized that the diagnostic work-up for malignancies should not be stopped in case of detection and treatment of H. pylori infection.

Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation.

BACKGROUND: The human commensal microbiota interacts in a complex manner with the immune system, and the outcome of these interactions might depend on the immune status of the subject. OBJECTIVE: Previous studies have suggested a strong allergy-protective effect for Gammaproteobacteria. Here we analyze the skin microbiota, allergic sensitization (atopy), and immune function in a cohort of adolescents, as well as the influence of Acinetobacter species on immune responses in vitro and in vivo. METHODS: The skin microbiota of the study subjects was identified by using 16S rRNA sequencing. PBMCs were analyzed for baseline and allergen-stimulated mRNA expression. In in vitro assays human monocyte-derived dendritic cells and primary keratinocytes were incubated with Acinetobacter lwoffii. Finally, in in vivo experiments mice were injected intradermally with A lwoffii during the sensitization phase of the asthma protocol, followed by readout of inflammatory parameters. RESULTS: In healthy subjects, but not in atopic ones, the relative abundance of Acinetobacter species was associated with the expression of anti-inflammatory molecules by PBMCs. Moreover, healthy subjects exhibited a robust balance between anti-inflammatory and TH1/TH2 gene expression, which was related to the composition of the skin microbiota. In cell assays and in a mouse model, Acinetobacter species induced strong TH1 and anti-inflammatory responses by immune cells and skin cells and protected against allergic sensitization and lung inflammation through the skin. CONCLUSION: These results support the hypothesis that skin commensals play an important role in tuning the balance of TH1, TH2, and anti-inflammatory responses to environmental allergens.

Environmental biodiversity, human microbiota, and allergy are interrelated.

Rapidly declining biodiversity may be a contributing factor to another global megatrend--the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations worldwide. According to the "biodiversity hypothesis," reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity. Analyzing atopic sensitization (i.e., allergic disposition) in a random sample of adolescents living in a heterogeneous region of 100 × 150 km, we show that environmental biodiversity in the surroundings of the study subjects' homes influenced the composition of the bacterial classes on their skin. Compared with healthy individuals, atopic individuals had lower environmental biodiversity in the surroundings of their homes and significantly lower generic diversity of gammaproteobacteria on their skin. The functional role of the gram-negative gammaproteobacteria is supported by in vitro measurements of expression of IL-10, a key anti-inflammatory cytokine in immunologic tolerance, in peripheral blood mononuclear cells. In healthy, but not in atopic, individuals, IL-10 expression was positively correlated with the abundance of the gammaproteobacterial genus Acinetobacter on the skin. These results raise fundamental questions about the consequences of biodiversity loss for both allergic conditions and public health in general.

Gastric cancers in Finnish patients after cure of Helicobacter pylori infection: A cohort study.

Helicobacter pylori infection is associated with gastric cancer. A total of 97% of the infected subjects have elevated levels of H. pylori antibodies. The antibody titers have been shown to decline rapidly (40-60% within 4-12 months) only after successful eradication therapy. We allocated 26,700 consecutive patients tested during 1986-1998 for H. pylori antibodies to 3 subcohorts: seropositive patients with rapidly falling antibody titers (Hp+CURED, n = 3,650), seropositive patients where no serological information indicating cure was obtained (Hp+NoInfo, n = 11,638) and seronegative patients (Hp-, n = 11,422). In the subcohorts, the standardised incidence ratios (SIRs) with 95% confidence intervals (CI) were defined for subsequent cancers of stomach, pancreas, colon, rectum, breast and prostate separately and for all cancers except stomach combined. The mean follow-up time was 10.1 years and the number of gastric cancers was 72. For the Hp+CURED, the SIR for gastric cancers for the first 5 follow-up years was 1.62 but decreased from the sixth follow-up year thereon to 0.14 (CI: 0.00-0.75). Likewise, the risk ratio, defined in a Poisson regression analysis using the Hp+NoInfo group as the reference, decreased from 1.60 to 0.13 (CI: 0.02-1.00, p = 0.049). The SIR for Hp- was not significantly higher than that for Hp+NoInfo for any of the cancers analysed. To conclude, cured H. pylori infection led to a significantly decreased incidence of gastric cancers from the sixth follow-up year. Advanced atrophic gastritis would be a plausible contributor to the elevated SIR in elderly Hp- patients.

Longitudinal analysis of serological responses of adults to Helicobacter pylori antigens.

Because Helicobacter pylori persist for decades in the human stomach, the aim of this study was to examine the long-term course of H. pylori-specific serum immunoglobulin G (IgG) responses with respect to subclass and antigenic target. We studied paired serum samples obtained in 1973 and in 1994 in Vammala, Finland, from 64 healthy H. pylori-positive adults and from other healthy control subjects. H. pylori serum immunoglobulin A, IgG, and IgG subclass responses were determined by antigen-specific enzyme-linked immunosorbent assays. H. pylori-specific IgG1 and IgG4 subtype responses from 47 subjects were similar in 1973 and 1994, but not when compared with unrelated persons. H. pylori-specific IgG1:IgG4 ratios among the participants varied >1000-fold; however, 57 (89.1%) of 64 subjects had an IgG1:IgG4 ratio >1.0, consistent with a predominant IgG1 (Th1) response. Furthermore, ratios in individual hosts were stable over the 21-year period (r = 0.56; P < .001). The immune response to heat shock protein HspA was unchanged in 49 (77%) of the 64 subjects tested; of the 15 whose serostatus changed, all seroconverted and were significantly younger than those whose status did not change. These findings indicate that H. pylori-specific antibody responses are host-specific with IgG1:IgG4 ratios stable over 21 years, IgG1 responses predominating, and HspA seroconversion with aging.

A "screen-and-treat" approach for Helicobacter pylori infection: a population-based study in Vammala, Finland.

BACKGROUND: To accelerate the decline of Helicobacter pylori infection, and to study the significance of the possible risk factors for H. pylori infection in Finland, we started a voluntary H. pylori"screen-treat-retest-and-retreat" program for all young adults at primary health care in Vammala, Finland after a pilot study in 1994 including 504 subjects aged 15-75. MATERIALS AND METHODS: A total of 3326 aged 15-40 in 1996, and 716 aged 15 and 584 aged 45 in 1997-2000 were screened for H. pylori using serology. Helicobacter pylori positive were treated, cure was verified by serology. RESULTS: The eradication rates were 93.8%, 82.2%, and 77.6% per protocol in pilot study in 1994, in subjects invited in 1996 and 1997-2000, respectively. Helicobacter pylori seroprevalence rates were calculated to have decreased from 36% to 14% in pilot study, from 12% to 4% among subjects invited in 1996, from 3% to 2% among subjects aged 15 and from 27% to 12% among subjects aged 45 in 1997-2000. An epidemiologic questionnaire in 1996 revealed that crowding in the childhood household, low education of the mother, current smoking and alcohol consumption, unfavorable housing conditions, and sick leaves due to dyspepsia were independently associated with H. pylori infection. CONCLUSIONS: This intervention with high participation rates resulted in a significant decline in calculated H. pylori seroprevalence rates. Although the low prevalence of H. pylori infection may limit the cost efficiency of the program, the intervention is expected to reduce the burden of H. pylori-associated diseases.

Helicobacter pylori-induced indoleamine 2,3-dioxygenase activity in vivo is regulated by TGFB1 and CTLA4 polymorphisms.

The chronic gastric infection caused by Helicobacter pylori is known to be associated with several, probably interrelated, immunomodulatory effects, such as protection from atopic diseases, induction of CD4+ CD25+ T regulatory (T(reg)) cells and increase in indoleamine-pyrrole 2,3-dioxygenase (IDO) -dependent suppressive mechanisms. As these mechanisms, as well as the strength of the infection, are very probably genetically controlled, we selected candidate genes (TGFB1, CTLA4) known to be involved in the activation of T(reg) cells. We examined the association of their polymorphisms (TGFB1 C-509T, CTLA4 A+49G) with blood IDO activity in H. pylori seropositive individuals. Genotypes were determined from 391 healthy adults. H. pylori infection was verified by detecting H. pylori IgG antibodies in sera. Concentrations of tryptophan (trp) and kynurenine (kyn), the main metabolite, were determined by reverse-phase high-performance liquid chromatography, and kyn/trp ratio was used as an indicator of IDO activity. The activity was higher in H. pylori seropositive individuals, but this increase was only detected in individuals with CTLA4+49 AA genotype or in carriers of TGFB1-509 allele T. This suggests that H. pylori induced IDO activity is regulated by TGFB1 and CTLA4, and that IDO is a mediator of the T cell suppressive effects of these genes.

Clinical significance of widespread gastric metaplasia in the duodenal bulb.

BACKGROUND: All the risk factors of peptic ulcer disease are not thoroughly understood. GOALS: To assess duodenal gastric metaplasia (DGM) in relation to Helicobacter pylori status and endoscopy findings with special reference to the effects of highly selective vagotomy. STUDY: The study population consisted of 1056 adult patients and an additional 154 patients who had had a highly selective vagotomy. Their clinical and endoscopy records as well as the histology of gastric and duodenal biopsies were evaluated retrospectively. H. pylori infection had been determined by serology and culture. RESULTS: Widespread (more than 20%) DGM was strongly associated with H. pylori positive duodenal ulcer disease (in 59.7% of patients). The prevalence of DGM diminished progressively the more proximally the ulcer was located in the stomach, and was 2.5% in proximal gastric ulcers patients. In vagotomized patients, the prevalence of widespread DGM (8.4% of patients, median 14 years after operation and the majority still H. pylori positive) was close to that of patients with H. pylori gastritis without peptic ulcer disease (4.5%). CONCLUSIONS: Widespread DGM is an indicator for an increased risk of duodenal ulcer among H. pylori positive patients and it could be used to select patients for eradication therapy.

Infectious burden as a determinant of atopy-- a comparison between adults in Finnish and Russian Karelia.

BACKGROUND: Evidence of the influence of pathogen exposure on the development of atopy and atopic disease is not unequivocal. We investigated the association between markers of infections and occurrence of atopy among adults in eastern Finland and western Russia, two adjacent areas with profound differences in living conditions and lifestyles. METHODS: Randomly selected adults aged 25-54 years from Finland (n = 790) and from Russia (n = 387) participated in the study. Skin prick tests were performed to 11 common airborne allergens, and at least one positive prick reaction was considered to indicate atopy. Antibodies to different pathogens including hepatitis A virus (HAV), Helicobacter pylori, Toxoplasma gondii, herpes simplex virus (HSV), Chlamydia pneumoniae and the periodontal pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans were measured. RESULTS: In Finland 34.3% and in Russia 23.3% of the study population was atopic (p < 0.001). Seroprevalences to all these pathogens were significantly higher among the Russians. In multivariate logistic regression analysis, only H. pylori was inversely associated with atopy in Russia. A further stepwise analysis revealed that H. pylori alone can explain 32% of the difference in atopy between the countries, and T. gondii, A. actinomycetemcomitans, HSV and C. pneumoniae had a slightly additive effect, whereas, unexpectedly, seropositivity to HAV and, to a lesser extent, P. gingivalis had an opposite effect. The net result of the stepwise analysis showed that 44% of the difference in atopy between the countries could be explained by seropositivity to these seven pathogens. CONCLUSIONS: Seropositivity to select pathogens, particularly to H. pylori, could explain a substantial part of the difference in atopy prevalence between Finland and Russia. Exposure to HAV was not associated with protection against atopy in this adult population.

Helicobacter pylori IgA and IgG antibodies, serum pepsinogen I and the risk of gastric cancer: changes in the risk with extended follow-up period.

The prediction of Helicobacter pylori antibodies immunoglobulin A (IgA) and immunoglobulin G (IgG) and serum pepsinogen I (PG I) on gastric cancer occurrence was studied in a nested case-control study, based on 225 incident cancer cases and 435 matched controls from a Finnish cohort followed from 1966-1991. The odds ratio of noncardia gastric cancer between infected and noninfected persons was 3.12 (95% confidence interval (CI)=1.97-4.95) for elevated IgA and 2.88 (CI: 1.63-5.07) for elevated IgG antibodies. The odds ratio between low and high PG I was 2.24 (CI: 1.43-3.49). The strength of association was significant for IgA antibodies during the total follow-up, but for IgG antibodies this was only true for follow-up periods of 15 years or more. IgA antibodies were significantly associated with all registered histological subtypes apart from intestinal type adenocarcinoma. The highest gastric cancer risk was found among individuals with simultaneously elevated IgA and IgG antibodies and low PG I with an odds ratio of 10.9 (CI: 4.31-27.7) in comparison with those who were negative for both antibodies and had normal PG I. Elevated IgA and IgG antibodies and low PG I were not associated with cancers of the gastric cardia. The findings support the hypothesis that H. pylori infection is a cause of noncardia gastric cancer. Although elevated H. pylori IgA and IgG antibodies and low PG I independently could predict the occurrence of noncardia gastric cancer, their power to do so varied with the stage and length of the follow-up period and it increased when they were applied in combination.

Growing disparities in atopy between the Finns and the Russians: a comparison of 2 generations.

BACKGROUND AND OBJECTIVE: Western lifestyle has consistently been associated with the current asthma and atopy epidemics. We examined the occurrence and risk factors of atopy among schoolchildren and their mothers in 2 geographically adjacent areas with fundamental differences in living conditions and lifestyles. METHODS: A population-based study of 2 generations was carried out in eastern Finland and in western Russia. Randomly selected schoolchildren aged 7 to 16 years (367 in Finland and 446 in Russia) and their mothers (365 and 437, respectively) were enrolled. Data were obtained by using a modified International Study of Asthma and Allergies in Childhood questionnaire and by performing skin prick tests against 14 common airborne and food allergens. RESULTS: In children a 4-fold higher risk for atopy (> or =1 positive prick test result) was found in Finland compared with Russia. Sensitization rates in Finland were generally higher among children compared with those of their mothers, whereas in Russia the opposite trends emerged. Parental farming in early life (<1 year) in Finland (odds ratio [OR], 0.53; 95% CI, 0.28-0.99) and in Russia (OR, 0.47; 95% CI, 0.22-1.03) and currently in Finland (OR, 0.45; 95% CI, 0.22-0.91) conferred protection against atopy. Having pets, dogs in Finland (OR, 0.57; 95% CI, 0.35-0.95) and cats in Russia (OR, 0.43; 95% CI, 0.24-0.80), in early life was also inversely associated with atopy. CONCLUSION: Atopy was several-fold more common in Finland compared with in Russia, and disparities in sensitization rates between the countries have further increased during these generations. The similarity of explanatory variables of atopy in both countries suggests that determinants of atopy are shared, at least in similar geoclimatic conditions.

Indoleamine 2,3-dioxygenase (IDO) activity is lower in atopic than in non-atopic individuals and is enhanced by environmental factors protecting from atopy.

Tryptophan catabolism activated by the indoleamine 2,3-dioxygenase (EC 1.13.11.42) (IDO) enzyme in antigen presenting cells has a central role in induction of mechanisms suppressing T cell activation or clonal expansion. There is evidence suggesting that IDO activity is mainly upregulated by typical Th1-differentiating signals such as interferon-gamma and bacterial lipopolysaccharide (LPS). Therefore, we hypothesized that IDO activity would be lower in a Th2-associated disease such as atopy and that it would be higher in the presence of environmental factors known to favor Th1 differentiation. Here we show that this was the case. Concentrations of tryptophan (trp) and kynurenine (kyn), the main metabolite, were determined by reverse phase liquid chromatography from serum samples of a cohort of 392 non-asthmatic individual of whom 149 were atopics (one or more positive skin test when tested with a panel of 22 allergens). Kyn/trp ratio, as an indicator of IDO activity, was significantly lower in atopic than in non-atopic individuals. The cohort was stratified according to two known atopy-protecting factors, presence of antibodies against Helicobacter pylori or anamnestic information about childhood on a farm environment. As expected, IDO activity was significantly higher in their presence than absence.

Helicobacter pylori eradication as the sole treatment for gastric and duodenal ulcers.

OBJECTIVES: It is uncertain whether eradication of Helicobacter pylori--without a prolonged suppression of acid secretion--is sufficient to allow healing of peptic ulcers. We evaluated whether eradication of H. pylori with no following anti-secretory medication then administered is sufficient for treatment of peptic ulcers. We also looked at the impact of non-steroidal anti-inflammatory drug (NSAID) and acetylsalicylic acid (ASA) use on ulcer relapses. METHODS: The effect of eradication on ulcer healing and relapse rate was analysed in 115 patients, randomly allocated to four treatment groups: (1) quadruple therapy (28); (2) dual therapy (n-30); (3) triple therapy (n=27); and (4) lansoprazole and placebo (n=30). Endoscopic assessment was performed at 0, 8, and 52 weeks. RESULTS: The ulcer healing rate was 100% [95% confidence interval (CI), 95-100%] in H. pylori-negative and 83% (95% CI, 67-94%) in H. pylori-positive patients (P<0.01). In patients who used NSAIDS or ASA, the healing rates was 100% (95% CI, 73-100%) and 75% (95% CI, 19-99%) in H. pylori-negative (12 patients) and H. pylori-positive patients (four patients) (P = not significant). Ulcer relapses occurred in 5% (95% CI, 1-13%) of H. pylori-negative and in 36% (95% CI, 19-56%) of H. pylori-positive patients (P < 0.01). In H. pylori-negative patients who used NSAIDs or ASA the ulcer relapse rate was 30% (95% CI, 7-65%), whereas the ulcer relapse rate was 2% (95% CI, 0.4-10%) in patients who did not use NSAIDs or ASA (P < 0.05). No difference in ulcer relapse rate in H. pylori-positive patients who used or did not use NSAIDs or ASA was found. The eradication rate of H. pylori was 93% (95% CI, 76-99%) in the quadruple therapy group, 83% (95% CI, 64-94%) in the dual therapy group, 100% (95% CI, 87-100%) in the triple therapy group, and 0% (95% CI, 0-12%) in the lansoprazole and placebo group. CONCLUSIONS: Eradication treatment for H. pylori-positive gastric or duodenal ulcer is sufficient, with no need to follow it with anti-secretory medication. Cure of the infection reduces ulcer relapses in patients who did not use NSAIDs or ASA.

Association of Helicobacter pylori IgA antibodies with the risk of peptic ulcer disease and gastric cancer.

AIM: To compare the prevalence of Helicobacter pylori (H pylori) IgG and IgA antibodies between adult subjects, with defined gastric diseases, non-defined gastric disorders and those representing the population. METHODS: Data on H pylori IgG and IgA antibodies, determined by enzyme immunoassay, were analyzed in 3,252 subjects with DGD including 482 patients with gastric ulcer, 882 patients with duodenal ulcer, 1,525 patients with chronic gastritis only and 363 subjects with subsequent gastric cancer, 19,145 patients with NoDg and 4,854 POPUL subjects. The age-adjusted prevalences were calculated for 1- and 20-year age cohorts. RESULTS: The prevalences of IgG antibodies were equally high (89-96%) in all 20-year age cohorts of the DGD groups, whereas the prevalences of IgG antibodies were lower and increased by age in the POPUL and NoDg groups. The prevalences of IgA antibodies were also higher in the DGD groups; among them CA (84-89%) and GU groups (78-91%) showed significantly higher prevalences than DU (68-77%) and CG patients (59-74%) (OR 2.49, 95%CI 1.86-3.34 between the GU and DU groups). In the CA, GU, and DU groups, the IgA prevalences showed only minor variation according to age, while they increased by age in the CG, POPUL, and NoDg groups (P<=0.0001). The IgA response, but not the IgG response, was associated with an increased risk of CA (OR 2.41, 95%CI 1.79-3.53) and GU (OR 2.57, 95%CI 1.95-3.39) in comparison with CG patients. CONCLUSION: An IgA antibody response during H pylori infection is significantly more common in CA and GU patients as compared with CG patients.

Helicobacter pylori infection in Finland.

Helicobacter pylori causes chronic gastritis worldwide and it is the most important single factor in peptic ulcer disease. Up to half of H. pylori infected individuals develop atrophic gastritis over years and decades. H. pylori infection has also been classified as a class I carcinogen in human gastric cancer. Most infections are obtained in childhood, in Finland mainly before the age of 7 years but the exact transmission routes are not known. The infection shows an age-dependent pattern, the infection being rare among children but gradually becoming more prevalent among older age groups. As new infections are few in adults and the infection only rarely disappears without effective anti-microbial therapy, the occurrence of the infection in the old actually reflects the prevalence of the infection in their childhood. In developed countries, such as Finland, a rapid decline of H. pylori prevalence rate has been demonstrated. In order to speed up this natural decline of the infection, a unique population based 'screen and treat' project was started in Vammala, a semiurban south-western community in Finland. In this survey, young inhabitants were offered diagnosis and treatment for H. pylori.

Accelerated decline in Helicobacter pylori seroprevalence rate during the screen and treat project in Vammala, Finland, as demonstrated in 29- to 45-year-old pregnant women.

The potential preventability of serious helicobacter-associated diseases - especially gastric cancer - has evoked interest in eradicating this pathogen from the population. We assessed the efficacy of the pioneering screen and treat intervention project in Vammala by studying helicobacter seroprevalence in pregnant women representing the normal population. Consecutive maternity clinic samples from native Finnish females at five different localities in 1995 (n=701) and 2000 (n=772) were investigated for class IgG H. pylori antibodies by enzyme immunoassay (Pyloriset EIA-G III, Orion Diagnostica, Espoo, Finland). In Vammala the change in helicobacter seroprevalence was -13%-units (between 1995 and 2000; p=0.0125, chi-square test) in > or =29-year-old females, +1.6%-units (difference statistically non-significant) in <29-year-old females, and -5.5%-units (difference statistically non-significant) in the whole study population. In the four reference localities studied, all the corresponding changes remained statistically non-significant. Thus, in Vammala the programme applied accelerated the decline of helicobacter infections in 29- to 45-year-old females and in 2000 the seroprevalence rate had also become significantly lower than that of the four reference communities combined (7.6% versus 13.5%, respectively, p=0.0433, chi-square test). The final outcome of the intervention project, i.e. the long-term effect of this decline on gastric cancer and peptic ulcer disease, remains to be evaluated.

Eradication of Helicobacter pylori improves the healing rate and reduces the relapse rate of nonbleeding ulcers in patients with bleeding peptic ulcer.

OBJECTIVE: A causal relationship between Helicobacter pylori (H. pylori) and peptic ulcer complications remains obscure. The aim of this study was to determine the importance of H. pylori and other risk factors for healing rate, ulcer recurrence, and rebleeding in patients with bleeding peptic ulcer. METHOD: A total of 223 patients with H. pylori positive bleeding peptic ulcer were randomly allocated to three treatment groups: 1) quadruple therapy (QT) (88 patients); 2) dual therapy (DT) (88 patients); and 3) omeprazole and placebo therapy (OPl) (47 patients). Endoscopic assessment was performed initially and at 8 and 52 wk. Ulcer healing and eradication rates were assessed; endpoints were ulcer relapse and ulcer rebleeding during 52 wk. RESULTS: Results after 8 and 52 wk were available for 211 and 179 patients, respectively. Eradication rate was 100% (95% CI = 96-100%) in the QT, 84% (95% CI = 74-91%) in the DT, and 4% (95% CI = 1-15%) in the OPl group. Ulcer healing rate was 95% (95% CI = 91-98%) in H. pylori negative and 8% (95% CI = 70-91%) in H. pylori positive patients. Ulcer relapses occurred in 2% (95% CI = 0.5-6%) of H. pylori negative and in 38% (95% CI = 24-54%) of H. pylori positive patients, and rebleeding occurred in five patients (three H. pylori positive and two negative). CONCLUSIONS: Eradication of H. pylori infection enhances healing of bleeding peptic ulcers after endoscopic therapy. H. pylori infection is an important independent risk factor for relapsing of nonbleeding ulcers in patients with bleeding peptic ulcer.

Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis.

Background. Only a few reported studies focus on the natural history and course of advanced and severe chronic atrophic gastritis. Methods. In this study we followed 47 men (mean age 62 years) with advanced (moderate or severe) Helicobacter pylori-positive atrophic corpus gastritis. Duration of endoscopic follow-up was 6 years and follow-up based on serum levels of pepsinogen I and antibodies to H. pylori covered a period of 10 years. None of the patients was treated for H. pylori infection prior to end of follow-up. Results. The median H. pylori antibody titre declined (IgG from 4000 to 1300; IgA from 200 to 50) in the study population, and 11 men (23%) converted to seronegative (p=0.0005, Fisher's exact test). There was a small but significant (p=0.0004, Page's test) declining trend in mean atrophy score of the corpus during follow-up (from 2.5 to 2.2). However, no significant changes were observed in grade of atrophy or intestinal metaplasia of the antral mucosa or in grade of intestinal metaplasia in the corpus. The mean SPGI level remained at the initial low level during the entire follow-up. Conclusions. H. pylori antibodies disappear spontaneously within 10 years in almost one fourth of patients with advanced atrophic corpus gastritis. The disappearance of H. pylori antibodies is accompanied by no or more than a mild improvement of the gastric mucosa.

Prevention and suppression of Helicobacter felis infection in mice using colostral preparation with specific antibodies.

BACKGROUND: Specific antibodies against Helicobacter were enriched from the colostra of hyperimmunized cows. Efficacies of colostral control preparation and immune preparation containing specific antibodies against Helicobacter felis were studied in the prevention and treatment of experimental H. felis infection in mice. MATERIALS AND METHODS: H. felis-infected mice were given either immune or control preparation with or without complement or amoxicillin orally in four different trials. H. felis status was assessed on the basis of bacterial stainings, gastric histology and serum antibodies. RESULTS: Immune, but not control preparation, prevented H. felis infection (p > 0.01), the efficacy being dependent on the presence of specific antibodies. In the trial on infected Balb/c mice treatment with immune preparation (p = 0.029) but not control preparation decreased the colonization of gastric antrum by H. felis. In the further trials with infected SJL-mice, treatments with colostral preparations did not decrease colonization. Amoxicillin treatment decreased the colonization with trend-setting significance (p = 0.056; infected mice as controls), whereas amoxicillin combined with immune preparation had a significant effect (p < 0.0005). CONCLUSIONS: Specific colostral antibodies were useful in the prevention of Helicobacter infection in a mouse model. The results of the treatment trials were controversial but a similar colostral immune preparation against H. pylori could be effective and useful in preventing infections in humans and during antibiotic treatment.