Ribotyping patterns and emergence of metronidazole resistance in paired clinical samples of Helicobacter pylori.

Metronidazole-susceptible pretreatment isolates and metronidazole-resistant posttreatment isolates of Helicobacter pylori from 11 patients before and after unsuccessful triple therapy consisting of metronidazole, amoxicillin, and colloidal bismuth subcitrate were studied. Ribotyping (rRNA gene restriction pattern analysis) of the isolates demonstrated that all patients except one had identical digest patterns for pre- and posttreatment isolates.     

Intraluminal casein model of necrotizing enterocolitis for assessment of mucosal destruction,bacterial translocation,and the effects of allopurinol and N-acetylcysteine

An intraluminal casein model (ICM) of necrotizing enterocolitis (NEC) is able to produce small-bowel changes reminiscent of human NEC in neonatal animals. We studied bacterial translocation (BT) in NEC induced by using the ICM in neonatal piglets. We also studied whether allopurinol (AL) and N-acetylcysteine (NAC) have an effect on BT and mucosal changes in the ICM of NEC. Twenty-eight neonatal piglets were randomized into four groups. NEC was induced in 21 by injecting casein-d-gluconate into a loop of terminal ileum: group Cas (n = 7) had no premedication, in group Cas/AL (n = 7) intravenous (i.v.) Al (100 mg/kg), and in group Cas/NAC (n = 7) i.v. NAC (200 mg/kg) was given. Group Sham (n = 7) had the ileum injected with 0.9% saline with no premedication. Immediately after the injection a mesenteric lymph node (MLN) adjacent to the loop was harvested for quantitative aerobic bacterial culture; 4 h after the injection another MLN and samples of spleen, liver, kidney, and lung were harvested and cultured. Comparison of the incidence of samples with positive bacterial cultures and the number of colony-forming units (CFU) in samples was made between groups. The severity of NEC in the ileum was graded from 0 to 3 according to macroscopic and histologic findings. NEC changes in the bowel were most severe in Cas piglets, less severe in Cas/NAC piglets ( P < 0.5), and sham piglets had the least severe changes ( P < 0.05). piglets with NEC changes in the ileum had a higher incidence of BT into the MLN than piglets without NEC changes ( P < 0.05), but the difference in CFU was not significant ( P > 0.05). In Cas and Cas/NAC piglets a high incidence of BT into the MLN was noted as early at -5 min after casein injection. The incidence of BT into the MLN was significantly higher in Cas and Cas/NAC piglets than in Sham piglets ( P < 0.05), the difference in CFU being not significant ( P > 0.05). BT in Cas/Al piglets was not significantly different from that of Cas piglets ( P > 0.05), but less than in Cas/NAC piglets ( P < 0.05). Four hours after casein injection into the ileum there was significant BT into the MLN. Premedication with NAC was associated with less severe NEC changes, but neither NAC nor AL significantly affected BT.     

Temporal and geographical distribution and overlap of Penner heat-stable serotypes and pulsed-field gel electrophoresis genotypes of Campylobacter jejuni isolates collected from humans and chickens in Finland during a seasonal peak

The association of Penner heat-stable serotypes and pulsed-field gel electrophoresis genotypes of 208 human and 30 chicken Campylobacter jejuni isolates was studied. Overall, 46% of the human strains had overlapping sero- and genotype combinations with chicken strains. The percentage was reduced to 31% for strains that were considered temporally related. This suggests common environmental sources.     

Campylobacters: the most common bacterial enteropathogens in the Nordic countries

Campylobacters have been known as important human pathogens since the late 1970s. Campylobacter jejuni and coli are the most common bacterial enteropathogens in the developed countries. During the past years an increasing incidence of campylobacteriosis has been reported in many developed countries. C. jejuni is the most common Campylobacter species while C. coli accounts for about 5-10% of the cases. Although the genome of C. jejuni NCTC 11168 strain was sequenced recently, the exact pathogenetic mechanisms are still not known. Furthermore, there are no reliable animal models available. The epidemiology of this common infection is not well understood; however, eating and handling poultry, contaminated drinking water, and contact with pet animals have been recognized as important risk factors. Most of the cases are sporadic although large water-borne outbreaks have also been reported. Discriminatory typing methods are helpful in tracing the sources and transmission routes. In addition to traditional serotyping, genotyping methods, such as pulsed-field gel electrophoresis, have been developed. As Campylobacter infections probably precede Guillan-Barré syndrome in many cases, a great interest has lately been focused on the possible triggering mechanisms underlying this phenomenon.     

Swimming and Campylobacter infections

A matched case-control study was conducted to study risk factors for domestically acquired sporadic Campylobacter infections in Finland. Swimming in natural sources of water was a novel risk factor. Eating undercooked meat and drinking dug-well water were also independent risk factors for Campylobacter infection.     

A three-year study of Campylobacter jejuni genotypes in humans with domestically acquired infections and in chicken samples from the Helsinki area

Campylobacter jejuni isolates from stool samples of patients with domestically acquired sporadic infections and from chicken from retail shops were studied during seasonal peaks from June to September over a 3-year period from 1996 to 1998. A large number of pulsed-field gel electrophoresis (PFGE) genotypes (a combined SmaI-SacII pattern) were identified each year. Certain genotypes persisted for the whole study period, and predominant genotypes represented 28 to 52% of the strains during a restricted period of time. The peak level of positive chicken samples was between July and August of each study year, when 10 to 33% of the samples were positive for campylobacter. The same PFGE genotypes found in humans were also detected in the chicken samples. This suggests that common genotypes were circulating in the area.     

Survival of Helicobacter pylori From complement lysis by binding of GPI-anchored protectin (CD59)

BACKGROUND & AIMS: Although Helicobacter pylori is sensitive to complement lysis in vitro, chronic infection persists for years. We tested whether H. pylori acquires complement resistance by binding glycolipid-tailed inhibitors from the host. METHODS: Gastric biopsy specimens from H. pylori-infected patients (n = 10) and noninfected controls (n = 6) were analyzed for complement deposition and expression of the complement regulators protectin (CD59) and DAF. Protectin binding and complement sensitivity analyses were performed with the NCTC strain 11637 (CagA(+)) and 2 clinical isolates 9:0 (CagA(+)) and 67:20 (CagA(-)). RESULTS: In the noninfected mucosa, protectin was strongly expressed on the membranes of epithelial cells, but in the infected epithelia the expression was granular and more focused to the mucus. H. pylori bacteria in the gastric pits were often positive for protectin but negative for C5b-9. An opposite pattern was seen on the surface mucosa. In vitro analyses using (125)I-CD59 and bacteriolysis assays showed that protectin bound to H. pylori and protected CagA(+) strains against complement killing. In an enzyme-linked immunosorbent assay, the binding of CD59 correlated inversely with the appearance of the C5b-9 neoantigen. CONCLUSIONS: Binding of protectin inhibits membrane attack complex assembly on H. pylori and may thereby contribute to their survival on the gastric mucosa.     

Enhanced systemic matrix metalloproteinase response in Helicobacter pylori gastritis

Background. Helicobacter pylori causes chronic gastritis, peptic ulcer disease, and is the most important risk factor for non-cardia gastric cancer, and has been shown to upregulate matrix metalloproteinases (MMPs) in infected gastric mucosa. MMPs are proteolytic enzymes regulated by tissue inhibitors of metalloproteinases (TIMPs).

Aims. We set up this study to find out whether H. pylori gastritis induces systemic MMP response.

Methods. Serum samples were collected from patients undergoing gastroscopy; 26 patients had H. pylori gastritis and 18 were H. pylori-negative controls with normal gastric mucosa. Serum MMP levels were analysed by enzyme-linked immunosorbent assay.

Results. Significantly elevated serum levels of collagenase-2 (MMP-8), gelatinase B (MMP-9), neutrophil elastase (NE), and myeloperoxidase (MPO), and reduced serum levels of gelatinase A (MMP-2) and TIMP-1 were demonstrated in patients with H. pylori gastritis as compared to H. pylori-negative controls. No significant differences were shown in serum matrilysin-1 (MMP-7) levels.

Conclusions. For the first time, we show enhanced MMP-8 response in H. pylori infection together with other neutrophil degranulation products (MMP-9, MPO, NE). Elevated circulating neutrophil degranulation product levels in serum of H. pylori-positive patients reflect accelerated proteolysis and oxidative stress, and may contribute to extraintestinal sequelae, such as cardiovascular diseases.     

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.     

Dual role of infections as risk factors for coronary heart disease

AIMS: The aim of the study was to explore whether exposure to microbial agents determines the prevalence of acute coronary events. METHODS AND RESULTS: Patients with unstable angina pectoris and myocardial infarction (N=335) and their paired controls were investigated. The subjects answered a questionnaire about their childhood contagious diseases: varicella, scarlet fever, measles, rubella, mononucleosis and mumps. Blood samples were taken for bacterial and viral serology. The odds ratio for CHD was highest in the upper quartile of the enterovirus (EV), herpes simplex virus (HSV) and Chlamydia pneumoniae HSP60 IgG antibody titers (1.86, p=0.001, 1.57, p<0.048 and 1.70, p=0.016, respectively). The antibody titers increased cumulatively the risk for CHD (odds ratios 1.89, 2.24, 3.92 and p-values <0.001, 0.001 and 0.047). Childhood contagious diseases (n=6) had a protecting effect against CHD (odds ratio 0.86, p=0.013). The risk for acute coronary events decreased significantly with increasing number of childhood contagious diseases (p=0.007). CONCLUSIONS: Infections have a dual role in the genesis of CHD. EV, HSV and C. pneumoniae heat shock protein 60 IgG antibodies are associated with increased risk for CHD. Protection from infections usually suffered during the childhood before the era of MMR vaccination may predispose the individual to CHD.