Notizen: Gastric sucrose permeability is a noninvasive marker that reliably increases in association with gastrointestinal injury due to use of nonsteroidal antiinflammatory drugs. Despite the effect of Helicobacter pylori infection on the gastric mucosa, in a previous study we were unable to demonstrate that H. pylori infection was associated with abnormal gastric sucrose permeability. Our goal in this study was to explore further whether H. pylori infection changed gastric permeability; therefore, we evaluated the effect of treatment of H. pylori infection on gastric permeability to sucrose and the relation of sucrose permeability to density of polymorphonuclear leukocytes.〈section xml:id="abs1-2"〉〈title type="main"〉Materials and Methods.Five hundred milliliters of a solution containing 100 gm of sucrose was ingested by the subject at bedtime. Overnight urine was collected and assayed for sucrose by high-performance liquid chromatography. Sucrose permeability was assessed both before and approximately 4 weeks after anti–H. pylori therapy.〈section xml:id="abs1-3"〉〈title type="main"〉Results.Seventeen asymptomatic H. pylori–infected volunteers participated; 8 were cured. Sucrose permeability was in the range commonly found in normal controls both before and after anti–H. pylori therapy (mean excretion, 76.3 mg; range, 13–171 mg). Gastric sucrose permeability correlated with the density of polymorphonulcear cell infiltration of the mucosa. Cure of the H. pylori infection was associated with a small but significant decrease in sucrose permeability (98.8 ± 18 mg to 51.7 ± 9.8 mg (p = .01). Sucrose permeability was greater in those with a high density of mucosal polymorphonuclear cells compared to those with lower scores (119.5 ± 4 vs 71.4 ± 13 for those with scores ≥ 5 compared to scores ≤ 4;p = .023). Failed therapy resulted in an increase in the mucosal density of polymorphonuclear infiltration and sucrose permeability (56.4 ± 13 mg–99.7 ± 19 mg pretreatment vs posttreatment, respectively;p = .031).〈section xml:id="abs1-4"〉〈title type="main"〉Conclusion. H. pylori gastritis causes a small but measurable increase in gastric permeability to sucrose that may reflect epithelial transmigration of neutrophils.

Notizen: Background. The β-lactam group of antibiotics kills bacteria by inhibiting the terminal stages of peptidoglycan metabolism. We have recently identified amoxicillin-resistant Helicobacter pylori, none of which expressed β-lactamase. Penicillin-binding proteins (PBPs) represent a group of target enzymes for the β-lactam antibiotic family, and alterations in PBPs have been described in other penicillin-resistant bacteria. The amoxicillin-resistant phenotype characteristically was lost after freezing but could be restored by consecutive transfers into gradient plates.Materials and Methods. To determine whether amoxicillin resistance in H. pylori was related to alterations in any of the H. pylori PBPs, five H. pylori strains resistant to amoxicillin and three amoxicillin-sensitive strains were tested. PBPs were extracted from bacteria grown to logarithmic phase, labeled in vivo with 3H-benzylpenicillin, and analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and fluorography. Four main PBPs were separated from all amoxicillin-sensitive H. pylori strains.Results. Only three of the four main PBPs were found in the amoxicillin-resistant H. pylori strains. The differentially detectable PBP (PBP D) had an apparent molecular weight of 30 to 32 kD.Conclusion. These results suggest that PBP D might play a role in the amoxicillin-resistant phenotype of H. pylori strains lacking β-lactamase activity.

Notizen: Background. Although combinations of antibiotics and antisecretory drugs are useful for treatment of Helicobacter pylori infection, treatment failure is common. The aim of this study was to evaluate the relation between pretreatment antibiotic resistance and outcome by using six different treatment regimens for H. pylori infection.Patients and Methods. Three hundred sixty-nine consecutive H. pylori–infected patients with dyspeptic symptoms were enrolled in three consecutive randomized, controlled, single-center clinical trials: trial A, 128 patients; trial B, 125 patients; trial C, 116 patients. Treatments consisted of (A) a 15-day course of dual therapy (omeprazole, 20 mg bid, and amoxicillin, 1 gm bid, or clarithromycin, 500 mg tid) (OA vs OC); (B) a 7-day triple therapy of omeprazole, 20 mg bid, plus metronidazole, 500 mg bid, and amoxicillin, 1,000 mg bid, or clarithromycin, 500 mg tid (OMA vs OMC); or (C) omeprazole, 20 mg bid, plus metronidazole, 500 mg bid, plus tetracycline, 500 mg qid, or doxycycline, 100 mg tid (OMT vs OMD). Diagnostic endoscopy was made in all patients before and 5 to 6 weeks after therapy. Six biopsies were taken from each patient for histology, rapid urease test, and H. pylori culture; antibiotic susceptibility testing was performed using the E-test method.Results. Overall cure rates were poor for both dual therapies OA and OC (38% and 37%, respectively) and for triple therapies OMA, OMC, and OMD (57%, 55%, and 58%, respectively). The OMT combination was successful in 91% (95% confidence interval [CI], 80.4%–97%). Metronidazole resistance was present in 29.7% (95% CI, 24%–35%), amoxicillin resistance was present in 26% (95% CI, 21%–32%), clarithromycin resistance was present in 23.1% (95% CI, 18%–29%), tetracycline resistance was present in 14% (95% CI, 10%–20%), and doxycycline resistance was present in 33.3% (95% CI, 21%–47%). Antibiotic resistance markedly reduced the cure rates and accounted for most of the poor results with the triple therapies: 89% versus 23%; 77% versus 26%; 100% versus 60%; and 67% versus 23% for OMC, OMA, OMT, and OMD, respectively. OMT appeared to be the best because of the high success rate with metronidazole-resistant H. pylori (71%) and in low-level tetracycline resistance.Conclusions. Pretreatment antibiotic-resistant H. pylori can, in part, explain the low cure rate of the infection and the variability in outcome in reported trials.

Notizen: It has been suggested that H. pylori infection is associated with abnormalities in total leukocyte count as well as the number of basophils and lymphocytes. In addition, CagA seropositivity has been associated with an increase in serum transaminase (SGOT) values. The aim of this study was to confirm the findings of previous subgroup analyses in patients before and after treatment for H. pylori infection and to ascertain whether the abnormalities reversed following successful treatment.〈section xml:id="abs1-2"〉〈title type="main"〉Methods.Blood counts and serum transaminase levels were obtained prior to and following treatment of H. pylori infection of H. pylori-infected duodenal ulcer patients. CagA status was assessed by Western blot of the H. pylori isolates obtained from the patients.〈section xml:id="abs1-3"〉〈title type="main"〉Results.Ninety-four ulcer patients were studied, including 77 with CagA-positive H. pylori isolates (82%) and 17 with CagA-negative H. pylori isolates. All study parameters remained within normal limits both before and after therapy. There were no significant changes in any study parameter in those who failed therapy. Successful therapy resulted in a significant fall in total white cell count (7413 ± 520 cmm to 6738 ± 410 cmm, for pretreatment vs. cured, respectively, p = 0.04) and was almost entirely accounted for by a reduction in the number of circulating polymorphonuclear leukocytes (4595 ± 370 cmm to 3855 ± 270 cmm for pretreatment vs. cured, respectively, p = 0.015). The pretreatment SGOT and basophil count were significantly higher in those with CagA-positive H. pylori (SGOT = 23 ± 1 vs. 18.5 ± 1 U). Successful or failed therapy with follow-up for 3 months post therapy did not result in a significant change of SGOT levels.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions.We confirmed an increase in total leukocyte count and number of polymorphonuclear leukocytes in those with H. pylori infection. We also confirmed higher SGOT levels with CagA-positive H. pylori infection, but the failure to resolve within 3 months of cure of the infection makes it unlikely to be a direct result of the H. pylori infection.

Notizen: Helicobacter pylori infection is accepted to be associated with two mutually exclusive diseases: duodenal ulcer and gastric cancer. Attention has recently focused on possible relationships between H. pylori and gastroesophageal reflux disease and its complications such as adenocarcinoma of the gastric cardia. The aim of this study was to provide a framework for explaining the seemingly paradoxical associations between H. pylori and various gastrointestinal diseases.〈section xml:id="abs1-2"〉〈title type="main"〉Methods.Available data regarding H. pylori infection, cagA, acid secretion, corpus gastritis, and gastroesophageal reflux disease (GERD) and its complications are reviewed, and testable hypotheses are presented.〈section xml:id="abs1-3"〉〈title type="main"〉Results.Linking the type of H. pylori (cagA-positive vs. cagA-negative), the pattern and intensity of inflammation, and acid secretion explains the apparent paradoxes in the associations between H. pylori and gastric cancer, duodenal ulcer, and GERD. Although H. pylori is inhibited by bile, a duodenal acid load sufficient to lower the average pH to precipitate bile acids overcomes that inhibition. H. pylori that contain a functional cag pathogenicity island produce a vigorous inflammatory response. The severity of mucosal inflammation predicts likelihood of different outcomes (e.g., in the bulb with likelihood of developing duodenal ulcer, and in the corpus with the degree of reduction in acid secretion and the rate of development of multifocal atrophic gastritis). Development of H. pylori corpus gastritis is promoted by profound inhibition of acid secretion (e.g., childhood infections or a high level of antisecretory therapy). The CagA protein, or the cagA gene, is a marker for enhanced inflammation, but CagA is not directly involved in the pathogenesis of gastric cancer or duodenal ulcer disease, nor is it a reliable indicator of the presence of a functional cag pathogenicity island.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusion.The relationship between the type of H. pylori infection, presence or absence of a functional cag pathogenicity island, corpus inflammation, and acid secretion explains the duodenal ulcer/gastric cancer paradox and the relationship between H. pylori infection and the complications of GERD. The predicted rank order for the presence of GERD and its complications (peptic stricture, Barrett’s esophagus, and adenocarcinoma of the gastric cardia) is highest in the population without H. pylori infection, less in those with H. pylori infection, and least in those infected with cagA-positive H. pylori. Controversy and confusing epidemiological observations will continue unless future studies provide data on the gastric corpus histology (or acid secretion) as well as regarding the presence or absence of a functional and intact cag pathogenicity island of the infecting organism.

Notizen: Background. Because patients who fail to be cured of H. pylori infection following macrolide or imidazole therapy are difficult to treat, there is a clear need for a reasonably effective and simple second-line treatment regimen. The purpose of these two studies was to evaluate the efficacy of ranitidine bismuth citrate (RBC) plus amoxicillin for the cure of H. pylori infection and for healing duodenal ulcers and preventing ulcer relapse. Materials and Methods. Two identically designed randomized, double-blind, double-dummy studies were conducted in patients with an H. pylori-associated duodenal ulcer. Patients were treated with either RBC 400 mg bid for 4 weeks plus amoxicillin 500 mg qid for 2 weeks, RBC 400 mg bid for 4 weeks and placebo qid for 2 weeks, placebo bid for 4 weeks and amoxicillin 500 mg qid for 2 weeks, or placebo bid for 4 weeks and placebo qid for 2 weeks. Patients with healed ulcers after 4 weeks of treatment were eligible for entry into a 24-week observation phase for the assessment of H. pylori status (culture, histology, and CLOtestTM) and ulcer relapse. Results. A total of 229 patients with confirmed H. pylori infection at baseline were evaluated. Of these, 132 whose ulcers had healed entered the 24-week posttreatment observation phase. The combination of RBC plus amoxicillin resulted in higher H. pylori cure rates (55%) and higher duodenal ulcer healing (74%) than did either treatment alone. All treatments were well tolerated. Conclusions. The combination of ranitidine bismuth citrate plus amoxicillin cures H. pylori infection in more than half of the patients treated. This treatment regimen shows promise as the basis for future non-macrolide, non-imidazole triple therapy regimens for curing H. pylori infection. Such regimens may be appropriate second-line treatment for patients who are resistant to or who are unable to tolerate macrolide- or imidazole-containing therapies.

Notizen: Since the bacterium H. pylori was identified in 1982, overwhelming evidence has implicated it as the causal factor in the occurrence and relapse of peptic ulcer disease. The major objective of this study was to examine the extent to which physicians recognize H. pylori as a causal agent in peptic ulcer disease or as potential cofactor in other gastrointestinal diseases, and the extent to which this knowledge has influenced diagnostic and therapeutic practices.〈section xml:id="abs1-2"〉〈title type="main"〉Materials and Methods.Using a national mail survey in Germany in September 1995, 1197 family practitioners and 1197 gastroenterologists were selected for the study.〈section xml:id="abs1-3"〉〈title type="main"〉Results.Of the surveyed physicians, 756 (32%) responded. Family practitioners treated almost 50% of their patients with initial presentation of suspected ulcer disease without ordering further diagnostic tests. More than 25% of the family practitioners and 14% of the gastroenterologists reported that they do not treat diagnosed H. pylori infection in the first presentation of duodenal ulcer. At the time we conducted the study, 22% of responding family practitioners and 5% of responding gastroenterologists treated the first presentation of H. pylori-positive ulcer disease with regimens determined to be ineffective according to the available literature.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions.Gastroenterologists preferred to treat H. pylori infection when the associated disease was one for which a causal relationship had been more clearly established, while family practitioners showed less discrimination. In order to provide optimal therapy aimed at minimizing the course and consequences of H. pylori-related diseases, researchers in the field must ensure continuous dissemination of current knowledge.

Notizen: The Holy Grail of physiological studies in acid secretion has been to identify a specific abnormality in gastroduodenal physiology responsible for the development of duodenal ulcer disease.〈section xml:id="abs1-2"〉〈title type="main"〉Methods.We review the available data relating duodenal ulcer and Helicobacter pylori infection to perturbations in gastric physiology, especially acid secretion.〈section xml:id="abs1-3"〉〈title type="main"〉Results.It is known now that elevated serum pepsinogen levels, reduced inhibition of acid secretion with antral acidification or distention, exaggerated gastrin response to meals or infusion of bombesin or gastric-releasing peptide, exaggerated acid output in response to gastric-releasing peptide, and abnormalities in duodenal bicarbonate secretion in response to instillation of acid are reversible epiphenomena related to the H. pylori infection and are not in themselves responsible for duodenal ulcer disease. H. pylori is inhibited by bile, yet can thrive in the duodenal bulb of duodenal ulcer patients. Glycine-conjugated bile acids are precipitated by acid; thus, any mechanism that would increase the duodenal acid load may remove the inhibitory bile and allow unrestrained growth of H. pylori.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusion.These data and speculations offer one possible explanation for why duodenal ulcer occurs in only some people—those with high acid secretion—and suggest that the combination of high duodenal acid load and H. pylori infection is sufficient to result in duodenal ulcer disease.

Notizen: A murine model for Helicobacter pylori infection could facilitate vaccine development. This study was designed to determine the effect of various conditions of dose, frequency of administration, and fasting on H. pylori infection of mice.〈section xml:id="abs1-2"〉〈title type="main"〉Materials and Methods.Balb/c and C3H/HeN mice were inoculated orogastrically with clinical isolates of H. pylori grown in liquid culture. At 2-week intervals, the stomachs were removed for secondary culture on horse blood agar and for histological analysis. H. pylori from secondary cultures or homogenized stomach tissue from infected mice was inoculated a second time in naïve animals.〈section xml:id="abs1-3"〉〈title type="main"〉Results. H. pylori was cultured with high frequency only from the stomachs of C3H/HeN mice. Fasting the mice and increasing the number of organisms inoculated did not increase the rate of infection. Histological analysis detected no inflammation, but mucus depletion and erosion were present in the stomachs of C3H/HeN mice. H. pylori organisms were not observed. Secondary cultures of H. pylori or homogenized infected stomach tissue did not cause infection when inoculated in naïve mice.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions.Clinical isolates of H. pylori transiently infect C3H/HeN mice. This murine model is suitable for testing oral vaccines. Effective vaccination against H. pylori could prevent transient infection and reduce subsequent gastritis.

Notizen: Helicobacter-like organisms (HLOs) usually are present in the stomachs of cats. Although the histopathology of natural (H. felis or H. heilmannii) infections has been reported, their invasion into the lymphoid aggregates has not been described previously.〈section xml:id="abs1-2"〉〈title type="main"〉Materials and Methods.Gastric tissues were obtained from 17 adult cats living in a natural urban environment. Biopsy sites were selected by the presence of urease on the mucosal surface stained by Genta stain and periodic acid–Schiff stain.〈section xml:id="abs1-3"〉〈title type="main"〉Results.Spiral organisms morphologically similar to H. felis or to H. heilmannii were detected in all the cats, distributed predominantly over the oxyntic mucosa. Seven cats had prominent lymphoid follicles with germinal centers within the oxyntic mucosa, and in six of these seven cats, extracellular organisms were present within the lymphoid follicles. Scattered organisms also were found over sites of gastric metaplasia in the duodenum of six cats.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions.This study extends previous observations by showing that HLO infection in cats is associated with large lymphoid follicles in the stomach. In additon, HLOs were demonstrated submucosally within gastric lymphoid follicles and on patches of gastric metaplasia in the duodenum.