F. Di Mario

Helicobacter pylori infection enhances mucosal interleukin-1 beta, interleukin-6, and the soluble receptor of interleukin-2

It is thought thatHelicobacter pylori colonization of the gastric mucosa might stimulate the production of several cytokines, which might trigger and maintain the gastric inflammation associated withHelicobacter pylori infection. In the present study we evaluated interleukin-1β, interleukin-6, and the soluble receptor of interleukin-2 both in mucosal homogenates and in the sera ofHelicobacter pylori-infected (39 cases) and uninfected (40 cases) patients to investigate whether there was any relationship between variations in cytokines and (1) the severity ofHelicobacter pylori-associated gastritis or (2) CagA-positiveHelicobacter pylori strains. Mucosal, but not serum levels of interleukins-1 and-6 and interleukin-2 receptor were significantly higher in infected than uninfected patients, Serum levels ofHelicobacter pylori antibodies were significantly higher in infected than uninfected patients, These levels correlated with mucosal interleukin-1β. The degree of antral or body inflammatory grade was higher in infected than in uninfected patients; cytokines levels were higher in patients with high-grade gastritis, most of whom wereHelicobacter pylori positive. Patients infected with CagA-positive strains also had higher levels of interleukin-1β, but not of interleukin-2 receptor or interleukin-6. In conclusion,Helicobacter pylori infection results in a local increase in interleukins-1β and-6 and interleukin-2 receptor associated with high-grade mucosal inflammation. Interleukin-1β seems to favor anti-Helicobacter pylori antibody production, and mucosal levels are enhanced mainly in patients infected with cytotoxicHelicobacter pylori strains.

Prevalence of Helicobacter pylori resistance to antibiotics in Northeast Italy: a multicentre study

Abstract Aims. To evaluate prevalence of primary Helicobacter pylori antibiotic resistances in Northeast Italy and to identify risk factors associated with this resistance. Materials and methods. A total of 248 patients undergoing upper gastrointestinal endoscopy were enrolled from 19 Endoscopy Units over a 6-month period. From each patient, 4 gastric biopsies were taken for histology and 2 were sent to the Central Referral Microbiological Laboratory for culture and determination of antibiotic activity against Helicobacter pylori by means of E-test. Strains were considered resistant when minimum inhibitory concentration was >8 μg/ml for metronidazole and > 1 μg/ml for clarithromycin. No cut-off value was predefined for amoxycillin. Results. Culture of Helicobacter pylori was successfully performed in 167 patients. Primary resistance to metronidazole, clarithromycin or amoxycillin was 14.9%, 1.8% and 0.%, respectively. Patients infected with Helicobacter pylori strains resistant to antibiotics were more frequently females than males (70.3% vs 41.4%), had a significantly lower coffee intake (66.6% vs 86.6%) and lower body mass index (23.7±2.6 vs 25.3±3.6) than patients with susceptible Helicobacter pylori strains. Age, smoking, alcohol use, family history of Helicobacter pylori infection, concomitant diseases and treatments, endoscopic diagnoses, Helicobacter pylori density and histological activity of chronic gastritis were not associated with antibiotic resistance. Multivariate analysis confirmed that female gender (odds ratio = 2.74, 95% confidence interval = 1.03–7.27) was the only significant risk factor associated with antibiotic resistance. Conclusions. In this population, primary Helicobacter pylori resistance to metronidazole was higher than resistance to clarithromycin, and female gender was significantly associated with this resistance. The low prevalence of resistance to metronidazole, clarithromycin and amoxycillin identified in this geographical area suggests that proton pump inhibitor-based triple regimens including these antibiotics may still be used as first line therapies against Helicobacter pylori infection.

Incidence of secondary Helicobacter pylori resistance to antibiotics in treatment failures after 1-week proton pump inhibitor-based triple therapies: a prospective study

BACKGROUND Antibiotic-resistant Helicobacter pylori strains are becoming increasingly prevalent, although it is not clear to what extent the new resistant organisms will spread. AIM To evaluate the incidence of secondary Helicobacter pylori resistance to metronidazole, clarithromycin and/or amoxycillin after one-week proton pump inhibitor based triple therapy failure in patients who were, before therapy infected with Helicobacter pylori strains susceptible to these antibiotics. PATIENTS AND METHODS Enrolled in the study were 97 consecutive Helicobacter pylori-positive subjects infected by Helicobacter pylori strains susceptible to metronidazole, clarithromycin and amoxycillin. Activity of tested antibiotics was determined by means of the E-test. Patients were treated for seven days with a proton pump inhibitor, omeprazole 20 mg twice daily or pantoprazole 40 mg once daily, plus clarithromycin 250 mg twice daily and metronidazole 250 mg four times daily; or with a proton pump inhibitor plus amoxycillin 1 g twice daily and clarithromycin 500 mg twice daily. Two months after completion of therapy, endoscopy and gastric biopsies for histology, rapid urease test and culture were repeated. RESULTS Four patients were dropped from the study Overall Helicobacter pylori cure rates expressed as both intention-to-treat and per-protocol analyses, were, respectively 80% (40/50) and 81.6% (40/49) with proton pump inhibitor, clarithromycin and metronidazole and 76.6% (36/47) and 81.8% (36/44) with proton pump inhibitor amoxycillin and clarithromycin. No significant differences were observed between the two treatments. Subjects in whom treatment failed were significantly younger and had less active ulcer than cured patients. Of treatment failures, 70.6% (12 out of 17 subjects) de veloped a secondary resistance to metronidazole (35.33% and/or clarithromycin (64.7%). Secondary antibiotic resistance occurred in 77. 8% of treatment failures treated with proton pump inhibitor, clarithromycin and metronidazole and in 62.5% of those treated with proton pump inhibitor, amoxycillin and clarithromycin. Considering all patients treated, the overall incidence of secondary metronidazole and/or clarithromycin resistance after therapy was reported in 12.9% of subjects (12 out of 93 treated patients). CONCLUSIONS Secondary Helicobacter pylori resistances to metronidazole and/or clarithromycin occurred in large percentages in patients with treatment failure after the one-week proton pump inhibitor-based triple therapies, proton pump inhibitor, clarithromycin and metronidazole and proton pump inhibitor, amoxycillin and clarithromycin. It is likely that new antibiotics or treatment strategies will be needed in the near future to successfully treat Helicobacter pylori infection.

Pathology of the gastric antrum and body associated with Helicobacter pylori infection in non-ulcerous patients: is the bacterium a promoter of intestinal metaplasia?

A series of 115 consecutive, non‐ulcerous, dyspeptic patients were examined for Helicobacter pylori (H. pylori) colonization in the gastric antral and/or body mucosa using Giemsa staining. Findings were correlated with the presence and degree of activity of superficial gastritis, deep gastritis, atrophic gastritis and with the presence of intestinal metaplasia. The prevalence of H. pylori positivity was 61.7%. In 59 of the 71 positive patients (83%), H. pylori was detected in the antrum or in both the antral and oxyntic mucosa. In the remaining 12 positive patients, H. pylori was detected only in the oxyntic mucosa and in all these cases, the antrum showed intestinal metaplasia associated with atrophic gastritis (25%). In both antral and oxyntic mucosa, the activity of the gastritis was significantly correlated with H. pylori colonization. Linear logistic regression analysis showed that in patients with intestinal metaplasia the presence of H. pylori infection was significant in predicting the presence of more extensive intestinal metaplasia after adjusting for age. The prevalence of intestinal metaplasia types II and III was 65.5% in the H. pylori positive and 25% in the H. pylori negative patients. The antral mucosa is thought to be the elective site for H. pylori related histological lesions. At a later stage, H. pylori can be detected only in the oxyntic area while the antral mucosa shows extensive metaplastic or atrophic lesions. We would suggest that H. pylori plays a promotional role in the morphogenesis of intestinal metaplasia.

Cure of Helicobacter pylori infection in the elderly : effects of eradication on gastritis and serological markers

Background: Specific data on anti‐H. pylori treatments in elderly people are very scarce. The aim of the study was to evaluate in the elderly the efficacy of different anti‐H. pylori therapies and the behaviour of serum anti‐H. pylori antibodies, pepsinogen A and C, and PGA/PGC ratio induced by the anti‐H. pylori treatment.

Changes in Parietal and Mucous Cell Mass in the Gastric Mucosa of Normal Subjects with Age: A Morphometric Study

Whether or not the gastric mucosa undergoes significant changes in normal aging subjects is still open to debate. In 51 subjects undergoing endoscopy and lacking any significant endoscopic or histologic modification we evaluated mucosal thickness, gland number, numbers of parietal, chief and mucous cells at the fundus and of mucopeptic cells at the antrum, with a morphometric method, subgrouping the patients according to their age class. Our findings demonstrate that the number of parietal cells tends to increase with age and, on the other hand, the number of mucous cells is reduced in elderly subjects (p < 0.05). When considering the parietal-to-mucous cell ratio, this is significantly increased (p = 0.0005) with age. Acid secretion being an offensive factor and mucus a fundamental component of the gastric mucosal barrier, these findings suggest an increased susceptibility of the gastric mucosa to damage in the elderly.

The Long-Term Clinical Outcome of Elderly Patients with Helicobacter pylori-Associated Peptic Ulcer Disease

The objective of this study was to evaluate the long-term efficacy of Helicobacter pylori (HP) eradication treatment in elderly patients with HP-associated peptic ulcer. A total of 56 subjects, 25 affected with gastric ulcer (GU, 9 males, 16 females, mean age 77.8 years, range 67–93) and 31 with duodenal ulcer (DU, 19 males, 12 females, mean age 76.5 years, range 65–87) were confirmed to be HP-positive by gastric histology and the rapid urease test. All patients were then consecutively treated with omeprazole for 4 weeks plus one or two antibiotics for 1 week as anti-HP treatment. Clinical checkups were then performed every 3 months for 1 year for the evaluation of symptoms and clinical recurrences. Endoscopy with gastric biopsies was repeated after 1, 3 and 12 months for the evaluation of ulcer healing, HP infection and chronic gastritis activity. Statistical analysis was performed by means of the Student t test for unpaired data, the Fisher exact test (two-tailed), and the McNemar χ2 test. After 4 weeks of treatment, endoscopy confirmed healing of the ulcer in all patients, regardless of the treatment used to cure HP infection. Two months after the end of therapy, a total of 44 patients were HP-negative and 12 patients were still HP-positive. During the 1-year follow-up period 1/44 (2.2%) of the HP-eradicated patients and 5/12 (41.6%) of the still HP-positive patients suffered relapses (p = 0.001): the difference between the two groups remained statistically significant when patients were divided into the subgroups, GU (p = 0.01) and DU (p = 0.04). Two months after the end of therapy, there was still a significant reduction of symptoms both in HP-eradicated (p < 0.0000) and in HP-positive (p = 0.002) patients. After 1 year, however, there was a significantly decreased symptomatology only in HP-eradicated subjects (p < 0.0000) and not in patients still HP-positive. After both 2 months and 1 year of follow-up, chronic gastritis activity demonstrated a significant improvement only in HP-eradicated patients (p = 0.0000). In conclusion, the eradication of HP infection significantly improved the long-term clinical outcome of peptic ulcer disease in the elderly, reducing the recurrences of GU and DU, the patient’s symptomatology and the histological signs of chronic gastritis activity. The cure of HP infection is, therefore, strongly recommended in elderly patients with HP-associated peptic ulcer disease.

Cure of Helicobacter pylori infection in elderly patients: comparison of low versus high doses of clarithromycin in combination with amoxicillin and pantoprazole

Advancing age may influence clarithromycin’s pharmacokinetics. No studies have yet compared the effects of different dosages of clarithromycin in combination with a proton pump inhibitor and amoxicillin in elderly patients.

Low dose of clarithromycin in triple therapy for the eradication of Helicobacter pylori: One or two weeks?

The aims of this pilot study were: (i) to compare the efficacy of low‐dose clarithromycin (250 mg twice daily) for 1 or 2 weeks; and (ii) to evaluate possible therapeutic advantages in associating the low‐dose clarithromycin with an anti‐secretory agent or tripotassium dicitrate bismuthate (De Nol; Yamanouchi Pharm, Corugate Milano, Italy). A prospective, randomized, open trial was carried out on consecutive outpatients with dyspeptic symptoms and Helicobacter pylori infection. We enrolled 129 patients in one of the following schedules: (A) De Nol 120 mg q.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2 weeks; (B) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2 weeks; or (C) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 1 week. Results were evaluated by Per Protocol (PP) and Intention‐To‐Treat analysis (ITT). Eradication rate was 100% after treatment A, 92.6% after treatment B and 86.5% after treatment C by PP and 83.3, 75.7, and 68.1%, respectively by ITT. Side effects were reported by 16 subjects: 26.6% in group A; 9.1% in group B; and 7.5% in group C; in two cases side effects led to the withdrawal of the treatment. In conclusion, 500 mg clarithromycin per day in association with omeprazole and metronidazole, for 1 week gave comparable results to the same schedule for a 2 week period. The use of clarithromycin with bismuth and metronidazole produced a therapeutic gain compared with both of the anti‐secretory schedules, although this was not statistically significant.

The effect of aging on oro-cecal transit time in normal subjects and patients with gallstone disease

To ascertain whether aging and/or cholelithiasis can influence oro- cecal transit time (OCTT), we studied a total of 70 subjects, i.e., 10 healthy young adult controls, 22 healthy elderly controls, 18 elderly cholelithiasis patients and 20 elderly subjects with a history of cholecystectomy for gallstones. OCTT was measured by means of the hydrogen breath test after administering a liquid meal of 10 g of lactulose in 200 mL of water, and collecting exhaled breath samples every 10 minutes for 200 minutes. Of all subjects in the group of patients with a history of cholecystectomy, 6/20 were non- hydrogen producers, and therefore were not included in the study. The OCTT was found to be significantly longer in healthy elderly controls, than in healthy young adult controls; the elderly subjects who had undergone cholecystectomy had a longer OCTT than the healthy elderly controls, while no difference was detected when compared to elderly patients with gallstones. In conclusion, OCTT seems to increase in healthy aging. Cholecystectomy also increases OCTT in the elderly, suggesting a link between intestinal motility and the biliary tract which may be of pathophysiological significance. (Aging Clin. Exp. Res. 7: 234–237, 1995)