Idiopathic thrombocytopenic purpura and Helicobacter pylori infection.
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Biomedical subjects
Publications and source records attributed to M Candelli.
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Antibiotic-associated diarrhoea is a common event. In some cases, it could represent a life-threatening event. Clostridium difficile colitis is a further distinct complication of antibiotic administration. Treatment options for antibiotic-associated diarrhoea and Clostridium difficile colitis include supplementation with several types of probiotics, as overviewed in this paper. Three randomised, double-blind, controlled clinical trials show a therapeutic effect of Saccharomyces boulardii in antibiotic-associated diarrhoea. The efficacy of Lactobacillus acidophilus and bulgaricus has also been ascertained in two double-blind controlled studies. Other studies focusing on Lactobacillus as a new preventive agent for antibiotic-associated diarrhoea are not double-blind. Among these, a positive effect of Lactobacillus rhamnosus GG, Bifidobacterium longum and Enterococcus faecium SF68 has been reported. Effectiveness of probiotics in antibiotic-associated diarrhoea has, therefore, a consistent scientific rationale, however few studies have performed an assessment of bacterial recovery in stools, and this approach may be helpful in deciding a more rigorous dose standardisation.
BACKGROUND: Moxifloxacin is a broad spectrum fluoroquinolone with single daily administration, currently used, above all, for respiratory tract infections. AIM: To compare the efficacy of different 1-week moxifloxacin-based Helicobacter pylori eradication regimens. METHODS: One hundred and twenty H. pylori-positive subjects were randomized to receive moxifloxacin (400 mg/day), moxifloxacin (400 mg/day) and lansoprazole (30 mg/day) or moxifloxacin (400 mg/day), lansoprazole (30 mg/day) and clarithromycin (500 mg b.d.). H. pylori status was reassessed 6 weeks after the end of therapy, and both intention-to-treat and per protocol analyses were performed. RESULTS: One hundred and nineteen of the 120 patients completed the study. H. pylori eradication was achieved in 22.5% of patients treated with moxifloxacin, in 33.3% of subjects treated with moxifloxacin and lansoprazole and in 90% of patients treated with moxifloxacin, clarithromycin and lansoprazole. CONCLUSIONS: Mono and dual moxifloxacin-based therapies are not acceptable for H. pylori eradication; conversely, moxifloxacin-based triple therapy may be considered as a new, effective, first-line therapy option.
Carbon-labelled breath tests were proposed as tools for the evaluation of human liver function 30 years ago, but have never become part of clinical routine. One reason for this is the complex role of the liver in metabolic regulation, making it difficult to provide essential information for the management of patients with liver disease with a single test and to satisfy the hepatology community. As a result, a battery of breath tests have been developed. Depending on the test compound administered, different metabolic pathways (microsomal, cytosolic, mitochondrial) can be examined. Most available data come from microsomal function tests, whilst information about cytosolic and mitochondrial liver function is more limited. However, breath tests have shown promise in some studies, in particular to predict the outcome of patients with chronic liver disease or to monitor hepatic function after treatment. Whilst we await new substrates that can be used to measure liver function in a more valid manner, and large prospective studies to assess the usefulness of available test compounds, the aim of this review is to describe how far we have come in this controversial and unresolved issue.
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BACKGROUND: One-week triple therapy is currently considered the golden standard against Helicobacter pylori. However, gastrointestinal side-effects are among the major pitfalls in such regimens. Probiotic supplementation might help to prevent or reduce such drug-related manifestations. AIM: To determine whether adding the probiotic Lactobacillus GG to an anti-H. pylori regimen could help to prevent or minimize the gastrointestinal side-effects burden. METHODS: Sixty healthy asymptomatic subjects screened positive for H. pylori infection were randomized to 1 week rabeprazole (20 mg b.d.), clarithromycin (500 mg b.d.), tinidazole (500 b.d.) and the probiotic Lactobacillus GG for 14 days or to the same regimen with a placebo preparation. Patients completed validated questionnaires during the week of treatment and during the following 3 weeks, to determine the type and severity of side-effects and an overall judgement of tolerability. RESULTS: Diarrhoea, nausea and taste disturbance were significantly reduced in the Lactobacillus GG supplemented group (relative risk=0.1, 95% CI: 0.1-0.9; relative risk=0.3, 95% CI: 0.1-0.9; relative risk=0.5, 95% CI: 0.2-0.9, respectively). An overall assessment of treatment tolerability showed a significant difference in favour of the Lactobacillus GG supplemented group (P=0.04). CONCLUSIONS: Lactobacillus GG supplementation showed a positive impact on H. pylori therapy-related side-effects and on overall treatment tolerability.
BACKGROUND: Helicobacter pylori plays a key role in production of reactive oxygen metabolites (ROMs). However, the importance of virulent CagA-positive H. pylori strains remains to be determined. The aim of this study was to assess ROMs production in gastric biopsies of patients infected by H. pylori. Results were correlated to CagA status and acute inflammatory infiltration. METHODS: Patients undergoing gastroscopy were enrolled. H. pylori infection was assessed by histology and 13C urea breath test. CagA status was assessed through serology. ROMs were assayed in gastric biopsies by luminol-enhanced chemiluminescence (CLS). Gastric mucosal inflammation was histologically graded and neutrophils were individually counted. Macroscopical damage was scored according to a modified Lanza score. RESULTS: 40 out of 60 patients evaluated were H. pylori (HP) positive. Of the 40 infected patients, 24 were CagA-positive. CLS emission was significantly higher in HP-CagA-positive patients than in HP-CagA-negatives and uninfected. ROMs production showed a significant correlation to neutrophil infiltrate in all groups. CONCLUSIONS: Gastric mucosa of patients infected by HP-CagA-positive strains is characterized by a higher generation of ROMs and by greater neutrophil counts than that observed in HP-CagA-negative subjects. Since ROMs production is associated with DNA oxidative damage, a long-term stimulation by these strains might be relevant in the pathogenesis of gastric malignancies. Assessment of CagA status might be useful to discriminate patients in which H. pylori eradication is advisable.
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OBJECTIVES: To evaluate the prevalence of and the risk factors for Helicobacter pylori in a population of medical and non-medical workers at a teaching hospital in Rome, Italy. DESIGN: A cross-sectional study. METHODS: From January to October 1998, 655 subjects (65% of the total population) underwent a 13C-urea breath test to assess H. pylori infection. Subjects completed a questionnaire concerning sociodemographic characteristics, work departments and history of some gastrointestinal symptoms. Differences in means and proportions were evaluated and independent predictors of H. pylori infection status were assessed by multiple logistic regression analysis. RESULTS: Forty percent of the subjects were found to be H. pylori infected. The mean age of positive subjects was significantly higher than that of negative ones (38 +/- 14 versus 34 +/- 12 years; P < 0.01). No significant difference was found between males and females concerning the infection status (40.2% males versus 39.9% females). Lower years of father's education [odds ratio (OR), 3.1; 95% confidence interval (CI), 1.9-5.1] and age older than 35 years (OR, 2.0; 95% CI, 1.3-3.1) were the only independent predictors of the likelihood of H. pylori positivity. Prevalence of gastrointestinal symptoms was similar in infected and uninfected subjects. Physicians were significantly less infected than nurses and auxiliary personnel (26% versus 47% versus 55%, respectively); however, a loss of association was observed after adjustment by multiple logistic regression (OR, 1.8; 95% CI, 0.9-3.7). In all groups, some specific departments appear to be associated with a higher infection status. CONCLUSIONS: Among healthcare workers, H. pylori infection was associated with specific sociodemographic characteristics, such as age and level of father's education. The prevalence of H. pylori infection was not associated with different professional categories. However, some specific departments seem to increase infection risk.
BACKGROUND: One-week triple therapy is currently regarded as the reference of anti-Helicobacter pylori treatment. However, antibiotic-associated gastrointestinal side effects are among the major pitfalls of such regimens. Probiotic supplementation may be regarded as a therapeutic tool to prevent or reduce these troublesome drug-related manifestations. AIM: To determine whether the addition of the probiotic Lactobacillus GG to an anti-H. pylori standard triple therapy could help to prevent or minimize the occurrence of gastrointestinal side effects. METHODS: One hundred and twenty healthy asymptomatic subjects screened positive for H. pylori infection and deciding to receive eradication therapy were randomized either to 1-week pantoprazole (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), tinidazole (500 mg b.i.d.) or to the same regimen supplemented with Lactobacillus GG for 14 days. Patients filled in validated questionnaires during follow-up to determine the type and severity of side effects and to judge overall tolerability. RESULTS: Bloating, diarrhea and taste disturbances were the most frequent side effects during the eradication week and were significantly reduced in the Lactobacillus GG-supplemented group (RR = 0.4, CI 0.2-0.8; RR = 0.3, CI 0.1-0.8; RR = 0.3, CI 0.1-0.7, respectively). The same pattern was observed throughout the follow-up period. Overall assessment of treatment tolerability showed a significant trend in favor of the Lactobacillus GG-supplemented group (p = 0.03). CONCLUSIONS: Lactobacillus GG supplementation beneficially affects H. pylori therapy-related side effects and overall treatment tolerance.
BACKGROUND: Helicobacter pylori, the main cause of gastritis and peptic ulcer, has been associated with idiopathic chronic urticaria (ICU), an immunological skin disorder of unknown origin. Eosinophilic cationic protein (ECP) is a cytotoxic molecule secreted by the activated eosinophils involved in the pathogenesis of ICU. We assessed serum/gastric juice ECP levels and gastric mucosal eosinophil infiltration in ICU patients infected or not with H. pylori and evaluated the modification after bacterium eradication. METHODS: 33 patients with ICU and 25 dyspeptic controls underwent upper gastrointestinal endoscopy for histological evaluation and assessment of H. pylori infection. One-week triple therapy was given to H. pylori-positive patients. Serum and gastric juice ECP levels, eosinophil infiltration from gastric mucosal sections and urticaria symptoms were evaluated in all patients at enrollment and 8 weeks after eradication. RESULTS: 19 of 33 (57%) ICU patients and 16 of 25 (64%) controls were found to be infected with H. pylori. Serum ECP was significantly higher in ICU patients compared to controls, regardless of infectious status. Gastric juice ECP and gastric eosinophil infiltration were significantly higher in infected ICU patients when compared both to uninfected ICU patients and controls. H. pylori eradication determined a significant decrease in gastric juice ECP and gastric eosinophil infiltration only in ICU patients. Moreover, a total or partial remission of urticaria symptoms was observed only in ICU patients in whom the bacterium was eradicated. CONCLUSIONS: Although H. pylori infection affects gastric juice ECP and eosinophil infiltration of ICU patients, the role of the bacterium in the pathogenesis of this skin disorder still remains uncertain.
BACKGROUND: Helicobacter pylori eradication therapies do not achieve 100% success rates. Antibiotic resistant strains are among the major causes of failure. Current recommendations concerning the management of treatment failures are not fully clear. AIM: To evaluate the efficacy of a multi-step therapeutic strategy in a large group of infected patients. METHODS: A total of 2606 H. pylori-positive patients were administered tinidazole, clarithromycin and a proton pump inhibitor for 1 week. Patients with continuing infection were then given a second 1-week course of amoxycillin, clarithromycin and ranitidine bismuth citrate. Patients still infected after the second course underwent upper gastrointestinal endoscopy with H. pylori culture, and then received a 1-week quadruple proton pump inhibitor-bismuth based scheme established on H. pylori antibiotic sensitivity. RESULTS: After the first step, eradication was achieved in 2063 out of 2413 patients [86% per protocol analysis (PP); 79% intention-to-treat analysis (ITT)]. First-step failures (350 out of 2413; 14.5% PP) showed second-step eradication rates of 82% (271 out of 329 patients, PP; 77% ITT). The specific quadruple therapy for second-step failures (58 out of 329, 18% PP) achieved 77% (30 out of 39 patients, PP) or 52% (ITT) success. This algorithm led to overall eradication rates of 99% (PP) or 91% (ITT). CONCLUSIONS: This multi-step strategy succeeded in a high percentage of H. pylori infected patients. Given the lack of precise guidelines on treatment failures, assessing H. pylori sensitivity to antibiotics only after failure of the second treatment could be suggested in clinical practice.
Recent studies have suggested an association between Helicobacter pylori infection and migraine. However, various strains of the bacterium are present, some endowed with greater pathogenicity. In particular, H. pylori type I CagA-positive strains induce a higher release of proinflammatory substances by the gastric mucosa that could trigger systemic vasospasms. The aim of the present study was to assess the prevalence of H. pylori CagA-positive strains in subjects with migraine. One hundred and seventy-five patients affected by migraine (49 with aura, 126 without aura) were consecutively enrolled and matched for sex, age, social background and geographical origin with 152 controls. Helicobacter pylori infection was assessed through 13C-urea breath test. Specific serological IgG against CagA were detected through ELISA. The prevalence of H. pylori infection was similar in migraine patients and in controls (40% vs. 39%, respectively). Among migraine patients, prevalence of infection was not related to presence or absence of aura (45% vs. 37%, respectively). However, among infected subjects, a significantly higher prevalence of CagA-positive strains was observed in patients affected by migraine with aura when compared with those affected by migraine without aura (41% vs. 19%, P < 0.01) and with controls (41% vs. 17%, P < 0.01). CagA-positive H. pylori strains were found to be strongly associated with migraine with aura. A higher inflammatory response of the gastric mucosa to more virulent strains could release substances that may act as triggers of vasospasm in peculiar cerebral arterial districts, probably implicated in the 'aura' phenomenon.
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Sucralfate is a cytoprotective drug widely used in clinical practice to prevent or treat several gastrointestinal diseases such as gastro-esophageal reflux, gastritis, peptic ulcer, stress ulcer and dyspepsia. Sucralfate is a safe and well tolerated drug, as demonstrated by the quite complete lack of side effects and it is, for this reason, one of the most important therapeutic choices in the management of acid related diseases during pregnancy. Moreover, sucralfate has recently been shown to be useful in non-acid related gastrointestinal disease as well. In fact, sucralfate has also been administered topically in patients with radiation-induced mucosal procto-sigmoiditis or ulcerative colitis with surprising results. The drug is actually able to form a physical barrier between epithelium and damaging agents (-bile salts, drugs, refluxate...). Moreover, sucralfate increases the local levels of fibroblast growth factors and induces a rise in the mucosal concentration of prostaglandins which are considered important factors in mucosal healing. The aim of this paper is to describe the current and probably forthcoming uses of sucralfate in the field of gastrointestinal disorders. Moreover, we investigate the role of sucralfate as a reliable means to prevent the occurrence of reflux-like symptoms after Helicobacter pylori eradication and in the management of Helicobacter pylori negative patients affected by non-ulcer dyspepsia.
BACKGROUND: Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections; however, antibiotic absorption may be influenced by the disease. Helicobacter pylori, the most common gastric infection worldwide, is the main acquired factor in the pathogenesis of gastritis and peptic ulcer. The aim of the study was to compare the H. pylori eradication rate obtained with a standard 7-day antibiotic regimen in a group of IDDM H. pylori infected patients and in a control group of infected dyspeptic patients. METHODS: Thirty-one patients (18 male, 13 female, 39+/-12 years) affected by IDDM and H. pylori infection, and 50 dyspeptic infected patients (23 male, 17 female, 37+/-10 years) were evaluated. H. pylori infection was assessed through 13C-urea breath test. A triple therapy with amoxycillin (1 g b.i.d.), clarithromycin (250 mg t.i.d.) and pantoprazole (40 mg b.i.d.) was given to both groups at the time of diagnosis for 7 days. Cure was defined as the absence of H. pylori infection, assessed by 13C-urea breath test, 6 weeks after completing anti-microbial therapy. Effects of H. pylori eradication on gastrointestinal symptoms (pyrosis, epigastric pain, belching, bloating, halitosis and nausea) were also evaluated. RESULTS: All enrolled patients completed the study. When compared to dyspeptic patients, the eradication rate was significantly lower in IDDM patients: 92% (46/50) versus 65% (20/31), respectively (P < 0.002). IDDM patients infected by H. pylori showed a different prevalence of some of the gastrointestinal symptoms assessed when compared to the infected dyspeptic patients; in particular, pyrosis, epigastric pain and belching were significantly more prevalent in the infected dyspeptic group. After H. pylori eradication, both groups showed a significant reduction of the intensity of all the gastrointestinal symptoms evaluated, except for nausea. CONCLUSIONS: IDDM patients showed a significantly lower H. pylori eradication rate when compared to that observed in dyspeptic subjects. The dosage and/or the duration of a standard eradication regimen does not appear to be sufficient to eradicate the infection in IDDM patients. The impairment of the gastrointestinal mucosa microvasculature with a reduction of antibiotic absorption, or the frequent use of antibiotics for other infections with development of resistant strains, may be the mechanisms underlying the observation.
In the past year, several studies have been carried out on the association between Helicobacter pylori infection and a miscellany of extradigestive diseases, such as cardiovascular, immunological, and various other pathologies. In particular, a higher prevalence of H pylori infection in patients affected by ischaemic heart disease has been described and there is growing evidence for an association between H pylori and some autoimmune diseases. Moreover, recent studies have shown that various helicobacter species have been detected in human bile; if confirmed, this finding could revise the diagnostic and therapeutic approach to diseases of the biliary tract.
Classical risk factors for cardiovascular and cerebrovascular diseases do not fully coincide with the prevalence of these conditions. Emerging evidences show that new factors may be predisposing for the development of ischemic events. It has been demonstrated that atherosclerosis has a strong inflammatory background; such state of chronic inflammation may be related to the presence of persistent infectious agent. Helicobacter pylori (H. pylori), among other microorganisms, has been extensively investigated for its possible role. Many molecular mechanisms have been hypothesized to explain its eventual action. Epidemiological studies do not exclude a correlation between the infection and cardiovascular and cerebrovascular diseases. Many confounding factors, however, make difficult a definitive evaluation of the huge number of data present in the literature. Moreover, various therapeutic studies have been attempted to show if antibiotic treatment improves prognosis in patients affected by ischemic heart disease. Still, none of these trials focused specifically on the effects of H. pylori eradication on the clinical progression of vascular lesions.