G. Gasbarrini

Meta-analysis: the effect of probiotic administration on antibiotic-associated diarrhoea

Background : Antibiotic‐associated diarrhoea can be attributed in part to imbalances in intestinal microflora. Therefore, probiotic preparations are used to prevent this diarrhoea. However, although several trials have been conducted, no conclusive evidence has been found of the efficacy of different preparations, e.g. Lactobacillus spp. and Saccharomyces spp.

Meta-analysis: the relationship between Helicobacter pylori infection and gastro-oesophageal reflux disease

Background: The relationship between Helicobacter pylori infection and its treatment and gastro‐oesophageal reflux disease (GERD) is controversial.

-Moxifloxacin-based strategies for first-line treatment of Helicobacter pylori infection.

Background : Standard anti‐Helicobacter pylori therapy may not achieve a satisfactory eradication rate. Fluoroquinolones, such as moxifloxacin, are safe and promising agents for H. pylori eradication.

Efficacy of different Helicobacter pylori eradication regimens in patients affected by insulin-dependent diabetes mellitus.

Background: Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections; antibiotic absorption, however, may be influenced by the disease. H. pylori eradication appears to be reduced in IDDM patients. The aim of the study was to evaluate the efficacy of the most common H. pylori eradication regimens in a population of IDDM-infected patients. Methods: One hundred and seventy-two IDDM patients were evaluated. H. pylori infection was assessed through the 13C-urea breath test. Infected patients were randomly assigned to three different standard 7-day eradication regimens: 1) amoxicillin, clarithromycin, pantoprazole; 2) tinidazole, clarithromycin, ranitidine bismuth citrate; or 3) tinidazole, clarithromycin, pantoprazole. Patients in whom eradication was not successful in the first cycle were subsequently submitted to a 7-day therapy with tinidazole, tetracycline, bismuth, and pantoprazole. Results: Thirty-seven per cent of IDDM patients were infected. None of the triple therapies used provided an eradication higher than 62%. Conversely, the quadruple regimen was successful in 88% of the patients. Ten per cent of the subjects undergoing the triple therapies showed minor side effects, without significant differences among groups, whereas side effects occurred in 25% of the patients treated with the quadruple therapy (P < 0.05). Conclusions: IDDM patients show a low H. pylori eradication rate with a standard triple therapy regardless of the regimen utilized, the dosage and/or the duration of the therapy used appearing not to be sufficient to eradicate the infection efficiently. The use of a quadruple regimen leads to the cure of a large percentage of the infected patients in whom the eradication was unsuccessful in the first therapy, although it is accompanied by a greater incidence of minor side effects.BACKGROUND Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections; antibiotic absorption, however, may be influenced by the disease. H. pylori eradication appears to be reduced in IDDM patients. The aim of the study was to evaluate the efficacy of the most common H. pylori eradication regimens in a population of IDDM-infected patients. METHODS One hundred and seventy-two IDDM patients were evaluated. H. pylori infection was assessed through the 13C-urea breath test. Infected patients were randomly assigned to three different standard 7-day eradication regimens: 1) amoxicillin, clarithromycin, pantoprazole; 2) tinidazole, clarithromycin, ranitidine bismuth citrate; or 3) tinidazole, clarithromycin, pantoprazole. Patients in whom eradication was not successful in the first cycle were subsequently submitted to a 7-day therapy with tinidazole, tetracycline, bismuth, and pantoprazole. RESULTS Thirty-seven per cent of IDDM patients were infected. None of the triple therapies used provided an eradication higher than 62%. Conversely, the quadruple regimen was successful in 88% of the patients. Ten per cent of the subjects undergoing the triple therapies showed minor side effects, without significant differences among groups, whereas side effects occurred in 25% of the patients treated with the quadruple therapy (P < 0.05). CONCLUSIONS IDDM patients show a low H. pylori eradication rate with a standard triple therapy regardless of the regimen utilized, the dosage and/or the duration of the therapy used appearing not to be sufficient to eradicate the infection efficiently. The use of a quadruple regimen leads to the cure of a large percentage of the infected patients in whom the eradication was unsuccessful in the first therapy, although it is accompanied by a greater incidence of minor side effects.

Helicobacter pylori CagA-positive Strains Affect Oxygen Free Radicals Generation by Gastric Mucosa

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.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.

Helicobacter pylori Infection Affects Eosinophilic Cationic Protein in the Gastric Juice of Patients with Idiopathic Chronic Urticaria

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 enrolment 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.

Helicobacter pylori is an aetiological factor for ischaemic heart disease: the case against.

Helicobacter pylori is one of four organisms often investigated for ari association with ischaemic heart disease. The four, including Chlamydia pneumoniae, Cytomegalovirus and Herpes virus, cause low-grade, life-long infections that can produce a persistent inflammation, the kind that leads to heart disease. Several studies suggest an association, but others suggest none. Patients with poor access to medical care are more likely to become infected and also more likely to suffer from coronary artery disease. Although the literature data are provocative and interesting, the two things may not be related. Helicobacter pylori infection is quite prevalent among individuals without ischaemic heart disease and absent in many of those with ischaemic heart disease. Thus, more definite answers about whether there is any link between Helicobacter pylori and cardiovascular disease are needed. It would be essential to establish the specific mechanisms that possibly confer vulnerability or protection toward coronaropathy. But a definite answer could come from clinical trials designed to test whether antibiotics can prevent the disease. Until now, no randomised trial has suggested a positive effect of Helicobacter pylori eradication in reducing the incidence of cardiac events.

Steatohepatitis during methylprednisolone therapy for ulcerative colitis exacerbation

Dear Sir, The occurrence of nonalcoholic fatty liver disease is a well-known side-effect of steroid therapy [1, 2]. In particular, treatment with high doses of glucocorticoid has been related to liver steatosis and more recently to nonalcoholic steatohepatitis (NASH) [3, 4]. We report a case of steatohepatitis induced by methylprednisolone therapy in a patient with an exacerbation of ulcerative colitis (UC). A 25-year-old man with a 10-year history of UC was admitted for the occurrence of bloody diarrhoea (8–10 bowel movements a day) and abdominal pain. Examination showed abdominal tenderness. Three stool cultures for parasites and bacteria were negative. Blood examinations showed normal ALT (32 U L; normal values 5–45) and AST (27 U L; normal values 10–45), and increased ERS (45 mm, normal values <10 mm) and C reactive protein (CRP-22 ng mL; normal values <5 ng mL). An abdominal ultrasound examination was then performed with no evidence of liver diseases. Colonoscopy showed left colitis with marked mucosal hyperaemia with small punctate ulcers, and biopsies showed severe chronic inflammation with presence of multiple crypt abscesses, epithelial flattening and ulceration consistent with UC exacerbation. Methylprednisolone therapy 40 mg day showed an improvement in symptoms within a few days with two daily bowel movements of formed stool without blood. Then he was dismissed. Therapy was tapered to 16 mg in 4 weeks. After 40 days blood examination showed an increase in ALT value (106 U L). AST remained normal (41 U L). ERS and CRP were normal (8 mm at first hour and 3 ng mL, respectively). An abdominal ultrasound examination was then repeated with the evidence of fat infiltration consistent with liver steatosis. Hepatitis virus (HAV, HBV, HCV, HEV, HGV, CMV and EBV) and antibodies against mitochondria, smooth muscle and nuclear antigens were not detected by serological tests. Liver biopsy showed macrovescicular hepatocellular fat accumulation, periportal inflammation and mild fibrosis (Fig. 1). The patient denied a history of alcohol abuse and the intake of hepatotoxic drugs and a diagnosis of nonalcoholic steatohepatitis was made [5]. He stopped the steroid treatment in 2 weeks and ALT value gradually decrease to normality. An abdominal ultrasound examination performed after 3 months showed an improvement in liver morphology with reduction in fat infiltration. Serological test for virus and autoantibodies were retested in the hypothesis of previous false negative results due to steroid therapy and were confirmed negative. The patient refused to participate in a second liver biopsy. After 6 months abdominal ultrasound showed a normal liver. Now, he is in remission with a 5-ASA maintenance therapy, with normal values of ALT and AST. Previously, steroid treatment has been related to steatohepatitis and fatal liver failure in two patients affected by systemic lupus erythematosus [3] and in our case steatohepatitis appears after starting steroid treatment in UC. Although drug discontinuation seems effective to induce remission of this condition a careful follow-up of patients submitted to steroids has to be performed because of the possibility of development of liver failure.

Disappearance of Gastric Mucosa-Associated Lymphoid Tissue in Coeliac Patients after Gluten Withdrawal

BACKGROUND Mucosa-associated lymphoid tissue (MALT) develops in gastric mucosa in response to chronic antigenic stimulation, such as Helicobacter pylori infection. However, reactive lymphoid follicles have been found also in the stomach of H. pylori-negative coeliac patients, suggesting that other environmental factors may be involved in MALT genesis. The aim of our study was to evaluate the effects of gluten withdrawal in H. pylori-negative coeliac patients with gastric MALT. METHODS We studied 23 H. pylori-negative untreated coeliac patients with gastric MALT. All patients underwent determination of antigliadin (AGA) and antiendomysium antibodies (EMA) and upper endoscopy with multiple biopsies in duodenum, gastric corpus, and antrum. Lymphoid follicles and H. pylori status were assessed by histopathologic and enzymatic analysis. All patients were started on a gluten-free diet and were reevaluated after 12 months. To consider their adherence to the gluten-free diet we relied on direct patient questioning. Thirteen patients who had strictly adhered to the gluten-free diet constituted our study group. Ten patients who had not strictly adhered to gluten withdrawal from their diet constituted the control group. RESULTS Regression of MALT was obtained in 9 of 13 (69%) patients who strictly followed the gluten-free diet; in the control group MALT disappeared in 2 of 10 (20%) patients (P=0.0361). DISCUSSION Disappearance of reactive lymphoid follicles in the gastric mucosa of H. pylori-negative coeliac patients after gluten withdrawal suggests that antigens related to alimentary gluten may constitute persistent stimuli for development of gastric MALT in coeliac patients.

Mild hepatitis at recommended doses of acetaminophen in patients with evidence of constitutionally enhanced cytochrome P450 system activity

Acetaminophen (paracetamol) is used throughout the world for pain relief and antipyresis in both children and adults. In many countries, it can be purchased without a medical prescription and it is also a common component of a number of over‐the‐counter remedies for colds, influenza and the like. Fasting, malnutrition and use of alcohol and/or other drugs are thought to play causal roles in hepatotoxicity associated with recommended doses of acetaminophen although liver injury provoked by therapeutic doses has also been observed in the absence of these factors. We describe two patients who experienced subclinical hepatotoxic reactions after taking acetaminophen at therapeutic doses. The results of an antipyrine metabolism test suggest the presence of constitutional hyperactivity of the cytochrome P450‐dependent mixed function oxidative system in both patients. We hypothesize that the latter contributed to the hepatotoxicity and that it may play a role in idiosyncratic reactions to this drug.