Azithromycin on soluble cell adhesion molecules and markers of inflammation in survivors of an acute coronary syndrome.
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Biomedical subjects
Publications and source records attributed to Antonio Gasbarrini.
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BACKGROUND: Double-balloon enteroscopy (DBE) is a new technique that allows high-resolution visualization, biopsies, and therapeutic interventions in all segments of the GI tract. The objective of the study was to evaluate the indications, the safety, and the clinical impact of DBE. METHODS: This is a retrospective analysis conducted at 4 European medical centers. A total of 62 patients with suspected or documented small-bowel diseases were investigated by DBE. A total of 89 procedures were performed (26 and 9 patients from the oral or the anal route, respectively; 27 patients from both). The main outcome measurements were complications, depth and time of insertion, diagnostics, and therapeutics rates. RESULTS: No complications occurred. Mean time was 70 +/- 30 minutes and 90 +/- 35 minutes from the oral and the anal route, respectively. Length of insertion was 254 +/- 174 cm beyond the pylorus, 180 +/- 150 cm beyond the ileocecal valve, whereas the entire small bowel was completely explored in 10 patients. DBE was diagnostic in 80% of the patients: in 29 of 33 of patients with GI bleeding, in one of 5 patients with iron deficiency anemia and positive fecal occult blood testing, in 3 of 5 patients with chronic diarrhea, in two of 3 patients with abdominal pain, in two of 3 patients with GI cancer (follow-up), in all patients with suspected or refractory celiac disease, and in two of 3 patients with Crohn's disease. Treatment was performed in 41.9% of patients (22 polyps and 29 angioectesias). CONCLUSIONS: DBE is a safe and feasible diagnostic and therapeutic tool for suspected or documented small-bowel diseases. At present, the best candidates for the procedure appear to be those with obscure GI bleeding.
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BACKGROUND: Probiotics are widely used for the cure or prevention of several clinical conditions. However, clinical decisions need to be substantiated by an analysis of the complex bacteria-host interplay in the intestinal lumen. AIMS: To identify the gene expression pattern induced by Bacillus clausii in the intestinal mucosa of healthy individuals. METHODS: Six male patients (mean age 38+/-5 years) affected by endoscopically confirmed mild oesophagitis were treated for one month with esomeprazole, and were randomly selected to receive or not B. clausii (groups I and II, respectively). Duodenal biopsies were taken pre and post-treatment to identify the modification of gene expression, using the GeneChip Human U133A array. To validate the microarray analysis, real-time reverse transcriptase-polymerase chain reaction (PCR) of five target genes was performed. RESULTS: After B. clausii administration, a total of 158 and 265 genes were up and downregulated, respectively. Quantitative PCR confirmed the microarray data. B. clausii mainly affected the expression of genes involved in immune response and inflammation, apoptosis and cell growth, cell differentiation, cell-cell signalling, cell adhesion, signal transcription and transduction. CONCLUSIONS: Our data represent the first global analysis of B. clausii effects on the gene expression profile in normal intestine, and provide the basis to identify the mechanisms by which these agents interact with the host and exert their beneficial effects. Future studies are needed to clarify the B. clausii-induced gene pattern in the clinical disorders in which probiotics have proved to be effective.
Coeliac disease is an autoimmune enteropathy triggered by the ingestion of gluten in susceptible individuals. The clinical presentation of coeliac disease is variable and several extra-intestinal manifestations, as well as an association with autoimmune diseases, have been described. In particular, there are many links between liver disease and coeliac disease. Here we report the case of a young Caucasian woman with acute liver failure, selected as a possible candidate for liver transplantation. Investigation of the patient led to the diagnosis of coeliac disease. A gluten-free diet led to the reversal of the severe liver failure, without the necessity for any surgical or medical treatment.
The involvement of Helicobacter pylori in the pathogenesis of extragastric diseases continues to be an interesting topic in the field of Helicobacter-related pathology. Although conflicting findings have been reported for most of the disorders, a role of H. pylori seems to be important especially for the development of cardiovascular and hematologic disorders. Previously isolated human and animal Helicobacter sp. flexispira and "Helicobacter heilmannii" strains have been validated using polyphasic taxonomy. A novel enterohepatic Helicobacter has been isolated from mastomys and mice, adding to the list of helicobacters that colonize the liver. Genetic targets that may aid the classification of novel Helicobacter species have emerged. Animal models of Helicobacter-induced gastric and hepatobiliary diseases have offered insights to the mechanisms associated with premalignant transformation.
OBJECTIVES: Increased homocysteine contributes to the pathophysiology of several chronic inflammatory diseases. Whether homocysteine could participate in mucosal inflammation in inflammatory bowel disease (IBD) has not been explored yet. Our aims were to study the levels of plasma and mucosal homocysteine in IBD patients and to assess whether homocysteine can trigger an inflammatory reaction on human intestinal microvascular endothelial cells (HIMECs). METHODS: Homocysteine was measured in the plasma, mucosal biopsy, and lamina propria mononuclear cell (LPMC) supernatants from normal and IBD subjects. HIMEC were cultured in presence of homocysteine, TNF-alpha, or folic acid, alone or in combination. Expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular cell adhesion molecule 1 was measured by flow cytometry and monocyte chemoattractant protein-1 (MCP-1) production by ELISA. Phosphorylation of p38 and p42/44 was assessed by immunoblot in HIMEC extracts. T-cell- and monocyte-HIMEC adhesion assays were used to evaluate the impact of homocysteine on leukocyte adhesion to intestinal endothelial cells. RESULTS: Patients with IBD displayed significantly higher homocysteine plasma and mucosal levels than control subjects. IBD-derived LPMC released higher homocysteine than control-derived LPMC. Treatment of HIMEC with homocysteine, and synergistically with the combination of TNF-alpha and homocysteine, triggered HIMEC inflammation, resulting in VCAM-1 up-regulation, MCP-1 production, and p38 phosphorylation. These events lead to an increased capacity of HIMEC to adhere T- and monocyte cells and were blocked by folic acid treatment. CONCLUSIONS: Homocysteine is increased in both the mucosa and plasma of patients with Crohn's disease and ulcerative colitis and contributes to the inflammatory state of the mucosal IBD endothelium. Therefore, homocysteine could play a proinflammatory role in IBD, which can be efficiently targeted by folic acid supplementation.
Idiopathic thrombocytopenic purpura (ITP), an autoimmune disease caused by sensitization of platelets by autoantibodies leading to platelet destruction, has been associated with some infectious agents, including Helicobacter pylori. The study by Suzuki et al., published in this issue, provides further evidence of the role of H. pylori infection in the pathogenesis of ITP, as confirmed by the increase in the platelet count in patients with ITP, following H. pylori eradication. Interestingly, H. pylori infection has also been shown to play a role in other diseases in which autoimmune mechanisms may be predominant, such as acne rosacea, idiopathic chronic urticaria, and atherosclerosis. While H. pylori eradication is usually recommended in patients with gastric diseases, there are no specific indications for extraalimentary diseases. In the light of the recent findings, a revision of the current guidelines for the management of H. pylori infection may be needed.
Helicobacter pylori infection has been indicated as the main pathogenic factor in the development of chronic gastritis, peptic ulcer disease, and gastric malignancies. Although the vast majority of infected subjects do not carry but a mild, asymptomatic gastritis, still there are some cases in which the eradication of the infection appears mandatory. This review addresses current anti-Helicobacter regimens and pharmacological resources, and highlights the pros and cons of each of them, according to the most recent and reliable clinical trials. Also, basic recommendations are given, regarding treatment choice in the event of the failure of a first or second line eradicating strategy, and about the implementation of standard regimens with newer antibacterial devices as probiotics.
BACKGROUND/AIMS: Non-steroidal anti-inflammatory drugs cause enterocyte damage inducing an increase of intestinal permeability. Tight junctions are the key structures in the permeability of the intestinal mucosa. ZO-1 is a tight junction associated protein considered a good marker of their integrity. It has been suggested that probiotics could play a protective role in the intestinal barrier function. We determined, in vitro, whether the heat-killed Lactobacillus acidophilus strain LB (LaLB) with its spent culture supernatant protects tight junctions of HT-29 cells from aspirin (ASA) damage. METHODS: HT-29 cells were treated with ASA alone or ASA and LaLB with its spent culture supernatant together. Morphological alterations of tight junctions were evaluated by immunofluorescence using an anti-ZO-1 antibody. Moreover, a semiquantitative assay for ZO-1 was performed by Western blot. RESULTS: Immunofluorescence analysis showed a fragmented and granulous ZO-1 staining, after ASA treatment. Using both ASA and LaLB with its spent culture supernatant together, we found a fine continuous linear web at cell-cell contacts similarly to control. Western blot revealed that ASA inhibited ZO-1 expression and LaLB with its spent culture supernatant counteracted this effect. CONCLUSIONS: This pilot study shows, for the first time, the protective effect of LaLB with its spent culture supernatant on tight junctions from ASA damage. These results suggest that probiotics could play a role in the prevention of ASA-induced alterations of intestinal permeability.
BACKGROUND: Neurological and psychiatric disorders occur in approximately 10% of patients with celiac disease. Although some of these alterations respond to a gluten-free diet, the etiology of these abnormalities is uncertain. Because of a case report that cerebral hypoperfusion in a celiac patient resolved after a gluten-free diet, we studied brain perfusion changes in untreated celiac patients, treated celiac patients, and healthy controls. METHODS: A total of 15 untreated celiac patients without conditions affecting brain perfusion were enrolled; none had neurological or psychiatric disorders other than anxiety or depression. We also studied 15 celiac patients who were on a gluten-free diet for almost 1 year, and 24 healthy volunteers of similar sex and age. All subjects underwent cerebral single photon emission computed tomography examination. RESULTS: Of the 15 untreated celiac patients, 11 (73%) had at least one hypoperfused brain region, compared with only 1 (7%) of the 15 celiac patients on a gluten-free diet and none of the controls (P = 0.01). Cerebral perfusion was significantly lower (P <0.05) in untreated celiac patients, compared with healthy controls, in 7 of 26 brain regions. No significant differences in cerebral perfusion were found between celiac patients on a gluten-free diet and healthy controls. CONCLUSION: There is evidence of regional cerebral blood flow alteration in untreated celiac patients.
AIMS: There is contrasting evidence on the relevance of chronic infection by Helicobacter pylori (H. pylori) as a risk factor for stroke. We performed a meta-analysis of case-control studies to assess association of H. pylori infection and more virulent H. pylori strains, bearing the cytotoxin-associated gene-A (CagA) antigen, with different types of stroke. METHODS: Outcome measures were: H. pylori and CagA seroprevalence in (1) patients with stroke versus controls, and (2) patients with stroke due to large vessel stroke versus patients with other types of stroke and controls. RESULTS: Seven cross-sectional, case-control studies were included. Odds ratio for individual case-control studies and pooled OR for the association between H. pylori seropositivity and stroke was 1.49 (95% CI 1.24-1.81), for the association between stroke and anti-CagA positivity was 2.23 (95% CI 1.49-3.36). Patients with large vessel stroke had higher odds for H. pylori infection than patients with other types of stroke (odds ratio 1.65; 95% CI 1.12-2.45), and than controls (odds ratio 1.61; 95% CI 1.13-2.32). CONCLUSIONS: Association between H. pylori positivity, anti-CagA positivity and stroke is modest and seems higher with stroke due to large vessel disease. This meta-analysis suggests that the role of CagA positive H. pylori strains in different stroke etiologic subclasses should be the target of future prospective investigation.
AIMS: Previous studies suggested an association between infection by cytotoxic CagA-positive Helicobacter pylori strains and atherosclerotic stroke. It has been hypothesized that CagA strains could increase the risk for stroke by affecting carotid plaque irregularity. Our aims were: (1) to confirm the association between CagA strains and atherosclerotic stroke, and (2) to assess the association between CagA strains and carotid plaque irregularity. METHODS AND RESULTS: We enrolled 105 consecutive patients affected by atherosclerotic stroke and 130 sex, age, social background-matched controls without relevant vascular diseases. Risk factors for atherosclerotic stroke, H. pylori infection and CagA status were evaluated in all subjects. The presence of plaque instability was evaluated by colour Doppler ultrasound. The prevalence of CagA-positive strains was significantly higher in patients than in controls (adjusted OR 2.99, 95% CI 1.52-5.88, P=0.002). The CagA seropositivity was the only factor independently associated with carotid plaque irregularity (adjusted OR 8.42, 95% CI 1.58-44.64, P=0.004). CONCLUSION: The evidence of significant associations between CagA-positive H. pylori strains and the presence of carotid plaque instability support their possible involvement in the pathophysiology of atherosclerotic stroke.
Current treatment for Helicobacter pylori infections generally includes two or more antimicrobials (amoxicillin, clarithromycin, nitroimidazoles, tetracycline, etc.), but treatment fails in 10-20% of all cases, often because of drug resistance. Levofloxacin has been proposed as an alternative for these refractory infections. We examined 67 H. pylori isolates from patients unsuccessfully treated with amoxicillin, clarithromycin, metronidazole and levofloxacin. Minimum inhibitory concentrations determined with the epsilometer test revealed clarithromycin and metronidazole resistance in 91 and 82.1% of the isolates, respectively; 52 (77.6%) were resistant to both drugs. All 67 isolates were susceptible to amoxicillin and tetracycline. Fifty-two isolates had levofloxacin MICs of 0.01-2 mg/l; the remaining 15 (22.4%), all clarithromycin- and metronidazole-resistant, had MICs >/= 8 mg/l. Levofloxacin may be an option for refractory H. pylori infections, but the choice should be based on in vitro susceptibility data, and physicians should consider local resistance patterns when treating these infections empirically.
BACKGROUND: Upper endoscopy is not routinely performed to directly detect abnormalities of the duodenal villi. The reliability of the immersion technique for assessment of duodenal villi was evaluated in a series of patients with dyspepsia. METHODS: A total of 396 patients who were to undergo standard EGD for dyspeptic symptoms were enrolled. Patients with suspected malabsorption were excluded. By performing a "modified immersion technique," duodenal villi were scored as the following: definitely present, partially present, or definitely absent. Three duodenal biopsy specimens were obtained from each patient, and villi also were scored histologically as the following: normal, partial villous pattern, or total villous atrophy. RESULTS: Sensitivity, specificity, and positive and negative predictive values of the modified immersion technique for detection of total villous atrophy were 100%, 99.7%, 85.7%, and 100%, respectively. Sensitivity, specificity, and positive and negative predictive values of modified immersion technique for detection of partial villous patterns were 75%, 99.5%, 60%, and 99.7%, respectively. Sensitivity, specificity, and positive and negative predictive values for modified immersion technique detection of any villous abnormality (partial or total villous atrophy) were 90.9%, 99.5%, 83.3%, and 99.7%, respectively. CONCLUSIONS: During standard EGD, duodenal evaluation by modified immersion technique can reliably detect abnormalities of duodenal villi. This simple diagnostic technique may be performed routinely during endoscopic exploration of duodenum.
BACKGROUND: New generation videoendoscopes potentially may visualize duodenal villi. This study compared endoscopic findings with this type of instrument to the histopathologic evaluation of duodenal villi. METHODS: A total of 191 patients underwent upper endoscopy for the purpose of obtaining duodenal biopsy specimens. The findings were assessed independently by 3 experienced observers by using a commercially available, high-resolution, high-magnifying (x2) videoendoscope. The duodenal villous profile was determined by endoscopic magnification and by endoscopic magnification after filling the duodenum with water. With both endoscopic magnification and endoscopic magnification after filling the duodenum with water, villous patterns were scored as the following: definitely present, partially present, or definitely absent. Villous patterns also were histopathologically scored as the following: normal, partial villous pattern, or total villous atrophy. RESULTS: Interobserver variability was excellent (kappa = 0.93). The concordance between either endoscopic magnification or endoscopic magnification after filling the duodenum with water and histology was 100% for presence/absence of villi. The sensitivity, the specificity, and the positive and negative predictive values of endoscopic magnification for detection of any villous abnormality were 95%, 99%, 95%, and 99%, respectively; the respective values of endoscopic magnification after filling the duodenum with water were 95%, 98%, 92%, and 99%. CONCLUSIONS: High-resolution magnifying upper endoscopy can reliably predict the presence or the absence of duodenal villi.