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Biomedical subjects

Giovanni Gasbarrini

Publications and source records attributed to Giovanni Gasbarrini.

At least 55 records · Page 3Linked to original sources

Bacillus clausii effect on gene expression pattern in small bowel mucosa using DNA microarray analysis.

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.

Adult↗

Contrast-enhanced gray-scale harmonic ultrasound in the efficacy assessment of ablation treatments for hepatocellular carcinoma.

BACKGROUND: The aim of this study was to compare contrast-enhanced gray-scale harmonic ultrasound with multiphasic spiral computed tomography in the assessment of treatment efficacy of non-surgically treated HCC. METHODS: We studied 56 HCCs treated by percutaneous ethanol injection (31 cases), radiofrequency ablation (three cases), trans-arterial chemoembolization (12 cases), and combined treatment (10 cases). The efficacy of therapies was blindly assessed by multiphasic computed tomography and gray-scale harmonic ultrasound with a second-generation contrast agent (sulfur hexafluoride). RESULTS: On computed tomography 30 tumors (53.6%) showed complete necrosis, while 26 lesions (45.4%) were still viable. On contrast-enhanced ultrasound examination 33/56 nodules (58.9%) had no contrast enhancement in the arterial phase, while 23/56 lesions (41.1%) were still vascularized. All the nodules assessed as completely necrotic on computed tomography did not show arterial enhancement on contrast-enhanced ultrasound and diagnostic agreement was found in 53/56 cases (94.6%) (P<0.001). Contrast-enhanced ultrasound demonstrated relative sensitivity and specificity of 87.0% and 98.4%. CONCLUSIONS: Contrast-enhanced harmonic ultrasound is promising in the efficacy evaluation of ablation treatments for HCC. Nodules vascularized in the arterial phase on contrast harmonic ultrasound should be considered still viable and addressed to additional treatment without further evaluation.

Aged↗

Helicobacter pylori and extragastric diseases--other Helicobacters.

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.

Animals↗

Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease.

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.

Adolescent↗

Biliopancreatic diversion as a novel approach to the HAIR-AN syndrome.

BACKGROUND: The HAIR-AN syndrome is a rare multisystem disorder in women, that consists of hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN). The IR is likely due to a primary defect of the insulin receptor. METHODS: We report the case of a 42-year-old Caucasian woman with HAIR-AN syndrome, impaired glucose tolerance (IGT), mild hyperlipemia, and hypertension, who underwent biliopancreatic diversion (BPD). RESULTS: Within 24 months follow-up after BPD, impaired glucose tolerance, mild hyperlipemia, and hypertension completely reversed. Although insulin sensitivity, estimated by the euglycemic hyperinsulinemic clamp, did not improve, signs and symptoms of hyperandrogenism and acanthosis nigricans resolved fully. CONCLUSION: In HAIR-AN syndrome, malabsorptive bariatric surgery is effective in improving hyperandrogenism and acanthosis nigricans, with noteworthy esthetic consequences. BPD was followed by disappearance of co-morbidities of the syndrome, such as IGT, hypertension and hyperlipemia.

Acanthosis Nigricans↗

Treatment of H. pylori infection: a review.

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.

Amoxicillin↗

Recurrent acute hepatitis associated with use of cetirizine.

OBJECTIVE: To describe a case of recurrent acute hepatitis related to the use of cetirizine, a selective histamine(1)-receptor antagonist approved for the treatment of common allergic diseases. CASE SUMMARY: A 26-year-old man was hospitalized with a week-long history of weakness, nausea, anorexia, and hyperchromic urine, which had developed after 6 days of therapy with oral cetirizine 10 mg/day for allergic rhinitis. Admission laboratory testing revealed evidence of acute hepatitis and seropositivity for liver-kidney microsome antibodies. Liver biopsy findings of diffuse portal tract and lobular inflammation with a prominent eosinophilic infiltrate were consistent with drug-related hepatitis. The patient was discharged after one week of treatment with tocopherol and glutathione. Three months after discharge, transaminase levels were normal. At 6 months, seropositivity for liver-kidney microsome antibodies was still present, but considerably less intense. The patient had suffered 2 previous episodes of "acute hepatitis of unknown origin," and both had occurred after cetirizine use. DISCUSSION: Use of the Naranjo probability scale indicated cetirizine as the probable cause of acute hepatitis, and the positivity for liver-kidney microsome antibodies is suggestive of an autoimmune mechanism for liver damage. As of September 13, 2004, ours is the fourth reported case of acute hepatitis associated with cetirizine and the second in which liver-kidney microsome antibodies have been documented. CONCLUSIONS: Although cetirizine is considered to have low potential for severe hepatic toxicity, the possibility that it can provoke autoimmune-mediated hepatotoxicity should be considered.

Acute Disease↗

Lactobacillus acidophilus protects tight junctions from aspirin damage in HT-29 cells.

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.

Adenocarcinoma↗

Circulating levels of cyclosporin A in inflammatory bowel disease: relationships with lymphocyte inhibition and the age of patients.

OBJECTIVE: To determine in the same blood sample the concentrations of cyclosporin A (CsA) and the degree of CsA-induced lymphocyte inhibition; to establish a relationship between these parameters; and to investigate the factor(s) influencing such a putative relationship. METHODS: Ten patients with a diagnosis of Crohn's disease (n=7) or ulcerative colitis (n=3) were enrolled in the study. The patients, who had never been immunosuppressed, were treated with microemulsion CsA twice daily by the oral route; at steady-state, blood samples were collected 0, 0.5, 1, 2, 3, 5, 7 and 12 h after the morning dose. CsA blood levels were measured by means of radioimmunoassay. The percentages of lymphocytes during the S-phase were assessed by flow-cytometry on the same blood specimens, only for samples collected at 0 h and 2 h. RESULTS: An inverse relationship emerged between CsA blood concentrations and the percentage of lymphocytes during the S-phase: the latter was maximal before the beginning of treatment and minimal in association with peak CsA levels. Furthermore, a highly significant correlation was found between trough CsA levels and the age of the patient, since the percentage of inhibited lymphocytes increases with age.

Administration, Oral↗

Regional cerebral hypoperfusion in patients with celiac disease.

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.

Adult↗

The relationship between chronic H. pylori infection, CagA seropositivity and stroke: meta-analysis.

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.

Age Distribution↗

CagA-positive cytotoxic H. pylori strains as a link between plaque instability and atherosclerotic stroke.

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.

Aged↗

Reliability of the "immersion technique" during routine upper endoscopy for detection of abnormalities of duodenal villi in patients with dyspepsia.

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.

Atrophy↗

Direct visualization of intestinal villi by high-resolution magnifying upper endoscopy: a validation study.

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.

Adolescent↗