13C-methacetin breath test for monitoring hepatic function in cirrhotic patients before and after liver transplantation.
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Biomedical subjects
Publications and source records attributed to G Gasbarrini.
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BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for atherosclerosis. It is often related to low levels of vitamin B12 and/or folate, enzymatic co-factors of methionine metabolism. Atrophic gastritis, often caused by Helicobacter pylori infection, may impair vitamin absorption. AIM: To assess whether the presence of atrophic gastritis is associated with hyperhomocysteinaemia via deficiency of its vitamin co-factors. METHODS: Thirty-one patients with atrophic gastritis were recruited. The control group consisted of 28 patients with non-atrophic gastritis, matched with patients for sex, age and body mass index. The presence and degree of gastric atrophy were assessed by histology. H. pylori infection was assessed by histology/serology. Blood samples were collected for the measurement of homocysteine, vitamin B12 and folates. RESULTS: Multiple logistic regression analysis showed that atrophic gastritis (odds ratio, 5.3; 95% confidence interval, 1.23-25.26; chi2=5.2; P=0.01) and low vitamin B12 (odds ratio, 3.7; 95% confidence interval, 1.03-22.08; chi2=3.6; P<0.05) were both predictors of hyperhomocysteinaemia. None of the other variables considered in the analysis, including H. pylori status, showed a significant association with hyperhomocysteinaemia. CONCLUSIONS: The present study suggests that atrophic gastritis, rather than H. pylori infection per se, may be a contributing factor to hyperhomocysteinaemia, possibly via vitamin B12 malabsorption.
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BACKGROUND: Intercellular adhesion molecule 1 plays an important role in the recruitment of leucocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease. Intercellular adhesion molecule 1 gene lies on chromosome 19p13, implicated in determining susceptibility to inflammatory bowel disease. Recently, the polymorphism K469E of intercellular adhesion molecule 1 gene has been identified. AIM: To assess the potential association of this polymorphism with inflammatory bowel disease. PATIENTS: A total of 165 inflammatory bowel disease patients, 75 with Crohn's disease and 90 with ulcerative colitis, and 187 controls were studied. METHODS: The K469E polymorphism was detected by polymerase chain reaction and restriction enzyme analysis. Statistical analysis was performed by chi2-test. RESULTS: In inflammatory bowel disease, the distribution of intercellular adhesion molecule 1 genotypes was 24.9% E/E, 44.2% E/K and 30.9% K/K. In controls, 11.8% showed E/E genotype, 55.6% E/K and 32.6% K/K. The frequency of the E/E genotype was significantly higher in inflammatory bowel disease (Crohn's disease and ulcerative colitis) patients than in controls. Subgroup analysis showed that the frequency of the E469 allele was significantly increased only in Crohn's disease patients with ileocolonic location of disease and penetrating behaviour compared with controls. CONCLUSIONS: We found an association of inflammatory bowel disease with the E/E genotype of intercellular adhesion molecule 1 gene, while allele E469 was associated with a subgroup of Crohn's disease patients with more extensive location of disease and penetrating behaviour. However, further studies are needed to confirm our findings.
BACKGROUND: Several studies have demonstrated that bone marrow contains a subpopulation of stem cells capable of participating in the hepatic regenerative process, even if some reports indicate quite a low level of liver repopulation by human stem cells in the normal and transiently injured liver. AIMS: In order to overcome the low engraftment levels seen in previous models, we tried the direct intraperitoneal administration of human cord blood stem cells, using a model of hepatic damage induced by allyl alcohol in NOD/SCID mice. METHODS: We designed a protocol based on stem cell infusion following liver damage in the absence of irradiation. Flow cytometry, histology, immunohistochemistry and RT-PCR for human hepatic markers were performed to monitor human cell engraftment. RESULTS: Human stem cells were able to transdifferentiate into hepatocytes, to improve liver regeneration after damage and to reduce the mortality rate both in both protocols, even if with qualitative and quantitative differences in the transdifferentiation process. CONCLUSIONS: We demonstrated for the first time that the intraperitoneal administration of stem cells can guarantee a rapid liver engraftment. Moreover, the new protocol based on stem cell infusion following liver damage in the absence of irradiation may represent a step forward for the clinical application of stem cell transplantation.
We evaluated the prevalence and features of colonic polyps in a population of acromegalic subjects, compared to a control group of patients with irritable bowel syndrome (IBS). Colonic polyps were found in 30 acromegalic subjects (40%) and in 10 controls (13%) (P < 0.0001). Among the acromegalic patients, polyps were of the hyperplastic type in 27 subjects (90%) and adenomatous in 3 (10%). In the control group, polyps were hyperplastic in nine subjects (90%) and adenomatous in one (10%). We also observed a significant association (P < 0.0001) between the presence of hyperplastic polyps and the older age in both the acromegalic and the control groups. There were no differences between the two groups regarding sex, site, size, or macroscopic and histological types of polyps. Acromegalic patients have a higher prevalence of colonic hyperplastic polyps than IBS subjects, while the prevalence of adenomatous polyps is similar in the two groups.
OBJECTIVES: One-week triple therapy, a combination of acid suppression with two antibiotics, is the gold standard for anti-Helicobacter pylori treatment. There is increasing evidence of H. pylori resistance to classical triple therapy. Recently, it was reported that the amoxicillin-clavulanate combination had a slightly higher activity than amoxicillin alone against H. pylori, and that beta-lactamase inhibitors had 'in-vitro' antibacterial activity against H. pylori. SETTING: To evaluate the efficacy of 1 week triple therapy omeprazole, clarithromycin and amoxicillin plus clavulanate compared with omeprazole, clarithromycin and amoxicillin for H. pylori eradication. The study was open randomized. SUBJECTS: Sixty dyspeptic patients (36 male, 24 female; mean age 53 +/- 9 years) with Helicobacter pylori infection never treated before, were enrolled and randomly assigned to two different 7-day triple therapies: (i) (n = 30) amoxicillin 875 mg plus clavulanic acid 125 mg b.i.d., clarithromycin 500 mg b.i.d., omeprazole 20 mg b.i.d. (ACCO); (ii) (n = 30) amoxicillin 1 g b.i.d., clarithromycin 500 mg b.i.d., omeprazole 20 mg b.i.d. (ACO). Bacterial eradication was assessed by 13C-urea breath test 4-6 weeks after therapy. Information on gastrointestinal symptoms and antibiotic-related side-effects were recorded using a questionnaire. RESULTS: All patients completed the study. A significantly higher H. pylori eradication rate with ACCO compared with ACO: (26/30) 86.6 vs. (20/30) 66.6%, respectively (P < 0.05) were observed. No major side-effects were reported, whilst 8% patients complained of mild side-effects; no significant differences were noted between the two groups. CONCLUSIONS: Our results suggest that amoxicillin and clavulanate in combination achieve a higher H. pylori eradication rate than amoxicillin alone, without any increase in side-effects. The combination of amoxicillin and clavulanate may represent an alternative therapeutic scheme for the treatment of H. pylori infection.
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BACKGROUND: Crohn disease (CD) manifests with highly variable signs and symptoms, and assessment of the status of the disease in the single patient can be difficult. This study was conducted to evaluate the efficacy of power colour Doppler ultrasonography, with and without echo-enhancement, in distinguishing active from quiescent CD. METHODS: Resistance Index (RI) of the superior mesenteric artery (SMA), bowel thickness of the affected loops and the presence of colour signals at power Doppler analysis prior to and after ultrasonography contrast agent injection (Levovist) were evaluated in 48 patients with CD. RESULTS: In our series, 26/48 patients had active and 22/48 had quiescent CD. A CDAI score > or = 150 and a pathological (> 5 mg/dL) C reactive protein were significantly correlated with active disease (P < 0.001 and P = 0.004, respectively). Intestinal wall thickness showed no significant correlation with disease status (7.5 +/- 1.3 mm in active disease versus 6.8 +/- 1.3 mm in quiescent disease; P = 0.11). Vascular signals in the affected loops were revealed in 11/22 patients (50%) with active disease and in 5/26 (20%) with quiescent disease (P = 0.052). After Levovist injection, colour signals were found in 22/22 with active and in 8/26 with quiescent CD (P < 0.001). SMA RI was significantly lower in active CD patients (0.81 +/- 0.01 versus 0.83 +/- 0.02; P = 0.001). CONCLUSIONS: Our data suggest that in patients with CD a finding of a SMA RI < or = 0.81, or the presence of a colour signal in the wall of the affected loops, at power Doppler sonography, is indicative of active disease. Utilization of echo-enhancer media can greatly improve the diagnostic sensitivity of intestinal wall power Doppler scan. A finding of intestinal wall thickening is not associated with active disease in our series.
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OBJECTIVES: This study describes a new method to detect autoantibodies against actin filaments (AAA) as a serological marker of intestinal villous atrophy (IVA) in celiac disease (CD), and reports the results of an Italian double-blind multicenter study. METHODS: IgA-AAA were analyzed by immunofluorescence using a newly developed method based on intestinal epithelial cells cultured in presence of colchicine. IgA-AAA were blindly evaluated prospectively in 223 antiendomysial antibody (AEA) and/or antitransglutaminase antibody (TGA) positive subjects and in 78 AEA and TGA negative subjects. IgA-AAA positive patients underwent an intestinal biopsy to confirm the diagnosis. Moreover, IgA-AAA were retrospectively investigated in 84 biopsy-proven CD patients and in 2,000 new consecutively collected serum samples from AEA and TGA negative nonbiopsied subjects. RESULTS: IgA-AAA were positive in 98.2% of the CD patients with flat mucosa, in 89% with subtotal villous atrophy, and in 30% with partial villous atrophy. IgA-AAA were present in none of the AEA and TGA negative nonbiopsied controls. In AEA and/or TGA positive CD patients IgA-AAA positivity significantly correlated with IVA (p < 0.000 in the prospective study, p = 0.005 in the retrospective study). In the prospective study, the values of sensitivity, specificity, the positive predictive value, the negative predictive value, and the efficiency of the IgA-AAA test to identify patients with IVA were, respectively, 83.9%, 95.1%, 97.8%, 69.2%, and 87.0%. Furthermore, a significant correlation (p < 0.0001) was found between the IgA-AAA serum titre and the degree of IVA (rs 0.56). CONCLUSIONS: The results of this multicenter study show that the new method for IgA-AAA detection could represent a practical diagnostic tool in AEA and/or TGA positive subjects, which would be especially useful when IVA shows a patchy distribution, when the histological picture is difficult to interpret, or when a biopsy could represent a life-threatening risk.
Up to 70% of patients with typical symptoms of gastroesophageal reflux disease (GERD) have neither definite endoscopic oesophageal breaks nor Barrett's oesophagus at upper endoscopy. These patients suffer from non-erosive reflux disease (NERD), also termed endoscopy-negative reflux disease or symptomatic GERD. NERD patients appear as a heterogeneous population with multiple and substantially different mechanisms implicated in the genesis of symptoms. In fact, patients with NERD may be divided into 3 groups on the basis of 24-hour pH monitoring: 1) patients with an abnormal acid exposure time (AET); 2) patients who demonstrate a normal AET, but in whom symptoms and reflux events are significantly correlated (hypersensitive oesophagus) and 3) patients with typical reflux symptoms but in whom all parameters of the pH study are normal. There is no gold standard for the diagnosis of NERD but a well-taken history can be, usually, sufficient to confirm the diagnosis and begin therapy. Thus, the more sensitive tool for the diagnosis of NERD is proton pump-inhibitor (PPI) test. The aims of NERD treatment are: symptoms relieve, restore quality of life and maintain clinical remission. Proton pump-inhibitors (PPIs) in full doses represent the treatment of choice of NERD patients, even if overall, clinical trials showed a lower efficacy in symptoms control when compared to patients with erosive oesophagitis. Patients with NERD often need long-term therapy for symptoms control. ''On demand'' PPI therapy has been considered as the most cost-effective strategy for the long-term treatment of NERD. In conclusion, many data indicate that NERD is a disorder in its own right that shares symptoms with other GERD groups. However further studies are needed to better define the natural history and improve the treatment of this disorder.
AIM: Alteration in body fluid distribution may have relevant implications in several human diseases. The use of oligomineral water is associated with increased diuresis and this could be extremely useful in subjects with water retention. The aim of the present study was to evaluate the effect of daily administration of 1.5 liters of oligomineral water over 4 weeks on body water compartment (extracellular and intracellular water [ECW and ICW]) in healthy overweight women who underwent a hypocaloric dietary regimen. METHODS: Twenty-four healthy premenopausal women (aged 32+/-6 years; body mass index [BMI]: 27.4+/-2 kg/m(2)) were randomly divided into 2 groups and assigned to consume 1.5 liters daily of either tap (Group A) or oligomineral water over a 4-week period. Body composition was assessed by anthropometry and multifrequence bio-impedance analysis. RESULTS: Body weight and fat mass significantly decreased after dietary treatment in the 2 groups examined; although not statistically significant, a higher difference in body weight before and after treatment was found in Group B when compared to Group A (2.2+/-1 kg vs 1.7+/-0.8 kg; p=0.057). Body weight reduction was related to fat mass decrease, while no significant difference was found in fat-free mass among groups. TBW and ECW were reduced in both groups after treatment, while a greater reduction in both variables was found in Group B (p<0.01). The post-treatment ECW/TBW ratio was lower in Group B with respect to Group A (p<0.01). CONCLUSIONS: A supplementation with oligomineral water in overweight women, when associated to a hypocaloric dietary treatment, is able to reduce total and extracellular water content; this findings could have relevant implication in planning a successful dietary regimen for achieving and maintaining a normal body weight.
BACKGROUND: Levofloxacin has been shown to be effective in Helicobacter pylori eradication. Two 10-day levofloxacin-based triple therapies were compared with standard 7- and 14-day quadruple regimens in second-line treatment. METHODS: Two hundred and eighty consecutive patients who failed to respond to standard triple therapy (clarithromycin, amoxicillin, rabeprazole) were randomly assigned to four groups: (1) levofloxacin 500 mg o.d., amoxicillin 1 g b.d., rabeprazole 20 mg b.d. for 10 days (LAR, n = 70); (2) levofloxacin 500 mg o.d., tinidazole 500 mg b.d., rabeprazole 20 mg b.d. for 10 days (LTR, n = 70); (3) tetracycline 500 mg q.d.s., metronidazole 500 mg t.d.s., bismuth salt 120 mg q.d.s., rabeprazole 20 mg b.d. for 7 days (7TMBR, n = 70); and (4) for 14 days (14TMBR, n = 70). Helicobacter pylori status and side-effects were assessed 6 weeks after treatment. RESULTS: The eradication rate was 94% in the LAR group and 90% in the LTR group in both intention-to-treat and per protocol analyses. Helicobacter pylori eradication was achieved in 63 and 69% of the 7TMBR group and in 69 and 80% of the 14TMBR group in intention-to-treat and per protocol analysis, respectively. Side-effects were significantly lower in the LAR and LTR groups than in the 14TMBR group. CONCLUSION: Ten-day levofloxacin-based therapies are better than standard quadruple regimens as second-line option for H. pylori eradication.
Cell-based therapies, comprising isolated hepatocyte transplantation, ex vivo gene therapy and bioartificial liver devices, may actually design a new scenario in the treatment of patients with liver failure. Recent advances in the liver repopulation field and the considerable excitement surrounding the use of haematopoietic stem cells for a 'regenerative medicine', allow us to see under a new light the alternative cell sources actually under investigation. In particular, the major drawbacks and the most important advantages of xenogenic primary cells, tumour-derived cell lines, immortalised hepatocytes and stem cells in the wide range of experimental and clinical applications are presented. Even if up to now none of them represent a 'gold standard' in the clinical practice, the intersecting advances in the development of mechanical components of artificial devices and in the liver biology and bioengineering will open tantalising possibilities to treat patients with liver failure, by tailoring the therapeutic choice on the basis of the aetiology and the stage of liver disease.
BACKGROUND: The relationship between Helicobacter pylori infection and its treatment and gastro-oesophageal reflux disease (GERD) is controversial. AIMS: To establish if H. pylori infection is associated with the presence of GERD and if anti-H. pylori treatment leads to de novo GERD or rebound/exacerbation of GERD. METHODS: A search of MEDLINE and EMBASE databases was made. Pooled odds ratios (OR) were calculated for de novo GERD and rebound/exacerbated GERD after anti-H. pylori therapy in case-control studies and in therapeutic trials. RESULTS: Fourteen case-control studies and 10 clinical trials were included. Among case-control studies, pooled OR for the association between H. pylori negative status and GERD was 1.34 [95% confidence interval (CI) 1.15-1.55]. Among therapeutic trials, pooled OR for the association anti-H. pylori therapy - GERD was 2.54 (95% CI 1.92-3.37). The OR for de novo GERD was 3.25 (95% CI 2.09-5.33), and for rebound/exacerbated GERD was 2.39 (95% CI 1.75-3.34). Associations were higher among Asian studies than among North American and European studies. CONCLUSIONS: This meta-analysis shows significant association between absence of H. pylori infection and GERD symptoms, and a positive association between anti-H. pylori therapy and occurrence of both de novo and rebound/exacerbated GERD. The significance of these associations appears to have been inflated by the effect of single trials and by geographical variations.
Maintaining abstinence from alcohol is the main goal in the treatment of alcohol dependence. Naltrexone (NTX) and gamma-hydroxybutyric acid (GHB) have proved able to maintain alcohol abstinence in alcoholic subjects. The aim of our study was to evaluate the efficacy of GHB compared with NTX in maintaining abstinence from alcohol after 3 months of treatment. A total of 35 alcohol-dependent outpatients were randomly enrolled in two groups: the GHB group consisted of 18 patients treated with oral doses of GHB (50 mg/kg of body weight t.i.d) for 3 months; the NTX group consisted of 17 patients treated with oral doses of NTX (50 mg/day) for 3 months. At the end of the study, a statistically significant difference (P=0.02) was found in the number of abstinent patients between the GHB and the NTX groups. In patients who failed to be abstinent, no relapses in heavy drinking were observed in the NTX group, while in the GHB group all patients relapsed. The results of the present study show that GHB is more effective than NTX in maintaining abstinence from alcohol in a short-term treatment period; on the other hand, NTX confirmed its ability to reduce alcohol relapses.
BACKGROUND: Oxygen-free radicals generation is considered to be a major cause of gastric injury during reperfusion. Chemiluminescence has been used to assess real-time free radical release on the surface of isolated organs. AIMS: To evaluate the combined use of chemiluminescence and gastroendoscopy techniques and to assess the real-time production of free radicals during ischemic damage of the gastric wall in an animal model. PATIENTS AND METHODS: For the experiment, an optical junction was set up between a fibroendoscope and a luminograph apparatus. Three pigs were submitted to gastrofibroendoscopy before, during and after 30 min of clamping of the coeliac artery. Under basal conditions, at the end of the ischemic phase and at the beginning of reperfusion, 1 mM of lucigenin, a specific superoxide enhancer, was injected in the left gastric artery of the animal. The endoscopic live images and chemiluminescence emission were recorded and successively superimposed to measure rate and spatial distribution of photon emission (photons/s). RESULTS: Free radical production was not observed under basal conditions or during the ischemic phase, but significantly increased during reperfusion reaching a maximum peak after 15 min (0.6+/-0.2 photons x 10(5)/s) and decreased progressively thereafter. The superimposition of live and chemiluminescence images allowed the determination of the regional production rate and distribution of photons. CONCLUSIONS: Preliminary observations, in an animal model, on an innovative imaging system which allows the visualization of rate and spatial distribution of reactive oxygen species formation are presented. This new endoscopic technique could be useful for the assessment of oxidative gastric mucosal injury in several gastric diseases; however, further studies remain necessary to determine the applicability of this technique in humans.