Small intestinal bacterial overgrowth and symptoms of irritable bowel syndrome.
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Biomedical subjects
Publications and source records attributed to G Gasbarrini.
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OBJECTIVES: Patients with inflammatory bowel disease (IBD) have an increased risk of thrombotic complications. Moreover, a hypercoagulable state has been hypothesized as a contributing factor in the pathogenesis of IBD. Recently, a growing amount of interest has focused on mild-to-moderate hyperhomocysteinemia as a risk factor for thromboembolic disease. We aimed to evaluate the prevalence of hyperhomocysteinemia in patients with IBD and to investigate the contribution of genetic defects in the enzymes involved in homocysteine (Hcy) metabolism and vitamin status in determining increased levels of plasma total Hcy (tHcy). METHODS: The concentrations of tHcy, folate, and vitamin B12 as well as the prevalence of methylenetetrahydrofolate reductase (MTHFR) 677C to T mutation and the 68-bp insertion at exon 8 of cystathionine beta-synthase (CBS) were measured in patients with IBD and healthy controls. RESULTS: In all, 17 out of 64 IBD patients (26.5%) and four out of 121 (3.3%) controls had hyperhomocysteinemia with a statistically significant difference (p < 0.0001). No significant difference was found between IBD patients and controls with regard to the prevalence of homozygotes for the C677T variant (TT) of MTHFR or the prevalence of heterozygotes for the CBS-gene mutation (IN). Among the IBD patients the only independent factor significantly associated with hyperhomocysteinemia was folate deficiency (p = 0.0002), regardless of the MTHFR or the CBS genotype. CONCLUSIONS: IBD patients have a higher prevalence of hyperhomocysteinemia than do healthy controls. Folate deficiency is the only independent risk factor in developing hyperhomocysteinemia.
BACKGROUND: Alterations in epithelial proliferation and apoptosis in colonic mucosa are associated with an increased risk of colon cancer. It is unclear if these alterations represent a generalised "field defect". AIMS: To analyse segmental patterns of cell proliferation and apoptosis in the colon of subjects with a high and no apparent risk of colon cancer. METHODS: Pancolonoscopy was performed in 15 patients with resected adenomas (> or =1.5 cm) and in nine subjects without an apparent risk of colorectal cancer. Mucosal biopsies were taken from the right colon, left colon, and sigmoid rectum. Crypt cell proliferation and apoptosis were evaluated, respectively, with bromodeoxyuridine immunohistochemistry and terminal deoxyuridine nucleotidyl nick end labelling of DNA strand breaks. Results are expressed as total labelling index (TLI) and labelling index (LI) for each of the five compartments in which colonic crypts were divided (fourth and fifth compartments were evaluated together) for cell proliferation and as apoptotic index (AI) for apoptosis assessment. RESULTS: No significant segmental variations in proliferation were found in either group. Compared with controls, adenoma patients had higher TLIs for the right (p>0.05), left (p<0.005), and sigmoid rectum (p<0.05) segments, and higher left colon LIs for crypt compartments (compartment 1, p<0.01; compartment 2, p<0.005; compartment 3, p<0.001; compartments 4-5, p<0.01). Control AIs were similar in all segments but in the adenoma patients left colon and sigmoid rectum AIs were lower than their right colon indexes (p<0.05, p<0.05) and corresponding values for controls (p<0.01, p<0.05). CONCLUSIONS: The colonic mucosa of patients with past adenomas presents diffuse hyperproliferation and, distally, abnormally distributed proliferating cells and markedly reduced apoptosis. These changes represent a significant risk for malignancies and could account for the high prevalence of left colon tumours.
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BACKGROUND: The role of interferon treatment on the natural history of hepatitis C virus related cirrhosis is under debate. AIM: To evaluate the effect of interferon on the clinical course of compensated hepatitis C virus related cirrhosis. PATIENTS AND METHODS: Seventy two cirrhotic patients treated with interferon and 72 untreated controls matched treated patients with for quinquennia of age, sex, and Child-Pugh's score were enrolled in a prospective non-randomised controlled trial. Treated patients received leucocytic interferon alfa, with an escalating schedule for 12 months. The incidence and risk (Cox regression analysis) of clinical complications (hepatocellular carcinoma, ascites, jaundice, variceal bleeding, and encephalopathy) and death were calculated. RESULTS: Over median follow up periods of 55 months for treated and 58 for untreated subjects, seven and nine patients, respectively, died, and 20 and 32, respectively, developed at least one clinical complication (ns). Hepatocellular carcinoma developed in six treated and 19 untreated patients (p=0.018). Seven treated patients showed sustained aminotranferase normalisation and none died or developed complications. Clinical complications were significantly associated with low albumin, bilirubin, and prothrombin activity while hepatocellular carcinoma was significantly related to no treatment with interferon, oesophageal varices, and high alpha fetoprotein levels. By stratified analysis, the beneficial effect of interferon was statistically evident only in patients with baseline alpha fetoprotein levels > or =20 ng/ml. CONCLUSIONS: Interferon does not seem to affect overall or event free survival of patients with hepatitis C virus related cirrhosis while it seems to prevent the development of hepatocellular carcinoma. Patients who achieved sustained aminotransferase normalisation survived and did not develop any complications during follow up.
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Many new therapeutic strategies are studied to improve Helicobacter pylori eradication rate. Probiotics are live microorganisms which, upon administration, may interact with the human microflora and positively affect the health status. The use of probiotics in the field of H. pylori infection has been proposed for improving eradication rate and tolerability and for compliance of multiple antibiotic regimens used for the infection. Results from laboratory studies and from clinical trials seem to confirm the expectancies, but there is lack of standardization in terms of type of probiotic strain used, dosage and timing of supplementation. Before further ongoing trials and future studies will clarify these points, probiotics could remain a useful adjunct to standard anti-H. pylori therapies, but cannot take the place of other validated options.
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.
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BACKGROUND: In surgical patients, operative stress causes protein catabolism, muscle mass loss, and impaired glucose tolerance. We investigated fuel metabolism and glucose and protein turnover in 15 obese subjects who underwent biliopancreatic diversion (BPD) by using stable labelled isotopes. METHODS: 6 males and 9 females (age 45.11 +/- 8.9 years, BMI of 48.85 +/- 4.43 kg/m2) who underwent BPD were studied, and the APACHE II score was calculated. Patients were studied 3 times (before BPD, 1st and 3rd postoperative day). Glycemia was stable--maintained by continuously infusing Rapid insulin. Each day of the study, the patients received a primed, constant infusion of [15N2] urea, and, 180 min after, a [6.6-2H] glucose infusion started and continued for 3 hours. Indirect calorimetry was performed during the study, under TPN (30 kcal/kg). RESULTS: The APACHE score was lower on the 3rd postoperative day than on the 1st postoperative day (7.4 +/- 2.7 vs 6.3 +/- 2.6, p < 0.05). The npRQ was different throughout the post-operative period (0.82 +/- 0.03 vs 0.9 +/- 0.06, p < 0.05), while urinary nitrogen excretion, energy expenditure and glycemia did not change. The insulin amount infused was lower during the 3rd post-operative day (44.25 +/- 12.3 vs 64.12 +/- 11 UI on the 1st one, p < 0.05). Insulinemia was lower during the 3rd than during the 1st postoperative day (66.4 +/- 9.49 vs 117.44 +/- 8.49 microU/ml, p < 0.05). Non-essential fatty acid levels were higher on the 3rd post-operative day than on the 1st one (0.98 +/- 0.6 vs 0.45 +/- 0.34 mmol/L, p < 0.01). No differences were observed in glucose and urea turn-over. CONCLUSION: The metabolic pattern of morbidly obese patients operated by BPD was similar to that of other critically ill patients previously studied in the literature. Furthermore, the increased glucose oxidation rate observed on the 3rd post-operative day was coupled with an improved clinical condition.
OBJECTIVE: To obtain a pharmacokinetic profile of cyclosporin microemulsion formulation in patients with inflammatory bowel disease. PATIENTS AND PARTICIPANTS: 58 consecutive patients (19 women and 39 men), aged 16 to 64 years (mean age 38 years), with a diagnosis of ulcerative colitis (29 patients) or Crohn's disease (29 patients). METHODS: Patients were treated with oral doses of cyclosporin microemulsion ranging from 200 to 400 mg daily. Blood samples were collected after 7 days of treatment; blood was drawn at 0, 0.5, 1, 2, 3, 5, 7 and 12 hours after the morning dose. In 23 patients out of 29 with ulcerative colitis and 23 out of 29 with Crohn's disease, these profiles were repeated immediately before hospital discharge, which took place an average of 18 days after admission. Blood specimens were assayed for cyclosporin immunoreactivity on the day of blood withdrawal by a radioimmunoassay technique. MAIN OUTCOME MEASURES AND RESULTS: In the range of doses employed, the average peak plasma drug concentration (Cmax) and area under the concentration-time curve to 12 hours tended to increase linearly with the dose (from 782.35 to 1,607.98 microg/L and from 3,612 to 7,221 microg x h/L for doses of 200 mg and 400 mg, respectively), whereas the time to Cmax (tmax) and elimination half-life (t 1/2beta) ranged between 78 and 95.2 min and 85.5 and 162 min, respectively, and did not appear to change with the dose. After dose-normalisation by transformation of data into percentage increase over baseline (trough) concentration for each patient, single kinetic parameters for the whole study population (n = 58) could be calculated (Cmax 620% vs baseline. tmax 86.5 min, t 1/2 115 min). Comparison between patients with Crohn's disease and ulcerative colitis showed that the latter had higher Cmax values (702% compared with 543% vs baseline, p < 0.05) whereas tmax and t 1/2beta values overlapped. CONCLUSIONS: The pharmacokinetic parameters of cyclosporin microemulsion in patients with inflammatory bowel disease are broadly similar to those previously measured in healthy volunteers and in other disorders requiring cyclosporin treatment.
BACKGROUND: Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections. H. pylori is one of the most common infection worldwide. Aim of the paper was to evaluate the prevalence of H. pylori infection, the efficacy of the most common H. pylori eradication therapies and the incidence of H. pylori reinfection after 12 months follow-up in IDDM and in a control group of dyspeptic patients matched for sex and age. METHODS: 116 IDDM patients and 50 dyspeptic controls were evaluated for H. pylori infection through 13C-urea breath test (UBT). 64 IDDM infected patients and 50 dyspeptic infected controls were randomly assigned to 3 different 7-day eradication regimens: 1) amoxicillin, clarithromycin, pantoprazole; 2) tinidazole, clarithromycin, ranitidine bismuth citrate; 3) tinidazole, clarithromycin, pantoprazole. Patients not eradicated by the first cycle were subsequently submitted to a 7-day quadruple therapy with tinidazole, tetracycline, bismuth and pantoprazole. Gastrointestinal symptoms and side effects were evaluated. Thirty-four IDDM patients and 40 dyspeptic patients previously treated for H. pylori infection and successfully eradicated (confirmed both by UBT and histology) were re-evaluated after 12 months. RESULTS: 37% of IDDM patients were infected. Mean age of IDDM infected patients was higher than negative (40+/-12 vs 32+/-10 yrs). None of the triple therapies used allowed an eradication higher than 62%. Conversely, the quadruple regimen eradicated 88% of patients. Minor side effects were observed in 10% of patients submitted to the triple therapies and in 25% of patients treated with the quadruple therapy (p<0.05). H. pylori re-infection was significantly higher in IDDM patients compared to controls: (38% vs 5% respectively, p<0.001). Mean age of IDDM re-infected patients was higher than negative (40+/-12 vs 32+/-10). Among IDDM patients daily insulin requirement and glicate haemoglobin were significantly higher in re-infected compared to uninfected patients (44+/-9 vs 35+/-8 U/I and 7,2+/-1 vs 6,8+/-0,8). CONCLUSIONS: Prevalence of H. pylori infection in IDDM patients was similar to controls. IDDM patients show a low H. pylori eradication rate with a standard triple therapy regardless of the regimen utilized. The use of a quadruple regimen leads to the cure of a large percentage of the infected patients not eradicated by the first therapy, although it is accompanied by a greater incidence of minor side effects. A significantly higher incidence of H. pylori re-infection was observed in IDDM patients when compared to not IDDM controls. The data suggest that vaccine development seems to be the only effective long run treatment for this subset of patients.
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The immunomodulatory properties of interferon may concur to precipitate or worsen an underlying autoimmune disorders. We report the cases of two men who displayed the various features of coeliac disease during a treatment with 4-interferon (in one case associated with ribavirin) for chronic hepatitis C. The patients stopped the interferon treatment and the symptoms and histological disorders improved after a gluten-free diet. Alpha-interferon is available worldwide for treatment of chronic viral hepatitis. Before treatment with this drug, the patients would have to be monitored for coeliac disease.
Women having recurrent miscarriages or intrauterine growth retardation could have subclinical coeliac disease, which can be detected by serological screening tests.