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Biomedical subjects

G Gasbarrini

Publications and source records attributed to G Gasbarrini.

At least 649 records · Page 36Linked to original sources
PubMedDate not supplied

[Helicobacter pylori and gastric carcinoma].

Among the suspected bacterial causes of cancer, H. pylori is the agent more consistently linked to malignancy. After its discovery in 1983 and the later confirmation as the leading cause of chronic gastritis, several studies were performed to prove an association between H. pylori infection and gastric carcinoma. The epidemiological data have been so strong that in 1994 the International Association for Research on Cancer stated that "there was sufficient evidence" to classify H. pylori as a group I carcinogen in humans. However, the exact mechanisms underlying the link between H. pylori infection and gastric carcinoma remain still to be elucidated. The natural history of H. pylori infection shows that, although roughly half of the world's human population bears the organism, only a minority of individuals develop clinically important outcomes (e.g. peptic ulcer, lymphoproliferative diseases, atrophic gastritis and gastric carcinoma): host's genetic make-up, duration of infection, diet and differences between H. pylori strains have been proposed as factors potentially able to influence the outcomes in different individuals. The damaging agents by which H. pylori could promote gastric carcinogenesis are produced either by the organism or as a consequence of the host inflammatory response to the infection. Gastric mucosal chronic damage may, therefore, lead to changes in the pattern of epithelial cell kinetic (increase in cell proliferation and induction of apoptosis) in gastric glands which may induce DNA injury with irreversible genetic lesions. Finally, a direct association between H. pylori infection and the induction of gastric carcinoma has been recently demonstrated in an animal model, giving further credence to the role of this organism in gastric carcinogenesis.

Helicobacter Infections↗
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An unusual case, in Italy, of hepatocarcinoma characterized by portal hypertension and absence of cirrhosis.

We report a case of a 40-year-old man of Bantu origin, affected by both HBV infection and primitive hepatocarcinoma in the absence of cirrhosis. The fine-needle aspiration specimen reported a rare variant of liver cancer resembling an adenocarcinoma. The neoplasm was certainly a hepatic primitive carcinoma, because chest X-ray, cranial computed tomography, colonoscopy, and abdominal computed tomography did not detect neoplastic lesions and alpha-fetoprotein was > 1000 ng/mL. The present neoplasm, characterized by severe portal hypertension and absence of cirrhosis, is rare in Italy, but largely diffused in Bantu people in Africa.

Adult↗
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Pharmacological approaches to the management of alcohol addiction.

Alcohol abuse and alcoholism represent a world-wide problem, both from a medical and a social point of view. In the past the therapy for patients affected by alcoholism was based mainly on the psychological approach. In recent years the use of pharmacotherapy together with psychosocial interventions have enhanced the percentage of success in maintaining alcoholic patients in remission. The present review discusses the main drugs experimented both in preclinical and clinical studies. Pharmacotherapy of alcohol dependence seems to be effective in both alcohol-related emergencies and prevention relapse. However, pharmacotherapy should not be considered as the only form of treatment but as an integrated part of a multimodal approach including psychological and social support.

Alcohol Deterrents↗
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Antibodies to Saccharomyces cerevisiae: are they useful in clinical practice?

BACKGROUND/AIMS: Antibodies to Saccharomyces cerevisiae are associated with Crohn's disease. The aim of this study was to assess the sensitivity and specificity of antibodies to Saccharomyces cerevisiae for Crohn's disease in an Italian population and to evaluate their clinical role. METHODOLOGY: Antibodies to Saccharomyces cerevisiae serum levels were assessed in 72 inflammatory bowel disease patients (30 Crohn's disease; 42 ulcerative colitis) and 35 age-matched controls. Patients were divided into subgroups on the basis of disease behavior and clinical feature were evaluated. RESULTS: Antibodies to Saccharomyces cerevisiae sensitivity and specificity for Crohn's disease patients were 50% (31-68) and 91% (77-98), for IgG and 56% (37-64) and 94% (80-99), respectively, for IgA. No correlation was observed between the presence of antibodies to Saccharomyces cerevisiae and clinical features. Antibodies to Saccharomyces cerevisiae were more prevalent in Crohn's disease than in ulcerative colitis patients (IgA: 57% vs. 26%; IgG: 50% vs. 17%; p < 0.05). Interestingly, in Crohn's disease patients, the prevalence of antibodies to Saccharomyces cerevisiae was higher in patients with small bowel involvement than in patients with pure colonic disease (IgA: 66% vs. 17%; IgG: 58% vs. 17%). No difference in antibodies to Saccharomyces cerevisiae prevalence was observed between ulcerative colitis and pure colonic Crohn's disease patients. CONCLUSIONS: Our data show an association between Crohn's disease and antibodies to Saccharomyces cerevisiae. However, it does not seem useful in discriminating between ulcerative colitis and colic Crohn's disease.

Adult↗
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Cell-based therapy for liver diseases.

Although liver transplantation has become standard therapy in the treatment of patients with liver failure, several problems should be considered in the management of these patients. Other approaches have been proposed, in particular cellular-based procedures. Isolated hepatocytes may be used instead of whole organ transplantation or integrated within the bioartificial devices, in order to replace the missing synthetic and metabolic liver functions. Moreover patient's own hepatocytes may be ex vivo genetically modified to provide the function of a mutant gene. However, new cell sources alternative to adult hepatocytes are actually under investigation, on the basis of recent advances in the field of liver repopulation. Xenogenic primary cells, human hepatoma cells, immortalized hepatocytes and stem cells have been testing in several experiments, even if up to now none of them represent a "gold-standard" for cell-based treatment of liver diseases. In the next future, it is possible that different clinical situations will require different therapeutic approaches, that will be finally defined from the concomitant advances in the development of artificial devices and liver cell biology.

Cell Transplantation↗
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Effects of propionyl-L-carnitine topical irrigation in distal ulcerative colitis: a preliminary report.

BACKGROUND/AIMS: To study the tolerability of propionyl-L-carnitine administered as rectal irrigation and its efficacy in improving the clinical picture of distal ulcerative colitis. METHODOLOGY: Ten male subjects (aged 18 to 55 years, with a body mass index ranging from 21 to 25 Kg/m2) with distal ulcerative colitis were treated with propionyl-L-carnitine enemas (6 g in 200 mL physiological solution) twice a day over 120 minutes each. All subjects had a disease activity index from 0 to 1. A clinical, laboratory, endoscopy and biopsy evaluation was performed at baseline and 14 days after treatment. Serum tumor necrosis factor-alpha and interleukin-2 concentration was measured. RESULTS: No side effects were reported by the entire patient population and the clinical conditions remained constant throughout the study period. The disease activity index improved significantly between the beginning and the end of the study in 80% of the patients. Histologic features (mucosal erosion, distortion of crypt architecture, inflammation and lamina propria gap) significantly improved in all treated patients. Serum interleukin-2 levels did not change significantly after propionyl-L-carnitine treatment (respectively: 14.7 +/- 15.8 before vs. 9.9 +/- 13.2 pg/mL), while tumor necrosis factor-alpha levels were undetectable both before and after propionyl-L-carnitine administration. CONCLUSIONS: The topical treatment with a new formulation containing propionyl-L-carnitine seems to be safe and effective in improving the histologic features in patients with inactive or mild ulcerative colitis, as an alternative to conventional therapy.

Adult↗
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Non-absorbable antibiotics and small bowel bacterial overgrowth.

The normal gastrointestinal flora includes no more than 10(3) organisms/ml of gastric aspirate and no more than 10(5) organisms/ml of duodenal or jejunal juice. The organisms are primarily gram-positive and aerobic bacteria. In particular anatomical or functional predisposing conditions, an abnormal colonization takes place in the small bowel with microbial concentrations > or = 10(7)/ml of aspirate and with a predominance of anaerobes and coliforms. At times this small bowel bacterial overgrowth remains asymptomatic, but more often leads to a true malabsorption syndrome with symptoms, such as diarrhoea, weight loss and megaloblastic anemia. The most accurate procedure for confirming the presence of this condition is represented by the bacterological analysis of the jejunal aspirate. The routine use of this method is, however, notably hindered by the need for intubation of the patient and by the lack of laboratories suitably equipped for anaerobe culture. As an alternative to this complex procedure, numerous non-invasive tests have been perfected over the last few years, including the glucose- or lactulose- H2 breath test. The main aim of the treatment of the small bowel bacterial overgrowth is the suppression of the bacterial colonization using antimicrobial therapy. Among the local-action non-absorbable antibiotics, rifaximin, was shown to have bactericidal activity against aerobes and anaerobes bacteria, such as bacteroides, lactobacilli and clostrides. In controlled clinical trials the antibiotic has demonstrated therapeutic efficacy in bacterial origin diarrhoea, in porto-systemic encephalopathy, in diverticulosis and, finally, in small bowel bacterial overgrowth.

Bacterial Infections↗
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13C-breath tests in the study of mitochondrial liver function.

Breath tests for "dynamic" liver function evaluation have been proposed several years ago. A variety of carbon-labelled breath tests for the assessment of mitochondrial, microsomal and cytosolic liver function have been described with the aim to increase data on liver disease staging, prognosis, and response to therapy. In the last years a great interest is developed about the use of breath test for liver mitochondrial function evaluation since it results impaired in a wide range of liver diseases either of genetic or acquired origin. In these cases mitochondrial oxidative metabolism of some substrates, as far as recovery of the hepatic energy state after a metabolic insult, results impaired because of the disfunction of the electron transport chain and/or ATP synthesis. Ketoisocaproic acid and methionine are the best studied carbon-labelled substrates for the investigation of mitochondrial functional damages related to structural alterations that occur in many liver diseases. Although these tests are simple, cost-effective and safe, to date there is still not general approval for their usefulness in clinical settings since they should fulfill several requirements to overcome the drawbacks of traditional quantitative tests. On the other hand, this field is relatively young and further studies are needed in order to assess the suitable substrate for the evaluation of the complex mitochondrial metabolism both in healthy subjects and in patients with liver disease.

Breath Tests↗
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13C-breath tests in the study of microsomal liver function.

Conventional liver tests can be used to estimate a mixture of injury and function but none of these may be regarded as a reliable marker either to quantify functional hepatic reserve or to reflect life-threatening complications of acute and chronic liver diseases. To overcome this limit, many dynamic tests have been developed in order to evaluate the "hepatic functional mass". Among these tests we can include breath tests with 13C-labeled substrates undergoing different metabolic pathways. As concerning the evaluation of microsomal function, two main categories of breath tests have been developed based on the limiting step in the different substrates metabolism. The first group include aminopyrine, caffeine and diazepam, all substrates with a metabolism independent from hepatic blood flow and dependent almost exclusively from the enzymatic activity of different cytochromes P450. The other group is composed of substrates with flow dependent metabolism like methacetin, phenacetin, erythromycin. The aim of this review is to describe the clinical applications of microsomal liver breath tests in different hepatic diseases.

Acetamides↗
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Intercellular adhesion molecule 1 gene polymorphisms in inflammatory bowel disease.

Intercellular adhesion molecule (ICAM)-1 is a single-chain cell surface glycoprotein that plays an important role in the recruitment of leukocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease (IBD). ICAM-1 gene lies on chromosome 19p13, implicated in determining susceptibility to IBD. The human ICAM-1 gene contains two polymorphic sites in codon 241 (G241R) and 469 (K469E) which have been implicated in the susceptibility to a range of degenerative and inflammatory diseases. Recently, several reports have shown discordant data regarding the association of these polymorphisms with IBD. In particular, we found an association of IBD with the E/E genotype while allele E469 was associated with a subgroup of patients with more extensive location of Crohn's disease and penetrating behaviour. However, other studies reached different conclusions. A possible explanation for the discrepancy of results is probably the influence of the different geographic distribution of the genetic mutations.

Gene Frequency↗
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Platelets: new players in the mucosal scenario of inflammatory bowel disease.

Besides their classical haemostatic task, platelets are now recognized as novel cells deeply involved in inflammation. Compelling evidence support their role as active player in mucosal tissue injury that occurs in Crohn's disease and ulcerative colitis. In both forms of inflammatory bowel disease platelets contribute to microvascular endothelial activation and recruitment of inflammatory cells, thus fostering and amplifying mucosal inflammation.

Blood Platelets↗
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Infliximab in the treatment of steroid-dependent ulcerative colitis.

BACKGROUND AND OBJECTIVES: Infliximab has proven efficacious in the treatment of Crohn's disease. Limited and contrasting data are available on effectiveness of anti-TNF alpha therapy in ulcerative colitis. We evaluated the efficacy of infliximab in the management of steroid-dependent ulcerative colitis. METHODS: We report preliminary data from a randomized, open-label, methylprednisolone-controlled trial of infliximab in the induction and maintenance of remission of patients with moderate to severe steroid-dependent ulcerative colitis. Twenty patients received either three infusion of infliximab (5 mg/kg) at 0, 2 and 6 weeks and thereafter every 8 weeks (group A) or methylprednisolone (0,7-1 mg/kg) daily for one week followed by a tapering regimen up to the minimal dose to maintain a symptom-free condition (group B). Clinical remission was defined as a DAI score less than 3. RESULTS: Ten patients in group A (DAI: 8.9+/-1.4) achieved remission after the first infusion (DAI: 1.6+/-0,7; p = 0.005) and steroids were progressively discontinued. At present (mean follow-up: 9.8+/-1.1 months), 9 out of 10 patients maintain clinical remission, while one patient relapsed at 3 months. Ten patients in group B (DAI: 8.7+/-1.4) reached clinical remission at one week (DAI: 1.9+/-0.3; p = 0.005). Eight out of 10 patients were maintained at a minimal steroid dosage without any relapse at 9.7+/-1.0 months follow-up. Two patients relapsed at 6 and 8 months, respectively. CONCLUSIONS: Infliximab seems to be as effective as steroids in the management of moderate to severe steroid-dependent ulcerative colitis. These preliminary data suggest the potential efficacy of repeated treatment with infliximab for short-term maintenance of remission and steroid withdrawal in glucocorticoid-dependent ulcerative colitis.

Adult↗
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Nonalcoholic fatty liver disease: defining a common problem.

Non Alcoholic Fatty Liver Disease (NAFLD), with prevalence of 10-51% in general population involving all ages, is the major cause of elevation of ALT and a common finding by ultrasound screening and may range from simple steatosis, to Non Alcoholic Steatohepatitis (NASH) and its clinical consequences as cirrhosis and hepatocellular carcinoma. In this review will be analyse factors influencing the onset of the disease. NAFLD, primarly associated with insulin resistance, is in fact considered the hepatic manifestation of the metabolic syndrome: a cluster of disorder that includes obesity, diabetes mellitus, dyslipidaemia, arteriosclerosis and hypertension. The increased incidence and prevalence of obesity and diabetes may explain growing interest in NAFLD. Racial, ethnic, enviromental and behaviour models are also reviewed.

Alanine Transaminase↗
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Nutritional aspects in patients with non-alcoholic steatohepatitis (NASH).

BACKGROUND AND OBJECTIVES: Metabolic alterations are a common feature in patients affected by non-alcoholic steato-hepatitis (NASH). A strong correlation exists between overweight, in particular visceral fat accumulation, and prevalence of NASH, especially in men. Thus, diet-induced weight loss represents a fundamental tool in disease management of these patients. The aim of the present study was to evaluate body composition and nutrient utilisation in patients with NASH, comparing them with patients affected by chronic hepatitis related to hepatitis C virus (HCV) infection and with healthy subjects. MATERIALS AND METHODS: Twenty male outpatients with NASH (age: 41 +/- 11 yr; BMI: 26.2 +/- 2.1 kg/m2) and 14 HCV male patients (age 44.6 +/- 13 yr; BMI: 24.8 +/- 2.8 kg/m2) were enrolled in the study. A group of 20 healthy male subjects (age: 39 +/- 10 yr; BMI: 23.3 +/- 1.1 kg/m2) were studied as controls. Body composition was assessed by anthropometry and dual-energy X-ray absorptiometry; resting metabolic rate and nutrient oxidation by indirect calorimetry. A 7-day food diary was collected. The main biochemical parameters were measured using standardised laboratory techniques. RESULTS: Body weight was higher in NASH patients with respect to HCV patients and control subjects (respectively 75.2 +/- 8.9 vs 68.5 +/- 9.4 and vs 67.0 +/- 8.0 kg; P < 0.01) and this was essentially due to fat mass increase. Fat-free mass reduction was found in HCV patients with respect to both NASH and control subjects. Patients with NASH had a significantly higher waist circumference (P < 0.01) and a lower resting metabolic rate (RMR) with respect to HCV and control subjects. Energy intake was significantly higher in NASH patients (P < 0.01) compared to the other two groups. CONCLUSIONS: NASH patients showed an increase in body weight, fat mass and visceral fat accumulation with respect to HCV and control subjects. The reduction in RMR, coupled with increase energy intake may explain the body composition alterations found in these patients.

Adult↗
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Hepatic steatosis and vascular disease.

Nonalcoholic fatty liver disease (NAFLD) refers to a wide picture of liver damage, ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. The epidemiological studies demonstrated an association of NAFLD with obesity, type 2 diabetes and hyperlipidemia. Under this light the metabolic syndrome (MS), including NAFLD, obesity, central fat distribution, diabetes, dyslipidemia, hypertension and atherosclerotic cardiovascular disease (CVD) can be considered the link to explain the presence of vascular diseases in patients with NAFLD. In NHANES III, the authors demonstrated that the presence of MS was associated with increased risk of myocardial infarction, stroke or both. In a prospective study on 1209 Finnish middle-aged men without CVD or diabetes at baseline, Lakka showed that MS per se is associated with an increased risk of CVD and all-cause mortality. Finally the Atherosclerosis Risk in Communities (ARIC) confirmed that subjects with MS were 2 times more likely to have prevalent coronary heart disease. From a pathophysiological point of view, growing evidences implicate the oxidative stress as the unifying mechanism for many CVD risk factors. Under this light there is emerging evidence suggesting that there is a significant increase in vascular oxidative stress in patients with MS, with the presence of endothelial dysfunction in the early stage of the syndrome. Indeed, the inflammation process evidentiated in these patients is initiated at the endothelial level, stressing the key role of this active and dynamic tissue in the pathophysiological pathways. Under this light the endothelium can be considered as the last effector of a multi-syndrome and the main target of all the future studies focused on the underlying mechamisms of this complex network. Because of the potential serious public health impact, the comprehension of these patophysiological pathways will be crucial to design new preventive measures and therapeutic strategies.

Animals↗
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The natural history and risk factors for progression of non-alcoholic fatty liver disease and steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is a condition of increasing incidence in western Countries seldom associated to other diseases of high prevalence in general population (i.e. diabetes and obesity). NAFLD ranges from simple fatty liver to steatohepatitis (NASH), which may lead to cryptogenic cirrhosis and in some cases hepatocellular carcinoma (HCC). Natural history of NAFLD in humans is poorly understood and progression of liver disease seems to be due to interaction between hosting (i.e. genetic, gut flora, insulin resistance) and environmental factors (social and eating behaviours) that should be responsible of increased oxidative stress within hepatocytes. Even if we need non-invasive markers able to describe the progression of liver disease, only meaning of liver biopsy is useful to characterize the stigmata of worsening such as inflammation and fibrosis.

Animals↗
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Fatty liver and drugs.

Drug-induced liver diseases (DILD) are clinico-pathologic patterns of liver injury caused by drugs or other foreign compounds. Steatohepatitis is a rare form of DILD, and drugs account for fewer than 2% of non-alcoholic steatohepatitis (NASH). Drugs known to be capable of inducing steatosis and steatohepatitis can be divided into three broad groups: those that cause steatosis and steatohepatitis independently (e.g., amiodarone, perhexiline maleate); drugs which can precipitate latent NASH (e.g., tamoxifen); drugs whic duce sporadic events of steatosis/steatohepatitis (e.g., carbamazepine). Clinical DILD syndromes include acute viral hepatitis-like injury, acute liver failure, cholestatic hepatitis,liver disease with signs of hypersensitivity, autoimmune hepatitis-like injury, acute venous-Outflow obstruction, chronic cholestasis, ciirrhosis, steatosis and steatohepatitis. The clinical picture is by no means dependent on the mechanism of injury (direct hepatotoxicity, idiosyncratic reactions, hypersensitivity reactions). Reliable diagnosis of drug-induced liver disease requires demonstration of close correlation between the patient history and clinical, laboratory, and histological data.

Amiodarone↗