Search PubMed⌕ Search

Biomedical subjects

A Floreani

Publications and source records attributed to A Floreani.

At least 19 recordsLinked to original sources
PubMed2006

Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study.

BACKGROUND: Many reports of autoimmune hepatitis (AIH) were written in the 'pre-Hepatitis C era' and data on the natural history are still incomplete. AIM: To evaluate the clinical presentation and the natural history of type I AIH. METHODS: Seventy-three consecutive patients with a regular follow-up of at least 2 years were prospectively included in the study. The mean follow-up was 91 +/- 61 months. RESULTS: Patients with 'acute' onset at presentation were significantly older than patients with 'chronic' onset (P < 0.05) and had significantly higher serum levels of transaminase, gamma-glutamyltransferase and bilirubin; Prothrombin time was significantly lower in the said group compared with AIH patients with 'chronic' onset. In 4 of 63 (6.3%) female patients, AIH had the onset during pregnancy; in all of them the outcome of pregnancy was favourable. The major events during the follow-up included oesophageal varices (n = 9) and ascites (n = 4), and 60 patients remained in remission while receiving immunosuppression. None of the patients died during the follow-up, but seven patients were transplanted. The cumulative transplant-free probability of survival was 73.5% at 280 months. CONCLUSIONS: Elderly patients have more frequently an acute onset at presentation. Survival in AIH is apparently good; with early diagnosis, and improved medical therapy, liver transplantation for AIH will become a rare event in future.

Adult↗
PubMed2006

Intrahepatic cholestasis of pregnancy: three novel MDR3 gene mutations.

BACKGROUND: The aetiology of intrahepatic cholestasis of pregnancy is unknown, but more than 10 different MDR3 gene mutations have recently been identified. AIM: To evaluate the genetic contribution of the MDR3 gene in the pathogenesis of intrahepatic cholestasis of pregnancy in Italian subjects. METHODS: We performed a multicentre prospective case-control study, enrolling 80 women with intrahepatic cholestasis of pregnancy at the third trimester of pregnancy and 80 pregnant women without intrahepatic cholestasis of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes using standard procedures. The polymerase chain reaction was used to amplify exon 14 of the MDR3 gene and the polymerase chain reaction products were sequenced using a Big Dye Terminator Cycle Sequencing kit. RESULTS: Three novel non-synonymous heterozygous mutations in exon 14 were found (4%; E528D, R549H, G536R) among the 80 intrahepatic cholestasis of pregnancy patients, whereas the pregnant controls were all negative for exon 14 polymorphisms. The three patients involved had normal GGT and bilirubin, but high levels of both ALT and serum bile acids. One had cholesterol bile stones. The outcome of pregnancy was normal for two (with vaginal delivery), while foetal distress was recorded in the third. CONCLUSIONS: These three novel mutations add further information on the involvement of the MDR3 gene in intrahepatic cholestasis of pregnancy. As in other studies, we found only heterozygous mutations that could cause an impaired transport protein function, not its absence (which is responsible for more severe liver disease). Different genetic backgrounds might justify the presence of novel MDR3 gene mutations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Assessing patients' understanding of hepatitis C virus infection and its impact on their lifestyle.

AIMS: To assess how much patients with hepatitis C virus infection know about their condition and what impact it has on their lifestyle. MATERIALS AND METHODS: A multiple-choice questionnaire was administered anonymously to 364 hepatitis C virus-infected subjects just before their first specialist visit. RESULTS: Even before hepatitis C virus infection was diagnosed, 257 subjects (70.6%) already knew something about this infection. Overall, 36% of patients had changed the way they behaved within the family, 25.5% had changed their sexual habits, 46.9% had changed their diet, and 69% reported having stopped or limited their alcohol intake after being told they were hepatitis C virus positive. Hepatitis C virus infection had a negative impact on the psychological status in 44.2% of patients. This effect was significantly greater among women and was independent of either the duration of their infection or any counselling received from the general practitioner. The need for specific treatment was reported by 59.8%. A demand for more detailed information about hepatitis C virus was expressed by 89.9% of patients. CONCLUSIONS: Hepatitis C virus changes all aspects of lifestyle and psychological status. The patients' strong demand for more information suggests that counselling and educational programmes must be an integral part of the activities of both the general practitioner and the specialist.

Adolescent↗
PubMed2006

Primary biliary cirrhosis: when and why does the disease develop?

Primary biliary cirrhosis is a chronic cholestatic liver disease with an autoimmune pathogenesis, that generally develops in adult life, often in perimenopausal age. The clinical features are heterogeneous, ranging from an asymptomatic presentation to end-stage liver disease. Primary biliary cirrhosis is unknown in children and its natural history has yet to be elucidated. Following a Canadian report of primary biliary cirrhosis in two girls (16 and 15 years old), we describe a clinical case developing at 17 years of age. A temporal association between Borrelia Burgdorferi infection and diagnosis of primary biliary cirrhosis was observed.

Adolescent↗
PubMed2006

Is hepatitis C virus a risk factor for thyroid autoimmunity?

The role of hepatitis C virus (HCV) in inducing thyroid autoimmunity is still under discussion and to assess the prevalence of thyroid autoantibodies and thyroid disease in the general population and to analyse the role of HCV in inducing thyroid autoimmunity. We studied 697 subjects residing in Arsita (a small town in central Italy). Thyroid autoantibodies and nonorgan-specific autoantibodies (NOSAs) were tested in each subject, who were also screened for anti-HCV antibodies; all subjects found positive to HCV-RNA were considered as being HCV-infected. Thyroid function tests were performed in all subjects positive for thyroid autoantibody. Seventy-one subjects were found HCV-positive; four of these (5.6%) were positive for at least one thyroid autoantibody, as opposed to 7 (4.9%) of the 142 sex- and age-matched controls of the same population (P = n.s.). Thyroid dysfunction was found in 2/4 HCV-positive, and in 1/7 HCV-negative subjects with thyroid autoantibodies (P = n.s.). NOSAs were significantly more common in HCV-positive than in HCV-negative subjects (P < 0.0001). Hence HCV per se is not responsible for thyroid autoimmune dysfunction, whereas HCV does seem to induce NOSAs. It should be taken into account, however, that the phenotypic expression of autoimmune diseases is obviously influenced by a number of risk factors, including genetic predisposition, female sex and infectious agents, that could trigger the onset of the disease.

Adult↗
PubMed2005

Impact of liver steatosis on virological response in [corrected] Italian patients with chronic hepatitis C treated with peg-interferon alpha-2b plus ribavarin.

BACKGROUND: Whether liver steatosis affects sustained virological response in patients with chronic hepatitis C is still under discussion. AIM: To evaluate the impact of liver steatosis in patients treated (for chronic hepatitis C) with combination therapy. METHODS: We evaluated 97 (male/female 82/15, mean age 41.1 years) consecutive naive patients treated with pegylated interferon alpha-2b plus ribavirin. RESULTS: Prevalence and severity of liver steatosis were significantly associated with genotype 3a [grade 3-4 in 14 of 32 patients (44%) vs. 8 of 65 patients (12%) with other genotypes; P = 0.001], while steatosis grade 1 (<10% of hepatocytes affected) was more frequently associated with genotype 1a/1b [9/39 (23%) vs. 4/57 (7%); P = 0.02]. Overall, sustained virological response was 62.8%, and was statistically uninfluenced by the presence/absence of liver steatosis. On the contrary, the following variables were independently associated with sustained virological response at logistic regression analysis: genotype other than 1a/1b, positive association, (odds ratio 3.4, P < 0.04), and low-grade liver steatosis, negative association, (odds ratio 9.0, P = 0.009), whereas sustained virological response was unaffected by severe liver steatosis, which was mainly associated with genotypes 2 and 3 [steatosis grade 2, 18/29 (62%); grade 3, 10/12 (83%); grade 4, 7/10 (70%)]. CONCLUSIONS: Only low-grade liver steatosis negatively affects the outcome of combination therapy, with peginterferon alpha-2b plus ribavirin, while severe steatosis (which is virus-related in most cases) has no impact on virological response.

Adult↗
PubMed2004

Imaging of primary sclerosing cholangitis: preliminary results by two new non-invasive techniques.

BACKGROUND: Magnetic resonance cholangiography is a new technique which has already gained a role in primary sclerosing cholangitis. Computerised tomographic cholangiography is another non-invasive technique which has been used in assessing abnormal biliary tree, but has never been applied to evaluating primary sclerosing cholangitis. AIMS: To evaluate the ability of both magnetic resonance cholangiography and computerised tomographic cholangiography to detect bile duct changes in primary sclerosing cholangitis. PATIENTS AND METHODS: Magnetic resonance cholangiography and computerised tomographic cholangiography were performed in 16 primary sclerosing cholangitis patients. The computerised tomographic cholangiography data set was transferred to a processing workstation to obtain tridimensional reconstructions. Magnetic resonance cholangiography and computerised tomographic cholangiography images were analysed blind by two radiologists to assess: primary sclerosing cholangitis involvement, quality of imaging and the radiologist's certainty in determining the presence and location of the disease. RESULTS: Mean imaging quality was significantly better with computerised tomographic cholangiography compared with magnetic resonance cholangiography. Primary sclerosing cholangitis was identified in 15 cases with computerised tomographic cholangiography and 10 with magnetic resonance cholangiography (P < 0.05). Sensitivity in diagnosing primary sclerosing cholangitis was 94% with computerised tomographic cholangiography versus 63% with magnetic resonance cholangiography. Intrahepatic location was found in 14 cases, definitely present in 10 cases with computerised tomographic cholangiography and five with magnetic resonance cholangiography. Extrahepatic location was found in 13 cases, definitely present in 11 cases with computerised tomographic cholangiography and four with magnetic resonance cholangiography (P < 0.05). Computerised tomographic cholangiography also offered dynamic information about biliary excretion. CONCLUSIONS: Computerised tomographic cholangiography enables more accurate detection and location of primary sclerosing cholangitis than magnetic resonance cholangiography. Since computerised tomographic cholangiography offers additional information about biliary excretion, it may be proposed as an integrative technique in the diagnosis and follow-up of patients with primary sclerosing cholangitis.

Adult↗
PubMed2004

Chemokine receptor 5 and primary biliary cirrhosis: a two-centre genetic association study.

BACKGROUND: Chemokines and their receptors are important mediators of leucocyte trafficking and are suggested to be critical for establishment of inflammatory autoimmune processes. CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4+ T cells. We hypothesised that the CCR5delta(Delta)32 genotype, which impairs surface expression of CCR5 in heterozygotes and is linked to a functional polymorphism of CD45RA expressed on suppressor-inducer-like 'naive' CD4+ T cells, may modulate the inflammatory process in primary biliary cirrhosis (PBC). METHODS: CCR5Delta32 polymorphism was determined by PCR in 226 Caucasian PBC patients and 197 racially matched controls from two geographical areas, Newcastle, UK and Padua, Italy. (UK: 144 PBC, 105 controls, Italy: 82 PBC, 92 controls). RESULTS: When the two series were analysed separately, there were no significant differences in the genotype distribution comparing patients and controls (UK: wt/wt 72% vs 76%; wt/Delta32 28% vs 22%; Delta32/Delta32 0% vs 2%, P=0.24; Italy: wt/wt 72% vs 82%; wt/Delta32 27% vs 17%; Delta32/Delta32 0% vs 1%, P=0.14). However, when the data for the two series were pooled and reanalysed, we found an increase in the CCR5Delta32 mutation in PBC patients vs controls (28% vs 21%, OR=1.43, P=0.03), but there was no evidence that this Delta32 polymorphism is associated with less severe disease. CONCLUSIONS: Although this two-centre genetic association study is large compared with others performed in PBC, taken separately, each geographically based cohort of patients and controls is underpowered to detect a small effect of this functional polymorphism. This emphasises the need for far larger case-control collections to address which polymorphic markers or haplotypes might modify the pathogenesis and clinical course of PBC. We propose that multi-centre collaboration on an international scale in 'orphan' complex liver diseases such as (PBC) is supported by the International Association for the Study of the Liver and promoted via their journal with development of a brief format for web-based publication of studies.

Base Sequence↗
PubMed2003

Type 1 diabetes mellitus in patients with chronic hepatitis C before and after interferon therapy.

Type 1 diabetes mellitus is the result of an autoimmune process characterized by pancreatic beta cell destruction. It has been reported that chronic hepatitis C infection is associated with type 2 diabetes mellitus, but not with type 1. Although the prevalence of markers of pancreatic autoimmunity in hepatitis C virus-positive patients is not significantly different to that reported in the general population, it increases during alpha-interferon therapy from 3 to 7%, probably due to the immunostimulatory effects of this cytokine. To date, 31 case reports of type 1 diabetes mellitus related to interferon treatment have been published. Type 1 diabetes mellitus occurs more frequently in patients treated for chronic hepatitis C than for other conditions and is irreversible in most cases. In 50% of these patients, markers of pancreatic autoimmunity predated treatment, the majority of cases having a genetic predisposition. Thus, in predisposed individuals, alpha-interferon can either induce or accelerate a diabetogenic process already underway. We suggest that islet cell autoantibodies and glutamic acid decarboxylase autoantibodies should be investigated before and during interferon treatment in order to identify subjects at high risk of developing type 1 diabetes mellitus.

Antiviral Agents↗
PubMed2003

Treatment of primary sclerosing cholangitis with low-dose ursodeoxycholic acid: results of a retrospective Italian multicentre survey.

BACKGROUND: Data concerning the usefulness and type of drugs employed to treat patients with primary sclerosing cholangitis are controversial. Ursodeoxycholic acid has been shown to be a useful agent, however the drug dosage and its effect on the clinical course are still under debate. AIM: To evaluate the efficacy of low-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis. METHODS: We retrospectively analysed data from 86 patients with primary sclerosing cholangitis from eight centres in Italy between 1987 and 1997: 69 were treated with ursodeoxycholic acid (8-13 mg/kg/day), while 17 received symptomatic treatment and served as controls. The effect of therapy was evaluated by standard liver function tests and symptom analysis. RESULTS: Ursodeoxycholic acid treatment was associated with significant improvement in serum alkaline phosphatase (735+/-833 vs. 519+/-448 U/l, p<0.001), gamma-glutamyl transpeptidase (401+/-352 vs. 234+/-235 U/l, p<0.001), aspartate aminotransferase (87+/-70 vs. 56+/-42 U/l, p=0.001), alanine aminotransferase (146+/-139 vs. 76+/-73 U/l, p<0.001), and total bilirubin (1.88+/-2.44 vs. 1.76+/-4.12 U/l, p=0.01); there was also amelioration of fatigue (p=0.007), jaundice (p=0.002), and body weight loss (p=0.002). CONCLUSIONS: Ursodeoxycholic acid, at a dose of 8-13 mg/kg/day was beneficial for the general condition and liver biochemistry of patients with primary sclerosing cholangitis; high-dose ursodeoxycholic acid treatment requires further evaluation.

Adult↗
PubMed2003

Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population.

AIMS: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries.

Adult↗
PubMed2002

Familial primary biliary cirrhosis and autoimmune cholangitis.

AIM: Autoimmune cholangitis has been proposed as a separate disease entity from primary biliary cirrhosis without serum antimitochondrial antibodies. The ultimate answer to the question of whether autoimmune cholangitis and primary biliary cirrhosis are distinct will require detailed comparison of aetiologic factors and pathogenic mechanisms. METHODS AND RESULTS: Two families are described each of which has one member with classical antimitochondrial antibody positive biopsy-proven primary biliary cirrhosis and a first degree relative with antimitochondrial antibody negative but antinuclear antibody positive autoimmune cholangitis (biopsy proven in one case). Study of such families should allow analysis of the contribution of shared genetic risk factors versus varying environmental triggering mechanisms to disease pathogenesis. CONCLUSIONS: We suggest a European registry of families, such as the two described, which are rare within one centre, to facilitate elucidation of pathogenetic factors.

Adult↗
PubMed2002

Cytokine, infiltrating macrophage and T cell-mediated response to development of primary and secondary human liver cancer.

BACKGROUND: Kupffer cells, monocytes and infiltrating T cells have been considered the major source of interleukin-1beta and tumour necrosis factor-alpha in the liver. AIMS; To explore the expression of interleukin-1beta and tumour necrosis factor-alpha and to evaluate the density and the distribution of T lymphocytes and monocytes/macrophages in the liver of patients with primary and secondary tumours. METHODS: Tumoural and peritumoural liver samples were examined from 21 patients with hepatocellular carcinoma, 10 with hepatic metastases, 5 with benign focal liver lesions and 4 healthy adult livers. Interleukin-1beta and tumour necrosis factor-alpha mRNAs were detected by a semiquantitative comparative reverse transcriptase polymerase chain reaction. T lymphocytes and monocytes/macrophages were detected by immunohistochemistry. RESULTS: Higher levels of interleukin-1beta, tumour necrosis factor-alpha, CD3+ and CD68+ cells were found in the tissue surrounding hepatocellular carcinoma and metastases than in the tumour itself. A strong expression of CD68+ and CD3+ cells was found mainly along the tumour-host interface but the highest expression of CD3+ cells was found at the metastasis interfaces. Interleukin-1beta expression, CD3+ and CD68+ cell densities were higher in peritumoural samples than in so-called "normal" liver tissue. CONCLUSIONS: An increased production of interleukin-1beta and, to a lesser extent, of tumour necrosis factor-alpha mRNA coincides with the presence of cancer be it primary or secondary, both in healthy and cirrhotic livers. The presence of cancer, irrespective of the presence of underlying liver damage, appears to play the most important role.

Adult↗
PubMed2002

Prevalence of coeliac disease in primary biliary cirrhosis and of antimitochondrial antibodies in adult coeliac disease patients in Italy.

BACKGROUND: Although an association between primary biliary cirrhosis and coeliac disease has recently been reported in Northern Europe, there are still conflicting data concerning this issue. AIM: To evaluate both the prevalence of coeliac disease in a series of primary biliary cirrhosis patients and that of antimitochondrial antibodies in a series of adult biopsy proven coeliac disease patients from Northern Italy. PATIENTS AND METHODS: A total of 87 primary biliary cirrhosis patients (79 female, 8 male) were screened for both IgA-transglutaminase antibodies and antiendomysium antibodies and, in those with either IgA-transglutaminase antibodies or antiendomysium antibodies positivity, upper endoscopy with distal duodenum biopsy was offered. In those who refused upper endoscopy, the intestinal permeability test with lactulose/mannitol excretion was performed. RESULTS: Antiendomysium antibodies positivity was detected in 3 subjects (3.4%), all of whom had serum IgA-transglutaminase antibodies above the normal range, and fulfilled the diagnosis of coeliac disease. Of 21 other patients with serum IgA-transglutaminase antibodies above the normal range, 17 underwent upper endoscopy which revealed normal duodenum architecture. The remaining 4 patients underwent the lactulose/mannitol excretion test which was within the normal range. Sera from 108 adult coeliac disease patients were tested for antimitochondrial antibodies and positivity was found in 4 patients (3.7%): all had normal liver biochemistry tests, whereas 2 of them also presented thyroid disease. Antibodies directed to the 74-kDa polypeptide of antimitochondrial antibodies were found in 3 out of 4 antimitochondrial antibodies+ve patients. CONCLUSIONS: These results suggest an association between primary biliary cirrhosis and coeliac disease similar to that observed in the Northern European series. In conclusion, screening for coeliac disease with antiendomysium antibodies in primary biliary cirrhosis is justified, and screening for antimitochondrial antibodies is advisable in adult coeliac disease patients.

Aged↗
PubMed2001

Comparison of three different influenza vaccines in institutionalised elderly.

The reactogenicity and the humoral immune response to three influenza vaccines were evaluated in a randomised, double-blind trial at nursing homes in north-east Italy in winter 1998-1999. Of the 285 subjects, who completed the follow-up, 93 were administered virosomal vaccine, 99 received MF59-adjuvanted vaccine and 93 had split vaccine. Ten subjects (0.3%) reported local and/or systemic reactions in the first week after immunisation. After 4 weeks, protection rates (> or = 40) were near 100% for the H1N1 and B strain and 76.0% against H3N2. The MF59-adjuvanted vaccine group had higher geometric mean titres than the other two. However, the true clinical benefit of the new adjuvanted vaccine should be further substantiated by comparative protective studies. Our results suggest that immune response to influenza vaccination in institutionalised elderly is satisfactory.

Adjuvants, Immunologic↗
PubMed2001

Bone metabolism and gonad function in male patients undergoing liver transplantation: a two-year longitudinal study.

Osteodystrophy is a major complication of end-stage liver disease, especially in postmenopausal women. Our aim in this study was to evaluate bone metabolism and gonad function in men undergoing orthotopic liver transplantation (OLTx). Twenty-three consecutive men (mean age 48+/-13 years) evaluated for OLTx were studied, assessing the following parameters at baseline and 3, 6, 12 and 24 months after OLTx: lumbar spine (L2-L4) bone mineral density (BMD), parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D (25OHD), free testosterone (FT) and gonadotropins (FSH, LH). At baseline, 12 patients (52%) had a T-score <-2.5 SD and the mean BMD was 0.806+/-0.11 g/cm2 (range 0.470-1.045 g/cm2). The BMD was lower 3 months after OLTx and significantly higher 12 and 24 months after OLTx. A significant increase in serum BGP was observed at 6, 12 (p<0.05) and 24 months (p<0.005) after OLTx. The mean serum PTH level was 26.6+/-3.1 pg/ml at baseline and increased significantly at 12 and 24 months (to 49.4+/-9.9 and 61.2+/-10.1 pg/ml, respectively; p<0.05). 25OHD serum levels were low at baseline and returned to the normal range after 12 and 24 months (baseline, 8.73+/-1.54 ng/ ml; 12 months, 16.4+/-2.6 ng/ml; 24 months, 17.67+/-3.1 ng/ml; p<0.05). FT was significantly lower at baseline than in a group of 10 healthy controls (5.09+/-10.99. vs 10.3+/-1.1 pg/ml; p<0.0001). After OLTx a significant increase in FT was recorded at 6, (p<0.05) and 24 months (p<0.005). FT was not correlated with BMD, however. After OLTx an increase in FSH and LH was observed (but failed to reach statistical significance) at 3 and 6 months, followed by a slight reduction at 12 and 24 months. Thus a high proportion of men with end-stage liver disease do have osteoporosis. After OLTx, an early recovery of gonad function is observed, followed by an increase in bone mass, which occurs from the sixth month onward.

Adult↗