Search PubMed⌕ Search

Biomedical subjects

M Sampietro

Publications and source records attributed to M Sampietro.

At least 37 records · Page 2Linked to original sources
PubMed1998

High prevalence of the His63Asp HFE mutation in Italian patients with porphyria cutanea tarda.

Sporadic porphyria cutanea tarda (PCT) is caused by a reduced activity of uroporphyrinogen decarboxylase (URO-D) in the liver. Mild to moderate iron overload is common in PCT, as iron is one of the factors which trigger the clinical manifestations of the disease through the inactivation of URO-D. A role for genetic hemochromatosis in the development of iron overload in sporadic PCT has been hypothesized in the past. The aim of this work was to investigate whether mutations of HFE, which is a candidate gene for hemochromatosis, play the role of genetic susceptibility factors for PCT in Italian patients, who have a high prevalence of acquired triggering factors, such as hepatitis C virus (HCV) chronic infection and alcohol. We determined HFE genotypes of 68 male patients with PCT. Our data do not confirm an association of PCT with the Cys282Tyr HFE mutation, strongly associated with hemochromatosis in Northern European countries. A second mutation of HFE, His63Asp, however, had a significantly increased frequency as it was present in half of the patients. Surprisingly, the presence of the His63Asp mutation was not related to the iron status of patients, suggesting that a subtle abnormality of iron metabolism induced by this mutation could escape detection by the standard parameters of iron status. In PCT patients with liver disease, the presence of the mutation could contribute to the inactivation of URO-D, either directly or through a synergistic action with other factors that cause liver damage.

Adult↗
PubMed1998

Heterogeneity of hemochromatosis in Italy.

BACKGROUND & AIMS: Patients with hemochromatosis show variable phenotype expression. We evaluated the frequency of hemochromatosis gene (HFE) mutations and the contribution of HFE genotype, ancestral haplotype, ethnic background, and additional factors (alcohol intake, hepatitis viruses, and beta-thalassemia trait) to the severity of iron overload in a large series of Italian patients with a hemochromatosis phenotype. METHODS: HFE genotype was studied in 188 patients. Phenotype evaluation was available in 153 men and 20 women and was based mainly on iron removed. HFE genotype was determined by a polymerase chain reaction restriction assay and ancestral haplotype through D6S265 and D6S105 microsatellite analysis. RESULTS: The frequency of C282Y homozygotes was 64%, with a decreasing gradient from north to south. C282Y homozygotes showed more severe iron overload than the other HFE genotypes. In the same group, ancestral haplotype was associated with a more severe phenotype. Additional factors may favor the development of a relatively mild hemochromatosis phenotype in patients nonhomozygous for the C282Y mutation. CONCLUSIONS: Hemochromatosis in Italy is a nonhomogenous disorder in which genetic and acquired factors are involved. In patients with a single or no HFE mutation, further studies will enable a differentiation between true genetic disorders and interactions between genetic and acquired factors.

Adult↗
PubMed1998

TATA-box mutant in the promoter of the uridine diphosphate glucuronosyltransferase gene in Italian patients with Gilbert's syndrome.

BACKGROUND: A mutation in the promoter of the uridine diphosphate glucuronosyltransferase gene has been described in patients with Gilbert's syndrome from Northern Europe. AIMS: To assess the frequency of this mutation in Italian patients with Gilbert's syndrome and in normal controls, in order to establish the molecular basis and molecular epidemiology of the syndrome in Italy. PATIENTS: Forty-six patients with a clinical diagnosis of Gilbert's syndrome and 44 individuals from the general population unselected for bilirubin levels. METHODS: Polymerase chain reaction amplification of the TATA-box element in the promoter of uridine diphosphate glucuronosyltransferase and identification of wild-type and variant alleles by high-resolution polyacrylamide gel electrophoresis. RESULTS: A TATA-box variant in the promoter of uridine diphosphate glucuronosyltransferase was found on 93% of chromosomes from patients with Gilbert's syndrome. The same variant was present on 44% of chromosomes from controls, unselected for bilirubin levels. Only 55% of controls homozygous for the TATA-box variant, however, had increased bilirubin levels. CONCLUSIONS: The TATA-box variant in the promoter of uridine diphosphate glucuronosyltransferase is strongly associated with the phenotype of Gilbert's syndrome in Italy. The incomplete penetrance of the mutation observed in controls indicates that other acquired or inherited conditions affecting bilirubin production, uptake, cellular transport or excretion may contribute to the hyperbilirubinaemia of Gilbert's syndrome.

Adolescent↗
PubMed1998

Hepatitis G virus infection in the elderly.

BACKGROUND AND AIMS: At least 10% of post-transfusion and community-acquired hepatitis cases are not accounted for by the A to E viruses. Hepatitis G virus (HGV), a novel agent belonging to the Flaviviridae and distantly related to HCV has recently been identified. The epidemiology and clinical significance of this infection in the geriatric setting is still little known. Aim of the investigation was to assess the prevalence and clinical significance of HGV infection in the geriatric setting. PATIENTS: 105 unselected consecutive patients (mean age 73.4 years). METHODS: HGV-RNA was detected by a single-tube reverse-transcription heminested polymerase chain reaction with primers from the 5' untranslated region of the virus. Anti-HGV antibodies were detected with a commercial anti-E2 immunometric assay. RESULTS: 3/105 patients (2.9%) were viraemic, without a history or clinical evidence of hepatitis. Anti-HGV antibodies were detected in 25 patients (23.8%), 40% of whom had associated anti-HCV antibodies. The presence of HGV-RNA and anti-HGV antibodies was mutually exclusive. CONCLUSIONS: HGV infection is highly prevalent in our population and the cumulative risk of exposure is proportional to age. In most cases, HGV infection is self-limiting and clinically irrelevant. Immunity against E2 or other associated uncharacterized viral epitopes appears to be protective.

Age Distribution↗
PubMed1997

Genetic heterogeneity in heterocellular hereditary persistence of fetal hemoglobin.

A large English pedigree in which heterocellular hereditary persistence of fetal hemoglobin (HPFH) segregates is described. beta-globin cluster deletions and gamma gene promoter mutations associated with HPFH have been excluded. Of particular importance in this pedigree is the absence of any cosegregating hemoglobinopathy, thus allowing observation of the segregation pattern of this form of HPFH without the complicating effect of a beta-globin gene mutation. Information gained in this study confirms that the extent of elevation of hemoglobin (Hb) F and F cells varies between affected individuals. There are one example of incomplete penetrance and three examples of father-to-son transmission, thus excluding X-linked inheritance. Consistent with previous reports, the most likely mode of inheritance is autosomal codominant. Linkage studies using a beta-globin cluster microsatellite show no evidence of linkage to this chromosomal region implicating the presence of trans-acting regulatory factor(s). We have recently mapped one such locus to the chromosome 6q region in a very large Asian-Indian pedigree. Linkage to chromosome 6q in the English pedigree was excluded, thus indicating the presence of genetic heterogeneity in heterocellular HPFH.

Adult↗
PubMed1997

Hepatitis G virus infection in hemodialysis patients.

The increased risk of hemodialysis patients for infections sustained by hepatitis viruses is likely to extend to a newly discovered parenterally transmitted virus, HGBV-C/HGV, able to cause acute and chronic hepatitis. The aim of this study was to assess the prevalence and clinical relevance of this infection in Italian hemodialysis patients. Nineteen of 100 patients (19%) on maintenance hemodialysis were viremic for HGBV-C/HGV, and all of them were infected with a HGV-like genotype. Eight of these patients were coinfected by hepatitis B or hepatitis C viruses. A clinical picture of chronic hepatitis was not appreciable in patients with isolated HGV infection and the presence of HGV did not appear to modify the clinical course of hepatitis B and hepatitis C infections.

Adult↗
PubMed1997

Prevalence and clinical significance of hepatitis G virus infection in adult beta-thalassaemia major patients.

The risk of polytransfused patients for hepatitis C virus (HCV) infection is likely to extend to another recently identified member of the Flaviviridae, hepatitis G virus (HGV). We investigated the prevalence of HGV in 40 adult Italian patients with transfusion-dependent thalassaemia and evaluated the clinical significance of HGV infection. HGV-RNA was detected in 9/40 patients (22.5%). HGV infection was significantly associated with HCV viraemia (P = 0.0012), with all patients positive for HGV being also viraemic for HCV. Overall, the clinical picture of patients with HCV/HGV co-infection was not different from that of patients with isolated HCV. However, patients co-infected with both viruses had lower values of alanine-transferase (P = 0.035) and a lower titre of HCV viraemia (P = 0.042) in the absence of other evident factors which could influence the clinical expression of HCV infection. In conclusion, HGV is highly prevalent among Italian polytransfused patients. No evidence of a clinically significant pathogenic role for HGV in liver disease could be found in these patients. In a subset of cases a possible interference of HGV with HCV infection was observed.

Adolescent↗
PubMed1997

The expression of uridine diphosphate glucuronosyltransferase gene is a major determinant of bilirubin level in heterozygous beta-thalassaemia and in glucose-6-phosphate dehydrogenase deficiency.

We evaluated the effect of Gilbert's syndrome, the most common defect of bilirubin conjugation, on the bilirubin levels of subjects with inherited haematological disorders which cause increased bilirubin production. 57 patients heterozygous for beta-thalassaemia, 21 with G6PD deficiency and 44 controls were examined by typing the TATA-box in the promoter of the gene uridine diphosphate glucuronosyltransferase 1A. Nearly 80% of patients with increased bilirubin levels were heterozygous or homozygous for the UGT1A TA(7) variant associated with Gilbert's syndrome. These findings indicate that Gilbert's syndrome accounts for a large proportion of the variability of bilirubin levels in beta-thalassaemia and G6PD deficiency.

Gene Expression↗
PubMed1997

Diffusion of HCV through peritoneal membrane in HCV positive patients treated with continuous ambulatory peritoneal dialysis.

PURPOSE OF THE STUDY: We evaluated the presence of HCV in the peritoneal effluents of viraemic patients treated with continuous ambulatory peritoneal dialysis (CAPD) to evaluate the risk of transmitting the infection with this procedure. PROCEDURE: Fifteen of 81 CAPD patients (18.5%) had anti-HCV antibodies and eight were viraemic. At the beginning of CAPD two of the viraemic patients had ascites with a clinical picture of chronic active hepatitis and cirrhosis. Peritoneal dialysates were collected after an overnight exchange with 1.36% glucose and after a 4-h exchange with 3.86% glucose. Fluids from the overnight exchange were spun to obtain a cellular pellet and the supernatant 100-fold concentrated. RESULTS: No viral genome could be detected in unconcentrated samples and in cellular pellets, while HCV-RNA at low titre was detected in concentrated dialysates from the two patients with active liver disease. CONCLUSIONS: Our findings confirm that HCV may be present in the CAPD effluent of some patients; however, the titre of virus in the effluent was extremely low, at the limit of detection of the PCR assay. Peritoneal fluids originating from patients with HCV associated severe liver disease may be a potential source of infection.

Adult↗
PubMed1997

Liver iron influences the response to interferon alpha therapy in chronic hepatitis C.

OBJECTIVE: To define whether there is any relation between the iron status of patients with hepatitis C virus (HCV) chronic liver disease and their response to interferon therapy. DESIGN: To evaluate the long-term response to 1 year of interferon therapy with addition of phlebotomies after 3 months of treatment if at that time alanine aminotransferase (ALT) had not normalized in a group of patients with HCV-positive chronic liver disease whose iron status had been characterized. SETTING: A northern Italian hospital. PARTICIPANTS: Fifty-eight anti-HCV-positive patients (four HCV-RNA negative) with biopsy proven chronic hepatitis and no evidence of iron overload as indicated by normal transferrin saturation at the time of enrollment in the study. INTERVENTION: Three times a week intramuscular injection of alpha interferon 3 MU for 1 year with addition of phlebotomies (350 ml/week) till iron depletion if after 3 months of interferon therapy ALT had not normalized. RESULTS: A long-term response was observed in 19 of the 52 patients who completed the treatment, four HCV-RNA negative and 15 positive. The four RNA-negative and seven of the 15 RNA-positive long-term responders had been treated with interferon alone, and the other eight also with phlebotomies. At univariate analysis only HCV genotype, gamma-glutamyltranspeptidase and liver iron concentration were significantly associated with response whereas sinusoidal iron deposition was of borderline significance. No association was found with sex, age, duration of disease, histology, Knodell score, transferrin saturation %, serum ferritin, hepatocytic iron score, and portal iron score. HCV-RNA serum levels, measured in 29 patients, did not correlate with response. At multivariate analysis liver iron concentration was still significant and one unit reduction of liver iron concentration (natural logarithm transformed) was associated with 2.95 odds ratio of response. CONCLUSION: These results indicate that iron in the liver is more closely related to response to interferon than the other variables considered, including HCV characteristics.

Adult↗
PubMed1997

High prevalence of hepatitis C virus type 1b in Italian patients with Porphyria cutanea tarda.

BACKGROUND: A strong association between sporadic porphyria cutanea tarda and chronic hepatitis C virus infection was recently described in Italy, France and Spain. AIMS: To explore whether hepatitis C virus genotype plays a role in porphyria cutanea tarda complicating chronic hepatitis C. PATIENTS: Forty-seven hepatitis C virus-positive porphyria cutanea tarda patients and a control group of 45 patients of similar age with hepatitis C virus-associated chronic liver disease. METHODS: Comparison of frequency of hepatitis C virus genotypes in the two groups and in relation to the age of patients, hepatic histopathology and with the presence of other factors potentially able to trigger porphyria cutanea tarda. RESULTS: A single genotype, hepatitis C virus 1b, was found to be present in nearly 90% of porphyria cutanea tarda-associated chronic liver disease, significantly exceeding the frequency of the same genotype in the control group (p = 0.0001). The presence of hepatitis C virus 1b was not related to the age of patients or disease severity as evaluated by hepatic histopathology. CONCLUSIONS: Hepatitis C virus-associated chronic hepatitis found in the majority of Italian patients with porphyria cutanea tarda is usually sustained by hepatitis C virus genotype 1b. This viral strain might have a direct pathogenic role in inducing porphyria cutanea tarda or could increase the susceptibility of patients of other triggering factors such as iron overload or alcohol abuse.

Adult↗
PubMed1996

No association between genetic hemochromatosis and alpha1-antitrypsin deficiency.

Genetic hemochromatosis and alpha1-antitrypsin (AAT) deficiency are frequent in white populations. Conflicting data on the association of the two conditions and on the severity of the disease in those in whom these disorders coexist have emerged from analyses of small numbers of patients. To determine if the frequency of AAT deficiency is increased in genetic hemochromatosis, we characterized this protein by isoelectric focusing and DNA analysis in 115 Italian patients with the disease and 290 controls. The frequency of AAT deficiency in patients with genetic hemochromatosis was similar to that in controls (10% and 9%, respectively). The prevalence of cirrhosis in patients with genetic hemochromatosis with MM phenotype was 53%, compared with 58% in those with non-MM phenotype; that of hepatocellular carcinoma, occurring only in cirrhotic patients, was 22% and 28%, respectively. In conclusion, the frequency of AAT deficiency was not increased in our large series of Italian patients with genetic hemochromatosis. Patients in whom the two defects coexisted did not appear to have a more severe disease, but the limited number of subjects with non-MM phenotype does not allow a conclusive evaluation of clinical differences between them and patients with genetic hemochromatosis with MM phenotype.

Adolescent↗
PubMed1996

Hepatitis C virus genotypes and reinfection of the graft during long-term follow-up in 35 liver transplant recipients.

To understand the clinical outcome of hepatitis C virus (HCV) recurrence, data from 35 liver transplant recipients who survived more than 6 months were reviewed. The presence of HCV-RNA was evaluated and genotyping was performed. On the basis of alanine aminotransferase (ALT) levels, patients were sorted into four groups. In 20 patients, a chronic elevation in ALT was found; HCV-RNA detection was positive in 17/17 and the following genotypes were found in 15 of them: 1b in ten patients, 2a in four patients, and 3a in one patient. In 11 patients, ALT levels remained normal throughout follow-up; in nine of them HCV-RNA was positive; HCV genotyping was available in eight patients and identified type 1b in two, type 2a in five, and type 3a in another patient. In two patients, ALT fluctuated above and below the upper limits of normality; type 1b HCV-RNA was found in one of them. In two patients, after an initial period of normality, ALT levels showed an abrupt rise; HCV-RNA was positive and type 1b was identified in both patients. Eight patients developed HCV-related deep jaundice and three of them spontaneously recovered. Progressive hepatic injury occurred in eight patients, six with chronic ALT elevation and two showing a late ALT elevation; genotype 1b was present in seven patients while in one, genotype 3a was found; sub-acute graft failure developed in five of them, leading to death in two and retransplantation in the others; the other three patients are alive with recurrent overt cirrhosis. The 1, 3, and 5 year actuarial survivals were 89%, 79%, and 63% respectively. The 1, 3, and 5 year actuarial risks of progressive graft damage were 6%, 7%, and 15%, respectively. In conclusion, HCV reinfection causes a slow decrease in the long-term patients' survival. Persistent elevation of ALT is more frequently observed in patients with genotype 1b infection.

Adolescent↗
PubMed1996

Myelodysplastic syndrome with karyotype abnormality is associated with elevated F-cell production.

A sensitive F-cell assay has been used to examine the production of fetal haemoglobin (Hb F) in a group of 77 adult patients with myelodysplastic syndrome (MDS), and a control group composed of 100 normal blood donors. Although the mean F-cell percentage in the MDS group (6.0%) is not statistically different from that in the normal blood donors (3.1%), a higher proportion of myelodysplastic patients have elevated F-cell values and the magnitude of the increases is greater than that observed in blood donors. In order to investigate the association further, the karyotypes of the MDS patients have been examined. 13/21 (61.9%) of the MDS patients with karyotypic abnormalities have F-cell values > 5%, compared to only 6/56 (10.9%) of the MDS patients with a normal karyotype and 11/100 (11%) of the blood donors. The observed difference in the distributions of F cells between the two subgroups of patients with MDS is highly significant (P < 0.0001).

Adult↗
PubMed1996

The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients.

We evaluate the relation between genotype and phenotype in 47 Italian male patients with homozygous genetic hemochromatosis (GH). Phenotype evaluation was based on the ratio of amount of iron removed (IR) by phlebotomy and age (IR/age). Patients were divided in two classes of phenotype expression: class I included 26 patients with less severe iron overload (IR/age <0.33) and class II included 21 patients with a more marked one (IR/age >0.33). Genetic variability was assessed by haplotype analysis combining alleles at HLA-B, D6S265, HLA-A, and D6S105 loci. A common ancestral haplotype carrying D6S265-1, HLA-A3, and D6S105-8 alleles was present in 13 of 52 (25%) chromosomes in class I and in 24 of 42 (57%) chromosomes in class II (P = .0027). Homozygotes and heterozygotes for the ancestral haplotype had higher iron indices than patients carrying two haplotypes other than the ancestral one. Seven of the eight patients homozygous for the ancestral haplotype were in class II, heterozygotes were equally distributed between the two classes, whereas 14 of 18 carriers of other haplotype combinations were in class I. Our results suggests that the gene defect linked to the ancestral haplotype is the result of a single, severe mutation. The high variability of phenotype expression in heterozygotes for the ancestral haplotype could be accounted for the contribution of the mutation carried by the second haplotype. Combination of different mutations could be responsible for the variable degrees of iron overload found in patients with GH.

Adult↗