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Biomedical subjects

G Nebbia

Publications and source records attributed to G Nebbia.

At least 19 recordsLinked to original sources
PubMed2001

Hepatitis B virus infection in native versus immigrant or adopted children in Italy following the compulsory vaccination.

BACKGROUND: Compulsory vaccination of children against hepatitis B virus (HBV) infection was introduced in Italy in 1991. PATIENTS AND METHODS: To evaluate the current importance of pediatric HBV infection, we studied 359 HBsAg-positive children admitted to 16 centers in Italy from 1991 to 1998. 185 patients were natives of Italy and 174 (39 immigrants and 135 adopted) came from highly endemic countries (eastern Europe: 60.9%, Asia: 16.7%, Africa: 14.9% and Central and South America: 5.7%). RESULTS: Transaminase Levels were moderately altered in both Italian (mean 134 UI/L) and foreign children (mean 168 UI/L). In total, 77% of ItaLian children and 88% of foreign children tested HBeAg positive. High transaminase levels and HBeAg positivity were more frequent in adopted children. Follow-up of 317 patients showed that the incidence of HBeAg/anti-HBe serum conversion was similar in all cohorts, but in adopted children it occurred at an earlier age and was associated with HBsAg clearance in 5%. CONCLUSION: HBV is not frequent in Italian children today, but it is common among children coming from highly endemic areas. The vaccination of nonimmune native populations must be strongly recommended.

Adolescent↗
PubMed1999

Immunity to poliomyelitis, diphtheria and tetanus in pediatric patients before and after renal or liver transplantation.

Few studies have considered the safety, efficacy and appropriateness of vaccinations in pediatric patients before and after solid organ transplantation. The aim of this study was to evaluate the immune status after primary vaccination to diphtheria, tetanus and poliomyelitis in pediatric patients before and after hepatic transplantation and to poliomyelitis in pediatric patients before and after renal transplantation. All the patients had received a complete primary immunization schedule for diphtheria and tetanus and poliomyelitis. Immunity to the three polioviruses was evaluated in 56 patients with renal transplant, 27 on chronic dialysis and 33 controls and in 39 patients with hepatic transplant, 25 with chronic hepatic failure and their 36 controls. Immunity to diphtheria and tetanus was evaluated in 52 liver transplant patients, 29 children with chronic hepatic failure and 54 healthy children. Renal transplant patients were less protected and had lower antibody geometric mean titers than healthy controls for polioviruses 1 and 2. Whereas, protection in the children liver transplant patients was similar to that in their controls. Patients with chronic hepatic failure had higher antibody geometric mean titers to diphtheria and polioviruses 1 and 3 than their control group. Immunosuppression after transplantation has a negative influence on the immune status after primary vaccination in children with renal transplant. Whereas children with chronic hepatic failure have higher antibodies than a normal population. When possible, it could be advisable to individualize immunization schedules in patients at high risk.

Adolescent↗
PubMed1999

Construction of a human platelet alloantigen-1a epitope(s) within murine glycoprotein IIIa: identification of residues critical to the conformation of the antibody binding site(s).

The human platelet alloantigen 1 system (HPA-1) is determined by a polymorphism at position 33 in the N-terminus of human glycoprotein IIIa (GPIIIa). This naturally occurring substitution creates a conformation in the HPA-1a allelic form that can be antigenic when presented to an individual expressing the HPA-1b form. Anti-HPA-1a antibodies generated by this immune response can lead to the destruction of platelets, as seen in the clinical disorders, neonatal alloimmune thrombocytopenia (NAIT) and posttransfusion purpura (PTP). To understand better the structural requirements for recognition by these pathogenic antibodies, we investigated the N-terminal 66 amino acids from the HPA-1a form of human GPIIIa and the analogous amino acids from the nonimmunogenic murine homolog. Our objectives were to define further the boundaries of the HPA-1a epitope(s) in the N-terminus of human GPIIIa, to isolate the murine 5' nucleotide sequence and compare the deduced murine N-terminal sequence to that of human, and to mutate the murine sequence systematically to include an HPA-1a epitope(s). Murine amino acids that differed from human were changed by site-directed mutagenesis to the analogous residues in the HPA-1a form of human GPIIIa, starting and radiating from murine position 33 (site of human polymorphism). This systematic approach allowed us to pinpoint amino acids critical to a conformation recognized by anti-HPA-1a antibodies. Our results show that an HPA-1a epitope can be created within the N-terminus of murine GPIIIa and raise the possibility that murine models of HPA-1a sensitization can be developed.

Amino Acid Sequence↗
PubMed1999

Jagged-1 mutation analysis in Italian Alagille syndrome patients.

Alagille syndrome (AGS) is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, vertebrae, and craniofacial region. The Jagged-1 (JAG1) gene, which encodes a ligand of Notch, has recently been found mutated in AGS. In this study, mutation analysis of the JAG1 gene performed on 20 Italian AGS patients led to the identification of 15 different JAG1 mutations, including a large deletion of the 20p12 region, six frameshift, three nonsense, three splice-site, and two missense mutations. The two novel missense mutations were clustered in the 5' region, while the remaining mutations were scattered throughout the gene. The spectrum of mutations in Italian patients was similar to that previously reported. We also studied in detail a complex splice site mutation, 3332dupl8bp, which was shown to lead to an abnormal JAG1 mRNA, resulting in a premature stop codon. With the exception of the missense mutations, the majority of the JAG1 mutations are therefore likely to produce truncated proteins. Since the phenotype of the patient with a complete deletion of the JAG1 gene is indistinguishable from that of patients with intragenic mutations, our study further supports the hypothesis that haploinsufficiency is the most common mechanism involved in AGS pathogenesis. Furthermore, our data confirmed the absence of a correlation between the genotype of the JAG1 gene and the AGS phenotype.

Alagille Syndrome↗
PubMed1999

Hepatitis A vaccination in chronic carriers of hepatitis B virus.

Because hepatitis A infection may be more severe in patients with chronic liver disease, we vaccinated 33 children who were chronic HBsAg carriers against hepatitis A virus. Anti-hepatitis A virus seroconversion rates after the first, second, and third doses were 90.9%, 96.9%, and 100%, respectively.

Adolescent↗
PubMed1998

Apoptotic cell clearance in systemic lupus erythematosus. II. Role of beta2-glycoprotein I.

OBJECTIVE: To analyze the contribution of beta2-glycoprotein I (beta2-GPI) to apoptotic cell recognition by antiphospholipid antibodies (aPL) and macrophages from patients with autoimmune disease. METHODS: Phosphatidylserine expression by Jurkat cells undergoing apoptosis upon CD95 crosslinking or ultraviolet irradiation was verified by confocal microscopy of cells stained with fluorescein isothiocyanate-labeled annexin V. Beta2-GPI was purified by heparin/cationic-exchange chromatography and was biotinylated or used to purify beta2-GPI-specific antibodies by affinity chromatography. Binding to apoptotic cells was assessed by flow cytometry. The clearance of 3H-labeled, apoptotic cells by macrophages was assessed by beta counting. RESULTS: The array of epitopes generated by beta2-GPI association with apoptotic cells specifically targets their recognition and is required for their opsonization by human aPL. Nevertheless, beta2-GPI is not required for apoptotic cell clearance by human macrophages in the absence of aPL. CONCLUSION: The proinflammatory clearance of aPL-opsonized apoptotic cells, but not the nonphlogistic clearance of apoptotic cells by scavenger macrophages, depends on beta2-GPI.

Antibodies, Antiphospholipid↗
PubMed1997

Hepatitis G and C virus coinfection in children.

Infection with the hepatitis G virus (HGV), as indicated by the presence of HGV ribonucleic acid, was sought in 57 children with chronic hepatitis C virus infection. HGV infection was found in 2 children (3.5%), or 14% of the babies whose mothers were former drug abusers. Maternal drug abuse is an important risk factor for hepatitis G and C virus coinfection in children in our area.

Adolescent↗
PubMed1997

Factors influencing malnutrition in children waiting for liver transplants.

Nutrition deficiencies are common in children with chronic liver disease. To determine whether age, hepatic dysfunction, or energy intake influences this malnutrition, we evaluated the nutritional status of 49 children aged 2.5 mo to 13 y (mean: 35 mo; median: 12 mo). The children were divided into two groups according to age: group 1-29 patients aged < or = 1 y (mean: 7 mo; median: 7 mo); and group 2-20 patients > 1 y (mean: 75 mo; median: 59 mo). Hepatic dysfunction was defined according to the Malatack criteria. Seventy-two-hour dietary intakes were recorded by a nutritionist. Nutritional status was assessed by anthropometric measures when the patients were enrolled on the waiting list for liver transplants. We evaluated the following indexes: weight, height, fat body mass, and lean body mass on the basis of height-age (age at which height reached 50th Italian height percentile). Mean height Z scores were low in both groups, but the difference was not significant. Mean weight Z scores and mean percentages of fat body mass were significantly lower (P < 0.001) in group 1 than in group 2 patients. In group 2, lean body mass and fat body mass were significantly lower (P < 0.05) in patients with moderate-to-severe hepatic failure than in patients with mild hepatic dysfunction. The mean energy intake was in the range of the recommended daily allowances for age but was insufficient for both groups of patients. The evidence of significant acute and chronic malnutrition confirmed the need for nutritional support, especially for younger and older children with moderate-to-severe hepatic dysfunction. We emphasize the necessity of accurate assessment of nutritional status by simple anthropometric measurements to be sure of the effects and adequacy of the nutritional intervention.

Adolescent↗
PubMed1996

Non-organ specific autoantibodies in children with chronic hepatitis C.

BACKGROUND/AIMS: Recent studies in adult patients have established a relationship between hepatitis C virus infection and the presence of liver-kidney microsomal autoantibody type 1 (LKM1). Conversely, little is known regarding the relationship between hepatitis C and autoimmunity in children. In this study, we investigated non-organ specific autoantibodies in 40 otherwise healthy Italian children with chronic hepatitis C. METHODS: All but four patients included in the study were asymptomatic. Liver histology, obtained in 35, showed features ranging from minimal to mild chronic hepatitis. Autoantibodies were investigated by indirect immunofluorescence. HCV RNA was assayed by the polymerase chain reaction in 34 cases and viral genotypes were determined. RESULTS: Antinuclear antibodies were detected in three (7.5%) cases, one with a homogeneous pattern; smooth muscle autoantibodies in seven (17.5%) cases, always with V (vessels only) specificity and LKM1 in four (10%), at titers ranging from 1:20 and 1:2560. Clinical and virologic features did not significantly differ between autoantibody positive and negative cases, although infections with HCV genotypes 1a and 2 were more frequent in LKM1-positive patients. During observation, the child with the highest LKM1 titre was unsuccessfully treated with alpha interferon but responded to steroids. Twelve LKM1 negative children were also treated with interferon and one developed low LKM1 titers concomitant with an alanine aminotransferase flare. The sera of the five LKM1-positive children with investigated by immunoblotting with a human microsomal fraction and peptide 257-269 of cytochrome P450IID6. Only the serum of the child with the highest LKM1 titers was reactive. CONCLUSIONS: These results show that a consistent proportion of children with chronic hepatitis C circulate non-organ specific autoantibodies. The prevalence of LKM1 is greater than in adults and this could raise problems for the treatment of the disease with interferon. The analysis of LKM1 target antigens might help to identify putative cases of "true" autoimmune hepatitis with concomitant HCV infection that could benefit from steroid treatment.

Adolescent↗
PubMed1996

Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study.

We assessed the efficacy of prolonged interferon-alpha (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-alpha 2b (5 MU m-2, then 3 MU m-2 three times weekly for 12 (medium-term group MTG) or 24 months (long-term group, LTG). Compliance and tolerability were acceptable. At the end of therapy a complete biochemical response [normalization of alanine aminotransferase (ALT)] occurred in 12 children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in 10 cases (five in MTG and five in LTG). Two patients from the LTG had normal liver function tests during 12 months of follow-up. Six of the eight hepatitis B e antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later in two children. HDV RNA, present in 10/10 cases of MTG before treatment, persisted after 12 months IFN therapy in 3/10. One year after stopping therapy, 8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta antigen (HDVAg) from the liver. No significant improvements in liver histology were seen in both groups. Our experience suggests that IFN-alpha treatment in children with chronic type D hepatitis has a transient effect, and long-term treatment does not appear to induce a greater therapeutic benefit in terms of biochemical and virological response.

Adolescent↗
PubMed1996

Hepatitis C virus genotypes in chronic hepatitis C of children.

Several hepatitis C virus (HCV) genotypes have been recently identified and genotype 1b has been correlated with severe liver disease and a poor response to interferon therapy. HCV infection in children is an interesting model for evaluation of the relationship between HCV genotypes and liver disease, because of its relatively short duration and the infrequent association with confounding cofactors. We have investigated HCV genotypes, using a dot-blot hybridization assay with genotype-specific probes, in 36 Italian children with chronic hepatitis C who were otherwise well and had no other underlying disease. Only four patients were symptomatic; liver histology, obtained in 33 patients, showed minimal hepatitis in 17 and mild chronic hepatitis in 16. Infection with HCV genotype 1b was found in 55.5% of patients, with a peak prevalence of 83% in children from southern Italy (P < 0.05 vs other regions). The remaining children were infected with HCV genotype 1a (16.6%), genotype 2 (11.1%), and mixed (10.9%) or undetermined (2.7%) genotypes. In one patient, HCV viraemia was never detected. There was no statistically significant correlation between genotype and age, sex, source of infection, alanine aminotransferase pattern and histological activity index. These results indicate that genotype 1 b is widespread among Italian children with chronic hepatitis C, although with significant geographical variations. It is not associated with a more severe liver disease, therefore suggesting that the greater severity of liver disease recently reported in adults could reflect the cumulative effects of disease duration and of interfering cofactors.

Adolescent↗
PubMed1996

Paediatric liver transplantation in Italy.

The paediatric liver transplantation programme was started, at our institution, in 1988 and since then 75 children have received 79 transplants, which corresponds to about 85% of all the paediatric liver transplantations performed in Italy. The main indications to transplantation were biliary atresia, familiar cholangiopathies and metabolic diseases. The patients came from all the regions of Italy, except for 2 of them who came from abroad. Patients with malnutrition and impaired growth underwent an aggressive nutritional programme whilst waiting for transplantation. The transplants were performed using whole grafts, reduced size grafts and, recently, with grafts from split livers, in 7 cases. Immunosuppression was based on a double drug therapy with Cyclosporine and low dose steroids. Steroid resistant acute rejection was treated, with OKT3 until 1993 and with conversion from Cyclosporine to FK506, thereafter. Interventional radiology was most useful in treating biliary complications. The introduction of Gancyclovir greatly reduced the incidence and severity of cytomegavirus related complications. Three years survival after liver transplantation was 62% for children under 2 years of age and 78% for those between 2 and 15 years. These results do not differ substantially from those reported by the European Liver Transplant Registry.

Adolescent↗
PubMed1995

Recombinant interferon-alfa therapy in children with chronic hepatitis C.

The efficacy of recombinant interferon-alfa therapy in children with chronic hepatitis C has been evaluated in a randomized, controlled pilot study including 27 patients, aged 2 to 14 years, without underlying systemic diseases. On entry, all patients had abnormal alanine transaminase (ALT) levels, 22 were hepatitis C virus (HCV) RNA positive, 19 had mild chronic active hepatitis, and 8 had chronic persistent hepatitis on liver biopsy. Fourteen children received 5 MU/m2 of recombinant interferon-alfa2b thrice weekly for 4 months. If at this time ALT had been reduced to at least 50% the baseline level, treatment was continued up to 12 months. The other 13 children remained untreated. The whole follow-up period lasted 24 months. Interferon was stopped at 4 months in 4 children because of an ALT increase (2 cases), unchanged ALT and febrile convulsions (1 case), and slight ALT decrease (1 case). This latter patient, however, had normal ALT at 6 months and throughout further follow-up, and cleared HCV RNA, thus behaving as a sustained responder. All 10 children treated for 12 months had normal levels of ALT, and 9 were HCV RNA negative at the end of treatment. Of the 9 children who could be followed to 24 months, 4 relapsed soon after therapy withdrawal and 5 maintained a sustained biochemical and virologic response. Overall, 6 (43%) of 14 treated children had a sustained ALT normalization associated with HCV RNA clearance as compared with only 1 (7.5%) untreated child who had a sustained ALT normalization but did not clear HCV RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Patterns of antibodies to hepatitis C virus and hepatitis C virus replication in children with chronic non-A, non-B hepatitis.

Antibodies to hepatitis C virus (HCV), investigated by second- and third-generation assays, were detected in 74% of 43 children with chronic non-A, non-B hepatitis. The polymerase chain reaction identified HCV ribonucleic acid in 26 (93%) of 28 seropositive and in 1 of 10 seronegative cases. Intermittent HCV ribonucleic acid positivity, suggesting low and fluctuating viremia, was frequent in younger patients.

Adolescent↗