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Biomedical subjects

C Crivellaro

Publications and source records attributed to C Crivellaro.

At least 19 recordsLinked to original sources

Integrated PET/CT as a first-line re-staging modality in patients with suspected recurrence of ovarian cancer.

PURPOSE: The aims of this study were to compare CT with PET/CT results in patients with suspected ovarian cancer recurrence and to assess the impact of the PET/CT findings on their clinical management. METHODS: Thirty-two consecutive patients with suspected ovarian cancer recurrence were retrospectively included in the study. Abdominal contrast-enhanced CT and PET/CT with [(18)F]FDG, in addition to conventional follow-up, were performed in all 32 patients. After the comparison between CT and PET/CT results, based on clinical reports, changes in the clinical management of patients (intermodality changes) due to PET/CT information were analysed. RESULTS: Twenty of the 32 patients were positive at CT (62.5%) versus 29 (90.6%) at PET/CT. Intermodality changes in management, i.e. use of a different treatment modality, after PET/CT examination were indicated in 14/32 (44%) patients. In particular, before PET/CT study, the planned management was as follows: wait-and-see in 7/32 (22%), further instrumental examinations in 4/32 (12%), chemotherapy in 10/32 (31%), diagnostic surgical treatment in 6/32 (19%) and surgical treatment in the remaining 5/32 (16%). After PET/CT study, wait-and-see was indicated in 1/32 (3%), further instrumental examinations in 7/32 (22%), chemotherapy in 16/32 (50%), diagnostic surgical treatment in 2/32 (6%) and surgical treatment in the remaining 6/32 (19%). CONCLUSION: Integrated PET/CT could detect tumour relapse in a higher percentage of patients than could CT. A change in the clinical management was observed in 44% of cases when PET/CT information was added to conventional follow-up findings.

Adult↗

Spontaneous regression of hepatitis B virus-associated cirrhosis developed in childhood.

We reported two cases of hepatitis B virus infection-related cirrhosis developed during childhood and followed up for more than 20 years. Both the subjects remained untreated, and ultimately regression of cirrhosis was documented by clinical (including ultrasound) and histological examination. Recent studies have already suggested that hepatitis B virus-related cirrhosis may regress after treatment, but this is the first demonstration that hepatitis B virus-associated cirrhosis developed in childhood may be a spontaneously reversible process. Subsidence of virus replication and of necro-inflammatory process and the efficiency of liver regeneration and repair might contribute to this favourable outcome.

Age Factors↗

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↗

[Graves' disease. Clinical features and treatment results].

In the last years the diagnosis of Grave's disease has become easier and accelerated due to new laboratory and instrumental tests. The therapeutic possibilities improved also by using antithyroidal drugs, surgery and radioiodine application subsequently. In a retrospective study 278 outpatients with Graves disease, treated and controlled by our centre for thyroid diseases in 1992-1999, were investigated to evaluate the initial and leading subjective symptoms which led the patients to seek medical help ("guide symptoms"). These obtained guide symptoms were compared with the objective "clinical signs" observed at the beginning of the disease. Weight loss turned out to be the most frequent (26%) guide symptom, whereas tachycardia (> 90 beats/min) and moist skin were the most frequently observed clinical signs (71 and 61% respectively). The beginning of therapy, dosage of drugs, length of application and results of treatment are critically evaluated, with special emphasis on the rate and time of remission, on the frequency of recurrences and on the success of additional treatments such as surgery and/or radioiodine application. Pharmacological treatment alone induced a persistent remission (at least 6 months of euthyroidism) in 156 patients (in 113 after the first and in 43 after the 2nd drug trial). Surgery was successful in 46, radioiodine application in 40 patients. The sequential use of drug therapy, surgery and radioiodine as it is performed in our institution leads to a permanent remission in 242 of 278 (= 87%) patients.

Antithyroid Agents↗

Long term effect of alpha interferon in children with chronic hepatitis B.

BACKGROUND/AIMS: The purpose of this study was to better define the long term prognosis of infection and disease in children with chronic hepatitis B treated with interferon (IFN) alpha. PATIENTS: A total of 107 children with chronic hepatitis B who received IFN alpha for three or six months in two clinical trials were followed for a mean period of 69 (17) months. Response to treatment was defined as loss of hepatitis B e antigen (HBeAg) within 12 months after stopping treatment. A control group of 59 patients was also followed for a shorter mean time (46 (19) months). RESULTS: Sixteen (15%) treated children responded during therapy and 18 (17%) during post-treatment follow up; 31 (29%) non-responders lost HBeAg during subsequent years. High pretreatment levels of transaminases and a greater histological activity index were predictors of response. Kaplan-Meier estimates of cumulative HBeAg clearance rates at five years were similar between treated patients (60%) and controls (65%). After HBeAg clearance, all cases lost hepatitis B virus DNA and 94% had normal transaminase levels. Loss of hepatitis B surface antigen (HBsAg) occurred in four (25%) patients who responded during treatment but in none of the other treated or untreated patients. CONCLUSIONS: After five years' observation, the proportion of treated children with sustained HBeAg clearance comprised an equal number of responders and non-responders and did not differ from that observed in untreated controls, suggesting that IFN simply accelerated a spontaneous event. However, IFN significantly improved the rate of HBsAg loss in cases with more prominent disease activity who were early responders, and may be particularly useful in this type of patient.

Adolescent↗

Serum levels of hepatitis C virus RNA in infants and children with chronic hepatitis C.

BACKGROUND: The role of serum hepatitis C virus (HCV) load in infectivity, disease activity, and response to interferon treatment has been investigated in adults, and controversial results have been obtained. Little is known about HCV load in infants and children with HCV infection. PURPOSE: To investigate the relation between HCV load in serum and features of associated liver disease in infants and children with HCV infection. METHODS: Hepatitis C viral load was investigated in serial samples in 43 children with chronic HCV infection, including 32 patients aged 4 to 16 years infected by different routes and 11 vertically infected infants observed prospectively since birth. RESULTS: Overall viremia ranged between 2.7 and 6.9 log copies/ml (median, 5.56 log/ml) and fluctuated slightly during the follow-up. Median HCV RNA levels did not significantly differ among infants, children, and adolescents. Viral load was also independent of sex, route of infection, clinical manifestation, alanine aminotransferase levels, and liver histology. All 11 perinatally infected children became chronic HCV carriers, whatever their initial viral load; retrospective testing of sera taken in the first day of life in three infants showed high viremia levels. CONCLUSIONS: Viremia levels observed in children were similar to those reported in adults, were independent of age, biochemical activity of liver disease, and chronicity of infection. They were also relatively stable, suggesting that serial measurement of viral load is useless in untreated infants and children. The detection of viremia at birth in children in whom chronic hepatitis developed later suggests the possibility of in utero infection.

Adolescent↗

Changing epidemiologic pattern of chronic hepatitis C virus infection in Italian children.

OBJECTIVE: To evaluate the epidemiologic features of chronic hepatitis C virus (HCV) infection in children. STUDY DESIGN: All 106 children with chronic HCV infection consecutively observed in 3 Italian pediatric centers between 1991 and 1997 entered the study. RESULTS: Fifteen children had a history of non-A, non-B hepatitis, and 5 complained of nonspecific symptoms. The 86 remaining patients were free of symptoms and were recruited after HCV screening for intercurrent diseases, maternal infection, or other putative exposure; 39% (none of 30 children born after 1990) had received transfusions, whereas 44%, had a mother with HCV infection. Of the 47 infected mothers, 36% were or had been intravenous drug users, 15% had received transfusions, and 45% had no history of exposure. CONCLUSIONS: Children with chronic HCV infection are often free of symptoms, and thus HCV screening for putative risk has greatly increased the chances of diagnosis. Vertical transmission seems to now be the most common route of infection. Both current and past maternal intravenous drug abuse are risk factors for pediatric infection; however, in an area with relatively high prevalence of anti-HCV in the general population such as Italy, a consistent proportion of infectious mothers have no risk factors of HCV exposure.

Adolescent↗

Outcome of chronic hepatitis B in Caucasian children during a 20-year observation period.

BACKGROUND/AIMS: Chronic hepatitis B virus infection can lead to cirrhosis and hepatocellular carcinoma, particularly in men over 40 years of age and in areas where childhood-onset infection is common. The sequence of events from paediatric infection to severe disease in adults is only partially known. The aim of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood during 20 years of follow-up. PATIENTS: One hundred and eighty-five consecutive, otherwise healthy, Caucasian children were enrolled in Padua (Italy) and in Madrid (Spain) between 1975 and 1985, and followed for an average period of 13 years; 168 were hepatitis B e antigen (HBeAg) positive and five had cirrhosis. RESULTS: Thirty patients received steroids or levamisole and 21 interferon, but treatment did not significantly influence HBeAg clearance. Overall, two (1.1%) children, with initial cirrhosis, developed hepatocellular carcinoma and the other three (1.6%) cirrhotic patients became asymptomatic carriers of infection after anti-HBe seroconversion and biochemical remission; 14 (7.5%) children maintained HBeAg positive hepatitis; 155 (83.8%) became asymptomatic carriers of infection after anti-HBe seroconversion and biochemical remission; six (3.2%) experienced reactivation of liver disease and viral replication after remission and five (2.7%) maintained biochemical features of liver damage after HBeAg clearance. Only 6% cleared hepatitis B surface antigen. CONCLUSIONS: Even considering the bias of treatment, the large majority of Caucasian children with chronic hepatitis B became asymptomatic carriers of infection with normal alanine amino-transferase during the first 20 years of observation. Cirrhosis is an early, rare complication, and a risk factor for hepatocellular carcinoma. A subgroup of patients who experienced reactivation or maintained liver damage after HBeAg clearance seems to be at greater risk for disease progression during adult life.

Adjuvants, Immunologic↗

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↗

Hepatitis C virus infection and related liver disease in children of mothers with antibodies to the virus.

OBJECTIVE: To evaluate the clinical, biochemical, and virologic features associated with hepatitis C virus (HCV) infection acquired early in life from mothers with antibodies to HCV (anti-HCV). STUDY DESIGN: Multicenter prospective-retrospective study in Italian children. PATIENTS: Two groups of children were investigated. Group 1 included 14 infants, born to mothers with anti-HCV but without human immunodeficiency virus infection, who became seropositive for HCV RNA during the first year of life and were thus considered infected. Group 2 included 16 children with chronic hepatitis C, aged 1 1/2 to 14 years, whose mothers were the unique potential source of infection. Both groups were followed for 12 to 48 months. METHODS: Alanine transaminase (ALT), anti-HCV, and HCV RNA were investigated by the polymerase chain reaction on entry to the study and during follow-up. RESULTS: All children in group 1 had anti-HCV throughout follow-up, and all had ALT abnormalities, ranging from 1.5 to 10.5 times the normal value during the first 12 months. During further follow-up, 5 of 10 children had HCV RNA with abnormal ALT values, 3 had a return to normal of the ALT values but continued to have viremia, and 2 eventually had normal ALT values and clearance of HCV RNA. Of the 16 children in group 2, all were free of symptoms and 62% had only slight ALT elevations; 7 who underwent liver biopsy had histologic features of minimal or moderate hepatitis. CONCLUSIONS: HCV infection acquired early in life from mothers with anti-HCV is usually associated with biochemical features of liver damage during the first 12 months of life. Progression to chronicity seems to occur in the majority of cases, although HCV-associated liver disease is likely to be mild throughout infancy and childhood.

Alanine Transaminase↗

Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: a multicenter controlled trial.

The comparative efficacy of prednisolone followed by interferon alfa (IFN-alpha) versus IFN-alpha alone in enhancing the rate of antibody to hepatitis B e antigen (anti-HBe) seroconversion has not been evaluated in a large cohort of white children. To determine this, a multicenter-controlled trial was conducted in 95 hepatitis B virus (HBV)-DNA/hepatitis B e antigen (HBeAg)-positive children (median age, 9 years [range, 2-16 years]; 56 boys; 84 [89 percent] white), all having inflammatory changes on liver biopsy. Patients were randomized to receive either prednisolone followed by IFN-alpha (n = 34); placebo followed by IFN-alpha (n = 30); or no treatment (n = 31). The prednisolone/placebo was given on a double-blind basis. Lymphoblastoid IFN-alpha was given at 5 MU/m(2) three times a week for 12 weeks. Baseline clinical, biochemical, and histological features were similar for the three groups. The majority (85 percent) had a baseline aspartate aminotransferase (AST) level < or = 100 IU/L. On follow-up between 12 and 18 months (median, 15 months) after treatment, the loss of HBeAg with anti-HBe seroconversion was more common in patients pretreated with steroids (12 of 34 [35 percent]) or placebo [12 of 30 (40 percent)] as against controls (4 of 31 [13 percent], P< .05). Factors predictive of anti-HBe seroconversion were baseline HBV-DNA concentration of < or = 1,000 pg/mL and a greater degree of portal tract inflammation on pretrial biopsy. Our results show that in white children treatment with IFN-alpha, at the dose and duration used in this study, improves the rate of anti-HBe seroconversion. Steroid priming does not potentiate the effect of IFN-alpha.

Adolescent↗

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↗

Skewing of the T-cell receptor repertoire in the lung of patients with HIV-1 infection.

OBJECTIVES: A bias of the use of T-cell receptor (TCR) V beta regions has been reported both in peripheral blood and in several tissues in patients with AIDS, including lymph nodes, spleen and salivary glands. Although the disease is frequently characterized by an infiltration of T cells in the lung interstitium, no information is presently available on the configuration of the TCR repertoire in this microenvironment. This study was performed to address the question of whether a bias in T-cell selection occurs in the lung of patients with AIDS. METHODS: TCR beta-chain variable region (TCR-V beta) repertoire was analysed by flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung lymphocytes of 13 patients with HIV-1 infection at different stages of the disease. Blood and lung lymphocytes were also assessed for their responsiveness to different superantigenic stimuli represented by staphylococcal enterotoxins (SEA, SEB, SEC1, SEC2, SED and SEE). RESULTS: Flow cytometry analysis in AIDS patients demonstrated an overexpression of cells bearing V beta 2 and V beta 3 gene segments in the lung compared with peripheral blood of the same subjects, as well as to lung and blood lymphocytes of normal controls. PCR analysis performed in AIDS patients extended these observations and demonstrated a significant bias also in the use of T cells bearing V beta 7 and V beta 9 gene regions in the lung compartment with respect to the blood. Virtually all T cells bearing the overrepresented V beta segment belong to the CD8 subset. Interestingly, T-lymphocyte response to different superantigens demonstrated a low proliferative rate in the lung with respect to the blood in HIV-1-infected patients. CONCLUSIONS: These findings indicate a compartmentalization of cells bearing discrete V beta gene products in the pulmonary microenvironment of patients with AIDS and suggest that the expansion of specific-V beta region subsets occurring in the lung might result from triggering by a superantigen.

Adult↗

Long-term persistence of hepatitis B virus DNA in the serum of children with chronic hepatitis B after hepatitis B e antigen to antibody seroconversion.

To evaluate the prevalence and duration of viremia in relation to the features of liver disease, we investigated hepatitis B virus (HBV) DNA by the polymerase chain reaction in the serum of 39 children with chronic hepatitis B, after hepatitis B e antigen to antibody seroconversion. During a mean observation period of 8.2 +/- 3.8 years after seroconversion, all patients were asymptomatic; 36 had persistently normal alanine aminotransferase levels, and three had occasional mild alterations. Liver histology, checked in 21 patients, showed persistent hepatitis in nine, fibrosis in 10, and cirrhosis in two cases. HBV DNA was always undetectable by dot blot hybridization. Five children eventually cleared hepatitis B surface antigen, including one with cirrhosis who developed liver cancer at 19 years. HBV DNA was detected by polymerase chain reaction in 87% of children within 5 years of follow-up, in 58% of cases 6-10 years after seroconversion (p < 0.001), and in 50% of patients investigated later. Long-term viremia was found in two patients (40%) who cleared HBsAg, including the one who developed liver cancer. The chances of clearing viremia during follow-up were higher in children with acute hepatitis at the onset of illness (86%) than in those with asymptomatic onset (37%; p < 0.05). Our results show that low levels of HBV viremia, probably reflecting low levels of virus replication, persist for several years in children with chronic hepatitis B after hepatitis B e antigen to antibody seroconversion and remission of liver disease, even after the clearance of hepatitis B surface antigen. Persistent replication could support mild biochemical alterations and inflammatory liver lesions. It could allow late reactivation of liver disease and may play a role in the development of carcinoma.

Alanine Transaminase↗

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↗

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↗

HIV-1 infection of the thymus: evidence for a cytopathic and thymotropic viral variant in vivo.

As thymocyte infection may represent one of the mechanisms responsible for CD4+ T lymphocyte depletion in HIV-1-infected individuals, we studied the occurrence of HIV-1 infection in the thymus in vivo. Thymus (THYPD) and peripheral blood (PBLPD) primary viral isolates were obtained from an HIV-1-infected patient; restriction pattern analysis revealed the presence of a viral variant (THY) in the thymus isolate, from which biological viral clones containing this variant were obtained by limiting dilution infection of Molt-3 cells. The biological phenotype of the viral isolates and THY clones was studied in different cell lines and primary cultures. PBLPD, THYPD, and THY clones could efficiently infect T cell lines; the thymic variant showed a higher cytopathic activity in T cell lines, and a higher replication capacity in both unfractionated and CD4+CD8(+)-enriched primary thymocytes. Sequence analysis of the viral population patterns in vivo confirmed the presence of the THY variant in the thymic compartment, and revealed that the degree of V3 loop heterogeneity was higher in the thymocytes of the patient than in the peripheral blood lymphocytes. In addition to confirming thymocyte infection in vivo, our data also indicate that a differential distribution of viral variants may occur among different body compartments in a single individual; the emergence of cytopathic and tissue-specific variants in the thymus may play a relevant role in the pathogenesis of HIV-1 disease.

Acquired Immunodeficiency Syndrome↗