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Biomedical subjects

R Giacchino

Publications and source records attributed to R Giacchino.

At least 19 recordsLinked to original sources
PubMed2005

Interferon treatment in children with chronic hepatitis C: long-lasting remission in responders, and risk for disease progression in non-responders.

BACKGROUND AND AIM: Large interferon-based therapeutic trials are still lacking in children with hepatitis C and the long-term safety and efficacy of interferon is unknown. This study describes the outcome of hepatitis C in 43 children enrolled in an open-label interferon trial, and were followed up to 66 months after stopping treatment. PATIENTS AND METHODS: All patients received interferon alfa2a (5MU/m(2)) thrice weekly for 6 months; children with genotype 1b received 3MU/m(2) thrice weekly for 6 additional months. RESULTS: Nine children discontinued interferon for adverse events and three were not compliant to treatment. Eight (19%, intention to treat analysis), including 2/20 (10%) with genotype 1b and 6/12 (50%) with genotypes 2 or 3, were sustained responders 12 months after stopping therapy. During further follow-up (mean+/-S.D.: 44.7+/-14.6 months), response was maintained; two non-responders cleared viremia, while a young boy progressed to cirrhosis. CONCLUSIONS: Small sample size and therapy withdrawal are the major limitations in the interpretation of our results. Nevertheless, our data, suggesting that response to interferon in children with hepatitis C is genotype-related and stable, agree with the results of large studies in adults. The outcome in non-responders was variable, including persistence of viremia and mild-moderate cytolysis (most cases), progression to cirrhosis, or eventual sustained viremia clearance.

Adolescent↗
PubMed2005

Hepatitis C virus (HCV) genotypes in 373 Italian children with HCV infection: changing distribution and correlation with clinical features and outcome.

BACKGROUND AND AIMS: Little is known of hepatitis C virus (HCV) genotypes in HCV infected children. This retrospective, multicentre study investigated genotype distribution and correlation with clinical features and outcome in a large series of Italian children. METHODS: Between 1990 and 2002, 373 HCV RNA positive children, consecutively recruited in 15 centres, were assayed for genotypes by a commercial line probe assay. RESULTS: The following genotype distribution pattern was recorded: genotype 1b = 41%; 1a = 20%; 2 = 17%; 3 = 14.5%; 4 = 5%; other = 2.5%. The prevalence of genotypes 1b and 2 decreased significantly (p<0.001) among children born from 1990 onwards compared with older children (46% v 70%) while the rate of genotypes 3 and 4 increased significantly (from 8% to 30%). Children infected with genotype 3 had the highest alanine aminotransferase levels and the highest rate of spontaneous viraemia clearance within the first three years of life (32% v 3% in children with genotype 1; p<0.001). Of 96 children enrolled in interferon trials during the survey, 22% definitely lost HCV RNA, including 57% of those with genotypes 2 and 3. CONCLUSION: HCV genotypes 1 and 2 are still prevalent among infected adolescents and young adults in Italy but rates of infection with genotypes 3 and 4 are rapidly increasing among children. These changes could modify the clinical pattern of hepatitis C in forthcoming years as children infected with genotype 3 have the best chance of spontaneous viraemia clearance early in life, and respond to interferon in a high proportion of cases.

Adolescent↗
PubMed2005

Varicella and its complications as cause of hospitalization.

Varicella is an acute contagious disease that most commonly occurs in childhood. Although normally benign, varicella can occasionally develop into a more serious illness. Moreover, the infection can lead to serious complications, such as Staphylococcus aureus infections, otitis media, endocarditis, pneumonia, and rare central nervous system (CNS) events like cerebellar ataxia and encephalitis. This study was conducted to analyze the hospitalization rate due to varicella or its complications in a tertiary care hospital in Italy, where varicella vaccination has not yet been implemented. The review was carried out on cases of children with varicella identified by ICD9 and ICD9-CM diagnostic codes and admitted to the Giannina Gaslini Children's Research Hospital of Genoa, Italy, from January 1st, 1995 to December 31st, 2004. For each case reporting complications, the clinical report form was extracted and the events recorded. Varicella was recorded in 346 (0,16%) out of 212,647 total hospital discharges. Chickenpox with detailed complications and cerebrovascular diseases accounted for 56 discharges (12.14%), for a total of 728 days. Fifteen patients needed more than one hospitalization because of severe sequelae as result of CNS involvement. We reported three particular cases of invasive infections and four children affected with cerebrovascular diseases following varicella. Our retrospective data regarding a single tertiary care pediatric hospital shows that hospitalization due to varicella or its sequelae may present an important medical and indirect economic problem.

Cerebellar Ataxia↗
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↗
PubMed2001

Bacillus sphaericus bacteraemia in children with cancer: case reports and literature review.

In the period 1989-1999, Bacillus sphaericus was demonstrated to cause 12 out of 469 (2%) episodes of bacteraemia in children with cancer or receiving bone marrow transplant at G. Gaslini Children's Hospital, Genoa, Italy. Neutropenia was present in five episodes, six episodes, (all without neutropenia) were related to the presence of a central venous catheter, and one episode occurred in a patient with intestinal graft vs. host disease and gut colonization. All patients survived. Ciprofloxacin was the only drug active against all the isolated strains.Bacillus sphaericus represents a new cause of infection in the immunocompromised host, with low aggressiveness, but a peculiar pattern of antibiotic susceptibility.

Bacillaceae Infections↗
PubMed2001

An epidemiological survey of hepatitis C virus infection in Italian children in the decade 1990-1999.

BACKGROUND: A retrospective-prospective survey of Italian children with hepatitis C virus (HCV) infection was planned in 1998 to explore the epidemiologic features of infection during the past decade. METHODS: Anti-HCV-positive patients (or HCV RNA-positive infants) aged 1 month to 16 years, consecutively observed in 20 pediatric Institutions, were considered. An anonymous epidemiologic questionnaire based on clinical records was used. RESULTS: From 1990 through March 1999, 606 patients were observed (296 boys, average age 5.8 years). Maternal infection (46% of cases) and blood transfusions (34%) were the most frequent risk factors. Of 279 infected mothers, 61% did not recall a putative source of infection (by history, many could possibly have had exposure through routes such as therapeutic injections with nondisposable material), whereas 94 (34%) admitted drug abuse, including 49 (17%) coinfected with human immunodeficiency virus (HIV). Only 157 (26%) children were born after 1991: 90% of their mothers were infected (11% were HIV coinfected vs. 25% mothers of older children, P < 0.01). CONCLUSIONS: Maternal infection is a prominent source of pediatric HCV infection in Italy. The fact that most mothers had a history of covert exposure to HCV, probably through percutaneous routes that are no longer operating, and that the number of those with HIV coinfection has decreased suggests that the frequency of pediatric infection could decrease in the future.

Adolescent↗
PubMed2001

Hepatitis A vaccine in pediatric patients affected by metabolic liver diseases.

Twenty children with a variety of metabolic liver diseases were given two doses of hepatitis A vaccine. Adverse reactions were mild. All subjects responded to vaccine with seroconversion to hepatitis A virus antibodies after the first dose, regardless of transaminase values, and had a booster effect from the second doses.

Adolescent↗
PubMed2000

Clinical and laboratory features predicting a favorable outcome and allowing early discharge in cancer patients with low-risk febrile neutropenia: a literature review.

To value feasibility of early discharge in febrile granulocytopenic patients, 27 original paper published in the last 11 years were analyzed concerning these clinical and therapeutic approaches. A Medline search of English language literature published in the last 11 years (1988-1999) used the key words neutropenia, fever, cancer, home-antibiotic therapy, short course of antibiotic therapy, and early discharge. Twenty-seven original papers fulfilling the study criteria were identified. In these studies, 5208 episodes were evaluated: there were 538 failures with 87 deaths. Features of low-risk patients who developed life-threatening infectious disease were related to general clinical condition, cancer control, bone marrow function, presence of clinical signs of infection, and social features. Careful risk assessment can allow safe recognition of low-risk patients with febrile neutropenia who can be discharged early and can be used to follow outpatient treatment programs to improve patients' quality of life as well as the use of economic resources.

Adult↗
PubMed2000

Transmission of hepatitis C virus from infected mother to offspring during subsequent pregnancies.

BACKGROUND: Several studies have demonstrated that hepatitis C virus (HCV) may be transmitted from mother to offspring. To date, however, little is known about the risk of vertical transmission during subsequent pregnancies. The purpose of this study was to evaluate the risk of vertical HCV transmission in offspring in subsequent pregnancies of HCV infected women. METHODS: In a multicenter study, two groups of index cases were selected. Group 1 included 75 children investigated for HCV infection during prospective studies of vertical transmission. Group 2 included children born to HCV-infected mothers and found to be HCV infected, independent of studies on vertical transmission. All children in the index cases had one or more siblings. Anti-HCV, HCV-RNA (determined by polymerase chain reaction), and HCV genotype were evaluated in all the infected children, their mothers, and siblings. RESULTS: The results indicate that a mother who has already delivered an HCV-infected baby is not at greater risk of infecting her second child. Duration of maternal infection does not seem to be a risk factor in offspring infection, because HCV infection is equally distributed among first-born infants and infants of subsequent births. Because clustering of HCV infection among siblings appeared to be rare in this study, data also indirectly confirm that the risk of horizontal transmission of HCV among siblings is low. CONCLUSION: For practical purposes, the current observations indicate that mothers who have already delivered an HCV-infected child can be advised that this event does not increase the probability of infecting the second child.

Female↗
PubMed1999

SH2D1A mutation analysis for diagnosis of XLP in typical and atypical patients.

X-linked lymphoproliferative disease (XLP) is a rare inherited immunodeficiency to Epstein-Barr virus (EBV). The gene responsible for XLP has recently been identified as the four-exon SH2D1A gene encoding a 128-amino-acid protein that contains an SH2-domain. Functional studies indicate the SH2D1A protein acts as a regulator of at least two signal transduction pathways initiated by the cell surface molecules SLAM and 2B4, respectively, and possibly related to the host immune response to EBV infection. We have carried out a systematic mutation study of the SH2D1A gene in our series of 19 typical and 8 atypical XLP patients by polymerase chain reaction (PCR), reverse transcription/PCR, and sequencing, and have reconstructed the haplotypes of the patients. Four out of the 13 mutations detected are previously unreported. The identification of SH2D1A mutations in carriers from all three XLP families screened and the detection of mutations in two out of eight atypical patients indicates the usefulness of a DNA-based diagnosis for XLP disease.

Carrier Proteins↗
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↗
PubMed1999

Bloodstream infections can develop late (after day 100) and/or in the absence of neutropenia in children receiving allogeneic bone marrow transplantation.

We retrospectively evaluated the incidence and time from transplantation of bloodstream infections occurring in children receiving bone marrow transplant (BMT) at G Gaslini Children's Hospital between September 1984 and December 1997. During this period the incidence was 35% after allogeneic and 26% after autologous BMT (P=0.08). Among these episodes, 38% after allogeneic BMT and 90% after autologous BMT were detected in the presence of neutropenia within the first 30 days from reinfusion (P < 0.001). Incidence of catheter-related bloodstream infections was 40% after allogeneic and 8% after autologous BMT (P < 0.001). Bloodstream infections in the absence of neutropenia were 55% after allogeneic BMT vs 10% after autologous BMT (P < 0.001) and occurred later after reinfusion (mean 199 vs 41 days, P <0.001). Among the episodes occurring after allogeneic BMT and in the absence of neutropenia, 61% were related to the presence of a central venous catheter, 15% were related to the presence of GVHD, but 23% were not associated with any of major risk factors for infection. Finally, 38% of episodes following allogeneic BMT were detected after day 100 vs 1% after autologous BMT. We concluded that patients receiving allogeneic BMT experience a high incidence of bloodstream infections in the absence of neutropenia and that a significant proportion of these episodes is not clearly associated with well known risk factors such as GVHD or central venous catheters. Moreover, many episodes develop a long time after the transplantation procedure. Therefore, any febrile episode following allogeneic BMT even late and/or in the absence of neutropenia should be intensively managed.

Bone Marrow Transplantation↗
PubMed1999

Pharmacokinetic variability and strategy for therapeutic drug monitoring of saquinavir (SQV) in HIV-1 infected individuals.

AIMS: To investigate the pharmacokinetic profile of the protease inhibitor saquinavir (SQV) after multiple doses in HIV-positive patients and to evaluate the possibility of predicting total body exposure of SQV from concentrations determined at single time points. METHODS: Twenty HIV-positive patients on steady-state treatment with SQV (Hard-Gel-Capsule, Invirase(R)) were enrolled in this study. Serial blood samples were obtained during a dosing interval. SQV plasma concentrations were determined by high performance liquid chromatography (h.p.l.c.) and pharmacokinetic parameters were determined by noncompartmental techniques. RESULTS: There was a marked interindividual variability in SQV pharmacokinetic parameters with a 11-fold variability in total systemic exposure to SQV, as expressed by AUC(0,8h) values (range: 268-3009 ng ml-1 h, CV: 69%). The oral clearance shows an interindividual CV of 75%. A strong correlation (r=0.94) was found between SQV plasma concentration at 3 h (C3 h ) and AUC(0,8h). CONCLUSIONS: This study shows that C3 h is a good predictor for total body exposure of SQV and might be useful to predict SQV disposition in HIV-positive patients on steady-state treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Strategies for cost-containment: once-daily ceftriaxone plus amikacin as empiric therapy for febrile granulocytopenic children with cancer.

Administration of broad-spectrum antibiotics as empiric therapy to febrile granulocytopenic patients has become a widely accepted practice. In order to evaluate the cost-effectiveness of ceftriaxone plus amikacin in single daily doses as empiric treatment for febrile granulocytopenic children with cancer, a retrospective review (January-December 1996) of all febrile episodes at our institution was carried out. Overall, 101 febrile episodes in 89 granulocytopenic children with cancer were empirically treated with a once-daily ceftriaxone plus amikacin combination. 59/101 (59%) patients had absolute granulocyte count lower than 100/mm3 at entry; 46 (45%) were affected by solid tumors, 16 (15%) by Hodgkin's disease or lymphoma, and 30 (30%) patients underwent bone marrow transplantation. The ceftriaxone plus amikacin combination was effective in 72/101 (72%) patients with a median time to defervescence of 3 days (range, 1-4). We also evaluated the economic advantages of the ceftriaxone plus amikacin once-daily regimen when compared with another treatment regimen such as ceftazidime plus amikacin requiring three daily doses. Compared with the multiple daily dose regimen of ceftazidime plus amikacin, there is a cost saving of US $11 (17,500 Italian liras) and US $66 (105,000 Italian liras) for both 1-day and 6-day treatments, respectively, by using the single daily dose regimen of ceftriaxone plus amikacin. The potential of ceftriaxone to lower costs in hospitalized patients depends upon its comparable efficacy with other extended-spectrum beta-lactams, in which case it can reduce overall treatment costs because of its once-daily administration schedule.

Adolescent↗
PubMed1999

Mutation analysis in patients of Mediterranean descent with Wilson disease: identification of 19 novel mutations.

In this study, we report further results of mutation analysis of the ATP7B gene in Wilson disease (WD) patients of Mediterranean origin. A total of 136 WD chromosomes, 73 of which were of Italian, 43 of Turkish, 18 of Sardinian, and two of Spanish origin, were analysed and the mutation characterised in 84.5% of them. We found 50 different mutations of which 19 are novel, including three nonsense, one frameshift, and 15 missense mutations. The mutations detected were rare and mostly found in the compound heterozygous state together with other mutations and only rarely in homozygosity. Most of these mutations lie in the transmembrane and ATP binding loop regions. These data expand our knowledge of both the structure-function relationships of the WD protein and the molecular pathology of WD, thus improving our capability of prevention and genetic counselling.

Adenosine Triphosphatases↗