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Biomedical subjects

P A Tovo

Publications and source records attributed to P A Tovo.

At least 19 recordsLinked to original sources
PubMed2003

Successful unrelated cord blood transplantation in two children with severe combined immunodeficiency syndrome.

We describe the successful unrelated cord blood transplantation in two patients affected by a Zap-70 deficiency and an Omenn-like syndrome, respectively. The patients were hospitalised for recurrent infections at the age of 13 and 2 months, respectively. An unrelated cord blood unit was found for each. The conditioning regimen was cyclophosphamide, busulfan and antithymocyte globulin. The total number of infused cells was 15.1 x 10(7)/kg and 17 x 10(7)/kg, respectively. Neutrophil engraftment was achieved on days +15 and +23, and platelet count >50 x 10(9)/l was achieved on days +21 and +52, respectively. One patient presented acute Graft-versus-host disease (GVHD) grade I and the other grade III. Chimerism was mixed and full donor. Normal lymphoproliferative response to mitogens and alloantigens was detectable at 6 months for both. No chronic GVHD was observed in either. The patients are alive and well at 53 and 15 months after transplantation. In conclusion, umbilical cord blood represents a valid alternative source of haemopoietic stem cells.

Antilymphocyte Serum↗
PubMed2001

Legionella pneumophila pneumonia in a newborn after water birth: a new mode of transmission.

We report a case of Legionella pneumophila pneumonia in a 7-day old neonate. Because the hospital water, and particularly the pool water for water birthing, was contaminated by L. pneumophila serogroup 1, the newborn was infected following prolonged delivery in contaminated water, perhaps by aspiration. This is the first case of nosocomial Legionella pneumonia in neonate after water birth.

Delivery, Obstetric↗
PubMed2001

Puberty in perinatal HIV-1 infection: a multicentre longitudinal study of 212 children.

OBJECTIVE: To define age at entry into Tanner stages in children with perinatal HIV-1 infection. DESIGN: Multicentre longitudinal study including 212 perinatally HIV-1-infected children (107 girls and 105 boys) followed-up during puberty (from 8 and 9 years onwards in girls and boys, respectively). Healthy children (843 girls and 821 boys) provided reference percentiles. P2 or B2 stages in girls and P2 or G2 stages in boys defined onset of puberty. METHODS: The cumulative probability [95% confidence limit (CI)] of entry into each stage at different ages was estimated by the Kaplan-Meier product-limit method; differences were evaluated by log rank test. Relationships were tested using the Spearman's rank correlation coefficient. RESULTS: Ages of girls [years (95%CI)] at P2 [12.9 (12.6-13.2)], P3 [13.4 (13.0-13.8)], P4 [14.6 (14.0-15.2)], B2 [12.7 (12.2-13.2)], B3 [13.3 (12.8-14.0)] and B4 [14.6 (14.0-15.2)] stages were > 97th percentile (> or = 21 month delay) of controls. Ages of boys [years (95%CI)] at P2 [12.6 (12.1-13.1)], P3 [13.9 (13.4-14.4)], P4 [14.9 (14.2-15.6)], G2 [12.1 (11.5-12.7)], G3 [13.6 (13.1-14.1)] and G4 [14.9 (14.1-15.7)] stages were at the 75-97th percentiles (< or = 15 month delay). Age at onset of puberty was not related to clinical and immunological condition, antiretroviral treatment, weigh for height and age at onset of severe disease or immune suppression. CONCLUSION: Perinatal HIV-1 infection interferes with sexual maturation. The mechanisms by which this occurs should be elucidated and intervention strategies designed. Intervention could save much psychological distress, since associated linear growth failure can exacerbate adolescents' feelings of being different and unwell.

Adolescent↗
PubMed2001

Proteasomes are a target of the anti-tumour drug vinblastine.

Proteasomes, the proteolytic machinery of the ubiquitin/ATP-dependent pathway, have a relevant role in many processes crucial for cell physiology and cell cycle progression. Proteasome inhibitors are used to block cell cycle progression and to induce apoptosis in certain cell lines. Here we examine whether proteasomal function is affected by the anti-tumour drug vinblastine, whose cytostatic action relies mainly on the disruption of mitotic spindle dynamics. The effects of vinblastine on the peptidase activities of human 20 S and 26 S proteasomes and on the proteolytic activity of 26 S proteasome were assessed in the presence of specific fluorogenic peptides and (125)I-lysozyme-ubiquitin conjugates respectively. The assays of ubiquitin-protein conjugates and of inhibitory kappa B alpha (I kappa B alpha), which are characteristic intracellular proteasome substrates, by Western blotting on lysates from HL60 cells incubated with or without vinblastine, illustrated the effects of vinblastine on proteasomes in vivo. We also evaluated the effects of vinblastine on the signal-induced degradation of I kappa B alpha. Vinblastine at 3--110 microM reversibly inhibited the chymotrypsin-like activity of the 20 S proteasome and the trypsin-like and peptidyl-glutamyl-peptide hydrolysing activities of both proteasomes, but only at 110 microM vinblastine was the chymotrypsin-like activity of the 26 S proteasome inhibited; furthermore, at 25--200 microM the drug inhibited the degradation of ubiquitinated lysozyme. In HL60 cells exposed for 6 h to 0.5--10 microM vinblastine, the drug-dose-related accumulation of polyubiquitinated proteins, as well as that of a high-molecular-mass form of I kappa B alpha, occurred. Moreover, vinblastine impaired the signal-induced degradation of I kappa B alpha. Cell viability throughout the test was approx. 95%. Proteasomes can be considered to be a new and additional vinblastine target.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Nosocomial infections in pediatric cardiac surgery, Italy.

OBJECTIVE: To evaluate the incidence of nosocomial infection (NI) in pediatric patients who received cardiothoracic surgery and to identify possible associated risk factors. DESIGN: Prospective observational study. SETTING: The cardiac surgery and cardiac intensive care units at the Regina Margherita Children's Hospital, Turin, Italy. PATIENTS: All patients who underwent surgery from July 20, 1998, to July 19, 1999, were enrolled, except patients with operative catheterization only. METHODS: Clinical data were collected daily from July 20, 1998, to July 19, 1999. NIs were diagnosed according to US Centers for Disease Control and Prevention criteria. RESULTS: 104 patients were included in the present study, 80 (76.9%) of whom underwent extracorporeal circulation. The NI ratio was 48.1% (50/104); the percentage of patients with NI was 30.8% (32/104): 23.1% developed one infection, 7.7% two or more. The rate of NI was 2.17 per 100 days of hospitalization (50/2,304). The most common pathogen was Pseudomonas aeruginosa. Important risk factors were length of preoperative admission >5 days, total length of admission >10 days, open chest during postoperative phase, and cyanotic heart disease. There was a significant association between sepsis and central venous catheterization for 3 days or more. Rate of sepsis was 19 per 1,000 catheter days (16/852). CONCLUSION: NIs represent a frequent complication for children who undergo heart surgery. Based on our data, we suggest decreasing the preoperative stay as much as possible. The higher NI incidence in patients with an open chest postoperatively suggests that an alternative antibiotic strategy should be considered for these patients.

Adolescent↗
PubMed2000

Human immunodeficiency virus-related cancer in children: incidence and treatment outcome--report of the Italian Register.

PURPOSE: To outline the incidence, presenting features, treatment response, and outcome of human immunodeficiency virus (HIV)-associated malignancies in infancy and childhood, together with the estimated risk of HIV-associated cancer in children born to mothers infected with HIV. PATIENTS AND METHODS: The Italian Register for HIV Infection in Children collected data by specific registration and follow-up forms. By March 1999, 5,060 children were recruited, including 4,889 with perinatal exposure to HIV-1. Overall, 1,331 infected children were enrolled onto the Register and classified according to current Centers for Disease Control criteria; of them, 1,163 were vertically infected (24% of those with perinatal exposure). Of these 1,163, 569 (49%) were considered to have been prospectively followed-up since they had been registered at birth or within the first 3 months of age. RESULTS: Of the 1,331 children observed for a median time of 6.5 years, 35 developed 36 malignancies, four of which occurred in patients with blood-borne risk. For the 1,163 vertically infected children, the cumulative number of years of observation was 7,178 child-years and the cumulative incidence of HIV-associated tumors was 4.18 per 1,000 children/yr (95% confidence interval [CI], 2.92 to 5.98). When only the 569 vertically infected children prospectively followed up since birth were considered, the cumulative number of years of observation was 2,803 child-years. In this group, 10 tumors were observed, with a cumulative incidence of HIV-associated tumors of 3.57 per 1,000 children per year (95% CI, 1.92 to 6.63). CONCLUSION: The risk of cancer was significantly higher but not restricted to symptomatic and/or immune-compromised children. Cancer-directed treatment should be given promptly to these patients, who have a fair chance to survive their tumor in view of potential highly aggressive antiretroviral therapy-associated improvement in survival and quality of life.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry.

CONTEXT: Since the introduction of combined antiretroviral therapy, mortality rates in adults with human immunodeficiency virus type 1 (HIV-1) infection have decreased. However, little information is available outside the setting of controlled trials on survival of perinatally HIV-infected children treated with antiretroviral therapy. OBJECTIVE: To assess effect of availability of antiretroviral therapy on decreasing mortality in perinatally HIV-infected children. DESIGN: Population-based, multicenter longitudinal study involving data collected by the Italian Register for HIV Infection in Children. SETTING: A network of 106 pediatric clinical centers. SUBJECTS: A total of 1142 children born between November 1980 and December 1997 with perinatally acquired HIV infection with a median follow-up of 5.9 years. MAIN OUTCOME MEASURE: Time to HIV-related death calculated for birth cohort and calendar period and grouped by distribution of predominant type of antiretroviral therapy administered over time. RESULTS: Survival was longer in the 1996-1997 birth cohort (crude relative hazard [RH] of death, 0.39; 95% confidence interval [CI], 0.15-0.96) and 1996-1998 calendar period (crude RH of death, 0.65; 95% CI, 0.45-0.95) than in birth cohort and calendar period 1980-1995, but not when adjusted for maternal antiretroviral treatment during pregnancy and clinical condition at time of delivery, gestational age, and birth weight (adjusted RH of death, 0.55; 95% CI, 0.20-1.50, for birth cohort; and adjusted RH of death, 0.71, 95% CI, 0.43-1.16, for calendar period). In a multivariate model with 1980-1995 as comparison, the 1996-1997 birth cohort had an RH of 0.57 (95% CI, 0.22-1.47; P=.27) but RH for calendar period 1996-1998 was 0.63 (95% CI, 0.47-0.85; P<. 01). When the effects of birth cohort, calendar period, and type of antiretroviral therapy were evaluated simultaneously in the same model, the RH of death was not significantly different from 1.0 for the 1996-1997 birth cohort (P=.19) and calendar period 1996-1998 (P=. 83) suggesting a causal relationship between decreased risk of death and use of combination therapy. The RH of death in children receiving monotherapy or double or triple combination therapy was 0. 77 (95% CI, 0.55-1.08), 0.70 (95% CI, 0.42-1.17), and 0.29 (95% CI, 0.13-0.67), respectively, vs no antiretroviral therapy. CONCLUSION: Survival of perinatally HIV-infected children improved in 1996-1998 as a result of the introduction of combined antiretroviral therapies. JAMA. 2000;284:190-197

Adolescent↗
PubMed2000

Pertussis immunization in HIV-1-infected infants: a model to assess the effects of repeated T cell-dependent antigen administrations on HIV-1 progression. Italian Register for HIV infection in children.

Several data evidence that HIV-1 replication may increase in temporal association with immunizations, raising concerns on potential negative effects of vaccinations on HIV-1 progression. Among patients prospectively followed by the "Italian Register for HIV infection in children", we evaluated, using the Cox-Mantel method, conditional probabilities of progressing to CDC clinical categories 'B' or 'C', and immunological categories '2' or '3' in 88 children immunized against pertussis and 244 non-immunized. No selection criteria were followed in vaccinating children. No significant differences were observed between the two groups. The lack of a significant impact on clinical and immunological deterioration by the repeated administrations of a T cell-dependent vaccine endorses the current recommendations for routine immunizations in HIV-1-infected children.

Antigens, Bacterial↗
PubMed2000

Variable use of therapeutic interventions for children with human immunodeficiency virus type 1 infection in Europe.

UNLABELLED: Although a range of antiretroviral drugs are available for use in children, the appropriate paediatric regimen remains unclear. In a survey to investigate policies and practices relating to the therapeutic management of children infected by the human immunodeficiency virus (HIV), a postal questionnaire was sent to a named paediatrician in 70 major HIV centres in 13 European countries in early 1998. A total of 64 paediatricians (91%) responded. Pneumocystis carinii pneumonia prophylaxis was found to be routine in all centres, although considerable variation existed regarding the time of starting and stopping therapy. Prophylaxis for fungal infections and recurrent bacterial infections was common, with cytomegalovirus prophylaxis being less frequent. Although most centres (89%) used all five currently available nucleoside analogues (ziduvodine, lamivudine, stavudine, didanosine, zalcitabine), there was considerable variability regarding the availability of protease inhibitors. Most respondents delayed initiation of antiretroviral therapy until evidence of disease progression was apparent. The initial prescription of 38% of clinicians was triple therapy and that of 57% prescribed double therapy. Policies varied regarding the modification to regimens in response to disease progression and emergence of side effects and drug resistance. Clinical practice was informed by a number of sources, including centre-specific and national guidelines. Most respondents affirmed the need for European guidelines. CONCLUSION: Approaches to the therapeutic management of paediatric human immunodeficiency virus infection differ across Europe.

Antiviral Agents↗
PubMed2000

Polymorphisms in the MBL2 promoter correlated with risk of HIV-1 vertical transmission and AIDS progression.

We investigated the polymorphisms of the promoter region of the MBL2 gene, which codifies for the Mannose-binding protein (MBP). The study population included 90 children with vertically acquired HIV-infection, further divided on the basis of the disease rate, 27 HIV exposed-uninfected children, and 74 healthy control subjects matched for ethnic origin to evaluate the MBP involvement in the risk of HIV-1 infection and to assess the role of the MBP promoter in AIDS progression. A region of 380 bp in the promoter of the MBL2 gene was analysed by PCR and direct sequencing of both DNA strands. We found that the polymorphism at position -550 influences the risk of HIV-infection and AIDS progression. Also a 6 bp deletion at position -328 was correlated with HIV-1 infection. This study indicates that the promoter of the MBL2 gene influences vertical transmission of HIV and the course of perinatal infection.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Persistence rate and progression of vertically acquired hepatitis C infection. European Paediatric Hepatitis C Virus Infection.

Data were collected from 104 infected children who were followed up from birth for a mean of 49 (range, 6-153) months in 22 European centers, to outline the natural history of perinatal hepatitis C virus (HCV) infection. Fifty-four children were persistently HCV RNA positive, 44 were occasionally positive, and 6 never had detectable viremia. At least 90% of the children had evidence of ongoing infection at the latest analysis. Eighteen children became HCV RNA negative at their last assessments, but 40% of these had high alanine aminotransferase (ALT) concentrations. Infection was asymptomatic in all but 2 children, who developed hepatomegaly. Mean ALT concentrations decreased substantially after the first 2 years of life; 14 children had persistently normal ALT values. Signs of minimal to moderate inflammation were noted in all 20 patients who underwent liver biopsy. Perinatal HCV infection is usually asymptomatic in the first years of life, but the virus persists in most children, even in the absence of elevated ALT activity.

Adult↗
PubMed2000

Predictive value of the HIV paediatric classification system for the long-term course of perinatally infected children.

BACKGROUND: To compare the Centers for Disease Control and Prevention (CDC) paediatric classification system with the long-term course of perinatal human immunodeficiency virus type 1 (HIV-1) infection. METHODS: Prospective study on 366 perinatally infected children followed-up from birth and checked at least every 2 months. Survival, smoothed hazard, adjusted hazard ratio of death, and transition probabilities in clinical and immunological categories were outcome measures. RESULTS: Survival was 49% (95% CI : 40-58%) at 8 years. The risk of death was high before the age of 2, relatively low between ages 2 and 7, and contained thereafter. Children did not advance through the categories sequentially. Survival at 8 years was 61.7% (95% CI : 49.8-73.6%) in those children who had passed through clinical category A; the hazard ratio of death was 2.5 (95% CI : 1.7-3.8) for 175 (47.9%) children who skipped this category. Transition probability in clinical category B was 39.9% (95% CI : 32.3-45.6%) after one year, but 59.1% (95% CI : 51.4-66.8%) after 5 years. Before 2 years of age, the probability of entry into category C (40%; 95% CI : 35-45%) was higher than that of entry into immunological category 3 (28%; 95% CI : 22-34%). Conclusions The classification system stands comparison with the clinical reality, but the CD4-positive cell thresholds in infancy should be adjusted and category B indicator diseases better distributed to improve their predictive value.

CD4 Lymphocyte Count↗
PubMed2000

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

BACKGROUND: A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. MATERIALS AND METHODS: To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. RESULTS: No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). CONCLUSIONS: Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.

Adolescent↗
PubMed1999

European paediatric hepatitis C virus network. Antenatal hepatitis C virus screening and management of infected women and their children: policies in Europe.

UNLABELLED: A postal survey of 31 European centres was conducted to document current practices regarding screening and management of hepatitis C virus (HCV)-infected pregnant women and their children. Antenatal HCV prevalence was low. Universal antenatal screening programmes were in place in ten centres, selective screening occurred in ten other centres, two did not specify the type of policy, and there was no screening programme in nine centres. Numbers of HCV-infected children were low. Breastfeeding was recommended for infants of infected mothers in ten centres, discouraged in ten centres, in three centres women were merely informed of the risks, and there were no guidelines in eight centres. Polymerase chain reaction was available in all centres. In 17 centres children born to HCV-infected women were seen every 3 months for at least the 1st year. CONCLUSION: The optimum antenatal hepatitis C virus screening approach and the appropriateness of breastfeeding recommendations are unclear and this survey highlights the lack of uniformity in current practice.

Academic Medical Centers↗
PubMed1999

High rate of maternal-infant transmission of hepatitis G virus in HIV-1 and hepatitis C virus-infected women.

The prevalence of hepatitis G virus (HGV) infection was investigated in 56 mothers with both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection. Thirty-three (58.8%) women had markers of HGV infection, including 7/15 (46.6%) with no history of parenteral exposure to blood. Sixteen (48%) had HGV RNA in serum by a polymerase chain reaction assay, and 17 (52%) had antibody to E2 viral protein. No woman was positive for both markers. Of 20 infants born to the 16 mothers with HGV viremia, 9 (45%, 95% CI 34-56%) acquired the infection. No infected child seroconverted to HGV during the first year of life. At the latest visit (mean: 37.1 mo, range: 9-89 mo) 7 children were still seronegative HGV RNA carriers, 1 was both RNA- and antibody-negative, while 1 RNA-negative child had developed the E2 antibody. Of the 20 HGV-exposed infants, 2 contracted HCV and 1 HIV-1 (all 3 with HGV coinfection). No abnormalities in clinical findings and ALT levels were observed throughout the follow-up period in the six children with HGV infection alone. Our findings show that HGV infection is widespread among HIV-1- and HCV-infected women. Maternal-infant transmission of HGV is common and occurs independently from that of HIV-1 and HCV in women with triple infection. Most perinatally HGV-infected children develop persistent infection with no clinical or biological signs of liver damage, at least in the first years of life.

Child↗