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N Principi

Publications and source records attributed to N Principi.

At least 37 records · Page 2Linked to original sources

Fatty acid composition of plasma lipids in HIV-infected children. Comparison with seroreverters.

Children infected with the type-1 human immunodeficiency virus (HIV) are at risk of nutritional deficiencies leading to an impaired polyunsaturated fatty acid (PUFA) status. The aim of the present study was to compare the PUFA composition of plasma lipid classes (total lipids, phospholipids (PL), cholesteryl esters (CE) and triglycerides) in well-growing HIV-infected children with an age-matched group of HIV-seroreverter children born to infected mothers. Eighteen HIV children, of both sexes, mean age 4.6 y, most of whom under combined antiretroviral regimen, were compared with 18 seroreverters, mean age 5.4 y, comparable for demographic, anthropometric and dietary characteristics. All children had adequate growth parameters (weight and height > 3rd percentile). The plasma fatty acid content was similar in the two groups. HIV seropositive subjects showed lower linoleic acid (LA) levels in all the plasma lipid fractions, with higher 20:3n-9 and 20:5n-3 levels in PL and CE. The plasma PL triene/tetraene ratio (marker of relative LA deficiency) related positively to the viral load and negatively to the blood CD4+ lymphocyte count. Compared to age-matched seroreverter subjects, HIV-seropositive children show a lipid fatty acid status suggestive of relative LA deficiency and increased turnover of the PUFA series.

Child↗

Epidemiology of Streptococcus pneumoniae in Italian children.

In Italy, data regarding the aetiological role, antibiotic resistance, and serotype distribution of isolates of Streptococcus pneumoniae are scarce and based on very small population samples. We found that S. pneumoniae caused about 30% of lower respiratory tract infections and 15% of acute otitis media infections in Italian children. The incidence of S. pneumoniae meningitis in subjects aged 0-4y was 1.1 x 100,000. In children <5 y of age with meningitis, the most common S. pneumoniae serotypes were, in rank order, 14, 6, 23, 1 and 4; among 53 nasopharyngeal carriers the most frequent serotypes were 6 and 19. The actual percentage of resistance of S. pneumoniae to penicillin is 10.2%, while for macrolides it reaches 25.5%. More data on the distribution of serotypes in Italian children are urgently needed in order to obtain a better understanding of the impact of the new pneumococcal vaccines.

Acute Disease↗

Indinavir pharmacokinetics and parmacodynamics in children with human immunodeficiency virus infection.

The indinavir dosage regimen currently used for human immunodeficiency virus (HIV)-infected children is not based on pharmacokinetic data obtained in the target patient population. The purpose of our study was to characterize indinavir pharmacokinetics and pharmacodynamics in HIV-infected children. Eleven children (age range, 9.0 to 13.6 years; weight range, 21.7 to 56.0 kg) receiving indinavir (500 mg/m(2) every 8 h) in combination with lamivudine and stavudine were studied. The correlation of indinavir pharmacokinetic parameters and demographic parameters was evaluated. Also, the pharmacodynamic relationship between parameters of indinavir exposure and parameters of renal toxicity and immunologic recovery was studied. The area under the indinavir concentration-time curve (AUC) and patient body surface area (BSA) showed a significant negative correlation (r = 0.73; P = 0.012). Patients with smaller BSA had excessive indinavir AUC compared to adults. On the other hand, the median minimum drug concentration in plasma (C(min)) was lower than that reported for adults. The maximum indinavir concentration in serum was higher in patients with renal toxicity (5 out of 11 children), but the difference was not statistically significant (15.3 +/- 8.2 versus 9.8 +/- 4.4 mg/liter; P = 0.19). There was a trend toward higher immunologic efficacy in patients with greater indinavir exposure: the time-averaged AUC of the percentage of CD4(+) lymphocytes over the baseline value for patients with indinavir C(min) > 95% inhibitory concentration (IC(95)) was higher than in patients with C(min) < IC(95) (P = 0. 068). Our study suggests that a dose reduction may be appropriate for children with small BSA and that a 6-h dosage regimen may be indicated for a substantial percentage of patients. Due to the low number of patients enrolled in this study, our results should be confirmed by a larger study.

Adolescent↗

Thymus volume correlates with the progression of vertical HIV infection.

BACKGROUND: The thymus is the organ responsible for the maturation and selection of T lymphocytes and is thus pivotal in allowing the development of a functional immune system. Because in HIV infection cell-mediated immune responses are severely impaired, we studied the role of thymus in the control of the progression of HIV infection to AIDS. METHODS: Thymic volume was analysed by magnetic resonance imaging in 31 vertically HIV-infected children. Plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined in the same patients. RESULTS: Thymic volume was not correlated with age or nutritional status; thymic volume was nevertheless correlated with CD4 T-lymphocyte counts and with the percentage and absolute number of CD45RA+CD62L+ (naive) T lymphocytes. In addition, the ability of peripheral blood mononuclear cells to proliferate upon tetanus stimulation was directly proportional to thymic volume. Finally, a negative correlation was detected between thymic volume and HIV viral load. CONCLUSION: Because low HIV plasma viraemia and preserved immune function are favourable prognostic indices in HIV disease, these data indicate that an immunological, thymic-dependent control of the progression of HIV infection might be possible, at least in vertically transmitted HIV infection.

CD4-Positive T-Lymphocytes↗

Clinical and immuno-virologic characterization of the efficacy of stavudine, lamivudine, and indinavir in human immunodeficiency virus infection.

Clinical, virologic, and immunologic outcomes were analyzed in children with vertically transmitted human immunodeficiency virus (HIV) infection (n = 25) and clinical symptoms and evidence of immunosuppression to establish the efficacy of 18 months' treatment with stavudine, lamivudine, and indinavir. Children were naive for treatment with protease inhibitors and lamivudine and had minimal exposure to stavudine. At 1, 6, 12, and 18 months, the proportions of patients with HIV-RNA <400 copies/mL were 79%, 100%, 94%, 87% in Centers for Disease Control and Prevention (CDC) immunologic class 2 and 50%, 67%, 67%, 72% in CDC immunologic class 3. At 12 months, the median CD4(+) count and percent increased significantly in both CDC immunologic class groups, but to a greater extent in the class 3 group. In the 12- to 18-month period, there were no significant changes within the groups. In both groups there was a steady increase in the proportion and number of children with positive skin test responses. Children in class 2 were more likely to have a positive delayed-type hypersensitivity response and a greater number of positive responses. Lymphocyte proliferative response to recall antigens improved significantly in all patients. The rate of increase in positive test results was faster in children in class 2 than in those in class 3. Only minor clinical events occurred during 18 months of therapy. Potent antiretroviral therapy achieves a sustained benefit in HIV-infected children, but immune reconstitution is more likely achieved in children with less advanced disease.

Adolescent↗

Body composition in HIV-infected children: relations with disease progression and survival.

BACKGROUND: Malnutrition is common in HIV-infected children, but the body compartment that is most affected has been ill defined. OBJECTIVES: Our objectives were to 1) compare the fat-free mass (FFM) of children with HIV infection with that of control children, 2) assess the contribution of FFM to body weight in HIV-infected children compared with that of control children, and 3) study the relations between body weight, FFM, and mortality. DESIGN: A cross-sectional study was performed in 86 HIV-infected and 113 uninfected children (mean ages: 6.9 and 7.7 y, respectively). FFM was estimated from single-frequency bioelectrical impedance analysis by using 3 different published equations; a further estimate was obtained from triceps-skinfold-thickness measurements. RESULTS: All 4 estimates of body composition showed that FFM in HIV-infected children was significantly less than in control children of similar age. However, FFM as a percentage of body weight was not significantly different between groups. In the whole group of infected children, an age-specific z score < -2 for weight and for FFM was significantly associated with an increased risk of death [relative risk (95% CI) = 11.4 (3.1, 41.0) and 5.1 (1.5, 18.2), respectively]; when only children with more severe disease were considered, only z score for weight was significantly associated with an increased risk [4.6 (1.4, 14.9)]. CONCLUSIONS: These findings suggest that no preferential catabolism of FFM occurs in HIV-infected children and that body weight for age is a better prognostic indicator than is FFM estimated by bioelectrical impedance analysis.

Analysis of Variance↗

Behavioral and psychological disorders in uninfected children aged 6 to 11 years born to human immunodeficiency virus-seropositive mothers.

This study investigated the behavioral and psychological differences between 39 uninfected children born to human immunodeficiency virus (HIV)-seropositive mothers (HIV-seroreverter [SR]) and 78 children with no family history of HIV infection. Caretakers completed the Child Behavior Checklist and the Gittelman modification of the Conners' Parent's Questionnaire, whereas children completed the Children's Manifest Anxiety Scale and the Children's Depression Inventory. In 14 SR children and 28 controls, narrative task was also evaluated. The personalities of SR children, as measured by the caretaker-completed scales, revealed significantly more problems of social adjustment and attention and more externalizing symptoms than did the personalities of control children. On the child-completed scales, SR children showed significantly more anxiety and depression than did controls. Caretakers reported consistently fewer symptoms of anxiety and depression in the children than did the children themselves. Difficulties in verbal recall included aspects of depressive and anxious feelings; on the narrative task measure, SR children showed poorer skill in free verbal recall than did control children, and they simplified episodes with mixed emotions. In addition, ambiguous episodes elicited significantly more negative feelings in SR children than in controls. These findings show that there is a great necessity for assisting SR children. It will be important to determine whether these children will remain at risk for emotional consequences in their adult lives.

Adult↗

Risk factors for carriage of respiratory pathogens in the nasopharynx of healthy children. Ascanius Project Collaborative Group.

OBJECTIVES: To assess risk factors for nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in a large sample of healthy children. METHODS: In this point prevalence survey nasopharyngeal specimens were obtained from 1723 healthy children, ages 1 to 7 years, attending day-care centers or schools in 18 Italian cities. Written questionnaires for obtaining information about the demographics and medical history of the children were completed by the parents in the presence of a pediatrician. RESULTS: The overall carrier rate of respiratory pathogens was 17.9% (S. pneumoniae, 3.5%; H. influenzae, 11.9%; M. catarrhalis, 4.1%). Only 5% of S. pneumoniae strains were penicillin-resistant whereas approximately 40% were erythromycin-resistant. Beta-lactamase production was found in 5.8% of H. influenzae and 88.7% of M. catarrhalis isolates. By multivariate analysis age (< or = 3 years), having older siblings, a history of prolonged full-time day-care attendance and living in a rural area significantly influenced the odds of carrying nasopharyngeal respiratory pathogens, particularly in children ages 1 to 5 years. Sex, breastfeeding, passive smoking and recent upper respiratory tract infections were not significant variables. Antibiotic treatment in the previous 3 months did not affect nasopharyngeal carriage, whereas repeated treatments with a macrolide were associated with carriage of S. pneumoniae. CONCLUSIONS: Our results suggest that there is a strong and long term relationship between exposure to large numbers of children in the first years of life and nasopharyngeal carriage of all respiratory pathogens. In addition antimicrobial restrictive guidelines should be tailored to local microbiologic sceneries.

Carrier State↗

Outcome of mother to infant acquired GBV-C/HGV infection.

Twelve children born to hepatitis C virus antibody GBV-C/HGV RNA positive mothers who acquired GBV-C/HGV infection by the vertical or perinatal route were studied. Most (91%) were persistently GBV-C/HGV RNA positive up to 12 months of age. Four out of six cases who acquired GBV-C/HGV alone had normal alanine amino transferase activities. Long lasting evidence of hepatocellular injury was detected only in children with GBV-C/HGV and hepatitis C virus and HIV coinfection.

Flaviviridae↗

Differential development of type 1 and type 2 cytokines and beta-chemokines in the ontogeny of healthy newborns.

Interleukin (IL)-2, interferon gamma (IFN-gamma; type 1 cytokines), IL-4, and IL-10 (type 2 cytokines), and beta-chemokines (MIP-1alpha and RANTES) production by cord blood lymphocytes (CBL) and peripheral blood lymphocytes (PBL) of newborns was analyzed in a cross-sectional study to examine the maturation of these components of the immune response. Immunophenotyping was performed on the same specimens. Results showed that the CD4/CD8 ratio remains stable, the percentage of natural killer cells decreases, and the number and percentage of B cells increase after birth. Analysis of cytokine production suggested that the production of all cytokines increases gradually and steadily after birth, and that IFN-gamma and IL-10 production is reduced at birth whereas IL-2 and IL-4 production is not. Finally, mitogen-stimulated beta-chemokine production was present at birth and increased slightly but significantly with age. These data indicate that a differential functional maturation of immune response after birth favoring a more precocious development of IL-2 (a type 1 cytokine) is present and should help to analyze the ontogeny of the immune system.

Aging↗

Incidence of severe streptococcal-related diseases in Italian children in an era of high group A streptococcal resistance to macrolides. Italian Group A Streptococcal Resistance to Macrolides Study Group.

Macrolides are still widely prescribed for adult and pediatric respiratory infections in Italy despite the fact that it is known that the resistance of group A streptococci has dramatically increased since 1994. The aim of this study was to evaluate the incidence of severe streptococcal-related diseases from 1990 to 1996 on the basis of data derived from computer-generated lists of children hospitalized in 35 Pediatric Departments. The clinical record of each case was reviewed in order to gather data concerning clinical diagnoses, laboratory investigations and antibiotic therapies in the preceding four weeks. Six hundred and twenty of the total of 321,612 hospitalized children had severe streptococcal diseases; the overall annual rate remained stable at 2.13/1000 admissions in 1990 to 1.7/1000 admissions in 1996. Severe diseases were preceded by a microbiologically confirmed acute streptococcal infection treated with antibiotics in only 392 of the 620 children (63.2%). Between 1993 and 1996 (with the exception of 1995), macrolides were more frequently prescribed than beta-lactam antibiotics for acute streptococcal infections that subsequently developed into severe disease. There was no difference in the rate of severe streptococcal complications between the patients adequately treated with antibiotics and those who were inadequately or not treated. Possible explanations for the relatively stable rate of severe streptococcal complications in Italian children could be (1) a relative absence of invasive, rheumatogenic or nephritogenic strains and/or (2) a difference between in vitro and in vivo resistance of group A streptococci to macrolides. Further studies are needed to investigate the biological characteristics of resistant group A streptococcal strains and their relationships to short- and long-term clinical outcomes.

Adolescent↗

Comparative tolerability of erythromycin and newer macrolide antibacterials in paediatric patients.

The macrolides are a well established group of antibacterials frequently used in general practice. The most frequently used macrolides in paediatric patients are erythromycin, a naturally occurring compound, and clarithromycin and azithromycin, recently developed macrolides. Overall adverse effect rates of 7 to 26% for erythromycin, 14 to 26% for clarithromycin, and 6 to 27% for azithromycin have been described in children. Adverse gastrointestinal effects, including nausea, vomiting, diarrhoea and abdominal cramps, are the most common problems in children. Allergic reactions, hepatotoxicity, ototoxicity and adverse effects involving the central and peripheral nervous systems have also been observed in children. Stevens-Johnson, Schonlein-Henoch and Churg-Strauss syndromes have been rarely described in children. Treatment-related laboratory abnormalities have been recorded in 2 to 4% of erythromycin- and in 0 to 1% of both clarithromycin- and azithromycin-treated children. Elevation in liver function tests was the most common abnormality cited. Increased macrolide use in children in recent years has resulted in a growing potential for drug interactions between them and other pharmacologically active agents via the inhibition of cytochrome P450 (CYP) microsomal enzymes. Drug interactions with theophylline, cyclosporin, carbamazepine, terfenadine and warfarin limit erythromycin use. Clarithromycin is a weak inducer of CYP and exhibits fewer drug-drug interactions than erythromycin. However, its use with theophylline, carbamazepine and terfenadine is contraindicated. In contrast, no significant interactions have been reported with azithromycin to date. Macrolides have been proven to be well tolerated in the treatment of upper and lower respiratory tract infections, skin and soft tissue infections, and also in less frequent infections occurring in paediatric patients. In addition, clarithromycin and azithromycin have shown good tolerability profiles in immunocompromised paediatric patients. In conclusion, macrolides antibacterials have proven to be well tolerated in paediatric patients. Although the incidence of adverse effects is similar with the use of erythromycin and the newer macrolides, drug interactions occur significantly less when clarithromycin or azithromycin are administered.

Anti-Bacterial Agents↗

Zidovudine therapy and HIV type 1 mutations in children with symptomatic HIV type 1 infection: effect of switching to didanosine or zidovudine plus didanosine therapy. Italian Multicenter Study Group on HIV Mutations in Children.

Type and prevalence of zidovudine (ZDV) resistance mutations in HIV-1-infected children in clinically stable condition and on ZDV monotherapy were analyzed to evaluate the effect of switching to didanosine (ddI) monotherapy or to ZDV plus ddI on the pattern of mutations and on the clinical outcome. Monthly clinical and laboratory controls for HIV-1 infection status were performed; at enrollment and every 4 to 6 months after treatment randomization mutant proviral sequences were evaluated in all the children, whereas viral burden was performed only in a small subgroup of patients randomly selected in each of the three treatment groups. ZDV resistance-associated proviral DNA mutations were defined as low-level resistance (LLR) mutations or medium/high-level resistance (MHLR) mutations; clinical outcome was considered as stable or deteriorating. Results showed that at entry into the study the duration of ZDV therapy was significantly correlated with the presence of mutations, and that the level of resistance given by mutations was associated with the severity both of symptoms and immunodeficiency. After randomization to treatment, in patients with mutations that confer LLR a better clinical outcome with ddI monotherapy than with ZDV plus ddI and ZDV alone was observed in the subsequent 6 months, whereas in patients with mutations that confer MHLR no significant difference among the three treatment groups was found. Data showed also that levels of viral burden at the time of changing therapy are related to clinical outcome if measured by plasma viral load. These results suggest that genotypic resistance assays, together with viral load, may prove useful for rational treatment decisions both at the start of therapy and with failure.

Anti-HIV Agents↗

Immunization with both T cell-dependent and T cell-independent vaccines augments HIV viral load secondarily to stimulation of tumor necrosis factor alpha.

Vaccination of HIV-infected individuals increases HIV viral load, reduces CD4 cell counts, and might influence disease progression. Because these deleterious effects are postulated to be secondary to a direct activation of T lymphocytes induced by the immunogen, we compared immunologic and virologic effects of a T cell-dependent and a T cell-independent vaccine. Seventeen HIV-infected children were immunized with influenza (FLU) (T cell-dependent) or pneumococcal (PNEUMO) (T cell-independent) vaccines. HIV viral load and type 1 (IL-2 and IFN-gamma) and type 2 (IL-4 and IL-10) cytokine production were evaluated before and 7, 14, and 28 days after vaccination. Slopes of CD4 cell counts analyzed 6 months before and 6 months after vaccination were not significantly different. HIV viral load increased in both groups of children despite the fact that type 1 cytokine production and the type 1-to-type 2 ratio increased in FLU-vaccinated but not in PNEUMO-vaccinated patients. Thus, an increase in HIV viral load in the absence of T cell activation (as measured by cytokine production) was observed in PNEUMO-vaccinated children. Because polysaccharides of the bacterial cell wall stimulate TNF-alpha production by monocyte-macrophages and TNF-alpha was shown to stimulate HIV replication directly on activation of NF-kappa b after binding the long terminal repeat (LTR) sequences of HIV, we measured TNF-alpha production and observed a significant increase in both groups of vaccines. These data suggest that an increase in HIV viral load can be observed in vaccinated HIV-infected children even independent of direct antigen-induced activation of T lymphocytes, and that augmented production of TNF-alpha might play a role in this phenomenon.

Bacterial Vaccines↗

Multicenter trial on mother-to-infant transmission of GBV-C virus. The Lombardy Study Group on Vertical/Perinatal Hepatitis Viruses Transmission.

Evidence indicates that the GBV-C or hepatitis G virus can cause persistent infection in humans, but little is known on the importance of vertical transmission. To assess the risk of mother-to-infant transmission and the clinical outcome of infected babies, we investigated 175 anti-HCV positive mothers and followed-up their children for 3-33 months. GBV-C RNA was detected by RT-PCR and anti-E2 antibody was assayed by EIA. Thirty-four (19.4%) women were GBV-C RNA positive and transmission occurred to 21 (61.8%) babies; 20 (95.2%) acquired GBV-C alone, and one (4.8%) GBV-C and HCV. Maternal factors such as intravenous drug use, HIV coinfection, HCV-RNA positivity, and type of feeding were not correlated with GBV-C transmission. GBV-C RNA remained persistently positive in all infected babies but one baby who seroconverted to anti-E2. Seven (35%) babies with GBV-C alone developed marginally elevated ALT; the baby with HCV and GBV-C co-infection had the highest ALT peak value (664 IU/l). Seven of the 141 (5%) babies born to the GBV-C RNA negative mothers acquired HCV and six (85.7%) had abnormal ALT. The mean ALT peak value was significantly higher (P < 0.05) for babies with HCV than for those with GBV-C. None of the children with GBV-C or with HCV became icteric. GBV-C is frequently present in anti-HCV positive women. The infection is transmitted efficiently from mother to baby and rate of transmission is much higher than that for HCV. GBV-C can cause persistent infection in babies but usually without clear evidence of liver disease.

Adult↗