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N Principi

Publications and source records attributed to N Principi.

At least 73 records · Page 4Linked to original sources

Etiology of acute otitis media in human immunodeficiency virus-infected children.

BACKGROUND: Acute otitis media (AOM) is one of the most common infections that are implicated as significant contributors to morbidity in HIV-infected children. To establish the optimal antibiotic therapy tympanocentesis is indicated as the first line diagnostic procedure, because unusual pathogens may play a role in advanced stages of deficient humoral or cellular immunity. METHODS: The microbiology of 60 episodes of AOM diagnosed in 21 symptomatic HIV-infected children (ages 9 months to 12 years) was compared with that of 121 episodes of AOM occurring in 113 immunocompetent HIV-negative children (ages 6 months to 12 years) in the last 5 years. RESULTS: The prevalence of the three most common pathogens (Streptococcus pneumoniae, Haemophilus influenzae and group A beta-hemolytic Streptococcus) was similar in HIV-infected and in normal children (56.5% vs. 54.9% of the ears). Staphylococcus aureus was significantly more frequent in AOM diagnosed in severely immunosuppressed stages. A significantly lower proportion of middle ear effusions obtained in HIV-infected children yielded no bacteria compared with normal children. Beta-lactamase production among isolates of H. influenzae was a rare phenomenon, both in HIV-infected and in normal children. No penicillin-resistant S. pneumoniae was found. CONCLUSIONS: In HIV-infected children with absent or moderate immunosuppression empiric antibiotic therapy should be based on the recommendations given for immunocompetent children of the same geographic area. In severe immunosuppressed stages, given the possible role of Staph. aureus, extended spectrum antibiotics should be considered.

Bacterial Infections↗

Comparative study of once-weekly azithromycin and once-daily amoxicillin treatments in prevention of recurrent acute otitis media in children.

Continuous chemoprophylaxis is effective in the prevention of new episodes of acute otitis media (AOM) in otitis-prone children, but compliance can be a problem and thus efficacy can be decreased. Intermittent chemoprophylaxis has so far shown conflicting results. Azithromycin, which has a peculiar pharmacokinetics, resulting, even after a single dose, in persistently elevated concentrations in respiratory tissues, could permit a periodic administration with higher compliance. We compared a 6-month course of once-weekly azithromycin (5 or 10 mg/kg of body weight) with that of once-daily amoxicillin (20 mg/kg) in a single-blind, randomized study of prophylaxis for recurrent AOM in 159 children aged 6 months to 5 years with at least three episodes of AOM in the preceding 6 months. In the amoxicillin group, 23 (31.1%) of 74 children developed 29 episodes of AOM, while in the 10-mg/kg azithromycin group, 11 (14.9%) of 74 children experienced 15 episodes. The 5-mg/kg/week azithromycin trial was prematurely interrupted after nine cases, due to the high occurrence rate of AOM (55.5%). During the 6-month prophylaxis period, the proportion of children with middle ear effusion declined similarly in both groups. No substantial modification of the nasopharyngeal flora was noted at the end of prophylaxis in both antimicrobial groups. In the 6-month-postprophylaxis follow-up period, about 40% of children in both groups again developed AOM. Azithromycin at 10 mg/kg once weekly can be regarded as a valid alternative to once-daily low-dose amoxicillin for the prophylaxis of AOM. Although in the present study no microbiological drawback was noted, accurate selection of children eligible for prophylaxis is mandatory to avoid the risk of emergence of resistant strains.

Amoxicillin↗

Antigliadin antibodies in HIV-infected children.

Immunoglobulin A-antigliadin antibodies and total immunoglobulin A were assessed on serum samples from 52 children infected by Human Immunodeficiency Virus (HIV). Titers of antigliadin antibodies exceeding the normal range were found in 14 children (27%). No statistically significant difference was observed either between children with symptomatic or asymptomatic infection, or among children with different degrees of immunosuppression. Though total immunoglobulin A concentration increased with the progression of the disease, no significant correlation was found between antigliadin antibodies and total immunoglobulin A. Mean antigliadin titers showed no significant difference between children with or without chronic gastrointestinal complaints. These findings suggest that, although a raised immunoglobulin A-antigliadin activity is a common feature of children infected by HIV, this is not merely the consequence of elevated total immunoglobulin A concentration. Moreover, in these children a raised antigliadin antibody titer should not be regarded as a reliable marker either of disease progression or of intestinal mucosa damage.

Biomarkers↗

[Current problems in the treatment of bacterial meningitis].

This paper on bacterial meningitis looks at aspects inherent in the aetiology and mechanisms underlying neurological damage and pharmacological treatment. Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis are the pathogens most commonly responsible and are able to colonise the host's respiratory mucosae, invade the vascular space, cross the haematoliquoral barrier and survive in the cerebrospinal fluid. The presence of germs in the subarachnoid spaces leads to the onset of inflammation and neurological damage. The most often used pharmacological treatments include, apart from antibiotics, anti-inflammatory drugs (although we have clinical data for corticosteroids only), pentoxyphillin and monoclonal antibodies. Initially empiric, antibiotic therapy is based on the use of drugs that act against the probable pathogenic agents, are capable of surmounting the haematoliquoral barrier and are well tolerated. Prior to the Eighties, the antibiotic of choice was ampicillin associated or otherwise with aminoglycosides. Subsequently, the availability of new drugs (cefotaxime and ceftriaxone) and the appearance of resistance led to changes in therapeutic protocols. Of the carbapenemics, wide spectrum antibiotics with high resistance to beta lactamase, imipenem /cilastatin proved effective although there was a high risk of inducing convulsions in patients with previous neurological damage or kidney failure. Meropenem was able to surmount the haematoliquoral barrier in sufficient concentrations and was well tolerated in patients with prior neurological changes. It has proved effective in clinical studies carried out up to the present.

Aminoglycosides↗

Mother-to-infant transmission of hepatitis C virus. Lombardy Study Group on Vertical HCV Transmission.

To assess the risk of mother-to-infant transmission of hepatitis C virus (HCV), we followed up 116 babies of anti-HCV positive mothers, of whom 22 were coinfected with HIV and 94 had HCV alone. None of the babies whose mothers had HCV alone acquired HCV, while 8 babies (36%; p < 0.001) of mothers co-infected with HIV acquired HCV (5 babies) or HCV and HIV (3). There was no association between any specific maternal HCV genotype and enhanced risk of neonatal infection. HCV-RNA levels were significantly higher (p < 0.05) in mothers with HIV coinfection than in those with HCV alone. These data indicate that maternal HIV status correlates with enhanced level of viraemia which favours neonatal infection.

Adolescent↗

Multicentre comparative study of the efficacy and safety of azithromycin compared with amoxicillin/clavulanic acid in the treatment of paediatric patients with otitis media.

An open multicentre study was conducted in 484 children between the ages of 6 months and 12 years with otitis media to compare the efficacy, the safety and the tolerance of once-daily azithromycin given for three days versus thrice-daily amoxicillin/clavulanic acid (CA) given for ten days. A satisfactory response (cure plus improvement) was noted 10 to 14 days after the start of treatment in 199 of 215 (92.6%) azithromycin-treated children and in 186 of 198 (93.9%) amoxicillin/CA-treated children. The relationship between treatment and clinical response was independent of chronicity of infection and the presence or absence of a perforated eardrum. Improvement in signs and symptoms of otitis media occurred significantly more rapidly in the children treated with azithromycin. Treatment-related or possibly treatment-related adverse events were recorded in 11 of 243 (4.5%) azithromycin-treated patients and in 20 of 240 (8.3%) treated with amoxicillin/CA. No patients in the azithromycin treatment group were withdrawn from treatment, but six amoxicillin/CA patients, including two < 2 years of age, discontinued treatment prematurely because of adverse events; the difference between treatment groups was statistically significant (p = 0.0146). It is concluded that azithromycin given as an oral suspension once daily for three days is as safe and effective as amoxicillin/CA given thrice daily for ten days in the treatment of children with otitis media.

Amoxicillin↗

Immunologic characterization of children vertically infected with human immunodeficiency virus, with slow or rapid disease progression.

Cytokine production of unstimulated and mitogen-stimulated peripheral blood mononuclear cells of 31 children vertically infected with human immunodeficiency virus type 1 (HIV) and with different patterns of disease progression was evaluated to establish possible correlations between the immunologic and the clinical findings. Production of interferon gamma and interleukin-2 (type 1 cytokines), and of interleukin-4 and interleukin-10 (type 2 cytokines), was analyzed in seven symptom-free patients (Centers for Disease Control and Prevention class P-1B), 10 patients with mild symptoms (class P-2A), and 14 patients with severe symptoms (class P-2B-F). Cytokine production was compared with that of 10 age- and sex-matched control subjects who were seronegative for HIV. The HIV-infected patients produced significantly fewer type 1 cytokines and significantly more type 2 cytokines than the uninfected control subjects. No differences in the production of interferon gamma and interleukin-2 were detected among the different clinical categories of HIV-infected patients. In contrast, interleukin-4 production was augmented in the patients with class P-2A (p < 0.05) and class P-2B-F HIV infection (p < 0.03), in comparison with the children with class P-1B infection. The increase in interleukin-4 production was paralleled by an increase in the number of children with hyperimmunoglobulinemia E in each of the clinical groups (0% in class P-1B; 40% in class P-2A; and 71% in class P-2 B-F infection). Similarly, interleukin-10 production was increased both in patients with class P-2A and in those with class P-2B-F infection, in comparison with the children with class P-1B disease (p < 0.006 and < 0.04, respectively). These data indicate (1) that vertically acquired HIV infection results in decreased production of type 1 cytokines and in increased production of type 2 cytokines, and (2) that an increased production of type 2 cytokines correlates with hyperimmunoglobulinemia E and is present in, and may be characteristic of, the symptomatic phases of childhood HIV infection.

Case-Control Studies↗

Elevation of IgE in HIV-infected children and its correlation with the progression of disease.

BACKGROUND: According to recent data, a switch from a TH1 to a TH2 pattern of cytokines might be a critical step in the progression of human immunodeficiency virus (HIV) infection. Previous studies have demonstrated a disturbance in IgE synthesis in HIV-infected adults. METHODS: Fifty-eight children infected vertically with HIV and 35 children with seroreversion, aged 4 months to 11 years, were evaluated for IgE serum level, CD4+ cell count, skin prick test responses to common airborne and food allergens, individual and family history of atopy, and presence of opportunistic infections. In thirty of the 58 HIV-infected children serum interleukin-4 and interferon-gamma levels were assessed. Thirty-three of the 58 HIV-infected children had a follow-up of 1 year for IgE levels, CD4+ cell count, and occurrence of opportunistic infections and recurrent bacterial infections. RESULTS: Both IgE concentration and the percentage of children with IgE elevation were markedly increased (with no correlation to skin prick test responses or opportunistic infections) in the group of 58 HIV-infected children as compared with the 35 children with seroreversion (p < 0.05). The same parameters were higher in children with acquired immunodeficiency syndrome as compared with children with asymptomatic or mildly symptomatic disease (p < 0.05). Serum interleukin-4 and interferon-gamma levels do not account for IgE hyperproduction. There was a significant association between persistent IgE elevation and severe decline ( > or = 30% over 1 year) in CD4+ counts, as well as increased susceptibility to bacterial infections. CONCLUSIONS: Our study demonstrates a spectrum of IgE dysfunction in children, which is similar to that observed in adults. A persistent IgE hyperproduction appears to be associated with a severe decline in CD4+ cell count, suggesting that this clinical test is a useful marker of disease progression.

Analysis of Variance↗

Perinatal transmission and manifestation of hepatitis C virus infection in a high risk population.

We studied the perinatal transmission of hepatitis C virus (HCV) in 70 high risk mother/infant pairs. Seventy-six percent of the mothers (53 of 70) were coinfected with human immunodeficiency virus (HIV) and 79% (55 of 70) had a history of drug addiction. During the follow-up HCV RNA was detected in 14 of 70 (20%) infants: 12% (2 of 17) in infants born to HIV-negative mothers; and 23% (12 of 53) in infants to HIV-positive mothers. The rate of vertical transmission was significantly higher in vaginally delivered infants than in those delivered by cesarean section (32% vs. 6%; P < 0.05). All 56 uninfected infants lost passively acquired anti-HCV by age 9 +/- 4 months and only 2 of 56 infants (4%) had evidence of HIV infection. Four of 14 HCV RNA-positive infants (29%) had evidence of HIV coinfection. We observed 3 clinical patterns of HCV infection: a transient viremia in 2 infants; an acute pattern in 2 infants; and a chronic pattern in 10 infants. All 4 HIV-coinfected infants had chronic HCV infection. All infants with a chronic pattern, had increased alanine aminotransferase values for more than 6 months and 5 had a liver biopsy that showed signs of chronic persistent hepatitis. HCV perinatal transmission was more frequent in infants born to HIV-coinfected mothers than in infants born to HIV-noninfected women, particularly when delivered vaginally.

Alanine Transaminase↗

A randomised comparison of isepamicin and amikacin in the treatment of bacterial infections in paediatric patients.

The efficacy and safety of isepamicin 7.5 mg/kg of body weight twice daily or amikacin the same dosage regimen for the treatment of various infections in neutropenic and non-neutropenic paediatric patients were compared in a prospective randomised trial. In total, 306 patients were enrolled and received at least one dose of randomised treatment (204 isepamicin, 102 amikacin: intent-to-treat population); 181 patients satisfied all criteria for evaluability (120 isepamicin, 61 amikacin: efficacy population). Clinical cure or improvement rates in the isepamicin and amikacin groups were: intent-to-treat population, 188/204 (92%) and 94/102 (92%), respectively; efficacy population, 117/120 (98%) and 58/61 (95%), respectively. The bacteriological elimination rate (efficacy population) in the isepamicin and amikacin treatment groups was 75/76 (99%) vs 35/38 (92%). Nephrotoxicity, defined as an increase in serum creatinine of 0.5 mg/dL or > or = 44.2 mumol/L from baseline, occurred in 4/187 (2%) and 1/191 (1%) children treated with isepamicin and amikacin, respectively. Definite ototoxicity at the > or = 20 dB threshold occurred in 3 (1 isepamicin and 2 amikacin) out of 56 children evaluated with at least two audiograms. Thus isepamicin was as effective and as well tolerated as amikacin in the treatment of various infections in paediatric patients.

Adolescent↗

Treatment of oropharyngeal candidiasis in HIV-infected children with oral fluconazole. Multicentre Study Group [corrected].

In an open, noncomparative, multicentre study the efficacy and safety of oral fluconazole was evaluated in the treatment of oropharyngeal candidiasis in children with HIV infection. Fifty-one children with a mean age of five years were enrolled. Oropharyngeal candidiasis was caused by Candida albicans in 28 cases (55%). Fluconazole was given in a mean dosage of 3.4 mg/kg/d (range 2 to 5.6 mg/kg/d) for a mean duration of 12 days (range 6 to 28 days). By the end of treatment, 90% of the children were clinically cured, 6% had improved and 4% failed to respond. Candida was eradicated in 82% of the patients. Clinical failure occurred only in children given 3 mg/kg/d or less. Two and four weeks after therapy, clinical cure was confirmed in 88% and 82% of the children respectively as well as eradication in 76% respectively. Six children experienced mild side effects (1 skin rash, 5 mild elevation of liver enzyme levels). The data show that fluconazole is safe and effective in treating oropharyngeal candidiasis in HIV-infected children.

AIDS-Related Opportunistic Infections↗

HIV-1 reverse transcriptase codon 215 mutation and clinical outcome in children treated with zidovudine.

OBJECTIVE: In HIV-infected adults prolonged monotherapy with zidovudine may be associated with the appearance of HIV strains with decreased zidovudine sensitivity, owing to specific mutations in the reverse transcriptase (RT) gene, and this has been suggested to be a reason for reduced zidovudine efficacy. This study was undertaken to determine the appearance of mutation at codon 215 of the RT gene in proviral DNA from PBMCs in HIV-infected children. DESIGN: A prospective, open study. SETTING: A University Pediatric Department. PATIENTS AND METHODS: Nineteen HIV-infected symptomatic children were treated with zidovudine for a median of 24 months. Clinical and laboratory controls for HIV infection status were performed monthly. Mutant proviral sequences were evaluated at the start of therapy, every 3 months during the first 6 months of therapy, and every 6 months thereafter. Clinical outcome was defined as stable or deteriorating. RESULTS: No child had proviral sequences mutant at codon 215 before starting zidovudine. Ten of 13 children who had received zidovudine for more than 6 months developed mutant proviral sequences. All the children (10 of 10) with mutant proviral sequences had a deteriorating clinical condition, compared to none of those (0 of 9) without mutation at codon 215. CONCLUSION: The appearance of HIV-1 codon 215 mutation seems to be strongly associated with zidovudine therapy and with clinical progression of HIV disease in children.

Base Sequence↗

Ultrastructural changes in the duodenal mucosa of HIV-infected children.

We studied the ultrastructure of duodenal biopsy specimens from six HIV-infected children with chronic gastrointestinal symptoms. A monomorphic pattern of microvillar damage (short and irregular microvilli, joined at their bases) was seen in all cases, even when the mucosa was normal on conventional histology. Among nine HIV antibody negative children, a similar pattern was seen only in three out of four celiac children with severely atrophic mucosa. No viral, bacterial, or protozoan pathogen was found. In HIV-infected children tubuloreticular inclusions were also seen in endothelial cells. These ultrastructural changes could help to account for the gastrointestinal symptoms in HIV-infected children.

Biopsy↗

Ranitidine pharmacokinetics in newborn infants.

Few data are available for ranitidine pharmacokinetics in the first few days of life. Twenty seven newborn infants were treated with intravenous ranitidine because they were vomiting blood, although they had a negative Apt's test. Each infant provided two blood samples at randomly selected times 30-360 minutes after a 2.4 mg/kg intravenous bolus of ranitidine. A single exponential equation for the concentration-time graph was fitted to the mean serum concentrations at different times. From this model the following mean (SD) measurements wer derived: elimination half life, 207.1 (19.1) minutes; total volume of distribution, 1.52 (0.91) l/kg; and total plasma clearance, 5.02 (0.46) ml/kg/min. Assuming that these measurements do not change with different administered doses, regimens can be derived to assist in planning ranitidine treatment in newborn infants.

Gastrointestinal Hemorrhage↗

Ranitidine treatment in newborn infants: effects on gastric acidity and serum prolactin levels.

Data about the use of ranitidine in the early postnatal period are lacking. In this study, 30 term newborn infants < 2 days old with bleeding erosions in their upper gastrointestinal tracts were treated with ranitidine by continuous i.v. infusion (0.2 mg/kg/h) for 48 h and thereafter by mouth (5 mg/kg b.i.d.) for 1 month. Mean gastric pH (SD) rose from 4.27 (1.62) to 5.70 (0.95) during i.v. infusion; after oral therapy it was still 5.55 (1.25). Serum ranitidine concentrations were 642.4 (376.5) and 321.5 (368.2) ng/ml after i.v. and oral therapy, respectively, with wide interindividual variations; the correlation between serum ranitidine and gastric pH was found to be weak. No untoward effect was observed either on the cardiorespiratory rate or on creatinine and aminotransferase values. Mean serum prolactin concentration after i.v. therapy was found to be lower, although within the reference range, than in control infants; no significant correlation was observed between serum ranitidine and prolactin concentrations. From these data, a < 0.2 mg/kg/h rate seems to be advisable for continuous ranitidine infusion in neonates, whereas the 5 mg/kg b.i.d. regimen could be considered adequate for oral therapy.

Administration, Oral↗

Impaired response to hepatitis B vaccine in HIV infected children.

Eighteen human immunodeficiency virus (HIV) vertically infected children (HIV group) and 33 seroreverted children (SR group), who had completed hepatitis B vaccination (Engerix B, 20 micrograms dose) were studied. Four out of 18 (22%) HIV children failed to develop protective antibody levels (anti-HBs titres less than 10 mIU ml-1) compared with 1 out of 33 (3%) SR children (p less than 0.05). Magnitude of response among HIV children was significantly lower than among SR children. In HIV children the probability that anti-HBs titres persist above the protective levels was significantly lower than in the SR group at any time during the 24 month follow-up. These results show that HIV children have a suboptimal response to hepatitis B immunization and the protection is less durable. Further studies are needed to determine the optimal protocol for hepatitis B immunization in HIV children.

Child, Preschool↗