Adherence to antiretroviral therapy and its determinants in children with human immunodeficiency virus infection: a multicentre, national study

Aim: To investigate rates and determinants of adherence to antiretroviral therapy in Italian children infected with the human immunodeficiency virus (HIV). Methods: An observational, cross-sectional multicentre study was performed through a structured interview with the caregivers of HIV-infected children. The interview included quantitative information on adherence in the 4 d before interview. Sociodemographic, clinical and psychosocial characteristics of children were recorded. Results: 129 children (median age 96 mo) were enrolled, of whom 94 were on highly active antiretroviral therapy (HAART). Twenty-one (16%) omitted more than 5% of total doses in 4 d and were considered non-adherent. However, only 11% of caregivers reported that therapy had been administered at the correct times. No significant difference was found between age and the stage of HIV infection. Children aware of their HIV status were less adherent. Individual drugs showed a broad adherence pattern and children who received HAART were more adherent. Children receiving therapy from foster parents were more adherent than those receiving drugs from biological parents or relatives.

Conclusions: Adherence is a major problem in children. Psychological rather than clinical or sociodemographic features and types of drug are major determinants of adherence.     

Pharmacokinetics and tissue distribution of rifametane, a new 3-azinomethyl-rifamycin derivative, in several animal species

Single and repeated dose experiments in mice, rats, dogs and monkeys are reported in this study to assess the pharmacokinetics and tissue distribution of rifametane, a new semi-synthetic rifamycin with the chemical formula 3-[(1-diethylaminoethylidene)azinomethyl]rifamycin SV (CAS 94168-98-6, SPA-S-565). All the kinetic tests were carried out in comparison with known rifamycin derivatives, as rifampicin (CAS 13292-46-1) or rifamycin SV (CAS 6998-60-3). Mice received single i.v. and oral administration of 10 mg/kg of rifametane or of rifampicin and serum samples were obtained up to 96 h after dosing. The two antibiotics showed similar peak of serum concentrations, but rifametane showed a longer half-life and higher AUC values. In an additional experiment, the tissue/serum ratio after the 10 mg/kg oral dose was lower than unity for lungs and kidneys, while the liver/serum ratio exceeded the unity at all sampling times. After 4 weeks of once weekly administration measurable serum and tissue concentrations were observed, and after twice weekly administration for the same time period some blood and tissue accumulation was seen. Rats were treated with a single intravenous injection of 20 mg/kg of rifametane or rifampicin and with single oral or i.m. administration of 60 mg/kg of rifametane or reference standards (rifampicin and rifamycin SV resp.), in two separate trials. The serum half-life of the test antibiotic after i.v. dose was 6 times longer than that of rifampicin and the serum concentrations of rifametane after oral and i.m. doses were higher and longer-lasting than those of the reference compounds. Repeated daily administrations of rifametane at three dose levels (3, 10, 30 mg/kg p.o.) for 4 weeks induced very high serum and liver concentrations. Dogs received a single oral dose of 1.25 mg/kg of rifametane or 2.5 mg/kg of rifampicin. The serum half-life of rifametane resulted 3 times longer than that of rifampicin. Remarkable serum and tissue concentrations were observed after 3-4 weeks of daily oral administration of rifametane at 3, 10, 30 mg/kg dose. Monkeys were given single oral or i.m. administration of 30 mg/kg of rifametane or reference standards (oral rifampicin and i.m. rifamycin SV). The serum concentrations after rifametane were higher and more sustained than those of reference compounds and the half-lives of the test antibiotic were about 2.5 (p.o.) to 6 times (i.m.) longer. The urine excretion of rifametane after a single intravenous dose in rats and a single oral dose in dogs was very low, while rifampicin had a little higher urine concentrations.     

Acute inflammatory demyelinating polyradiculoneuropathy associated with perforin-deficient familial haemophagocytic lymphohistiocytosis

This study reports the first paediatric case of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) associated with a fatal haemophagocytic lymphohistiocytosis (HLH). The patient developed progressive weakness of the lower limbs in the context of a picture of infectious mononucleosis and Epstein-Barr virus (EBV) infection. After an apparent improvement, a fulminant hepatic failure and pancytopenia ensued, leading to death. Molecular genetic studies documented a compound heterozygosity for two mutations in the perforin (PRF1) gene as the background defect for a familial haemophagocytic lymphohistiocytosis (FHL). Conclusion: In this patient EBV infection triggered both AIDP and FHL. The latter condition was due to PRF1 deficiency. Two novel mutations in the PRF1 gene were concomitantly present in the patient. The first caused an amino acid change, while the second introduced a stop codon in the sequence which resulted in a truncated protein.     

Growth inhibition of fibroblasts from nasal polyps and normal skin by lysine acetylsalicylate

Some authors have shown that lysine acetylsalicylate (LAS) may help prevent nasal polyp relapses. As some anti-inflammatory drugs have been found to regulate cell growth, we investigated the antiproliferative effect of LAS on fibroblasts derived from nasal polyps. Moreover, we studied the effect of LAS on the growth of fibroblasts derived from normal skin to determine whether the response was similar to that obtained in the above-mentioned cells. Fibroblasts were obtaitied from tissue samples of nasal polyps from two aspirin-tolerant and two aspirin-intolerant patients, and from the normal skin of a healthy donor. The cells were treated with LAS (20–2000 μg/ml of culture medium). Cell growth and viability were evaluated after 3 and 6 days of culture. LAS had a growth-inhibitory effect on cells independently of their derivation. A reduction in cell growth was seen at the coticentrations of LAS tested, which correspond to those used in the local treatment of nasal polyposis.     

Morgagni-Larrey diaphragmatic hernia: report of a case

The Authors presents a Morgagni-Larrey's diaphragmatic hernia case, observed during subocclusive manifestation. They emphasize the utility to perform always the surgical intervention, also in the asintomatic cases.     

Pharmacokinetics of a new derivative of partricin A (SPA-S-753) in rodents

Pharmacokinetics of a new semisynthetic polyene antibiotic (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide) in the form of its diaspartate salt (code SPA-S-753) was studied in rats and mice following intravenous injection and in rats following oral administration at different dose levels. In rats the urinary and biliary recovery after intravenous administration was also determined. Rats and mice received a single intravenous injection of 1.25 and 2.5 mg/kg of SPA-S-753 (about 1-2 mg/kg of free base) or 1 mg/kg of amphotericin B as reference drug. Blood samples were obtained at 5 min to 96 h after injection. The half-lives at the elimination phase in serum were 21.3, 26.5, 10.8 h in rats and 11.7, 13.7, 19.8 h in mice, respectively, for 1.25 and 2.5 mg/kg of SPA-S-753 and 1 mg/kg of amphotericin B. The values of AUC(0-infinity) for SPA-S-753 were about 5 times higher in rats and twice higher in mice than those for amphotericin B. Rats received also a single oral dose of 200 or 500 mg/kg of SPA-S-753. Serum samples were obtained at 0.5-96 h after dosing. The compound is poorly absorbed by the oral route. The mean cumulative urinary recovery of SPA-S-753 at 48 h after intravenous injection of 1.25 mg/kg in rats accounts only for 0.5% of the dose, while the cumulative recovery from the bile at 10 h after 2.5 mg/kg i.v. administration in rats accounts for 5.5% of the dose.     

Early treatment with ursodeoxycholic acid for cholestasis in children on parenteral nutrition because of primary intestinal failure

BACKGROUND: There is conflicting evidence as to whether ursodeoxycholic acid (UDCA) reduces the incidence of parenteral nutrition-associated cholestasis. AIM: To investigate the efficacy of UDCA on parenteral nutrition-associated cholestasis in children with intestinal failure due to short bowel syndrome or to other causes. METHODS: Children with cholestasis received 30 mg/kg/day UDCA. Improvement or normalization of parenteral nutrition-associated cholestasis was evaluated at 6 months of therapy and at the last follow-up. In a subgroup of children, serum UDCA levels were measured while receiving UDCA and after 4 weeks withdrawal. RESULTS: Twelve children were treated with UDCA. Full remission or partial improvement of parenteral nutrition-associated cholestasis occurred in 11 of 12 children. In three of four children, withdrawal of UDCA was associated with a rebound rise of cholestasis. Only one of 12 treated children showed no improvement and in this patient, in contrast to four other patients, plasma levels of UDCA did not increase during treatment.CONCLUSIONS: Ursodeoxycholic acid was effective in controlling parenteral nutrition-associated cholestasis. The efficacy of UDCA also in children with short bowel is related to intestinal absorption.     

Anticandidal activity of SPA-S-843, a new polyenic drug

The activity of a new, soluble and stable polyene (SPA-S-843) against Candida albicans was assessed by contact and culture tests and by inhibition of germ-tube formation. The drug demonstrated a higher contact activity and lower MICs than amphotericin B. This antimicrobial activity was more evident under acid pH and low ionic strength. In addition, the ability of SPA-S-843 to inhibit Candida sp. conversion from yeast to mycelial form was evident at low drug concentrations (0.25-0.62 mg/L).