BackgroundRotavirus is the major cause of acute gastroenteritis and severe dehydrating diarrhea in young children.MethodsTo estimate the proportion of hospital admissions for rotavirus acute gastroenteritis and identify the circulating G and P genotypes among children under five years of age, we conducted a prospective observational study from January to December 2008, recruiting children consecutively admitted to six hospitals in Milan and nearby towns in northern Italy. Typing was done on stool samples by reverse transcriptase polymerase chain reaction amplification.ResultsOf the 521 stool samples from children with acute gastroenteritis, 34.9% (95%CI, 30.8 to 39.2%) were rotavirus-positive. Two thirds (67.6%) were under two years of age, and 13.2% were under six months. The predominant G type was G1 (40.7%), followed by G9 (22.5%), G2 (13.2%), G3 (5.5%), G4 (3.8%) and G10 (1.6%). Twenty-one (11.7%) mixed-G infections were identified: G1+G10 (8.8%); G1+G9 (1.6%); and G2+G10 (1.2%). Only P[8] (67.6%) and P[4] (12.6%) types were P genotyped. The predominant single G/P combination was G1P[8] (39.7%), followed by G9P[8] (25.3%), G2P[4] (14.3%), and G3P[8] (4.1%). All G-mixed types combined with P[8].ConclusionsThese findings show an high prevalence of rotavirus infections among children admitted to hospital for acute gastroenteritis caused by different rotavirus strains circulating in the area studied.

In a prospective, randomized, controlled, three-arm study, the pharmacokinetics of hydroxyurea administered as an antiviral agent in patients infected with human immunodeficiency virus type 1 (HIV-1) were evaluated. The three arms of the study consisted of azidothymidine (AZT) 250 mg twice daily, hydroxyurea 500 mg twice daily, or a combination of the two. Nine patients receiving hydroxyurea in monotherapy (n = 4) or in combination with AZT (n = 5) agreed to undergo multiple venipunctures for pharmacokinetic analysis. Sample collection was performed at steady-state conditions and serum concentration-time data for hydroxyurea were fitted using a one-compartment model. Mean (+/- standard deviation) peak concentration (Cmax) was 0.135 +/- 0.06 mmol/L and mean trough level (Cmin) was 0.0085 +/- 0.003 mmol/L. Mean concentration at steady state was 0.045 +/- 0.006 mmol/L. Apparent clearance (Cl/F) was 0.18 +/- 0.005 L/hr/kg, and half-life (t1/2) was 2.5 +/- 0.5 hours. Hydroxyurea given orally to patients infected with HIV-1 was well absorbed from the gastrointestinal tract, with a tmax of 0.85 to 0.96 hours after ingestion. Serum levels of hydroxyurea ranged from 0.01 to 0.13 mmol/L. These values are similar to the concentrations (between 0.01 and 0.1 mmol/L) demonstrated to inhibit HIV-1 in vitro. Our data show that hydroxyurea given at a dosage of 500 mg twice daily is sufficient to yield serum concentrations potentially useful for in vivo inhibition of HIV-1.

No abstract

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 (HardGel-Capsule, InviraseA ) 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 clearanceshows an interindividual CV of 75%. A strong correlation (r=0.94) was found between SQV plasma concentration at 3 h (C 3 h ) and AUC(0,8h). Conclusions This study shows that C 3 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.

Purpose We evaluated the rates of gastroenteritis admissions to the emergency department and of rotavirusrelated hospitalisations in children ≤5 years in 2006 at an Italian paediatric hospital; we calculated the number of rotavirus cases avoidable through the universal vaccination of children.Methods Epidemiological data were extracted from the Data Elaboration Centre. To calculate the hospitalisation rate due to rotavirus, the virus was sought in the faeces of children hospitalised for acute gastroenteritis by means of rapid immunochromatographic assay.Results Emergency department admissions due to gastroenteritis numbered 2396 (11.58% of total admissions).Of these, 276 children (11.52%) were examined and then sent home; 1286 (53.67%) were kept in short observation and 776 (32.38%) were hospitalised. In 27.83% of hospitalised cases, the rotavirus test proved positive. The RV hospitalization rate was 55 per 10000 children ≤5 years in Genoa in 2006. In 85.6% of hospitalised patients with community-acquired rotavirus infection, the disease was severe. ConclusionsThe number of avoidable cases confirmed that the vaccination of children ≤1 year of age could reduce the burden of rotavirus infection, especially with regard to hospitalisation (45 per 10000 children ≤5 years) and admissions to short observation (85 per 10000), generating benefits for Italian healthcare system.