Pharmacokinetics, microbial response, and pulmonary outcomes of multidose intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory colonization.

The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [n = 12] or a single 20-mg/kg dose [n = 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. A 2-compartment model with all PK parameters allometrically scaled on body weight best described the azithromycin pharmacokinetics in preterm neonates. The population pharmacokinetics parameter estimates for clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 0.15 liters/h · kg(0.75), 1.88 liters · kg, 1.79 liters/h · kg(0.75), and 13 liters · kg, respectively. The estimated area under the concentration-time curve over 24 h (AUC24)/MIC90 value was ∼ 4 h. All posttreatment cultures were negative, and there were no drug-related adverse events. One Ureaplasma-positive infant died at 4 months of age, but no survivors were hospitalized for respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in eradicating Ureaplasma spp. from the preterm respiratory tract.

[Response of testosterone to chorionic gonadotropin stimulus in prepubertal cryptorchidism and retractile testes. Age-related changes in gonadal steroidogenesis. Authors'experience]. / La risposta del testosterone allo stimolo con gonadotropina corionica nei prepuberi criptorchidi e con testicoli retrattili. Modificazioni della steroidogenesi gonadica in rapporto all'età. Nostra esperienza.

The aim of this analysis is to evaluate the gonadal function in children with true undescended testes and in those with retractile testes, in order to verify a possible impairment of the testicular steroidogenesis due to the permanent or transitory anomalous position of the gonad outside the scrotum. The authors carried out a prospective study on 29 prepubertal children affected by true undescended testes (monolateral in 20 cases and bilateral in 9), as well as on 25 prepubertal children with retractile testes (monolateral in 10 cases and bilateral in 15), assaying the testosterone (T) levels, basal and 72 hours after stimulus with human chorionic gonadotrophin (HCG) administered in a single dose of 100 U/kg i.m. Further-more, to verify the hypothesis of a possible progressive reduction of the Leydig cells function, particularly in the gonads bilaterally affected, the authors also evaluated the testosterone response to gonadotrophic stimulus compared to age (> 0 < 4 years). This study in agreement with data already published, confirms the normality of gonadal function both in children with mono or bilateral true undescended testes and in those with retractile testes. The lower the age of the subject the higher is the peak of testosterone after stimulus, confirming the active steroidogenesis of the gonads in infants and small children and sustaining the "non quiescence" of this organ during infancy, even in cases of true undescended testes.

Phagocytosis in patients with sickle cell disease.

Twenty sickle cell disease (SCD) patients, homozygous for sickle hemoglobin, were studied during asymptomatic periods. After clinical evaluation, several peripheral phagocyte parameters were evaluated. These were: ingestion rate, percentage of phagocytes with ingested particles, nitro-blue-tetrazolium (NBT) reduction rate, candidacidal activity; as well as serum levels of total haemolytic complement activity (CH50); third and fourth complement components (C3 and C4). Our data show a significant decrease of all studied phagocytosis parameters in the presence of sickle serum which indicate that asymptomatic SCD patients have basically deficient phagocytosis due to serum factors. Nine of the same patients were also evaluated during and after a painful crisis. Our results indicate that a painful crisis is not associated with further abnormalities of phagocytosis in SCD patients.