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Objectives To test the hypothesis that the gene expression of endothelin‐1 and adrenomedullin may be altered in stenotic tissues of patients with congenital hydronephrosis caused by pelvi‐ureteric junction (PUJ) obstruction. Materials and methods Using real‐time reverse transcription‐polymerase chain reaction, mRNA of smooth muscle‐constricting endothelin‐1 and of smooth muscle‐relaxing adrenomedullin was quantified in tissue specimens of 20 patients with PUJ obstruction (mean age 5.1 years, sd 7.0) and of 21 controls with normal PUJs (mean age 23.5 years, sd 24.2). Results The amount of endothelin‐1 mRNA in stenotic specimens was higher than in the controls, indicated by significantly lower threshold cycles (Ct values) in real‐time PCR for the target gene in the obstructive tissue, with mean (sd) values of 24.9 (1.6) and 26.0 (2.1) (P < 0.05), respectively. The endothelin‐1/CD31 ratio was significantly higher in the patients (P < 0.05) than in controls. In addition, adrenomedullin gene expression in the obstructed junctions was significantly lower than in normal junctions, with higher Ct values for the patient group of 26.7 (1.6) vs 25.2 (1.8) (P < 0.05) and lower adrenomedullin mRNA when standardized to glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) (P < 0.05), CD31 (P < 0.01) and smooth muscle α‐actin mRNA (P < 0.01). The two groups showed no significant differences for GAPDH and CD31 mRNA content, whereas there was about twice as much α‐actin mRNA in stenotic tissues than in unaffected PUJs, shown by the lower Ct values for the patient group of 16.9 (2.0) vs 17.9 (2.6) (P < 0.05). Furthermore, endothelin‐1, adrenomedullin and α‐actin mRNA amounts were independent of age. Conclusion Taken together these results provide evidence that the production of autocrine/paracrine acting endothelin‐1 and adrenomedullin is altered in tissues of patients with genuine PUJ obstruction, and may be involved in the pathogenesis of congenital hydronephrosis.

This multicentre, open-label, prospective, single-arm study was designed to evaluate the efficacy, pharmacokinetics, and safety of IqYmune®, a highly purified 10% polyvalent immunoglobulin preparation for intravenous administration in patients with primary immunodeficiency. IqYmune® was administered to 62 patients (aged 2–61 years) with X-linked agammaglobulinemia or common variable immune deficiency at a dose from 0.22 to 0.97 g/kg every 3 to 4 weeks for 12 months with an infusion rate up to 8 mL/kg/h. A pharmacokinetic study was performed at steady state between the 8th and the 9th infusion. A single case of serious bacterial infection was observed, leading to an annualized rate of serious bacterial infections/patient (primary endpoint) of 0.017 (98% CI: 0.000, 0.115). Overall, 228 infections were reported, most frequently bronchitis, chronic sinusitis, nasopharyngitis and upper respiratory tract infection. The mean annualized rate of infections was 3.79/patient. A lower risk of infections was associated with an IgG trough level > 8 g/L (p = 0.01). The mean annualized durations of absence from work or school and of hospitalization due to infections were 1.01 and 0.89 days/patient, respectively. The mean serum IgG trough level before the 6th infusion was 7.73 g/L after a mean dose of IqYmune® of 0.57 g/kg. The pharmacokinetic profile of IqYmune® was consistent with that of other intravenous immunoglobulins. Overall, 15.5% of infusions were associated with an adverse event occurring within 72 h post infusion. Headache was the most common adverse event. In conclusion, IqYmune® was shown to be effective and well tolerated in patients with primary immunodeficiency.

The present study was performed to investigate simultaneously total brain water, T1 and T2 relaxation times, and hyaluronan (HA) in fetal and neonatal rabbits. Attempts were also made to establish the relationship of HA to total brain water and to T2-derived motionally distinct water fractions, since HA is known to bind water and to limit tissue water mobility. Experiments were carried out in fetal Pannon white rabbit pups at gestational ages of 25, 27, 29, and 31 days and at a postnatal age of 4 days. The brain tissue water content (desiccation method), T1 and T2 relaxation times (H¹-NMR method), and HA concentration (radioassay HA 50) were measured, and free and bound water fractions were calculated by using multicomponent fits of the T2 relaxation curves. Compared with values in newborn pups, water and HA contents were found to be highly elevated in the preterm brain and decreased markedly during early postnatal life. The trends and time courses of T1 and T2 relaxation times proved to be similar, but the postnatal decrease in T2 was preceded by a significant decline in late gestation. Maturity-related changes occurred in the T2 relaxation derived bound water fraction which amounted to 4–19% of brain water. The bound water fraction appeared to be independent of total brain water and HA concentration, and HA is, therefore, unlikely to be the only factor controlling brain water mobility. The clear dissociation of bound water fraction from total water suggests restructuring of brain water during the perinatal period.