The chemical class of quinazoline compounds provides a core structure for the design of anticytomegaloviral kinase inhibitors.

HCMV is a member of the family Herpesviridae and represents a worldwide distributed pathogen with seropositivity rates in the adult population ranging between 40% and 90%. Notably, HCMV infection is a serious, sometimes life-threatening medical problem for newborns and immunosuppressed individuals, including transplant recipients and patients under antitumoral chemotherapy. Current standard therapy with valganciclovir has the disadvantage of inducing drug-resistant virus mutants and toxicity-related side effects. Our analysis stresses the earlier finding that kinase inhibitors of the quinazoline class exert an antiviral response by targeting the viral protein kinase pUL97 without inducing resistance. Therefore, quinazolines have been used as a core structure to gain insight in the mode of inhibitor-kinase interaction. Here, we demonstrate that (i) the novel quinazolines Vi7392 and Vi7453 are highly active against HCMV laboratory and clinically relevant strains including maribavir- and ganciclovir-resistant variants, (ii) antiviral activity is not cell-type specific and was also detected in a placental explant tissue model using a genetically intact HCMV strain (iii) the viral kinase pUL97 represents a target of the anticytomegaloviral activity of these compounds, (iv) induction of pUL97-conferring drug resistance was not detectable under single-step selection, thus differed from the induction of ganciclovir resistance, and (v) pUL97 drug docking simulations enabled detailed insights into specific drug-target binding properties providing a promising basis for the design of optimized kinase inhibitors. These novel findings may open new prospects for the future medical use of quinazoline drug candidates and the use of drug-target dynamic simulations for rational design of antivirals.

Indication and results of thoracic surgical procedures in premature infants.

This analysis concerns three groups of malformations: Congenital diaphragmatic hernia, patent ductus arteriosus, and oesophageal atresia. We registered a total mortality rate for all congenital diaphragmatic hernias and defects of 28.5%; the rate in full-term neonates was 27.6% and in premature infants 33.6%. Of 65 infants with a patent ductus arteriosus and a birth weight less than 1500 g, 14 died (21.5%). In most cases death was caused by sepsis. Among the 159 patients with oesophageal atresia who were treated in our hospital, 58 were premature infants. During the last 20 years, the total mortality rate among our patients was 28.9%. We had a mortality rate of 44.8% in premature infants and of 19.8% in full-term neonates. An analysis of the last 10 years showed a survival rate of 97% in healthy infants (group A in Waterston's classification). In group C, the most disadvantageous group (premature infants, severe anomalies), the rate was 61%.

The Dandy-Walker syndrome.

Ten cases of the Dandy-Walker syndrome are presented. The clinical manifestations are analyzed. Almost 80 percent of these children had associated anomalies. The characteristic findings are based on the magnetic resonance image scan. Satisfactory treatment of our patients had mostly consisted in shunting the lateral ventricular system to the peritoneum. The incidence of the complications was high.