Since the discovery of the Rh blood group system in 1940, a greater understanding of hemolytic disease of the fetus and newborn (HDFN) was gained. In the years thereafter, researchers and... Show moreSince the discovery of the Rh blood group system in 1940, a greater understanding of hemolytic disease of the fetus and newborn (HDFN) was gained. In the years thereafter, researchers and clinicians came to the current understanding that fetal and neonatal red blood cells (RBC) are hemolyzed by maternal alloantibodies directed against RBC antigens potentially leading to severe disease. Preventative measures, such as Rhesus(D) immunoprophylaxis (RhIG), have greatly decreased the prevalence of Rh(D)-mediated HDFN, although a gap between high-income countries and middle- to low-income countries was created largely due to a lack in availability and high costs of RhIG. Other important developments in the past decades have improved the identification, monitoring, and care of pregnancies, fetuses, and neonates with HDFN. Prenatally, fetal anemia may occur and intrauterine transfusions may be needed. Postnatally, pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for anemia in the late phase of the disease. Through this review, we aim to provide an overview of important historic events and to provide hands-on guidelines for the delivery and postnatal management of neonates with HDFN. Secondarily, we aim to describe recent scientific findings and evidence gaps. Conclusion: Multiple developments have improved the identification, monitoring, and care of pregnancies and neonates with HDFN throughout the centuries. Pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for late anemia in the late phase of the disease. Future studies should be set in an international setting and ultimately aim to eradicate HDFN on a global scale. What is Known: Developments have led to a greater understanding of the pathophysiology, an improved serological identification and monitoring of at-risk cases and the current pre- and postnatal treatment. What is New: This review provides the pediatrician with hands-on guidelines for the delivery and postnatal management of neonates with HDFN. Future studies should be set in an international setting with the ultimate aim of eradicating HDFN. Show less
Trautinger, F.; Eder, J.; Assaf, C.; Bagot, M.; Cozzio, A.; Dummer, R.; ... ; Knobler, R. 2017
In this thesis the thermal- and photo-substitution behavior of polypyridyl ruthenium complexes is described at the surface of lipid bilayers and in homogeneous solutions. It is shown that the... Show moreIn this thesis the thermal- and photo-substitution behavior of polypyridyl ruthenium complexes is described at the surface of lipid bilayers and in homogeneous solutions. It is shown that the successive thermal binding and light-induced unbinding of the cationic ruthenium complex at the surface of the lipid bilayer requires negatively charged liposomes and ruthenium complexes containing moderately hindered N-N bidentate ligands. Our results in homogeneous solution show that changing the steric hindrance of the bidentate ligand influences both the photo- and thermal reactivities of these complexes, by altering the mechanism of the Ru-S bond formation. It is also shown that the Ru-S bond formation at the surface of negative lipid bilayers is faster than the same reaction in homogenous aqueous solutions, and a two-steps mechanism is proposed for the thermal coordination of ruthenium aqua complexes at membrane-embedded ligands. Furthermore, the application of ruthenium-functionalized liposomes in drug delivery is discussed. In vitro tests on cancer cell lines show that neutral liposomes functionalized with ruthenium compounds are more readily taken up by cancer cells than ruthenium-free liposomes. The liposome samples with ruthenium compounds are shown to be poorly cytotoxic in the dark. After light irradiation, the cytotoxicity increased at least up to five times for ruthenium complexes supported on non-PEGylated liposomes. Finally, the photoactivation of polypyridyl complexes with low-energy photons was studied using a photosensitization approach. A photosubstitution reaction was made faster upon yellow light irradiation than upon blue light irradiation by covalently linking a rhodamine B dye to the ruthenium complex. Show less
In this thesis, several studies on neonatal red cell alloimmune hemolytic disease are presented, including various management options, associated complications and co-morbidities and the short-term... Show moreIn this thesis, several studies on neonatal red cell alloimmune hemolytic disease are presented, including various management options, associated complications and co-morbidities and the short-term and long-term outcome of children with Rhesus hemolytic disease. Show less
UVA 1 therapy is a relatively new form of light therapy for atopic dermatitis. We describe that after 4 weeks of UVA-1 patients were better capable to maintain clinical improvement than after 3... Show moreUVA 1 therapy is a relatively new form of light therapy for atopic dermatitis. We describe that after 4 weeks of UVA-1 patients were better capable to maintain clinical improvement than after 3 weeks of therapy. Furthermore, UVA 1 therapy proved to be better than placebo therapy in patients with dyshidrotic eczema. Also, we described the favorable effect of UVA 1 therapy in chronic, generalized lichen ruber planus. Because of deep penetration of UVA 1, it could not only influence dermal inflammatory infiltrates in T-cell mediated diseases mentioned above, but also reach circulating activated B-cells in dermal capillaries in SLE. We investigated the effect of 6 and 12 J/cm2 UVA 1 in SLE patients, in a double-blinded, placebo-controlled, cross over study. Three weeks of 12 J/cm2 resulted in improved disease activity and proved to be more effective than placebo. Furthermore, a decrease of auto-antibody titers was observed in several patients. In vitro we showed that 40% of UVA 1 reached the dermis and increasing numbers of PBMCs died after rising doses of UVA-1. Also, immunoglobulin production by activated B cells decreased after increasing doses of UVA 1. It would be interesting to investigate UVA 1 therapy for other auto immune diseases. Show less
