[Fever during blood transfusion. A case of coincidence instead of causality]. / Fieber während einer Bluttransfusion. Ein Fall von Koinzidenz statt Kausalität.

A boy aged 2 years and 5 months showed agitation, shivering and fever with a temperature of 38.9 °C during a red blood cell transfusion. Examination of the assumed adverse transfusion reaction gave no indications of erythrocyte incompatibility, hemolysis or IgA incompatibility. No antibodies against HLA class I antigens or HPA antigens were found in the recipient's blood. Sterility testing of the blood product showed no growth, but in the blood cultures taken from the patient immediately after the blood transfusion, Enterobacter cloacae was detected which also could be found in blood cultures and nose and throat swabs taken 3 days before. Therefore, the fever during blood transfusion was not a case of causality but of coincidence. This case underlines the recommendation to examine blood cultures from the recipient in all suspected cases of adverse transfusion reaction.

Tetracycline-inducible transgene expression mediated by a single AAV vector.

Regulated gene delivery systems are usually made of two elements: an inducible promoter and a transactivator. In order to optimize gene delivery and regulation, a single viral vector ensuring adequate stoichiometry of the two elements is required. However, efficient regulation is hampered by interferences between the inducible promoter and (i) the promoter used to express the transactivator and/or (ii) promoter/enhancer elements present in the viral vector backbone. We describe a single AAV vector in which transcription of both the reverse tetracycline transactivator (rtTA) and the transgene is initiated from a bidirectional tetracycline-responsive promoter and terminated at bidirectional SV40 polyadenylation sites flanking both ITRs. Up to 50-fold induction of gene expression in human tumor cell lines and 100-fold in primary cultures of rat Schwann cells was demonstrated. In addition an 80-fold induction in vivo in the rat brain has been obtained. In vitro, the autoregulatory vector exhibits an induced expression level superior to that obtained using the constitutive CMV promoter. Although extinction of the transgene after removal of tetracycline was rapid (less than 3 days), inducibility after addition of tetracycline was slow (about 14 days). This kinetics is suitable for therapeutic gene expression in slowly progressive diseases while allowing rapid switch-off in case of undesirable effects. As compared to previously described autoregulatory tet-repressible (tetOFF) AAV vectors, the tet-inducible (tetON) vector prevents chronic antibiotic administration in the uninduced state.