Cytotoxic drug sensitivity of Epstein-Barr virus transformed lymphoblastoid B-cells

BACKGROUND: Epstein-Barr virus (EBV) is the causative agent of immunosuppression associated lymphoproliferations such as post-transplant lymphoproliferative disorder (PTLD), AIDS related immunoblastic lymphomas (ARL) and immunoblastic lymphomas in X-linked lymphoproliferative syndrome (XLP). The reported overall mortality for PTLD often exceeds 50%. Reducing the immunosuppression in recipients of solid organ transplants (SOT) or using highly active antiretroviral therapy in AIDS patients leads to complete remission in 23–50% of the PTLD/ARL cases but will not suffice for recipients of bone marrow grafts. An additional therapeutic alternative is the treatment with anti-CD20 antibodies (Rituximab) or EBV-specific cytotoxic T-cells. Chemotherapy is used for the non-responding cases only as the second or third line of treatment. The most frequently used chemotherapy regimens originate from the non-Hodgkin lymphoma protocols and there are no cytotoxic drugs that have been specifically selected against EBV induced lymphoproliferative disorders. METHODS: As lymphoblastoid cell lines (LCLs) are well established in vitro models for PTLD, we have assessed 17 LCLs for cytotoxic drug sensitivity. After three days of incubation, live and dead cells were differentially stained using fluorescent dyes. The precise numbers of live and dead cells were determined using a custom designed automated laser confocal fluorescent microscope. RESULTS: Independently of their origin, LCLs showed very similar drug sensitivity patterns against 29 frequently used cytostatic drugs. LCLs were highly sensitive for vincristine, methotrexate, epirubicin and paclitaxel. CONCLUSION: Our data shows that the inclusion of epirubicin and paclitaxel into chemotherapy protocols against PTLD may be justified

BUREAUCRACY AND TIME CONSISTENCY

We construct a model that takes seriously the role of bureaucracy in the characterization of time-consistent policies. We argue that if the possibilities for governments to reduce the size of bureaucracy are limited, bureaucracy can be used as a means for influencing future governments. We show that the political process has implications for the size and growth of bureaucracy. Parties in power may hire bureaucrats of the opposite political color. This is a part of the time-consistent policy. Our model also gives an explanation for the growth of bureaucracy. This is a consequence of the time-consistent policies, i.e. policies that partially tie the hands of future governments. We also show that if public sector production is inefficient, the public sector will be too large in the long run. In the short run it may be too small. Copyright 1993 Blackwell Publishers Ltd..

Time cycles of homicide in the early modern Nordic area

An extensive body of criminological research has shown that criminal and violent behaviour manifests time patterns in terms of daily, weekly and annual cycles. This is consistent with criminological routine activities theory. Can we generalize these patterns to historical periods? In this article, we draw on a recently created unique dataset, covering the years 1608 to 1699 in three Nordic regions, to explore time cycles of offending in the early modern period. Examining daily, weekly and annual cycles, we find that lethal violence manifested strong time patterns in the early modern period. The role of public holidays was central especially in the period lasting from Christmas to Midsummer. Probing the role of key routines, we disaggregate the composition of homicide cycles by alcohol use and place of occurrence. The findings indicate that early modern homicide time cycles were associated with alcohol use and activities in private places (private homes, homesteads). We conclude by discussing the strengths and limitations of our data and by suggesting further research in the promising frontier of standardized long duration homicide research.Peer reviewe