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

Peak systolic velocity using color-coded tissue Doppler imaging, a strong and independent predictor of outcome in acute coronary syndrome patients

BACKGROUND: Traditional echocardiographic methods like left ventricular ejection fraction(EF) and wall motion scoring (WMS) and new methods like speckle tracking (ST) based 2D strain carry important prognostic information in acute coronary syndrome (ACS) patients. Parameters from tissue Doppler imaging (TDI), with its high time resolution, may further increase the prognostic value. Peak systolic velocity (PSV) of the basal segments of the left ventricle from TDI is a robust and user independent parameter. The aim was to investigate the prognostic value of PSV compared to EF, WMS, 2D strain and E/e'. METHODS: Echocardiographic images were collected and post processed in 227 ACS patients. Additional clinical data was prospectively gathered and patients were followed for 3-5 years regarding the combined endpoint of death or re-admission due to ACS or heart failure. RESULTS: The combined endpoint occurred in 85 (37%) patients. Those with an event had lower median PSV than those without (4,4 cm/s) vs. (5,3 cm/s), (p<0.001). In a ROC analysis, the AUC was larger for PSV (0.75) than for EF (0.68), WMS (0.63), 2D strain (0.67) and E/e'(0.70). The combined endpoint increased with decreasing PSV. When adjusting for differences in baseline characteristics in a COX-regression model, PSV remained independently associated with outcome where the others did not. PSV was also less sensitive to image quality with fewer values missing or unacceptable for analysis. CONCLUSION: Peak systolic velocity (PSV) is a robust measurement that seems to have a strong and independent association with outcome compared to traditional echocardiographic measurements in ACS patients

Dressling, Mathias (1833 - 1870)

This biographical summary was created by the Works Progress Administration (WPA) between 1936 and 1939

Hechtel, Mike (1847 - 1935)

This biographical summary was created by the Works Progress Administration (WPA) between 1936 and 1939

Johnson, Herman (1864 - 1928)

This biographical summary was created by the Works Progress Administration (WPA) between 1936 and 1939

Karsburg, August (1854 - 1919)

This biographical summary was created by the Works Progress Administration (WPA) between 1936 and 1939

Holmes, John S. (1865 - 1932)

This biographical summary was created by the Works Progress Administration (WPA) between 1936 and 1939

Henry, John A. (1884 - )

This biographical summary was created by the Works Progress Administration (WPA) between 1936 and 1939

Maus, Peter (1832 - )

This biographical summary was created by the Works Progress Administration (WPA) between 1936 and 1939

Young, Axel T. (1877 - )

This biographical summary was created by the Works Progress Administration (WPA) between 1936 and 1939