Successful Large-Volume Cerebrospinal Fluid Aspiration for an Accidental Overdose of Intrathecal Cytarabine.

Successful large-volume cerebrospinal fluid aspiration for an accidental overdose of intrathecal cytarabine.

Med Oncol. 2013 Jun; 30(2): 525
Makar G, Al-Zubaidi M, Amar S, Feiz-Erfan I, Mehta D

Intrathecal therapy with cytarabine is widely used in the treatment of acute lymphocytic leukemia. We report the first case of accidental intrathecal cytarabine overdose in an adult patient. Overdose of intrathecal chemotherapy has been reported to cause severe neurological damage including seizures, coma and death. Methotrexate levels can help guide intrathecal dosing of methotrexate, but no such test is commercially available for cytarabine. There are no standardized treatment recommendations for the management of this medical emergency. Intrathecal methotrexate overdose has been variously treated with cerebrospinal fluid drainage or exchange. Ventriculo-lumbar perfusion, steroids and leucovorin have also been used. It seems crucial to quickly remove as much drug as possible from the cerebrospinal fluid. Our patient was successfully treated with large-volume cerebrospinal fluid aspiration through an Ommaya reservoir. She did not suffer any significant immediate or late complications at 4 months of follow-up. HubMed – drug

 

Direct-To-Consumer Television Advertising Exposure, Diagnosis with High Cholesterol, and Statin Use.

J Gen Intern Med. 2013 Mar 6;
Niederdeppe J, Byrne S, Avery RJ, Cantor J

BACKGROUND: While statin drugs are recommended for secondary prevention of coronary heart disease (CHD), there is no medical consensus on whether or not a statin should be added to lifestyle change efforts for primary prevention of CHD. Previous research suggests that exposure to direct-to-consumer advertising (DTCA) increases drug demand among those at comparatively low risk. Research has yet to examine whether individual-level DTCA exposure may influence statin use among men and women at high, moderate, or low risk for future cardiac events. OBJECTIVE: To determine the relationship between estimated exposure to DTCA for statin drugs and two clinical variables: diagnosis with high cholesterol and statin use. DESIGN: We used logistic regression to analyze repeated cross-sectional surveys of the United States population, merged with data on the frequency of DTCA appearances on national, cable, and local television, between 2001 and 2007. PARTICIPANTS: American adults (n?=?106,685) aged 18 and older. MAIN MEASURES: Levels of exposure to statin DTCA, based on ad appearances and TV viewing patterns; self-reports of whether or not a respondent has been diagnosed with high cholesterol, and whether or not a respondent took a statin in the past year. KEY RESULTS: Adjusting for potential confounders, we estimate that exposure to statin ads increased the odds of being diagnosed with high cholesterol by 16 to 20 %, and increased statin use by 16 to 22 %, among both men and women (p?HubMed – drug

 

Mitochondrial modulation decreases the bortezomib-resistance in multiple myeloma cells.

Int J Cancer. 2013 Mar 5;
Song IS, Kim HK, Lee SR, Jeong SH, Kim N, Ko KS, Rhee BD, Han J

Multiple myeloma (MM) is an incurable hematological malignancy that causes most patients to eventually relapse and die from their disease. The 20S proteasome inhibitor bortezomib has emerged as an effective drug for MM treatment; however, intrinsic and acquired resistance to bortezomib has already been observed in MM patients. We evaluated the involvement of mitochondria in resistance to bortezomib-induced cell death in two different MM cell lines (bortezomib-resistant KMS20 cells and bortezomib-sensitive KMS28BM cells). Indices of mitochondrial function, including membrane potential, oxygen consumption rate, and adenosine-5′-triphosphate and mitochondrial Ca2+ concentrations, were positively correlated with drug resistance of KMS cell lines. Mitochondrial genes including CYPD, SOD2, and MCU were differentially expressed in KMS cells. Thus, changes in the expression of these genes lead to changes in mitochondrial activity and in bortezomib susceptibility or resistance, and their combined effect contributes to differential sensitivity or resistance of MM cells to bortezomib. In support of this finding, co-administration of bortezomib and 2-methoxyestradiol, an SOD inhibitor, rendered KMS20 cells sensitive to apoptosis. Our results provide new insight into therapeutic modalities for MM patients. Studying mitochondrial activity and specific mitochondrial gene expression in fresh MM specimens might help predict resistance to pro-apoptotic chemotherapies and inform clinical decision-making. © 2013 Wiley Periodicals, Inc. HubMed – drug