Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 6: magnetic resonance imaging and discography for patient selection for lumbar fusion

Discography is an exquisitely sensitive but not specific diagnostic test for the diagnosis of discogenic low-back pain. The restriction of the definition of a positive discographic study to one that elicits concordant pain from a morphologically abnormal disc improves the definition's accuracy. Fusion surgery based on discography alone, however, is not reliably associated with clinical success. Therefore, discography is not recommended as a standalone test for treatment decisions in patients with low-back pain. Magnetic resonance imaging is a sensitive and noninvasive test for the presence of degenerative disc disease. Discography should not be attempted in patients with normal lumbar MR images. Discography appears to have a role in the evaluation of patients with low-back pain, but it is best limited to the evaluation of abnormal interspaces identified on MR imaging, the investigation of adjacent-level disc disease, and as a means to rule out cases of nonorganic pain from surgical consideration.     

In vitro synergy and enhanced murine brain penetration of saquinavir coadministered with mefloquine

Highly active antiretroviral therapy has substantially improved prognosis in human immunodeficiency virus (HIV). However, the integration of proviral DNA, development of viral resistance, and lack of permeability of drugs into sanctuary sites (e.g., brain and lymphocyte) are major limitations to current regimens. Previous studies have indicated that the antimalarial drug chloroquine (CQ) has antiviral efficacy and a synergism with HIV protease inhibitors. We have screened a panel of antimalarial compounds for activity against HIV-1 in vitro. A limited efficacy was observed for CQ, mefloquine (MQ), and mepacrine (MC). However, marked synergy was observed between MQ and saquinavir (SQV), but not CQ in U937 cells. Furthermore, enhancement of the antiviral activity of SQV and four other protease inhibitors (PIs) by MQ was observed in MT4 cells, indicating a class specific rather than a drug-specific phenomenon. We demonstrate that these observations are a result of inhibition of multiple drug efflux proteins by MQ and that MQ also displaces SQV from orosomucoid in vitro. Finally, coadministration of MQ and SQV in CD-1 mice dramatically altered the tissue distribution of SQV, resulting in a >3-fold and >2-fold increase in the tissue/blood ratio for brain and testis, respectively. This pharmacological enhancement of in vitro antiviral activity of PIs by MQ now warrants further examination in vivo.