Adverse effects of antiretroviral drugs on HIV-1-infected and -uninfected human monocyte-derived macrophages.

Antiretroviral drugs approved for treatment of HIV-1 infection include nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs). Use of these drugs in combinations (highly active antiretroviral therapy) has delayed disease progression. However, long-term therapy is associated with potentially serious adverse effects. NRTIs are thought to contribute to these adverse effects via depletion of mtDNA. Inasmuch as macrophages (major targets for HIV-1) are highly metabolically active with large numbers of mitochondria, we investigated the effects of NRTIs (didanosine, stavudine, lamivudine, and zidovudine) on the viability and function of HIV-1-infected and -uninfected human monocyte-derived macrophages (MDMs). We demonstrate that the combinations didanosine/stavudine and lamivudine/zidovudine decrease mtDNA content in MDMs, with HIV-1-infected MDMs displaying a greater reduction than uninfected cells. This decrease correlated with decreased complement-mediated phagocytosis (C'MP) by MDMs, a process dependent on mitochondrial function. Inasmuch as PIs have previously been reported to interact with cellular proteases and given that cellular proteases are involved in the phagocytic process, we investigated the effects of the PI indinavir on C'MP. We demonstrate that indinavir augments C'MP by uninfected MDMs, but not HIV-1-infected MDMs. This study provides additional understanding on the effects of commonly used antiretroviral drugs on cellular immune function.

Functional measurement of knee joint position sense after anterior cruciate ligament reconstruction.

OBJECTIVE: To examine for differences in joint position sense (JPS) between knees with reconstructed anterior cruciate ligaments (ACLs) and uninjured knees by using a functional weight-bearing measurement method. DESIGN: Two-way repeated-measures in a convenience sample. SETTING: An Australian university rehabilitation laboratory. PARTICIPANTS: Nine subjects presenting at 12 to 16 months after unilateral ACL reconstruction using the semitendinosus/gracilis graft who were recruited from 2 orthopedic surgeons. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: JPS of the reconstructed and uninjured knees was examined by using the Peak Motus motion measurement system to record target joint angles and to calculate reproduced angles after limb movement into flexion and extension, performed in a weight-bearing position. RESULTS: There were no significant differences in JPS between reconstructed and uninjured knees (P=.68) or between the flexion and extension tasks (P=.47). CONCLUSION: There was no deficit in knee JPS 12 to 16 months after ACL reconstruction, as measured by a functional weight-bearing method. Further studies should examine the clinical utility of the method as a way to evaluate functional aspects of knee joint proprioception.

Self evaluation and functional testing two to four years post ACL reconstruction.

This study examined subjective perceptions of knee status and performance in single limb functional tests following anterior cruciate ligament reconstruction. The Tegner activity scale, modified Noyes and an analogue scale were administered to 20 subjects. Performance outcome in the 6m and 12m timed hop, cross-over hop and stairs hopple tests were described using the limb index. In general, subjects experienced minimal limitations during daily activities and a slight reduction in their present activity level. Poorer performance was noted in the operated limb in all functional tests. Subjective data gathered from the questionnaire compared favourably with functional outcome. Interpretation of subjective outcomes in relation to functional testing results potentially enhances the accuracy of post-operative knee evaluation.