Free mycophenolic acid should be monitored in renal transplant recipients with hypoalbuminemia

The current approach for therapeutic drug monitoring in renal transplant recipients receiving mycophenolate mofetil (MMF) is measurement of total mycophenolic acid (MPA) concentration. Because MPA is highly bound, during hypoalbuminemia the total concentration no longer reflects the free (pharmacologically active) concentration. The authors investigated what degree of hypoalbuminemia causes a significant change in protein binding and thus percentage free MPA. Forty-two renal transplant recipients were recruited for the study. Free and total concentrations of MPA (predose, and 1, 3, and 6 hours post-MMF dose samples) and plasma albumin concentrations were determined on day 5 posttransplantation. Six-hour area under the concentration-time curve (AUC(0-6)) values were calculated for free and total MPA, and percentage free MPA was determined for each patient. The authors found a significant relationship between low albumin concentrations and increased percentage free MPA (Spearman correlation = -0.54, P < 0.0001). Receiver operating characteristic (ROC) curve analysis was performed on the albumin versus percentage free MPA data. The cutoff value of albumin determined from the ROC analysis that differentiated normal from elevated percentage free MPA (defined as greater than or equal to3%) in this patient population was 31 g/L. At this cutoff value albumin was found to be a good predictor of altered free MPA percentage, with a sensitivity and specificity of 0.75 and 0.80, respectively, and an area under the ROC curve of 0.79. To rationalize MMF dosing regimens in hypoalbuminemic patients (plasma albumin less than or equal to 31 g/L), clinicians should consider monitoring the free MPA concentration.

Delayed onset of transversus abdominus in long-standing groin pain

Long-standing groin pain is a persistent problem that is commonly difficult to rehabilitate. Theoretical rationale indicates a relationship between the motor control of the pelvis and long-standing groin pain; however, this link has not been investigated. Purpose: The current experiment aimed to evaluate motor control of the abdominal muscles in a group of Australian football players with and without long-standing groin pain. Methods: Ten participants with long-standing groin pain and 12 asymptomatic controls were recruited for the study. Participants were elite or subelite Australian football players. Fine-wire and surface electromyography electrodes were used to record the activity of the selected abdominal and leg muscles during a visual choice reaction-time task (active straight leg raising). Results: When the asymptomatic controls completed the active straight leg raise (ASLR) task, the transversus abdominus contracted in a feed-forward manner. However, when individuals with long-standing groin pain completed the ASLR task, the onset of transversus abdominus was delayed (P < 0.05) compared with the control group. There were no differences between groups for the onset of activity of internal oblique, external oblique, and rectus abdominus (all P > 0.05). Conclusions: The finding that the onset of transversus abdominus is delayed in individuals with long-standing groin pain is important, as it demonstrates an association between long-standing groin pain and transversus abdominus activation.