Anterior knee symptoms after S-ROM hinge implantation

Purpose: To evaluate the performance of a canal filling hinge device for complex knee arthroplasty. Methods: Thirty-seven (4 primary hinge implantation and 33 revision cases) patients who had undergone arthroplasty with the S-ROM third generation hinge device for a combination of massive bone loss or ligamentous insufficiency were prospectively examined with a minimum of 5-year follow-up. Median age at surgery was 72 years (range: 43 to 87 years). Principal indications included aseptic loosening or massive osteolysis (24 cases), infection (8 cases) and periprosthetic fracture (4 cases). All patients exhibited either grade 2 (N = 12) or grade 3 (N = 25) AORI bone loss or a grade 3 medial ligament deficiency. Results: One patient experienced implant failure (71 months), and one patient suffered late deep infection (36 months). Mean WOMAC score improved from 27 to 62. Four patients required patellar resurfacing for persistent pain. The 5-year survivorship was 86%. Conclusions: While the S-ROM device may offer satisfactory medium term outcome for complex end stage knee disease, we report a high rate of debilitating anterior knee symptoms.

Role of P-glycoprotein in limiting the brain penetration of glabridin, an active isoflavan from the root of Glycyrrhiza glabra.

Purpose. Glabridin is a major active constituent of Glycyrrhiza glabra which is commonly used in the treatment of cardiovascular and central nervous system (CNS) diseases. Recently, we have found that glabridin is a substrate of P-glycoprotein (PgP/MDR1). This study aimed to investigate the role of PgP in glabridin penetration across the blood–brain barrier (BBB) using several in vitro and in vivo models.
Materials and Methods. Cultured primary rat brain microvascular endothelial cells (RBMVECs) were used in the uptake, efflux and transcellular transport studies. A rat bilateral in situ brain perfusion model was used to investigate the brain distribution of glabridin. The brain and tissue distribution of glabridin in rats with or without coadministered verapamil or quinidine were examined with correction for the tissue residual blood. In addition, the brain distribution of glabridin in mdr1a(-/-) mice was compared with the wild-type mice. Glabridin in various biological matrices was determined by a validated liquid chromatography mass spectrometric method.
Results. The uptake and efflux of glabridin in cultured RBMVECs were ATP-dependent and significantly altered in the presence of a PgP or multi-drug resistance protein (Mrp1/2) inhibitor (e.g. verapamil or MK-571). A polarized transport of glabridin was found in RBMVEC monolayers with
facilitated efflux from the abluminal (BL) to luminal (AP) side. Addition of a PgP or Mrp1/2 inhibitor in both luminal and abluminal sides attenuated the polarized transport across RBMVECs. In a bilateral in situ brain perfusion model, the uptake of glabridin into the cerebrum increased from 0.42 T 0.09% at 1 min to 9.27 T 1.69% (ml/100 g tissue) at 30 min and was significantly greater than that for sucrose. Coperfusion of a PgP or Mrp1/2 inhibitor significantly increased the brain distribution of glabridin by 33.6j142.9%. The rat brain levels of glabridin were only about 27% of plasma levels when corrected by tissue residual blood and it was increased to up to 44% when verapamil or quinidine was coadministered. The area under the brain concentration-time curve (AUC) of glabridin in mdr1a(-/-) mice was 6.0-fold higher than the wild-type mice.
Conclusions. These findings indicate that PgP limits the brain penetration of glabridin through the BBB and PgP may cause drug resistance to glabridin (licorice) therapy for CNS diseases and potential drugglabridin interactions. However, further studies are needed to explore the role of other drug transporters (e.g. Mrp1-4) in restricting the brain penetration of glabridin.

Heteroscedasticity robust panel unit root tests

This article proposes new unit root tests for panels where the errors may be not only serial and/or crosscorrelated,but also unconditionally heteroscedastic. Despite their generality, the test statistics are shown tobe very simple to implement, requiring only minimal corrections and still the limiting distributions underthe null hypothesis are completely free from nuisance parameters. Monte Carlo evidence is also providedto suggest that the new tests perform well in small samples, also when compared to some of the existingtests. Supplementary materials for this article are available online.