Component position is critical to longevity of knee arthroplasties. Femoral component rotation is typically referenced from the transepicondylar axis (TEA), the anterior-posterior (AP) axis or the posterior condylar axis. Other studies have shown high variability in locating the TEA while proposing digitization of other landmarks such as the AP axis as a less-variable reference. This study uses a navigation system to compare the reproducibility of computing a kinematically-derived, navigated knee axis (NKA) to digitizing the TEA and AP axis. Twelve knees from unembalmed cadavers were tested. Four arthroplasty surgeons digitized the femoral epicondyles and the AP axis direction as well as flexed and extended the knee repeatedly to allow for NKA determination. The variance of the NKA axis determined under neutral loading conditions was smaller than the variance of the TEA axis when the kinematics were measured in the closed surgical condition (P<0.001). However, varus, valgus, and internal loading of the leg increased the variability of the NKA. Distraction of the leg during knee flexion and extension preserved the low variability of the NKA. In conclusion, a kinematically-derived NKA under neutral or distraction loading is more reproducible than the TEA and AP axis determined by digitization.
Stress-like elevations in plasma glucocorticoids rapidly inhibit pulsatile LH secretion in ovariectomized sheep by reducing pituitary responsiveness to GnRH. This effect can be blocked by a nonspecific antagonist of the type II glucocorticoid receptor (GR) RU486. A series of experiments was conducted to strengthen the evidence for a mediatory role of the type II GR and to investigate the neuroendocrine site and cellular mechanism underlying this inhibitory effect of cortisol. First, we demonstrated that a specific agonist of the type II GR, dexamethasone, mimics the suppressive action of cortisol on pituitary responsiveness to GnRH pulses in ovariectomized ewes. This effect, which became evident within 30 min, documents mediation via the type II GR. We next determined that exposure of cultured ovine pituitary cells to cortisol reduced the LH response to pulse-like delivery of GnRH by 50% within 30 min, indicating a pituitary site of action. Finally, we tested the hypothesis that suppression of pituitary responsiveness to GnRH in ovariectomized ewes is due to reduced tissue concentrations of GnRH receptor. Although cortisol blunted the amplitude of GnRH-induced LH pulses within 1-2 h, the amount of GnRH receptor mRNA or protein was not affected over this time frame. Collectively, these observations provide evidence that cortisol acts via the type II GR within the pituitary gland to elicit a rapid decrease in responsiveness to GnRH, independent of changes in expression of the GnRH receptor.
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