The Effect of Geometric Variations in Posterior-stabilized Knee Designs on Motion Characteristics Measured in a Knee Loading Machine

Background

In different posterior-stabilized (PS) total knees, there are considerable variations in condylar surface radii and cam-post geometry. To what extent these variations affect kinematics is not known. Furthermore, there are no clearly defined ideal kinematics for a total knee.

Questions/purposes

The purposes of this study were to determine (1) what the kinematic differences are caused by geometrical variations between PS total knee designs in use today; and (2) what design characteristics will produce kinematics that closely resemble that of the normal anatomic knee.

Methods

Four current PS designs with different geometries and one experimental asymmetric PS design, with a relatively conforming medial side, were tested in a purpose-built machine. The machine applied combinations of compressive, shear, and torque forces at a sequence of flexion angles to represent a range of everyday activities, consistent with the ASTM standard test for measuring constraint. The femorotibial contact points, the neutral path of motion, and the AP and internal-external laxities were used as the kinematic indicators.

Results

The PS designs showed major differences in motion characteristics among themselves and with motion data from anatomic knees determined in a previous study. Abnormalities in the current designs included symmetric mediolateral motion, susceptibility to excessive AP medial laxity, and reduced laxity in high flexion. The asymmetric-guided motion design alleviated some but not all of the abnormalities.

Conclusions

Current PS designs showed kinematic abnormalities to a greater or lesser extent. An asymmetric design may provide a path to achieving a closer match to anatomic kinematics.

Clinical Relevance

One criterion for the evaluation of PS total knees is how closely the kinematics of the prosthesis resemble that of the anatomic knee, because this is likely to affect the quality of function.     

One-pot sequential multicomponent reaction between in situ generated aldimines and succinaldehyde: facile synthesis of substituted pyrrole-3-carbaldehydes and applications towards medicinally important fused heterocycles

An efficient sequential multi-component method for the synthesis of N-arylpyrrole-3-carbaldehydes has been developed. This reaction involved a proline-catalyzed direct Mannich reaction-cyclization sequence between succinaldehyde and in situ generated Ar/HetAr/indolyl-imines, followed by IBX-mediated oxidative aromatization in one-pot operation. The practical utility of this procedure is shown at gram-scale and the synthesis of diverse bioactive fused heterocyclic scaffolds such as pyrroloquinoline, pyrrolo-oxadiazole, dihydro pyrroloquinoline, and pyrrolo-phenanthridine.

An efficient sequential multi-component method for the synthesis of N-arylpyrrole-3-carbaldehydes has been developed.     

A prospective evaluation of cardiovascular magnetic resonance measures of dyssynchrony in the prediction of response to cardiac resynchronization therapy

Background

Many patients with electrical dyssynchrony who undergo cardiac resynchronization therapy (CRT) do not obtain substantial benefit. Assessing mechanical dyssynchrony may improve patient selection. Results from studies using echocardiographic imaging to measure dyssynchrony have ultimately proved disappointing. We sought to evaluate cardiac motion in patients with heart failure and electrical dyssynchrony using cardiovascular magnetic resonance (CMR). We developed a framework for comparing measures of myocardial mechanics and evaluated how well they predicted response to CRT.

Methods

CMR was performed at 1.5 Tesla prior to CRT. Steady-state free precession (SSFP) cine images and complementary modulation of magnetization (CSPAMM) tagged cine images were acquired. Images were processed using a novel framework to extract regional ventricular volume-change, thickening and deformation fields (strain). A systolic dyssynchrony index (SDI) for all parameters within a 16-segment model of the ventricle was computed with high SDI denoting more dyssynchrony. Once identified, the optimal measure was applied to a second patient population to determine its utility as a predictor of CRT response compared to current accepted predictors (QRS duration, LBBB morphology and scar burden).

Results

Forty-four patients were recruited in the first phase (91% male, 63.3 ± 14.1 years; 80% NYHA class III) with mean QRSd 154 ± 24 ms. Twenty-one out of 44 (48%) patients showed reverse remodelling (RR) with a decrease in end systolic volume (ESV) ≥ 15% at 6 months. Volume-change SDI was the strongest predictor of RR (PR 5.67; 95% CI 1.95-16.5; P = 0.003). SDI derived from myocardial strain was least predictive. Volume-change SDI was applied as a predictor of RR to a second population of 50 patients (70% male, mean age 68.6 ± 12.2 years, 76% NYHA class III) with mean QRSd 146 ± 21 ms. When compared to QRSd, LBBB morphology and scar burden, volume-change SDI was the only statistically significant predictor of RR in this group.

Conclusion

A systolic dyssynchrony index derived from volume-change is a highly reproducible measurement that can be derived from routinely acquired SSFP cine images and predicts RR following CRT whilst an SDI of regional strain does not.     

Thalidomide protects endothelial cells from doxorubicin-induced apoptosis but alters cell morphology

Summary.  Antiangiogenesis agents are now being used in clinical trials to reduce the risk of recurrence of cancer. Several of these agents, however, are associated with thrombosis, especially when used in combination with chemotherapy. Antiangiogenesis and thrombosis are both endothelial-related activities, and we therefore evaluated one presumed antiangiogenesis agent (thalidomide) on intact cultured endothelial cells, and on cultured endothelial cells injured by preincubation with doxorubicin. We evaluated cell viability, caspase-3 activation, morphology of cells using light microscopy, and protease activated receptor-1 (PAR-l) expression. In our experiments, doxorubicin induced a dose- and incubation time-dependent and caspase-3-mediated apoptosis of endothelial cells. Thalidomide alone caused no changes in intact endothelial cells in terms of morphology, cell viability or activation of caspase-3. In contrast, when thalidomide was added to doxorubicin-injured endothelial cells, there was protection from cell death, increase in viability of endothelial cells, induction of differentiation and formation of neotubules. Doxorubicin reduced the expression of thrombin receptor, PAR-1, as evaluated by immunostaining and flow cytometry. Thalidomide did not alter PAR-1 expression in untreated cells but restored its expression reduced by doxorubicin. These findings suggest that thalidomide may be procoagulant, not by enhancing doxorubicin-mediated endothelial cell injury, but by altering the expression of PAR-1 on injured endothelium and resulting in endothelial dysfunction, which may explain hypercoagulability in patients treated with chemotherapy followed by thalidomide.     

Pigmented Pheochromocytoma: an Unusual Variant of a Common Tumor

Pheochromocytoma is a neuroendocrine tumor arising from the adrenal medulla. A number of variants of pheochromocytoma are known; however, pigmented pheochromocytoma is extremely rare, with only few cases reported in literature. We report the cases of two patients with pigmented pheochromocytoma. Case 1 was a 28-year-old female who presented with complaints of breathlessness, palpitations, and anxiety for 5 years, which had worsened over the last 8 months. Computed tomography (CT) abdomen showed a right suprarenal mass. Case 2 was that of an 18-year-old girl who presented with similar complaints and was diagnosed with hypertension. CT abdomen showed bilateral adrenal masses. Urinary vanillyl mandelic acid was raised in both patients. Sections examined from all three tumors showed cells arranged in Zellballen pattern, separated by thin fibrovascular septae. Tumor cells showed moderate to marked nuclear pleomorphism in case 1. Mitoses were, however, not seen. There was no evidence of capsular or vascular invasion. Many of the tumor cells showed intracytoplasmic black pigment, which was positive for Fontana–Masson and was bleach-labile, confirming it as melanin. Hemosiderin deposition was also identified. Large areas of hemorrhagic necrosis were seen in case 1. Tumor cells were immunopositive for chromogranin and synaptophysin, while they were negative for HMB-45. Electron microscopy was performed. A final diagnosis of pigmented pheochromocytoma was rendered in both cases. Pigmented pheochromocytoma is a very rare tumor, which needs to be differentiated from other pigmented tumors like malignant melanoma of adrenal gland and pigmented adrenal adenoma. Histochemistry and immunohistochemistry help in making this distinction.