Biomechanical effects of patellar positioning on intraoperative knee joint gap measurement in total knee arthroplasty

Background

Balancing both the lateral/medial and extension/flexion joint gaps is a prerequisite for soft tissue balance in total knee arthroplasty. The purpose of this study was to quantify the effects of patellar positioning and quadriceps load during total knee arthroplasty on knee joint gap measurements.

Methods

Eight fresh-frozen cadaveric knees ranging in age from 65 to 85 years old were used. Using a medial parapatellar approach, posterior cruciate ligament sacrificing total knee arthroplasty was performed. The specimens were mounted on a custom knee testing system that allowed the femur to be locked in position for knee extension or flexion. Patellar positions of eversion, reduction, and following repair of the arthrotomy were examined. The influence of quadriceps muscle load was investigated by varying the quadriceps load from 0 to 125 N. The lateral and medial joint gaps, represented by the distance from the implanted femoral component surface to the cut tibia surface, were measured with 100 N tibial distraction force using a 3D digitizer in both extension (0°) and flexion (90°).

Findings

Both the medial and lateral joint gaps with patella eversion were significantly smaller than those with patellar reduction and arthrotomy repair (extension: all quadriceps loads, P < 0.0002; flexion: quadriceps loads less than 75 N, P < 0.0002). In patella eversion, quadriceps loading decreased the lateral joint gap more than the medial joint gap in both extension and flexion; however, the effect was greater in knee flexion with significant differences seen at all quadriceps loads, whereas in extension significant differences were only seen for quadriceps loading of 75 N and greater. Patella eversion also caused a lateral-posterior shift and external rotation of the tibia compared to the other conditions (P < 0.005). With patella reduction and repair of the arthrotomy lower quadriceps loading decreased the extension gap significantly more than the flexion gap (P < 0.01). Following repair of the arthrotomy higher quadriceps loading significantly decreased the flexion gap more than the extension gap (P < 0.04).

Interpretation

The patellar positioning and quadriceps muscle loading in total knee arthroplasty have a strong influence on intraoperative joint gap measurements.     

Restoration of Smad4 in BxPC3 Pancreatic Cancer Cells Attenuates Proliferation without Altering Angiogenesis

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive human malignancy in which the transforming growth factor beta (TGF-β) signal transducer, Smad4, is commonly mutated or deleted. BxPC3 human pancreatic cancer cells exhibit a homozygous deletion of the Smad4 gene, yet are growth inhibited by TGF-β1. In the present study, we sought to determine whether reintroduction of Smad4 into BxPC3 cells alters their behavior in vitro and in vivo. Sham transfected and Smad4 expressing BxPC3 cells exhibited similar responses to TGF-β1 with respect to p21 upregulation, hypophosphorylation of the RB protein, Smad2 phosphorylation, and Smad2/3 nuclear translocation. TGF-β1 did not alter p27 expression, and silencing of p21 with an appropriate siRNA markedly attenuated TGF-β1-mediated growth inhibition. Nonetheless, the presence of Smad4 was associated in vitro with a more prolonged doubling time, enhanced sensitivity to the growth inhibitory actions of exogenous TGF-β1, and a more flattened cellular morphology. In vivo, Smad4 expression resulted in delayed tumor growth and decreased cellular proliferation, without effects on either apoptosis or angiogenesis. These findings indicate that, in spite of the absence of Smad4, growth inhibition in BxPC3 cells by TGF-β1 is dependent on p21 upregulation and maintenance of RB in a hypophosphorylated, active state. Moreover, the presence of a functional Smad4 attenuates the capacity of BxPC3 cells to proliferate in vivo. However, this effect is transient, indicating that Smad4 growth inhibitory actions are circumvented in the later stages of pancreatic tumorigenicity.     

Inhibitory effect of amiloride and gadolinium on fine afferent nerves in the rat knee: evidence of mechanogated ion channels in joints

Synovial joints are complex sensory organs which provide continuous feedback regarding position sense and degree of limb movement. The transduction mechanisms which convert mechanical forces acting on the joint into an electrochemical signal which can then be transmitted to the central nervous system are not well understood. The present investigation examined the effect of the mechanogated ion channel blockers amiloride and gadolinium on knee joint mechanosensitivity. In deeply anaesthetised rats (sodium thiopental: 100–120 mg/kg, i.p.), single unit extracellular recordings were made from knee joint group III (Aδ) and group IV (C) primary afferents in response to mechanical rotation of the joint. Afferent firing rate was measured before and after topical application of either amiloride (0.1 mM, 1 mM) or gadolinium (250 μM) onto the receptive field of the sensory unit and recording was continued every 10 min up to a total of 50 min. With normal rotation of the knee, joint mechanosensitivity was significantly reduced by both amiloride (P<0.0001; n=10–21) and gadolinium (P=0.001; n=12) and this effect was sustained throughout the recording period. This investigation provides the first in vivo electrophysiological evidence that joint mechanotransduction involves the activation of amiloride and gadolinium-sensitive mechanogated ion channels. Future studies to determine the mechanogated ion channel subtypes present in joints and the modulation of their gating properties during inflammation may yield novel approaches for the control of arthritis pain. Funding: JJMcD is funded by the Alberta Heritage Foundation for Medical Research, the Canadian Institutes for Health Research, and the Arthritis Society of Canada.     

The physiological stress response to high-intensity sprint exercise following the ingestion of sodium bicarbonate

The purpose of this study was to investigate the effects of pre-exercise alkalosis on the physiological stress response to high-intensity exercise. Seven physically active males (age 22 ± 3 years, height 1.82 ± 0.06 m, mass 81.3 ± 8.4 kg and peak power output 300 ± 22 W) performed a repeated sprint cycle exercise following a dose of 0.3 g kg^?1 body mass of sodium bicarbonate (NaHCO₃) (BICARB), or a placebo of 0.045 g kg^?1 body mass of sodium chloride (PLAC). Monocyte-expressed heat shock protein 72 (HSP72) and plasma thiobarbituric acid reactive substances (TBARS) were significantly attenuated in BICARB compared to PLAC (p = 0.04 and p = 0.039, respectively), however total anti-oxidant capacity, the ratio of oxidised to total glutathione, cortisol, interleukin 6 and interleukin 8 were not significantly induced by the exercise. In conclusion, monocyte-expressed HSP72 is significantly increased following high-intensity anaerobic exercise, and its attenuation following such exercise with the ingestion of NaHCO₃ is unlikely to be due to a decreased oxidative stress.     

A guide to performing difficult bimanual coordination tasks: just follow the yellow brick road

Both discrete and continuous bimanual coordination patterns are difficult to effectively perform when the two limbs are required to perform different movements patterns, move at different velocities and/or move different amplitudes unless some form of integrated feedback is provided. The purpose of the present experiment was to determine the degree to which a complex bimanual coordination pattern could be performed when integrated feedback and movement template are provided. The complex bimanual coordination pattern involved reciprocal movements of the two limbs under different difficulty requirements. As defined by Fitts’ index of difficulty (ID), the left arm (ID = 3, A = 16°, W = 4°) task was of lower difficulty than the right arm task (ID = 5, A = 32°, W = 2°). Note that the left and right limb movements are also different in terms of movement time, movement velocity, accuracy requirements and amplitude as well as one movement was continuous and the other intermittent. Participants were provided 2 blocks of 9 trials in the bimanual condition (30 s/trial). Following the bimanual phase, participants performed two unimanual test trials—one with each limb. The results demonstrated that the performance for each limb in the bimanual condition was similar to the performance for the same limb and conditions in the unimanual control conditions. The similarity was indicated by the same movement speed, movement structure, endpoint variability and hit rates for the bimanual and unimanual conditions. The results support our hypothesis that people can overcome the intrinsic difficulties associated with performing complex bimanual coordination patterns when provided appropriate perceptual information feedback that allows them to detect and correct coordination errors.     

Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans

Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses through NFκB induction. Proteins involved in apoptosis and NFκB induction commonly contain evolutionarily conserved domains that can serve as signatures for identification by bioinformatics methods. Using a combination of public (NCBI) and private (RIKEN) databases, we compared the repertoire of apoptosis and NFκB-inducing genes in humans and mice from cDNA/EST/genomic data, focusing on the following domain families: (1) Caspase proteases; (2) Caspase recruitment domains (CARD); (3) Death Domains (DD); (4) Death Effector Domains (DED); (5) BIR domains of Inhibitor of Apoptosis Proteins (IAPs); (6) Bcl-2 homology (BH) domains of Bcl-2 family proteins; (7) Tumor Necrosis Factor (TNF)-family ligands; (8) TNF receptors (TNFR); (9) TIR domains; (10) PAAD (PYRIN; PYD, DAPIN); (11) nucleotide-binding NACHT domains; (12) TRAFs; (13) Hsp70-binding BAG domains; (14) endonuclease-associated CIDE domains; and (15) miscellaneous additional proteins. After excluding redundancy due to alternative splice forms, sequencing errors, and other considerations, we identified cDNAs derived from a total of 227 human genes among these domain families. Orthologous murine genes were found for 219 (96%); in addition, several unique murine genes were found, which appear not to have human orthologs. This mismatch may be due to the still fragmentary information about the mouse genome or genuine differences between mouse and human repertoires of apoptotic genes. With this caveat, we discuss similarities and differences in human and murine genes from these domain families.     

Local statistics in natural scenes predict the saliency of synthetic textures

The visual system is challenged with extracting and representing behaviorally relevant information contained in natural inputs of great complexity and detail. This task begins in the sensory periphery: retinal receptive fields and circuits are matched to the first and second-order statistical structure of natural inputs. This matching enables the retina to remove stimulus components that are predictable (and therefore uninformative), and primarily transmit what is unpredictable (and therefore informative). Here we show that this design principle applies to more complex aspects of natural scenes, and to central visual processing. We do this by classifying high-order statistics of natural scenes according to whether they are uninformative vs. informative. We find that the uninformative ones are perceptually nonsalient, while the informative ones are highly salient, and correspond to previously identified perceptual mechanisms whose neural basis is likely central. Our results suggest that the principle of efficient coding not only accounts for filtering operations in the sensory periphery, but also shapes subsequent stages of sensory processing that are sensitive to high-order image statistics.     

Localized retroperitoneal lymphangioleiomyomatosis mimicking malignancy. A case report and review of the literature

Lymphangioleiomyomatosis (lymphangiomyomatosis [LAM]), a rare disease of unknown etiology that is seen only in women usually in the reproductive period, generally presents with features of pulmonary involvement. Extrapulmonary involvement, such as angiomyolipomas and retroperitoneal adenopathy, can occur in up to 75% of cases. It is very rare, however, for patients to present with features of extrapulmonary LAM. We present an unusual, localized case of LAM presenting with neurologic symptoms related to a retroperitoneal mass in a 51-year-old woman. Magnetic resonance imaging showed that the mass involved retroperitoneal lymph nodes, and a clinical diagnosis of atypical sarcoma (possibly from a uterine primary) was made. The mass was resected, and a total abdominal hysterectomy was performed. On pathologic examination, the mass showed classic histologic features of LAM with spread along lymphatic channels in the lymph nodes. Intralymphatic projections simulated lymphatic metastasis; however, the cytologic features were benign. Immunostains revealed the tumor to be positive for smooth muscle actin and desmin, but negative for HMB-45. The uterus was unremarkable, except for a subserosal leiomyoma. Although intratumoral variability for HMB-45 has recently been described, to the best of our knowledge, this is the first documented case of HMB-45-negative, histologically classic LAM. Because of the presence of several atypical features in this case, such as age, location, compressive neurologic presentation, radiologic impression of atypical sarcoma, and HMB-45 negativity, we feel that this case may represent a distinct, as yet uncharacterized variant of LAM.     

Haemophilus ducreyi requires an intact flp gene cluster for virulence in humans

An intact Haemophilus ducreyi flp operon is essential for microcolony formation in vitro. tadA is the 9th of 15 genes in the operon and has homology to NTPases of type IV secretion systems. Fifteen human volunteers were experimentally infected with both H. ducreyi 35000HP and the tadA mutant, 35000HP.400. Papules developed at similar rates at sites inoculated with the mutant and parent, while pustules formed at 36.4% of parent sites and at 0% of mutant sites (P = 0.001). Compared to 35000HP, 35000HP.400 had only a modest but significant reduction in lesion scores in the temperature-dependent rabbit model of chancroid. These data suggest that proteins secreted by the flp locus are required for full expression of virulence by H. ducreyi in humans but have less of a role in virulence in an animal model of infection.