Evaluation of the effects of donepezil in psychotic disorders using Swiss albino mice

Background: Schizophrenia as a psychotic disorder is currently treated by various antipsychotic drugs. A large group of patients still remain resistant to the treatment and present in the form of residual cognitive deficits. Donepezil has been advocated at various conferences and seminars for using it in schizophrenia patients. Donepezil is currently approved drug for Alzheimer's disease to improve cognition. Hence, we have tried to assess its role for psychotic models induced by methylphenidate in mice.Methods: Methylphenidate 5 mg/kg was given by intraperitoneal (i.p) route to induce psychosis in Swiss albino mice (n=6). Donepezil was given alone in a dose of 1 mg/kg and in combination with low dose haloperidol 0.1 mg/kg and groups were compared with haloperidol 0.2 mg/kg. Activity of donepezil was also assessed on the haloperidol induced catalepsy test. Statistical analysis was done with ANOVA followed by Bonferroni’s test.Results: Methylphenidate successfully induced characteristic stereotypy behaviour in mice similar to amphetamine. Both donepezil 1 mg/kg and haloperidol 0.2 mg/kg showed significant reduction in stereotypy behaviour and there was no statistically significant difference between the two (p0.05).Conclusions: Methylphenidate can be used successfully to induce psychosis in animals and donepezil may be a promising and potentially useful drug as add on therapy to routine antipsychotics

Cemented femoral stem design and postoperative periprosthetic fracture risk following total hip arthroplasty

Polished taper-slip (PTS) cemented stems have an excellent clinical track record and are the most common stem type used in primary total hip arthroplasty (THA) in the UK. Due to low rates of aseptic loosening, they have largely replaced more traditional composite beam (CB) cemented stems. However, there is now emerging evidence from multiple joint registries that PTS stems are associated with higher rates of postoperative periprosthetic femoral fracture (PFF) compared to their CB stem counterparts. The risk of both intraoperative and postoperative PFF remains greater with uncemented stems compared to either of these cemented stem subtypes. PFF continues to be a devastating complication following primary THA and is associated with high complication and mortality rates. Recent efforts have focused on identifying implant-related risk factors for PFF in order to guide preventative strategies, and therefore the purpose of this article is to present the current evidence on the effect of cemented femoral stem design on the risk of PFF

Haemostatic abnormalities in solid malignancies

Background: Though the actual symptoms of any haemostatic abnormalities in patients of solid malignancies are not seen commonly screening in all such cases can guide us to correct those abnormalities in time and improve the outcome. The present study is undertaken with an objective to find out coagulation disorders in patients of solid malignancies and compare their levels according to the stage of the cancer.Methods: A prospective study was undertaken in a tertiary care centre in Maharashtra, India from December 2010 to September 2012. Total 102 cases with malignancies diagnosed on histopathology/cytological examination were tested for BT, CT, Platelet count, PT, APTT, TT and D-dimer levels. These tests were repeated on first postoperative or post chemotherapy day wherever possible. Early and advanced stages of cancer were divided according to the spread of the tumor. Results were compared between the two. DIC cases were also noted.Results: Out of 102 cases studied, haemostatic abnormalities were more common in adenocarcinomas that too in mucin secreting adenocarcinomas. The percentage of cases with increased D-dimer values was higher in the advanced disease compared to early disease. The PT, APTT, TT and platelet count showed statistically significant differences between the early and advanced disease groups. Compared to preoperative values, postoperative values were abnormal but the change was not statistically significant.Conclusions: Screening for coagulation profile in all solid malignancies can help to predict the chances of complication and therapeutic interventions can be done

Setting up an arthroplasty care practitioner-led virtual clinic for follow-up of orthopaedic patients

AbstractThis article provides an overview of the set up for an arthroplasty care practitioner (ACP)-led virtual orthopaedic clinic (VOC). Suitable patients attend a local hospital for an X-ray and complete a questionnaire, but do not physically attend a clinic. This has been running successfully in a university teaching hospital and has led to cost savings, a reduction in outpatient waiting times and high levels of patient satisfaction. Similar clinics have the potential to become normal practice across the NHS. This article outlines the steps necessary to implement a successful VOC. The lessons learnt during this exercise may be useful for other ACPs when setting up a VOC

Highly lubricious SPMK-g-PEEK implant surfaces to facilitate rehydration of articular cartilage

To enable long lasting osteochondral defect repairs which preserve the native function of synovial joint counter-face, it is essential to develop surfaces which are optimised to support healthy cartilage function by providing a hydrated, low friction and compliant sliding interface. PEEK surfaces were modified using a biocompatible 3-sulfopropyl methacrylate potassium salt (SPMK) through UV photo-polymerisation, resulting in a ∼350 nm thick hydrophilic coating rich in hydrophilic anionic sulfonic acid groups. Characterisation was done through Fourier Transformed Infrared Spectroscopy, Focused Ion Beam Scanning Electron Microscopy, and Water Contact Angle measurements. Using a Bruker UMT TriboLab, bovine cartilage sliding tests were conducted with real-time strain and shear force measurements, comparing untreated PEEK, SPMK functionalised PEEK (SPMK-g-PEEK), and Cobalt Chrome Molybdenum alloy. Tribological tests over 2.5 h at physiological loads (0.75 MPa) revealed that SPMK-g-PEEK maintains low friction (μ &lt; 0.024) and minimises equilibrium strain, significantly reducing forces on the cartilage interface. Post-test analysis showed no notable damage to the cartilage interfacing against the SPMK functionalised surfaces. The application of a constitutive biphasic cartilage model to the experimental strain data reveals that SPMK surfaces increase the interfacial permeability of cartilage in sliding, facilitating fluid and strain recovery. Unlike previous demonstrations of sliding-induced tribological rehydration requiring specific hydrodynamic conditions, the SPMK-g-PEEK introduces a novel mode of tribological rehydration operating at low speeds and in a stationary contact area. SPMK-g-PEEK surfaces provide an enhanced cartilage counter-surface, which provides a highly hydrated and lubricious boundary layer along with supporting biphasic lubrication. Soft polymer surface functionalisation of orthopaedic implant surfaces are a promising approach for minimally invasive synovial joint repair with an enhanced bioinspired polyelectrolyte interface for sliding against cartilage. These hydrophilic surface coatings offer an enabling technology for the next generation of focal cartilage repair and hemiarthroplasty implant surfaces.</p

Tibial Fracture after Unicompartmental Knee Replacement: The Importance of Surgical Cut Accuracy

Introduction and Objectives: Tibial fracture is a possible complication after unicompartmental knee replacement (UKR) which can have severe consequences for patient recovery and outcome [1]. It appears that the issue is not product specific, as peri-prosthetic fractures have been reported in numerous designs, both mobile and fixed. However, it has been suggested that cementless components might be at greater risk than cemented [2]. The exact causes of tibial fracture are unknown, although surgical factors are most commonly proposed in the literature [1,3]. The objectives of the study were to; (1) determine the range of positions and depths of the surgical cuts required to prepare the tibial plateau for a UKR, (2) use the measured parameters to create a representative range of finite element models, (3) statistically assess the influence of each surgical parameter on the risk of fracture. Methods: Tibial plastic Sawbones (n=23) were prepared for mobile UKR during an instructional course. The parametersmeasured from the sawbones were: (a) the resection depth, (b) the angle between the horizontal and vertical cuts, (c) the distance between the vertical wall and the keel slot, how excessively deep the vertical cut and horizontal cuts were anteriorly (d and e, respectively), and posteriorly (f and g, respectively), and (h) the depth of the pin hole (Figure 1). A parametric finite element model was created in ABAQUS software (v6.12, Dassault Systèmes) with an automated python script to create the surgical cuts. One hundred models were created, where the surgical cut parameters were varied within the distributions measured from the Sawbones. A mesh element size of 2.4 mm was used, selected as a result of a mesh convergence study. The tibia was modelled as a heterogeneous linear elastic material, with a Poisson's ratio of 0.3. The modulus of each element was assigned based upon the corresponding position of that element in the CT scan of the tibia. The equations used for this have been previously defined and the tibial model validated [4]. Muscle and joint loading of a tibia at 15% of the gait cycle was applied, corresponding to maximal medial contact force, and the distal portion of the tibial constrained in all degrees of freedom. The risk of fracture was quantified based upon the Maximum Principal Stress criterion equations defined by Schileo et al. [5]. The influence of each surgical parameter on the risk of fracture was assessed using linear regression with R (r-project). Results: In the tibial Sawbone measurements, the greatest surgical variation was observed in the depth of the posterior vertical cut and the pin hole, which had standard deviations of 3.9 and 6.8 mm respectively (Table 1). The only surgical cut parameters which were found to significantly affect the risk of fracture were the resection depth, and the posterior depth of the vertical cut (p=0.009, and p=0.000001, respectively). Some finite element models demonstrated a noticeable region at high risk of fracture, which extended diagonally from the vertical saw cut, past the base of the keel slot to the tibial cortex. This matched well with typical fracture paths observed clinically [1]. Conclusion: This study has shown accuracy in the depth of the vertical cut made to prepare the tibial plateau for UKR, has the greatest clinical variation and has the greatest influence on the risk of fracture out of all the parameters assessed in this study. It is therefore important that instrumentation be designed to improve surgical accuracy for this part of the operative technique. References: [1] Pandit, H., et al., Orthopedics, 30: 28-31, 2007.[2] Seeger, J.B., et al., Knee Surg Sports Traumatol Arthrosc, 20: 1087-1091, 2012.[3] Clarius, M., et al., The Knee 16: 314-316, 2009.[4] Gray, H.A., et al., J Biomech Eng, 130: 031016, 2008.[5] Schileo, E., et al., J Biomech, 41: 356-367, 2008

Minimising risk of tibial fracture after cementless unicompartmental knee replacement

Tibial fractures are a potential risk after unicompartmental knee replacement (UKR). The aim of this study was to (1) characterise the typical depth and positioning of saw cuts made by surgeons performing mobile UKR, and (2) to assess which bone cuts have the greatest influence on the risk of tibial fracture. In twenty four tibial sawbones used during a training course for UKR surgery the depth of the vertical and horizontal cuts and the depth and angle of the pin hole were measured. All the vertical bone cuts measured were most excessive posteirorly; cuts were 4.25±3.9mm (max:12mm) excessively deep posteriorly and 0.46±1.0mm (max:4mm) excessive anteriorly. The horizontal bone cuts posterior/anterior were not statistically different, and were excessive by 1.26±2.1mm (max:7.5mm) and 0.73±0.9mm (max:3mm), respectively. The tibial resection depth was 8.79±1.7mm on average. Of the 24 sawbones analysed, in 14 the pin hole penetrated the keel and one went through the posterior cortex. Based upon the sawbone measurements, three finite element simulations were performed; an implanted component with (1) no excessive bone cuts, (2) a vertical cut excessive 1mm anteriorly and 10mm posteriorly, (3) a horizontal cut 5 mm excessive both anteriorly and posteriorly. These preliminary experiments found the greatest bone strain in simulation (2). Therefore, to minimise the risk of tibial fracture care must be taken to ensure the vertical cut is not too deep posteriorly. One possible technique to prevent a deep vertical cut would be to saw down onto a shim inserted into a previously performed horizontal cut

Conservative Tibial Resection and Vertical Cut Minimise Risk of Tibial Plateau Fracture after UKR

Tibial fracture is a known complication after unicompartmental knee replacement (UKR) [1]. Furthermore, some studies have indicated an increased risk of tibial fracture with cementless UKR [2]. Our aim was to identify surgical factors that contribute to fracture. We examined the influence of tibial saw cuts on the risk of fracture after cementless UKR, to determine if changes in tibial preparation could minimise the risk of fracture. The range and distribution of typical saw cut positions were measured from 23 right tibial Sawbones used as part of an instructional course. Sawbones were prepared by both experienced and unexperienced orthopaedic surgeons but all had received training on the operative technique. Measured parameters were; resection depth, excessive vertical cut anterior/posterior, excessive horizontal cut anterior/posterior, pin depth and pin angle. One hundred finite element models were then created where each parameter was assigned using a random number generator within its measured distribution, and the risk of fracture assessed. Results from a multiple linear regression model indicated that a greater resection depth and a more excessive posterior vertical cut significantly increased the risk of fracture after UKR. Based upon these results, a surgical technique and instrumentation for UKR which minimises inaccuracies in the vertical cut and promotes a more conservative resection depth would be recommended to minimise the risk of tibial plateau fracture after UKR.[1] HG Pandit, DW Murray, CA Dodd, et al. (2007) Orthopedics 30: 28-31[2] JB Seeger, D Haas, S Jager et al. (2012) Knee Surg Sports Traumatol Arthrosc 20: 1087-109

Asymmetrical hip loading correlates with metal ion levels in patients with metal-on-metal hip resurfacing during sit-to-stand

The occurrence of pseudotumours following metal-on-metal hip resurfacing arthroplasty (MoMHRA) has been associated with high serum metal ion levels and consequently higher than normal bearing wear. Measuring ground reaction force is a simple method of collecting information on joint loading during a sit-to-stand (STS). We investigated vertical ground reaction force (VGRF) asymmetry during sit-to-stand for 12 MoMHRA patients with known serum metal ion levels. Asymmetry was assessed using two methods: a ratio of VGRF for implanted/unimplanted side and an absolute symmetry index (ASI). It was found that subjects with high serum metal ion levels preferentially loaded their implanted sides. The difference between the two groups was most apparent during the first 22% of STS. VGRF ratio showed significant and strong correlation with serum metal ion levels (Spearman's rho = 0.8, p = 0.003). These results suggest that individual activity patterns play a role in the wear of MoMHRA and preferential loading of an implanted limb during the initiation of motion may increase the wear of metal-on-metal hip replacements. </jats:p