Short-term outcome and complications of TPLO using anatomically contoured locking compression plates in small/medium-breed dogs with "excessive" tibial plateau angle.

OBJECTIVES: To report short-term radiographic and clinical outcome and complications following tibial plateau levelling osteotomy for the treatment of cranial cruciate ligament insufficiency in dogs less than 18·1 kg with tibial plateau angle greater than 35° using anatomically contoured six-hole locking compression plates. METHODS: Retrospective data were collected on: preoperative, postoperative and follow-up tibial plateau angles, plateau segment rotation, tibial tuberosity width and length of the cranial aspect of tibial tuberosity segment from the patellar tendon insertion and rotation of the tibial plateau below the level of the insertion of the patellar ligament. RESULTS: In 26 small dogs (29 stifles in total), mean preoperative, postoperative and follow-up tibial plateau angles were 38·2°, 4·8°, and 4·4°, respectively. Documented postoperative complications were limited to patellar tendinopathy in a single case (3·4%) and tibial tuberosity or fibula fracture were not observed. CLINICAL SIGNIFICANCE: Short-term radiographic and clinical outcome of tibial plateau levelling osteotomy stabilised with anatomically contoured six-hole locking compression plates for the treatment of small dogs with large tibial plateau angle suggests a very low risk of complications. Rotation beyond the "safe point" is necessary to perform full rotation in some cases, but does not appear to incur an increased risk of tibial tuberosity fracture.

Indirect assessment of stifle angle for improved accuracy of preoperative planning of tibial osteotomy procedures in dogs.

To assess reliability of the mechanical axes stifle angle in dogs positioned for radiography with a neutral stifle (neutral stifle angle (nSA)). To investigate radiographic landmarks for assessment of nSA from a collimated radiographic view. One hundred radiographs were taken of normal stifles belonging to 55 skeletally mature medium and large breed dogs, positioned using a repeatable protocol. Radiographs were widely collimated to include the femoral head and the talus. The angle of Blumensaat's line through the intercondylar fossa relative to the Mechanical Axis of the femur (intercondylar fossa angle, IFA), the angle of inclination of a tibial crest tangent line relative to the Mechanical Axis of the tibia (tibial crest angle, TCA) and the tibial plateau angle (TPA) were recorded. Mean nSA was 133.5°. Mean IFA was 155.5°. TCA had a mean of 6.7°. Estimates for nSA were calculated using mean IFA combined with mean TCA (enSA1), mean TPA (enSA2) and the mechanical axis of the tibia (enSA3). Mean percentage error relative was 2.99 per cent for enSA1, 2.82 per cent for enSA2, 1.67 per cent for enSA3. Blumensaat's line provides a consistent radiological feature for assessment of nSA. Assessment of nSA and correction for values varying from 135° may allow more consistent and accurate measurement of patellar tendon angle for presurgical planning.

Effect of use of different landmark methods on determining stifle angle and on calculated tibial tuberosity advancement.

OBJECTIVES: Firstly, to investigate the effect that using different landmarks has on the measured stifle angle. Secondly, to determine whether any differences in measured stifle angle would lead to variations in the required extent of tibial tuberosity advancement (TTA). METHODS: Three greyhound stifles were positioned in a total of 66 different angles. Radiographic exposures of each stifle angle were made. For each radiograph i) the stifle angle was measured using each of three sets of landmarks and ii) the extent of TTA required to obtain a patella tendon angle of 90° was measured. Each radiograph was plotted graphically according to the stifle angle and the extent of TTA required. Linear regression analysis was used to calculate the TTA required for a stifle angle of 135° measured using each of the three landmark sets. RESULTS: On average, the stifle angle determined by the Long Axes method differed by 18° from the stifle angle determined with the Kinematic method. The stifle angle determined using the Eminence method differed from that determined using the Kinematic method by three degrees. The use of the Long Axes of the tibia and femur as landmarks to determine a stifle angle resulted in 5 mm and 4 mm over-advancement of the tibial tuberosity compared to the use of Kinematic or Eminence landmark methods respectively. CLINICAL SIGNIFICANCE: The method used to measure the stifle joint angle can influence the value of the required TTA advancement. This is an additional variable that should be considered during TTA planning and when comparing in vivo and in vitro studies.

Oscillatory dynamics in a model of vascular tumour growth--implications for chemotherapy.

BACKGROUND: Investigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and have a negative impact on therapeutic outcome. In order to study the effects that occlusion may have on tumour growth patterns and therapeutic response, in this paper we develop and investigate a continuum model of vascular tumour growth. RESULTS: By analysing a spatially uniform submodel, we identify regions of parameter space in which the combination of tumour cell proliferation and vessel occlusion give rise to sustained temporal oscillations in the tumour cell population and in the vessel density. Alternatively, if the vessels are assumed to be less prone to collapse, stable steady state solutions are observed. When spatial effects are considered, the pattern of tumour invasion depends on the dynamics of the spatially uniform submodel. If the submodel predicts a stable steady state, then steady travelling waves are observed in the full model, and the system evolves to the same stable steady state behind the invading front. When the submodel yields oscillatory behaviour, the full model produces periodic travelling waves. The stability of the waves (which can be predicted by approximating the system as one of lambda-omega type) dictates whether the waves develop into regular or irregular spatio-temporal oscillations. Simulations of chemotherapy reveal that treatment outcome depends crucially on the underlying tumour growth dynamics. In particular, if the dynamics are oscillatory, then therapeutic efficacy is difficult to assess since the fluctuations in the size of the tumour cell population are enhanced, compared to untreated controls. CONCLUSIONS: We have developed a mathematical model of vascular tumour growth formulated as a system of partial differential equations (PDEs). Employing a combination of numerical and analytical techniques, we demonstrate how the spatio-temporal dynamics of the untreated tumour may influence its response to chemotherapy. REVIEWERS: This manuscript was reviewed by Professor Zvia Agur and Professor Marek Kimmel.

Mathematical modelling of the Aux/IAA negative feedback loop.

The hormone auxin is implicated in regulating a diverse range of developmental processes in plants. Auxin acts in part by inducing the Aux/IAA genes. The associated pathway comprises multiple negative feedback loops (whereby Aux/IAA proteins can repress Aux/IAA genes) that are disrupted by auxin mediating the turnover of Aux/IAA protein. In this paper, we develop a mathematical model of a single Aux/IAA negative feedback loop in a population of identical cells. The model has a single steady-state. We explore parameter space to uncover a number of dynamical regimes. In particular, we identify the ratio between the Aux/IAA protein and mRNA turnover rates as a key parameter in the model. When this ratio is sufficiently small, the system can evolve to a stable limit cycle, corresponding to an oscillation in Aux/IAA expression levels. Otherwise, the steady-state is either a stable-node or a stable-spiral. These observations may shed light on recent experimental results.

Modelling and analysis of planar cell polarity.

Planar cell polarity (PCP) occurs in the epithelia of many animals and can lead to the alignment of hairs, bristles, and feathers. Here, we present two approaches to modelling this phenomenon. The aim is to discover the basic mechanisms that drive PCP, while keeping the models mathematically tractable. We present a feedback and diffusion model, in which adjacent cell sides of neighbouring cells are coupled by a negative feedback loop and diffusion acts within the cell. This approach can give rise to polarity, but also to period two patterns. Polarisation arises via an instability provided a sufficiently strong feedback and sufficiently weak diffusion. Moreover, we discuss a conservative model in which proteins within a cell are redistributed depending on the amount of proteins in the neighbouring cells, coupled with intracellular diffusion. In this case, polarity can arise from weakly polarised initial conditions or via a wave provided the diffusion is weak enough. Both models can overcome small anomalies in the initial conditions. Furthermore, the range of the effects of groups of cells with different properties than the surrounding cells depends on the strength of the initial global cue and the intracellular diffusion.

Mathematical modelling of signalling in a two-ligand G-protein coupled receptor system: agonist-antagonist competition.

A new mathematical model of cell signalling for a two-ligand G-protein coupled receptor (GPCR) system is presented. This model extends the single-ligand cubic ternary complex to account for the possibility of an agonist and an antagonist competing for receptor sites. The G-protein cycle is included, and signalling as far as the dissociated G(alpha) subunit is considered. Numerical simulations are performed, and the effects on the system dynamics, such as peak and plateau behaviour, of antagonist "stickiness", and of the doses of agonist and antagonist, are discussed. Under certain parameter regimes, the plateau response is subject to surmountable antagonism, while the peak response is subject to insurmountable antagonism. The numerical results reveal responses evolving over a number of time-scales. An asymptotic analysis is presented which identifies dominant reactions and gives leading order solutions over these various time-scales, for a number of parameter regimes.

Modification of the ventral approach to the caudal cervical spine by resection of the manubrium in a dog.

A five-year-old neutered female Bassett Hound weighing 29 kg was presented with a two-day history of paraparesis. Neurological examination and magnetic resonance imaging confirmed the presence of extruded disc material ventral to the spinal cord, from the C7-T1 intervertebral disc. A ventral slot was performed to decompress the cord. In making the approach to the caudal cervical spine, the cranial aspect of the manubrium of the sternum was resected. This improved the exposure of a region normally difficult to expose via a conventional ventral approach to the cervical spine. The successful performance of the ventral slot procedure was greatly facilitated by this adaptation, which was quick and simple to perform, without any apparent adverse affects to the animal.

Does a fabella-tibial suture alter the outcome for dogs with cranial cruciate ligament insufficiency undergoing arthrotomy and caudal pole medial meniscectomy?

OBJECTIVES: The objective of this study was to evaluate the effects of fabella-tibial suture (FTS) on long-term outcome in dogs with cranial cruciate ligament (CCL) insufficiency and concurrent medial meniscal tear (MMT) that were managed by an open, caudal pole medial meniscectomy (CPMM). METHODS: A retrospective review was performed of the clinical records of dogs treated for CCL insufficiency with concurrent MMT by open CPMM, with or without the non-random addition of a nylon FTS according to surgeon preference, during the period of 2001 to 2004. The Bristol Osteoarthritis in Dogs questionnaire was modified for owner assessment of outcome using a visual analogue scale based on several criteria: level of activity, disability, severity of lameness and frequency of lameness before and after surgery. RESULTS: Completed questionnaires from 31 dog owners were received. A FTS was used after CPMM in 22 dogs (FTS group), but in nine dogs (control group) only a CPMM was performed. The median time to follow up was longer in the FTS group (25 months) than the control group (16 months) (P=0.03). There were not any significant differences between the two groups before and after surgery for the following: disability, activity, frequency of lameness, severity of lameness, ability to climb stairs and ability to sit down. CLINICAL SIGNIFICANCE: The placement of a FTS following stifle joint arthrotomy and CPMM in dogs with CCL deficiency and concurrent MMT may not be a significant factor affecting the ultimate surgical outcome, although our study is limited by the non-randomised study design.

Can owners and clinicians assess outcome in dogs with fragmented medial coronoid process?

OBJECTIVES: To investigate the long term reliability of clinician and owner visual analogue score (VAS) for dogs with unilateral forelimb lameness attributable to fragmented medial coronoid process (FMCP) when compared to objective gait analysis. METHODS: Nine dogs with unilateral thoracic limb lameness due to FMCP underwent inverse dynamics gait analysis at initial presentation, and at one, two, six and 12 months following diagnosis. Total support moments were calculated and a total support moment ratio (TSMR) derived as an objective assessment of thoracic limb asymmetry. A VAS questionnaire for lameness was completed by the owner of each dog for each visit. Video footage of each dog walking and trotting at each visit was compiled, assigned to random order and subjected to VAS for lameness by a specialist in small animal surgery. Data from owner and clinician VAS lameness questionnaires were compared to the thoracic limb TSMR. RESULTS: Statistical analysis demonstrated a significant negative correlation between TSMR and owner VAS at four weeks post treatment but at no other period of evaluation. There was no significant correlation between TSMR and clinician VAS score at any evaluation period. CLINICAL SIGNIFICANCE: Assessments by owner and clinicians using VAS appear to be of limited use as a long term outcome measure for dogs with unilateral lameness due to FMCP when compared to objective gait analysis. There is a tendency for owners to underestimate forelimb lameness with increasing time which is not supported by quantitative measures of gait.

Reliability of radiological assessment of ulnar trochlear notch sclerosis in dysplastic canine elbows.

OBJECTIVES: The objectives of this study were to quantify the sensitivity and specificity of visual assessment of radiographs of the canine elbow in detecting ulnar trochlear notch sclerosis, to establish interobserver and intra-observer variation for the presence and grade of sclerosis and to quantify the effect of radiographic exposure on observer grading. METHODS: Mediolateral elbow radiographs were obtained from Labrador retrievers (n=34) aged between six and 18 months. Radiographs from dogs with an arthroscopic diagnosis of fragmented medial coronoid process (n=17) and those from a control population (n=17) were subjected to observer grading for the presence or absence of and the grade of ulnar trochlear notch sclerosis. Interobserver and intra-observer variation and observer sensitivity and specificity were calculated. Digital data from the ulnar trochlear notch were correlated with mean observer grade to quantify the effect of radiographic exposure on observer grade. RESULTS: Interobserver agreement was "fair" (kappa=0.251 to 0.369) and intra-observer agreement was "moderate" to "substantial" (kappa=0.462 to 0.667). The sensitivity of observer assessment was 72 per cent with a specificity of 22 per cent. Mean observer grade was not significantly correlated with the degree of radiographic exposure (P=0.70). CLINICAL SIGNIFICANCE: Ulnar trochlear notch sclerosis is a phenomenon associated with fragmented medial coronoid process. However, interobserver agreement in grading this feature is only fair, being identified by observers with moderate sensitivity but with relatively poor specificity. This low specificity may predispose to overdiagnosis in clinical cases. Intra-observer agreement is moderate to substantial, suggesting that individuals can reliably quantify this radiological feature on multiple occasions. The ability of observers to assess the degree of sclerotic change is not significantly affected by radiographic exposure.

Joint angle, moment and power compensations in dogs with fragmented medial coronoid process.

Fragmented medial coronoid process (FMCP) is the most common cause of forelimb lameness in juvenile medium and large breed dogs; however methods of assessing the disruption to their gait remain subjective. The purpose of this study was to objectively quantify the mechanical disruptions to gait in dogs with arthroscopically confirmed unilateral FMCP. Seven dogs underwent full inverse dynamic analysis at the time of diagnosis. Kinematic and force data were collected from both forelimbs at trot. Stance phase joint angles, net joint moments and net joint powers were calculated using custom software. There were gross differences in kinetic and kinematic patterns between FMCP affected and compensating forelimbs. Stance time was 0.24 sec on the lame side and 0.26 sec on the compensating side. The shoulder and the elbow were more flexed at ground contact, and elbow, carpal and MCP joints had smaller ranges of motion on the lame side. Net joint moments were significantly reduced (P < 0.05) in the elbow, carpal and MCP joints of the FMCP affected limb. Net joint powers were likewise significantly smaller (P < 0.05). However, the overall moment and power patterns persisted. Total limb support moment was significantly smaller on the affected side (P < 0.05). Total limb power was significantly reduced on the affected side (P < 0.05) being most affected in its propulsive phase in the second half of stance. Inverse dynamic analysis of this clinical condition is an objective means by which to assess the mechanical disruption to gait.

Modelling the role of angiogenesis and vasculogenesis in solid tumour growth.

Recent experimental evidence suggests that vasculogenesis may play an important role in tumour vascularisation. While angiogenesis involves the proliferation and migration of endothelial cells (ECs) in pre-existing vessels, vasculogenesis involves the mobilisation of bone-marrow-derived endothelial progenitor cells (EPCs) into the bloodstream. Once blood-borne, EPCs home in on the tumour site, where subsequently they may differentiate into ECs and form vascular structures. In this paper, we develop a mathematical model, formulated as a system of nonlinear ordinary differential equations (ODEs), which describes vascular tumour growth with both angiogenesis and vasculogenesis contributing to vessel formation. Submodels describing exclusively angiogenic and exclusively vasculogenic tumours are shown to exhibit similar growth dynamics. In each case, there are three possible scenarios: the tumour remains in an avascular steady state, the tumour evolves to a vascular equilibrium, or unbounded vascular growth occurs. Analysis of the full model reveals that these three behaviours persist when angiogenesis and vasculogenesis act simultaneously. However, when both vascularisation mechanisms are active, the tumour growth rate may increase, causing the tumour to evolve to a larger equilibrium size or to expand uncontrollably. Alternatively, the growth rate may be left unaffected, which occurs if either vascularisation process alone is able to keep pace with the demands of the growing tumour. To clarify further the effects of vasculogenesis, the full model is also used to compare possible treatment strategies, including chemotherapy and antiangiogenic therapies aimed at suppressing vascularisation. This investigation highlights how, dependent on model parameter values, targeting both ECs and EPCs may be necessary in order to effectively reduce tumour vasculature and inhibit tumour growth.

Limb alignment of pes valgus in a giant breed dog by plate-rod fixation.

A 2-year-old, female, neutered Newfoundland presented with pelvic limb lameness due to a distal tibial valgus deformity. A left distal fibula ostectomy and disto-medial tibial cuneiform ostectomy were performed with reduction and stabilisation using plate-rod internal fixation. Following surgical correction of the deformity the dog regained good functional mobility of the limb.

Treatment of a shoulder luxation in a forelimb amputee dog.

An eight-year-old, male, thoracic limb amputee Whippet presented with a traumatic lateral luxation of the scapulohumeral joint. Surgical reduction and stabilisation of the shoulder joint by means of a modified Campbell scapulohumeral prosthesis and capsulorrhaphy was unsuccessful and reluxation of the shoulder joint occurred. Subsequent surgical stabilisation using bicipital tendon transposition and a modified Campbell scapulohumeral encircling prosthesis in combination with a novel body cast / Spica splint resulted in a return to satisfactory function of this limb.

Digital analysis of ulnar trochlear notch sclerosis in Labrador retrievers.

OBJECTIVES: To compare ulnar trochlear notch bone radiopacity in Labrador retrievers with and without fragmented medial coronoid process using quantitative analysis of film density on digitised radiographs. METHODS: Mediolateral view elbow radiographs from Labrador retrievers (n=34) aged between six and 18 months were obtained and digitised. Images from dogs with an arthroscopic diagnosis of fragmentation of the medial coronoid process (n=17) were compared with that of a control population (n=17), and this data subject to statistical analysis. RESULTS: A statistically significant relationship between the presence of increased trochlear notch radiopacity and a fragmented medial coronoid process was identified. Fractional analysis of this area shows the region of greatest difference in radiopacity between normal and fragmented medial coronoid process cohorts to be in the trochlear region of the medial coronoid process of the ulna. A decrease in radiopacity values in the dysplastic group versus the normal cohort was observed for the region of the proximo-caudal ulnar trochlear notch. CLINICAL SIGNIFICANCE: An increase in ulnar trochlear notch radiopacity is a finding associated with fragmentation of the medial coronoid process in Labrador retrievers.

Carpal derangement and associated carpal valgus in a dog.

This case report describes derangement of the numbered carpal bones resulting in a valgal growth deformity in the right carpus of a seven-month-old dog. Radiographic assessment of the right carpus revealed abnormalities in the size and shape of the numbered carpal bones and carpal valgus. Surgical correction of the growth deformity was planned by partial carpal arthrodesis; however medial collateral laxity associated with the carpal valgus necessitated a pancarpal arthrodesis to achieve correct limb alignment.

Modelling aspects of cancer dynamics: a review.

Cancer is a complex disease in which a variety of factors interact over a wide range of spatial and temporal scales with huge datasets relating to the different scales available. However, these data do not always reveal the mechanisms underpinning the observed phenomena. In this paper, we explain why mathematics is a powerful tool for interpreting such data by presenting case studies that illustrate the types of insight that realistic theoretical models of solid tumour growth may yield. These range from discriminating between competing hypotheses for the formation of collagenous capsules associated with benign tumours to predicting the most likely stimulus for protease production in early breast cancer. We will also illustrate the benefits that may result when experimentalists and theoreticians collaborate by considering a novel anti-cancer therapy.

Bumps, breathers, and waves in a neural network with spike frequency adaptation.

We introduce a continuum model of neural tissue that includes the effects of spike frequency adaptation (SFA). The basic model is an integral equation for synaptic activity that depends upon nonlocal network connectivity, synaptic response, and the firing rate of a single neuron. We consider a phenomenological model of SFA via a simple state-dependent threshold firing rate function. As without SFA, Mexican-hat connectivity allows for the existence of spatially localized states (bumps). Importantly recent Evans function techniques are used to show that bumps may destabilize leading to the emergence of breathers and traveling waves. Moreover, a similar analysis for traveling pulses leads to the conditions necessary to observe a stable traveling breather. Simulations confirm our theoretical predictions and illustrate the rich behavior of this model.

Retrospective study of bacterial infective arthritis in 31 dogs.

OBJECTIVES: To characterise the presenting signs and pathological changes of canine bacterial infective arthritis in 31 dogs, and to document the response to different treatment regimens. Risk factors that may predispose joints to bacterial infective arthritis and influence the success of treatment were also investigated. METHODS: A retrospective review of cases of bacterial infective arthritis that were presented to three university veterinary referral hospitals over a five-year period (January 1997 to January 2002) was performed. RESULTS: The elbow joint (38 per cent) and stifle joint (44 per cent) were most commonly affected. Radiographic changes consistent with pre-existing osteoarthritis were identified in 14 joints, which had no history of previous surgery (articular or periarticular) or penetrating wound. No significant difference (P = 0.78) was identified between the outcome of combined surgical and medical management, and medical management alone. There were trends for poorer outcomes with increased bodyweight of the dog, longer duration of lameness and a higher nucleated cell count of the affected joint fluid at presentation. The overall infection rate for articular surgical procedures at one institution was 1-3 per cent. CLINICAL SIGNIFICANCE: Medical and/or surgical management were usually successful in resolving infection (94 per cent). However, they were frequently unsuccessful in restoring full joint function; this may in part have been due to the nature of the underlying joint