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.

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.

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.

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.

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.

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.

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.

The mechanisms by which mild respiratory chain inhibitors inhibit hepatic gluconeogenesis.

(1) Liver cells from starved rats were incubated with 10 mM L-lactate, 1 mM pyruvate and 0.3 microM glucagon in the presence and absence of the mild respiratory inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) at 0.5 mM. (2) The whole cell concentrations of phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate increased about 2-fold, whilst the triose and hexose phosphate concentrations all decreased significantly. Similar results were obtained with 0.15 microM oligomycin and 10 microM atractyloside. (3) These data can be explained by a substantial decrease in the cytosolic free concentration ratio of ATP/ADP acting on the equilibrium of glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. (4) The increase in cytosolic phosphoenolpyruvate concentration can account for the observed increase in pyruvate kinase flux that occurs under these conditions (Pryor et al. (1987) Biochem. J. 247, 449-457). (5) An inhibition of pyruvate carboxylase was also implied by a decrease in calculated tissue oxaloacetate concentrations, confirming a role for both enzymes in the inhibition of gluconeogenesis. (6) Whole cell concentrations of effectors of pyruvate carboxylase activity were measured; only the ATP/ADP ratio decreased significantly. (7) Subcellular fractionation studies showed a good correlation between the measured mitochondrial ATP/ADP ratio and rates of gluconeogenesis both in the presence and absence of oleate. (8) A similar correlation could be observed between rates of pyruvate carboxylation and the measured matrix ATP/ADP ratio in isolated liver mitochondria from starved rats. (9) Data are also presented suggesting an additional effect of DCMU on the rate pyruvate carboxylation in situ under some circumstances, mediated by decreases in mitochondrial acetyl-CoA and cytosolic pyruvate concentrations. (10) It is noted that the effects of phenylethylbiguanide (phenformin) on the rate of gluconeogenesis and metabolite profiles in the perfused liver (Cooke et al. (1973) J. Biol. Chem. 248, 5272-5277) are similar to those caused by DCMU, supporting a mitochondrial locus of action for this hypoglycaemic agent.

Kinematic analysis of the gait of 10 labrador retrievers during treadmill locomotion.

The trotting gait of 10 sound, adult labrador retrievers was analysed using kinematic gait analysis on a purpose-built treadmill using video-based motion analysis software. The maximal angular displacement, minimal angular displacement, average angular displacement, and the maximal positive and negative angular velocities of the right elbow and right stifle were measured over five gait cycles at defined time points during each of five two-minute sessions. The dogs' trotting gait was not repeatable, either for individual dogs during the first session or between sessions, or between dogs at the same time points during a session.

Unusual presentation of avulsion of the lateral head of the gastrocnemius muscle in a dog.

A five-and-a-half-year-old, male neutered golden retriever was presented with sudden onset, plantigrade stance of the left pelvic limb one month after a traumatic incident. A diagnosis of avulsion of the lateral head of the gastrocnemius muscle was made based on clinical signs and radiographic assessment. Initial wire reduction and fixation were unsuccessful. However, reduction and fixation with monofilament leader line augmented with a trans-hock external fixator resulted in a successful outcome. The dog had a normal gait 18 months after revision surgery.

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

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.

Production and secretion of a bifunctional staphylococcal protein A::antiphytochrome single-chain Fv fusion protein in Escherichia coli.

A bifunctional molecule was genetically engineered which contained the secretory signal and four Fc-binding domains of Staphylococcus aureus protein A (FcA), fused to a single-chain Fv (scFv) derived from an immunoglobulin (Ig) G1 mouse monoclonal antibody (AS32) directed against the plant regulatory photoreceptor protein, phytochrome. The FcA::AS32scFv sequence was encoded in a single synthetic gene and expressed as a 60-kDa periplasmic protein in Escherichia coli. The bifunctionality of the fusion protein was established by its ability to bind to both IgG-agarose and phytochrome-sepharose. Growth of cultures, producing the FcA::AS32scFv, at 37 degrees C, resulted in a decrease in the periplasmic accumulation of the fusion protein, and an increased accumulation of an assumed degradation product which retained Fc-binding activity. Growth of cultures at lower temperatures favoured the accumulation of undegraded fusion protein. The recombinant fusion protein could be purified to homogeneity by a simple, rapid chromatography procedure.

How far can a juxtacrine signal travel?

Juxtacrine signalling is the process of cell communication in which ligand and receptors are both anchored in the cell membrane. We develop three mathematical models for this process, involving different mathematical representations of the dynamics of membrane-bound ligand and free and bound receptors, within an epithelial sheet. We consider the dynamics of this system following a localized disturbance, such as would be provided by a source of ligand or by the generation of a free edge via wounding. We study the ability of the juxtacrine mechanism to transmit a signal away from this disturbance, and show analytically that the spatial half-life of the signal can in fact be arbitrarily large. This result is quite general, since we use a generic reaction kinetic scheme; the key assumption is that ligand and receptor production are both upregulated by binding. Moreover, the result applies to all three of our model formulations. We conclude by discussing applications of the result to the particular case of the transforming growth factor alpha binding to epidermal growth factor receptor in epidermal wound healing.