Comparative efficacy of dermal fibroblast-mediated and direct adenoviral bone morphogenetic protein-2 gene therapy for bone regeneration in an equine rib model.

Cell-mediated and direct adenoviral (Ad) vector gene therapies can induce bone regeneration, including dermal fibroblasts (DFbs). We compared two effective therapies, DFb-mediated and direct Ad vector delivery of bone morphogenetic protein-2 (BMP2), for relative efficacy in bone regeneration. Equine rib drill defects were treated by percutaneous injection of either DFb-BMP2 or an Ad-BMP2 vector. At week 6, both DFb-BMP2- and Ad-BMP2-treated rib defects had greater bone filling volume and mineral density, with DFb-BMP2 inducing greater bone volume and maturity in the cortical bone aspect of the defect than Ad-BMP2. The transplantation of DFb alone induced modest bone formation. Increased mineral density and bone turnover were evident in the cortical and cancellous bone directly adjacent to the healing drill defects treated with either DFb-BMP2 or Ad-BMP2. Using our cell/vector dosage and model, BMP2, whether delivered by the DFb vector or direct Ad vector, induced greater and robust bone regeneration. DFb-mediated BMP2 therapy promoted greater cortical bone regeneration than did direct gene delivery, possibly because of an increased cellularity of the bone healing site. BMP2 delivery, regardless of gene delivery method, increased the mineral density of the neighboring bone, which may be beneficial clinically in repairing or weak bone.

Detection of congestive heart failure in dogs by Doppler echocardiography.

BACKGROUND: Echocardiographic prediction of congestive heart failure (CHF) in dogs has not been prospectively evaluated. HYPOTHESIS: CHF can be predicted by Doppler echocardiographic (DE) variables of left ventricular (LV) filling in dogs with degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM). ANIMALS: Sixty-three client-owned dogs. METHODS: Prospective clinical cohort study. Physical examination, thoracic radiography, analysis of natriuretic peptides, and transthoracic echocardiography were performed. Diagnosis of CHF was based upon clinical and radiographic findings. Presence or absence of CHF was predicted using receiver-operating characteristic (ROC) curve, multivariate logistic and stepwise regression, and best subsets analyses. RESULTS: Presence of CHF secondary to MVD or DCM could best be predicted by E:isovolumic relaxation time (IVRT) (area under the ROC curve [AUC]=0.97, P<.001), respiration rate (AUC=0.94, P<.001), Diastolic Functional Class (AUC=0.93, P<.001), and a combination of Diastolic Functional Class, IVRT, and respiration rate (R2=0.80, P<.001) or Diastolic Functional Class (AUC=1.00, P<.001), respiration rate (AUC=1.00, P<.001), and E:IVRT (AUC=0.99, P<.001), and a combination of Diastolic Functional Class and E:IVRT (R2=0.94, P<.001), respectively, whereas other variables including N-terminal pro-brain natriuretic peptide, E:Ea, and E:Vp were less useful. CONCLUSION AND CLINICAL IMPORTANCE: Various DE variables can be used to predict CHF in dogs with MVD and DCM. Determination of the clinical benefit of such variables in initiating, modulating, and assessing success of treatments for CHF needs further study.

Quantitative assessment of the equine hoof using digital radiography and magnetic resonance imaging.

REASONS FOR PERFORMING STUDY: Evaluation of laminitis cases relies on radiographic measurements of the equine foot. Reference values have not been established for all layers of the foot. OBJECTIVES: To establish normal hoof wall and sole measurements using digital radiography (DR) and magnetic resonance imaging (MRI) and to document tissue components present in the dorsal hoof wall and solar layers seen on DR. STUDY DESIGN: Prospective observational case-control study. METHODS: Digital radiography and MRI were performed on 50 cadaver front feet from 25 horses subjected to euthanasia for nonlameness-related reasons. Four observers measured hoof wall (dorsal, lateral and medial) and sole thickness (sagittal, lateral and medial) using DR and magnetic resonance images. One observer repeated the measurements 3 times. Inter- and intraobserver correlation was assessed. RESULTS: Digital radiography and MRI measurements for the normal hoof wall and sole were established. Inter- and intraobserver pairwise Pearson's correlation for DR (r>0.98) and MRI measurements (r>0.99) was excellent. Based on MRI, the less radiopaque layer on DR is comprised of the stratum lamellatum and stratum reticulare. CONCLUSIONS: Normal DR and MRI measurements for the hoof wall and sole were established. On DR images, the less radiopaque layer of the foot observed corresponds to the critical tissues injured in laminitis, the strata lamellatum and reticulare. These reference measurements may be used by the clinician to detect soft-tissue changes in the laminitic equine foot and provide a foundation for future research determining changes in these measurements in horses with laminitis.

Characterisation of the type and location of fractures of the third metacarpal/metatarsal condyles in 135 horses in central Kentucky (1986-1994).

The objective of this retrospective study was to provide a detailed description of the characteristics of condylar fractures represented in a population of 135 horses who sustained 145 fractures. Records and radiographic studies were examined. Fifty-nine percent of the horses were male and the majority Thoroughbreds. The distribution of fractures was 37% incomplete-nondisplaced, 30% complete-nondisplaced and 32% complete-displaced. The right front was more likely to sustain a complete-displaced fracture, whereas the left front was more likely to sustain an incomplete-nondisplaced fracture. Forelimbs (81%) and lateral condyles (85%) were more likely to be involved. Contrary to previous studies, the right forelimb was slightly more often involved than the left. Fractures tended to involve the middle portion of the condyle (59%). The mean length of all fractures was 75+/-3.8 mm. Axial fractures and medial condyle fractures tended to be longer. Fifteen percent of the fractures had definitive articular comminution. Ninety-five percent of fractures with articular comminution were associated with complete fractures. When fractures entered the middle area of the condyle, 23% had articular comminution. Eight of the fractures spiralled, all involved forelimbs. Concurrent lesions included proximal phalanx chip fractures, sesamoid fractures, sesamoiditis, proximal phalanx fractures, 'splint' bone periostitis and ligamentous injuries. The complete description of the fractures in this group of horses allows us better to define the condylar fracture, compare these fractures to previous studies and establish new data for use in defining prognosis.

Results of treatment of 145 fractures of the third metacarpal/metatarsal condyles in 135 horses (1986-1994).

The objectives of this study were to correlate condylar fracture characteristics and type of treatment with subsequent capacity for athletic ability, and to determine the characteristics of healing that affect prognosis after fracture fixation. Medical records, post operative radiographic studies and race records were examined for 135 horses sustaining 145 fractures. Sixty-five percent of horses overall started in a race post injury (SPI) in a mean time of 9.7 months with a mean of 13.7 races post injury. Having raced pre-injury did not confer an advantage to starting post injury, though nonstarters pre-injury tended to take longer to return. For horses starting pre- and post injury, 66% improved or maintained their race class level after injury, whereas 64.2% decreased their race earnings post injury. Eighty-five percent of the fractures received internal fixation, of which 70% were complete fractures. Eighty-seven percent of horses with incomplete-nondisplaced fractures treated conservatively raced post injury. The percent SPI for incomplete-nondisplaced, complete-nondisplaced and complete-displaced fractures treated with internal fixation were 74%, 58%, and 60%, respectively. Males (72%) raced post injury more frequently than fillies (53%), and may represent a truer probability of SPI. Spiral fractures tended to take longer until their first start (mean 13.3 months). Fifty-two percent of horses with articular fragments were able to race post injury. Horses were more likely to start if 2-4 month radiographic healing revealed no evidence of the fracture except the presence of lag screws. Based on this series of cases, the majority of horses, with proper treatment, were able to return to racing regardless of fracture characteristic. Prognosis appeared to be affected by the severity of the injury to the joint, the presence of articular comminution and the quality of surgical repair.

Ablation of the nephrosplenic space for treatment of recurring left dorsal displacement of the large colon in a racehorse.

Left dorsal displacement of the large colon was diagnosed in a 3-year-old Thoroughbred gelding. Conservative treatment that included lunging after administration of phenylephrine and rolling while under general anesthesia was not successful. The displaced segment of colon was reduced surgically through a ventral midline incision, but displacement recurred 4 days after surgery. Ablation of the nephrosplenic space by suturing the nephrosplenic ligament to the splenic capsule was performed through the left flank. At followup 1 year after surgery, the horse had not had further signs of colic and had returned to racing. Other methods to prevent large colon displacement, including colon resection and colopexy, are not recommended for athletic horses. Ablation of the nephrosplenic space, however, may be efficacious.