Mucopolysaccharidosis-like phenotype in feline Sandhoff disease and partial correction after AAV gene therapy.

Sandhoff disease (SD) is a fatal neurodegenerative disease caused by a mutation in the enzyme ß-N-acetylhexosaminidase. Children with infantile onset SD develop seizures, loss of motor tone and swallowing problems, eventually reaching a vegetative state with death typically by 4years of age. Other symptoms include vertebral gibbus and cardiac abnormalities strikingly similar to those of the mucopolysaccharidoses. Isolated fibroblasts from SD patients have impaired catabolism of glycosaminoglycans (GAGs). To evaluate mucopolysaccharidosis-like features of the feline SD model, we utilized radiography, MRI, echocardiography, histopathology and GAG quantification of both central nervous system and peripheral tissues/fluids. The feline SD model exhibits cardiac valvular and structural abnormalities, skeletal changes and spinal cord compression that are consistent with accumulation of GAGs, but are much less prominent than the severe neurologic disease that defines the humane endpoint (4.5±0.5months). Sixteen weeks after intracranial AAV gene therapy, GAG storage was cleared in the SD cat cerebral cortex and liver, but not in the heart, lung, skeletal muscle, kidney, spleen, pancreas, small intestine, skin, or urine. GAG storage worsens with time and therefore may become a significant source of pathology in humans whose lives are substantially lengthened by gene therapy or other novel treatments for the primary, neurologic disease.

Use of a locking compression plate as an external fixator for repair of a tarsometatarsal fracture in a bald eagle (Haliaeetus leucocephalus).

We describe the successful treatment of a tarsometatarsal fracture in a mature bald eagle (Haliaeetus leucocephalus) using a locking compression plate as an external fixator. The anatomy of the area (inelastic dermis and minimal subcutaneous space) and the high forces placed on a fracture at that site necessitated a unique approach to fixation. The unconventional use of a locking compression plate as an external fixator was minimally invasive, well tolerated by the eagle, and provided adequate stability in opposing fracture forces. This technique may serve as a method of fixation for tarsometatarsal fractures in other large avian species.

Pre- and postoperative force plate analysis of dogs with experimentally transected cranial cruciate ligaments treated using tibial plateau leveling osteotomy.

OBJECTIVE: Quantitative and objective assessment of hindlimb kinetics after cranial cruciate ligament (CrCL) transection and subsequent stifle stabilization using the tibial plateau leveling osteotomy (TPLO) in normal dogs. STUDY DESIGN: In vivo experimental biomechanical evaluation. ANIMALS: Six healthy adult foxhounds. METHODS: Dogs were screened by orthopedic and radiographic examination before study entry. Force plate analysis of gait was measured before extirpation of the right CrCL and TPLO and again at 8 and 18 weeks after surgery. RESULTS: There was a significant decrease in peak vertical forces (PVFs) and vertical impulse (VI) of the treated hindlimb at 8 weeks when compared with preoperative and 18-week measurements. When compared with preoperative values, there was no significant difference in 18 week PVF and VI in dogs that had TPLO. CONCLUSION: TPLO can restore kinetic measures of limb function at 18-weeks after surgery when compared with preoperative values after experimental transection of the CrCL in dogs. CLINICAL RELEVANCE: TPLO induces lameness that returns to near normal at 18 weeks. The severity and duration of lameness was similar to that reported for other experimental models of stifle instability repaired by different techniques.

Evaluation of small-intestinal submucosa implants for repair of meniscal defects in dogs.

OBJECTIVE: To assess the effects of porcine small intestinal submucosa (SIS) implants on the healing of meniscal lesions in dogs. ANIMALS: 16 adult Greyhounds of both sexes. PROCEDURE: Unilateral osteotomy was performed at time 0 to disrupt the medial collateral ligament attachment, and two (1 cranial and 1 caudal) 4-mm circular defects were created in the avascular portion of the medial meniscus. One defect was filled with an SIS graft, and the other defect remained empty (control). Three months later, the identical procedure was performed on the contralateral limb. Three months after the second surgery, dogs were euthanatized, and meniscal tissue specimens from both stifle joints were collected for gross, histologic, biomechanical, and biochemical evaluations. RESULTS: Regenerative tissue was evident in 4 (2 SIS-implanted and 2 control) of 16 defects examined histologically. In 3 defects, this thin bridge of tissue was composed of immature haphazardly arranged fibrous connective tissue with a relatively uniform distribution of fibroblasts. Aggregate modulus, Poisson ratio, permeability, and shear modulus were not significantly different between control and SIS-implanted defects either 3 or 6 months after surgery. Hydroxyproline content also did not differ between SIS-implanted and control defects at 3 or 6 months. CONCLUSIONS AND CLINICAL RELEVANCE: Implantation of porcine SIS into experimentally induced meniscal lesions in dogs did not promote tissue regeneration.