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Biodegradable, shape memory polymer (SMP) scaffolds based on poly(ε-caprolactone) (PCL) offer unique advantages as a regenerative treatment strategy for critical-sized bone defects. In particular, a conformal fit may be achieved following exposure to warm saline, thereby improving osseointegration and regeneration. Advancing the clinical translation of these SMP scaffolds requires establishment of efficacy not only in non-loading models, but also load-bearing or load-sharing models. Thus, the present study evaluated the biocompatibility and bone regeneration potential of SMP scaffolds in a rabbit distal femoral condyle model. Two distinct SMP scaffold compositions were evaluated, a "PCL-only" scaffold formed from PCL-diacrylate (PCL-DA) and a semi-interpenetrating network (semi-IPN) formed from PCL-DA and poly(L-lactic acid) (PCL:PLLA). Semi-IPN PCL:PLLA scaffolds possess greater rigidity and faster rates of degradation versus PCL scaffolds. In vivo biocompatibility was assessed with a rat subcutaneous implantation model, whereas osseointegration was assessed with a 4 mm × 8 mm rabbit distal femoral condyle defect model. Both types of SMP scaffolds exhibited excellent biocompatibility marked by infiltration with fibrous tissue and a minimal inflammatory response. When implanted in the rabbit distal femur, both SMP scaffolds supported bone ingrowth. Collectively, these results demonstrate that the SMP scaffolds are biocompatible and integrate with adjacent host osseous tissues when implanted in vivo in a load-sharing environment. This study provides key proof-of-concept data necessary to proceed with large animal translational studies and clinical trials in human subjects., (© 2024 Wiley Periodicals LLC.)

Proliferative tenosynovitis (PT) is an inflammatory and proliferative disorder of the synovial membrane of the tendon sheath that is rare in animals. The histological alterations are characterized by multinodular neovascularization, with infiltration of histiocytic and multinucleated giant cells and haemosiderin deposition. We reviewed necropsy and biopsy records of horses submitted to the Setor de Anatomia Patológica of the Universidade Federal Rural do Rio de Janeiro from January 2017 to December 2020 to select cases of PT. We identified PT in three adult Brazilian Mangalarga Marchador horses with nodular lesions on the metacarpophalangeal, metatarsophalangeal or carpal joints. The three horses were under 6 years of age and presented with lameness and pain on palpation. There were recurrences in two horses after surgical removal. Radiographic and ultrasound examinations detected masses in the flexor or extensor tendons and subtendinous bursa. Histological study of synovial membrane and tendon sheath revealed an increased number of vessels, fibroplasia, osseous metaplasia and infiltration of lymphocytes, plasma cells and siderophages. This is the first description of PT in horses, which should be included as an orthopaedic differential diagnosis, especially in Mangalarga Marchador horses with lameness., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Osteosarcoma (OSA) is the most common primary bone tumor in both dogs and humans. The dog is an important research model for OSA, yet dogs have much higher prevalence of bone tumors than do humans, a disparity that has yet to be explained. Neoplastic transformation of cells within or adjacent to bone infarcts into primary bone tumors has been described in humans but only sparsely characterized in the veterinary literature. In this study, 653 cases of canine bone infarcts were received through a referral veterinary osteopathology service over a 14-y period. We identified an idiopathic disorder affecting the nutrient artery, termed canine idiopathic arteriopathy (CIA), which to our knowledge has no direct counterpart in human medicine. This disorder was documented alongside ischemic necrosis of the medullary cavity in 114 bone infarcts in 108 dogs. We hypothesize that CIA precipitated an ischemic environment, resulting in development of a bone infarct down- stream of the abnormal artery. In 52% (59 of 114) of cases, bone infarcts demonstrated evidence of repair (termed reparative bone infarcts [RBI]), while in 48% (55 of 114) of infarcts, a bone tumor was also present, including pleomorphic sarcoma, OSA, fibrosarcoma, and chondrosarcoma. In some cases, a spectrum of tumors was present. We hypothesize that the ischemic infarct environment provoked bone marrow mesenchymal stem cells (MSCs) to attempt repair of the stroma, and in approximately half of cases, MSCs underwent neoplastic transformation (BINT) to produce tumors. The most common sites of bone infarcts were the distal femur, distal radius, proximal humerus, and distal tibia, coinciding with common sites of canine OSA. The authors propose that CIA leading to bone infarcts and infarct-derived tumors, in combination with possible underdiagnosis of canine bone infarcts and misdiagnosis of some RBI as neoplasia, may contribute to the higher reported proportion of bone tumors in dogs compared with humans.

This case report details a previously undescribed malignancy of the tendon sheath in a golden retriever. This dog originally presented with lameness of the left forelimb, at which point radiographs revealed a monostotic, lytic lesion of the distal radius with overlying soft-tissue swelling. A fine-needle aspirate was performed, and cytology was compatible with a sarcoma, with the primary differential being an osteosarcoma. After amputation, the leg was submitted for histopathology, which revealed inconsistencies with a typical osteosarcoma lesion, including lack of osteoid deposition. Second opinion histopathology showed a fibrosarcoma that appeared to have originated in the tendon sheath of an extensor tendon and then secondarily invaded the radius. At the time of publication, ∼17 mo after amputation, the dog continues to do well without any evidence of recurrent or metastatic disease., (© 2021 by American Animal Hospital Association.)

Objective: To describe the radiographic appearance of benign bone infarcts and bone infarcts associated with neoplasia in dogs and determine the utility of radiography in differentiating benign and malignancy-associated bone infarcts., Sample: 49 dogs with benign (n = 33) or malignancy-associated (16) infarcts involving the appendicular skeleton., Procedures: A retrospective cohort study was performed by searching a referral osteopathology database for cases involving dogs with a histologic diagnosis of bone infarction. Case radiographs were anonymized and reviewed by 2 board-certified veterinary radiologists blinded to the histologic classification. Radiographic features commonly used to differentiate aggressive from nonaggressive osseous lesions were recorded, and reviewers classified each case as likely benign infarct, likely malignancy-associated infarct, or undistinguishable., Results: Only 16 (48%) of the benign infarcts and 6 (38%) of the malignancy-associated infarcts were correctly classified by both reviewers. Medullary lysis pattern and periosteal proliferation pattern were significantly associated with histologic classification. Although all 16 (100%) malignancy-associated lesions had aggressive medullary lysis, 23 of the 33 (70%) benign lesions also did. Eight of the 16 (50%) malignancy-associated infarcts had aggressive periosteal proliferation, compared with 7 of the 33 (21%) benign infarcts., Conclusions and Clinical Relevance: Results suggested that radiography was not particularly helpful in distinguishing benign from malignancy-associated bone infarcts in dogs.

A 7-year-old neutered male domestic shorthair cat was presented with chronic lameness in the right forelimb. A cystic bony lesion was identified in the distal right humerus and amputation was performed. The epiphyseal trabecular bones of the capitulum and trochlea was replaced by a tan to pink, expansile mass that was surrounded by a thin rim of cortical bone. Microscopically, the tumour was composed of a bland, osteoid producing spindle cell population within a well-vascularized fibrous stroma. Radiographical and histological features were consistent with osteoblastoma. Osteoblastoma and the related osteoid osteoma are uncommon, benign osteoblastic tumours that are reported rarely in animals. These tumours should be considered as differential diagnoses for slow growing, cystic bony lesions in cats., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The objectives of this observational, cross-sectional study were to characterize and establish the prevalence of osseous proliferation of articular surfaces, joint margins and adjacent soft tissue attachments (i.e., joint capsule and deep spinal muscles) in a mixed population of horses of variable ages, sizes, and breeds to better capture the full spectrum of disease affecting the cervical articular processes. Cranial and caudal articular processes of the cervical and first three thoracic vertebrae (C2-T3) from 55 horses without a primary complaint of neck pain were evaluated for the presence and severity of abnormal bony changes. Data were analyzed to compare alterations in joint margin quadrants, paired articular surfaces within a synovial articulation, left-right laterality, and vertebral level distributions and to determine associations with age, wither height and sex. Seventy-two percent of articular processes had bony changes that were considered abnormal. Osteophyte formation was the most common bony change noted. Overall grades of severity included: normal (28%), mild (45%), moderate (22%), and severe (5%). The highest prevalence of mild changes was localized to the C3-C6 vertebral levels; moderate changes to C6-T2; and severe changes to C2-C3 and C6-T2. Most paired articular surfaces and left-right grades of severity were not significantly different. The grade of osseous pathology was positively associated with both age and wither height. A high prevalence and wide variety of abnormal bony changes of varying severity were found in articular processes across all vertebral levels. The clinical significance of the described lesions is unknown, but the findings are expected to enhance the reporting of articular process and periarticular changes noted on advanced diagnostic imaging of the equine cervical and cranial thoracic vertebral regions., Competing Interests: The authors have declared that no competing interests exist.

Background: Articular cartilage lacks a regenerative response. Embryonic stem cells (ESCs) are a source of pluripotent cells for cartilage regeneration. Their use, however, is associated with a risk of teratoma development, which depends on multiple factors including the number of engrafted cells and their degree of histocompatibility with recipients, the immunosuppression of the host and the site of transplantation. Colonies of sheep embryonic stem-like (ES-like) cells from in vitro-produced embryos, positive for stage-specific embryonic antigens (SSEAs), alkaline phosphatase (ALP), Oct 4, Nanog, Sox 2 and Stat 3 gene expression, and forming embryoid bodies, were pooled in groups of two-three, embedded in fibrin glue and engrafted into osteochondral defects in the left medial femoral condyles of 3 allogeneic ewes (ES). Empty defects (ED) and defects filled with cell-free glue (G) in the condyles of the controlateral stifle joint served as controls. After euthanasia at 4 years post-engraftment, the regenerated tissue was evaluated by macroscopic, histological and immunohistochemical (collagen type II) examinations and fluorescent in situ hybridization (FISH) assay to prove the ES-like cells origin of the regenerated tissue., Results: No teratoma occurred in any of the ES samples. No statistically significant macroscopic or histological differences were observed among the 3 treatment groups. FISH was positive in all the 3 ES samples., Conclusions: This in vivo preclinical study allowed a long-term evaluation of the occurrence of teratoma in non-immunosuppressed allogeneic adult sheep engrafted with allogeneic ES-like cells, supporting the safe and reliable application of ES cells in the clinic.

Osteogenesis imperfecta (OI) is a genetic disease that occurs in humans and animals. Individuals with OI exhibit signs of extreme bone fragility and osteopenia with frequent fractures and perinatal lethality in severe cases. In this study, we report the clinical diagnosis of OI in a dog and the use of targeted next-generation sequencing to identify a candidate autosomal dominant mutation in the COL1A2 gene. A 5-month-old male Chow Chow was examined with a fractured left humerus and resolving, bilateral femoral fractures. Radiographs revealed generalized osteopenia and bilateral humeral, radial, and femoral fractures. Targeted next-generation sequencing of genes associated with OI in humans (COL1A1, COL1A2, LEPRE1, SERPINH1, and CRTAP) revealed a G>A heterozygous mutation in the splice donor site of exon 18 of the COL1A2 gene (c.936 + 1G>A). The splice donor mutation was not detected among 91 control dogs representing 21 breeds. A comparative analysis of exon 18 and the exon-intron junction further showed that the mutated splice donor site is conserved among vertebrates. Altogether, these findings reveal a candidate autosomal splice donor site mutation causing OI in an individual Chow Chow.

Clinical summary: A 13-year-old, spayed Devon Rex with unilateral digital flexor musculotendinous contracture of the forelimb was treated by surgical tenotomy. The condition improved transiently, but recurred rapidly and became bilateral. Histopathologic analysis of necropsy tissues resulted in a morphologic diagnosis of fibromyositis of the antebrachial muscles causing contracture and flexural deformity of the carpi and phalanges of both thoracic limbs. A search for similar cases yielded the clinical notes of a second cat, a 10-year-old, spayed Devon Rex, also with bilateral disease. This second case responded well to surgical tenotomy but tissue biopsies were not obtained to permit microscopic assessment of the underlying pathologic process. Relevance and novel information: Acquired and permanent contracture of the digital flexor muscles and/or tendons of the forelimbs is a rare and poorly described condition of cats. The very limited number of documented cases describing disease affecting one or more digits (but not the carpus) infers a causal link with onychectomy, but reported histopathologic changes have been limited to the tendons. The two cases described in this report suffered contracture of the carpus and all digits bilaterally, one without previous onychectomy and the other 9 years after onychectomy. There were novel histopathologic findings in the muscles of the one case for which biopsy material was available. Information gained from these two cases provides a new perspective for the investigation and treatment of future cases. Specifically, consideration should be given to an underlying immune-mediated myopathic process and a possible genetic predisposition in the Devon Rex breed. Currently, the poorly understood etiopathogenesis hinders our ability to definitively recommend treatment options, which might include corticosteroids and other forms of immunosuppressive therapy.

Noninvasive identification of canine articular cartilage injuries is challenging. The objective of this prospective, cadaveric, diagnostic accuracy study was to determine if small field-of-view, three tesla magnetic resonance imaging (MRI) was an accurate method for identifying experimentally induced cartilage defects in canine stifle joints. Forty-two canine cadaveric stifles (n = 6/group) were treated with sham control, 0.5, 1.0, or 3.0 mm deep defects in the medial or lateral femoral condyle. Proton density-weighted, T1-weighted, fast-low angle shot, and T2 maps were generated in dorsal and sagittal planes. Defect location and size were independently determined by two evaluators and compared to histologic measurements. Accuracy of MRI was determined using concordance correlation coefficients. Defects were identified correctly in 98.8% (Evaluator 1) and 98.2% (Evaluator 2) of joints. Concordance correlation coefficients between MRI and histopathology were greater for defect depth (Evaluator 1: 0.68-0.84; Evaluator 2: 0.76-0.83) compared to width (Evaluator 1: 0.30-0.54; Evaluator 2: 0.48-0.68). However, MRI overestimated defect depth (histopathology: 1.65 ± 0.94 mm; Evaluator 1, range of means: 2.07-2.38 mm; Evaluator 2, range of means: 2-2.2 mm) and width (histopathology: 6.98 ± 1.32 mm; Evaluator 1, range of means: 8.33-8.8 mm; Evaluator 2, range of means: 6.64-7.16 mm). Using the paired t-test, the mean T2 relaxation time of cartilage defects was significantly greater than the mean T2 relaxation time of adjacent normal cartilage for both evaluators (P < 0.0001). Findings indicated that MRI is an accurate method for identifying cartilage defects in the cadaveric canine stifle. Additional studies are needed to determine the in vivo accuracy of this method., (© 2016 American College of Veterinary Radiology.)

Two cats, both over 10 yr old, were presented for evaluation of non-painful bony proliferations on the appendicular skeleton. These proliferations were identifiable via palpation. Radiographs showed a smooth, proliferative bony lesion of the distal femur (case 1) and tarsus (case 2) with mild soft tissue swelling. Surgical debulking with incomplete resection was performed in each cat. Subsequent histopathology resulted in a diagnosis of periosteal chondrosarcoma (PC). Although both cats have experienced local recurrence, both are still alive more than 2.5 yr after mass debulking. Periosteal chondrosarcoma is a differential diagnosis in proliferative cortical bony lesions near an articular surface in older cats. Partial resection of these masses can lead to an excellent quality of life, and proper diagnosis can avoid amputation or even euthanasia.

Purpose: the aim of this study was to determine whether local delivery of embryonic stem-like (ESL) cells into osteochondral defects in the femoral condyles of sheep would enhance regeneration of hyaline articular cartilage., Methods: male ESL cells embedded in fibrin glue were engrafted into osteochondral defects in the medial condyles (ESL-M) of the left femur in 22 ewes. An identical defect was created in the medial condyle of the contralateral stifle joint and left untreated as a control (empty defect, ED). The ewes were divided into 5 groups. Four sheep each were euthanized at 1, 2, 6, and 12 months from surgery, and 6 ewes were euthanized 24 months post-implantation. To study the effect of varying loads on the long-term regeneration process, an identical defect was also created and ESL cell engraftment performed in the lateral condyle (ESL-L) of the left stifle joint of the animals in the 12- and 24-month groups. The evaluation of regenerated tissue was performed by biomechanical, macroscopic, histological, immunohistochemical (collagen type II) and fluorescent in situ hybridization (FISH) assays., Results: no significant differences were found between treated and control sites in the biomechanical assays at any time point. ESL cell grafts showed significantly greater macroscopic evidence of regeneration as compared to controls at 24 months after surgery; significantly better histological evidence of repair in ESL-M samples versus controls was found throughout the considered period. At 24 months from surgery there was significantly improved integration of graft edges with the host tissue in the ESL-M as compared to the ESL-L samples, demonstrating that load bearing positively affects the long-term regeneration process., Conclusions: ESL cells enhanced the regeneration of hyaline cartilage. FISH confirmed that the regenerative tissue originated from ESL cells., Clinical Relevance: ESL cells are able to self-renew for prolonged periods without differentiation and, most importantly, to differentiate into a large variety of tissues.

Objectives: The purposes of this study were to determine: 1) the efficacy of polycaprolactone-g-polyethylene glycol (PCL-g-PEG) and polylactic-co-glycolic acid (PLGA-g-PEG) hydrogels and an absorbable collagen sponge (ACS) as carriers for lysophosphatidic acid (LPA), 2) the effect of LPA on bone healing in dogs, and 3) the ideal dose of LPA to maximally stimulate bone healing., Methods: Bilateral ulnar ostectomies were performed on purpose bred dogs. Control defects were filled with a PCL-g-PEG or PLGA-g-PEG hydrogel, or a saline soaked ACS. Contralateral defects were filled with a PCL-g-PEG or PLGA-g-PEG hydrogel, or an ACS with each carrying differing concentrations of an LPA solution. Dual-energy X-ray absorptiometry (DXA) was performed. Total bone area (TBA), mineral density (BMD), and mineral content (BMC) were determined at each time point. Relationships between the effect of treatment over time on TBA, BMC and BMD were determined., Results: Phase 1 - There was no significant difference in DXA-based TBA (p = 0.09), BMC (p = 0.33), or BMD (p = 0.74) over time between LPA treatments, or between the LPA treated and control groups TBA (p = 0.95), BMC (p = 0.99), or BMD (p = 0.46). Phase 2 - There was no significant difference over time between LPA treatments in DXA-based TBA (p = 0.33), BMC (p = 0.45), or BMD (p = 0.43), or between the LPA treated and control groups TBA (p = 0.94), BMC (p = 0.38), or BMD (p = 0.17). Phase 3 - There was no significant difference over time between LPA treatments in DXA-based TBA (p = 0.78), BMC (p = 0.88), or BMD (p = 0.35), or between the LPA treated and control groups TBA (p = 0.07), BMC (p = 0.85), or BMD (p = 0.06). There was a significant increase in TBA (p <0.0001) and BMC (p = 0.0014), but a significant decrease in BMD (p <0.0001) was noted over time when all groups were combined., Clinical Significance: Although LPA has shown promise as an osteoinductive agent in research, its performance as a bone graft substitute, as utilized in this study, is unsupported. Further studies are necessary to determine the incorporation and elution kinetics of LPA from the PLGA-g-PEG hydrogel and from an ACS. Hydrogels may have clinical applications for delaying or preventing bone formation.

Objectives: To report clinical signs, diagnostic imaging findings, and outcome in a dog with traumatic myositis ossificans of the origin of the extensor carpi radialis muscle., Study Design: Clinical report., Animals: An 8-month-old intact female Irish Setter Dog., Methods: After radiographic and computed tomographic evaluation of an osseous proliferation arising from the cranial cortex of the right distal humeral diaphysis, the protruding bone was surgically removed and evaluated by histopathology., Results: Traumatic myositis ossificans was successfully treated with surgical removal of the osseous proliferation resulting in improved postoperative range of motion of the right elbow joint. There was no evidence of lameness or abnormal bone regrowth associated with the surgical site radiographically at follow up., Conclusion: Surgical removal of a traumatic myositis ossificans lesion resulted in full return to function in a young, competitive show dog., (© Copyright 2014 by The American College of Veterinary Surgeons.)

Background: Articular cartilage has poor intrinsic capacity for regeneration because of its avascularity and very slow cellular turnover. Defects deriving from trauma or joint disease tend to be repaired with fibrocartilage rather than hyaline cartilage. Consequent degenerative processes are related to the width and depth of the defect. Since mesenchymal stem cells (MSCs) deriving from patients affected by osteoarthritis have a lower proliferative and chondrogenic activity, the systemic or local delivery of heterologous cells may enhance regeneration or inhibit the progressive loss of joint tissue. Embryonic stem cells (ESCs) are very promising, since they can self-renew for prolonged periods without differentiation and can differentiate into tissues from all the 3 germ layers. To date only a few experiments have used ESCs for the study of the cartilage regeneration in animal models and most of them used laboratory animals. Sheep, due to their anatomical, physiological and immunological similarity to humans, represent a valid model for translational studies. This experiment aimed to evaluate if the local delivery of male sheep embryonic stem-like (ES-like) cells into osteochondral defects in the femoral condyles of adult sheep can enhance the regeneration of articular cartilage. Twenty-two ewes were divided into 5 groups (1, 2, 6, 12 and 24 months after surgery). Newly formed tissue was evaluated by macroscopic, histological, immunohistochemical (collagen type II) and fluorescent in situ hybridization (FISH) assays., Results: Regenerated tissue was ultimately evaluated on 17 sheep. Samples engrafted with ES-like cells had significantly better histologic evidence of regeneration with respect to empty defects, used as controls, at all time periods., Conclusions: Histological assessments demonstrated that the local delivery of ES-like cells into osteochondral defects in sheep femoral condyles enhances the regeneration of the articular hyaline cartilage, without signs of immune rejection or teratoma for 24 months after engraftment.

The clinical, radiographic and histological features of synovial osteochondromatosis in multiple joints and an unrelated sclerosing osteosarcoma of the left tibia in a cat are reported. Radiographic evaluation showed signs of several nodular radiopacities in both stifles and both shoulders. Pathologic transverse fractures of the left tibia and fibula were also present. A midfemoral amputation of the left hindlimb was performed and treatment consisted of lifelong administration of nonsteroidal anti-inflammatory drugs. Histological evaluation confirmed synovial osteochondromatosis of the left stifle and sclerosing osteosarcoma of the left tibia. This is the first report of a feline patient with bilateral synovial osteochondromatosis that describes the clinical, radiographic and histological aspects of this disease.

The objective of this study was to characterize the clinical, clinicopathological, and histopathological findings of dogs with chronic pancreatitis. The necropsy database at Texas A&M University was searched for reports of dogs with histological evidence of chronic pancreatitis defined as irreversible histologic changes of the pancreas (i.e. fibrosis or atrophy). A reference necropsy population of 100 randomly selected dogs was used for signalment and concurrent disease comparisons. Cases were categorized as clinical or incidental chronic pancreatitis based on the presence of vomiting, decreased appetite, or both vs. neither of these signs. All archived pancreas samples were scored histologically using a published scoring system. Sixty-one dogs with chronic pancreatitis were included. The most frequent clinical signs were lethargy, decreased appetite, vomiting, and diarrhea. Compared to the reference necropsy population, chronic pancreatitis cases were more likely to be older, neutered, of the non-sporting/toy breed group, and to have concurrent endocrine, hepatobiliary, or neurological disease. Clinical cases had significantly higher histological scores for pancreatic necrosis and peripancreatic fat necrosis, and were significantly more likely to have hepatobiliary or endocrine disease as well as increased liver enzyme activities, or elevated cholesterol and bilirubin concentrations. In conclusion, clinical disease resulting from chronic pancreatitis might be related to the presence of pancreatic necrosis and pancreatic fat necrosis. The signalment, presentation, and concurrent diseases of dogs with chronic pancreatitis are similar to those previously reported for dogs with acute pancreatitis., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A 5-year-old male domestic rabbit had severe swelling of the left hindlimb. Radiographs demonstrated a proliferative, infiltrative lesion involving the stifle joint, femur and soft tissues of the thigh. Osteomyelitis or neoplasia was suspected and the limb was amputated. Grossly, there was a multilobular mass comprised of cystic spaces containing yellow mucinous material. Microscopically, the mass formed coalescing lobules of stellate to rounded cells embedded in varying amounts of myxoid to collagenous matrix, and some rimmed by narrow walls of metaplastic bone and/or cartilage, and some infiltrated by plasma cells, lymphocytes, heterophils and histiocytes. Immunohistochemically, neoplastic cells expressed vimentin but not cytokeratin, sarcomeric actin, Mac387 or BLA36. Cytokeratin was not detected in normal synovial cells. The radiographic, gross and histological findings were most consistent with synovial myxoma; however, because of the extensive involvement of the limb in the absence of confirmed metastatic disease, the term infiltrative synovial myxoma was applied., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Reasons for Performing Study: To describe the clinical symptoms, treatment, and outcome of meniscal cysts in horses. These structures have not been previously described in the literature as a potential cause of lameness in the horse., Hypothesis: Meniscal cysts are an uncommon condition of the femorotibial joint but can be a significant cause of lameness. Symptoms can be resolved by arthroscopic excision., Methods: Records of horses diagnosed with meniscal cysts and treated by cyst excision and meniscal debridement at 2 surgical practices were reviewed. Clinical outcome was determined by repeat veterinary examination and contact with owner., Results: Seven cases of meniscal cyst were treated with arthroscopic cyst excision and meniscal debridement. Five of 7 horses had lameness attributable to femorotibial joint pathology, while the remaining 2 horses had meniscal cysts found incidentally during diagnostic arthroscopy for the treatment of osteochondritis dissecans of the lateral trochlear ridge of the femur. Five of 6 horses with long-term follow-up were sound and a 7th horse was improved 11 months after surgery., Conclusions and Potential Relevance: Meniscal cysts, while uncommon, can be associated with progressive lameness in the horse. Surgical excision of the cysts results in resolution or improvement of symptoms, without evidence of recurrence on follow-up examination., (© 2011 EVJ Ltd.)

Balanced states in large networks are a usual hypothesis for explaining the variability of neural activity in cortical systems. In this regime the statistics of the inputs is characterized by static and dynamic fluctuations. The dynamic fluctuations have a Gaussian distribution. Such statistics allows to use reverse correlation methods, by recording synaptic inputs and the spike trains of ongoing spontaneous activity without any additional input. By using this method, properties of the single neuron dynamics that are masked by the balanced state can be quantified. To show the feasibility of this approach we apply it to large networks of conductance based neurons. The networks are classified as Type I or Type II according to the bifurcations which neurons of the different populations undergo near the firing onset. We also analyze mixed networks, in which each population has a mixture of different neuronal types. We determine under which conditions the intrinsic noise generated by the network can be used to apply reverse correlation methods. We find that under realistic conditions we can ascertain with low error the types of neurons present in the network. We also find that data from neurons with similar firing rates can be combined to perform covariance analysis. We compare the results of these methods (that do not requite any external input) to the standard procedure (that requires the injection of Gaussian noise into a single neuron). We find a good agreement between the two procedures.

Plastic changes in synaptic efficacy can depend on the time ordering of presynaptic and postsynaptic spikes. This phenomenon is called spike-timing-dependent plasticity (STDP). One of the most striking aspects of this plasticity mechanism is that the STDP windows display a great variety of forms in different parts of the nervous system. We explore this issue from a theoretical point of view. We choose as the optimization principle the minimization of conditional entropy or maximization of reliability in the transmission of information. We apply this principle to two types of postsynaptic dynamics, designated type I and type II. The first is characterized as being an integrator, while the second is a resonator. We find that, depending on the parameters of the models, the optimization principle can give rise to a wide variety of STDP windows, such as antisymmetric Hebbian, predominantly depressing or symmetric with one positive region and two lateral negative regions. We can relate each of these forms to the dynamical behavior of the different models. We also propose experimental tests to assess the validity of the optimization principle.

Magnetic resonance (MR) imaging and histopathology were used to diagnose an articular process synovial myxoma in a dog. On MR images, the tumor was characterized by distortion of the left L1-L2 articular process, widening of the articular process joint, and the presence of a mass contiguous with the synovium of the articular process that displaced the spinal cord. The tumor was T2-hyperintense, T1-hypointense, relative to muscle, and had mild contrast enhancement. The MR features of articular process synovial myxoma may be distinct from other diseases of the articular process joint., (© 2011 Veterinary Radiology & Ultrasound.)

Neoplastic diseases are typically diagnosed by biopsy and histopathological evaluation. The pathology report is key in determining prognosis, therapeutic decisions, and overall case management and therefore requires diagnostic accuracy, completeness, and clarity. Successful management relies on collaboration between clinical veterinarians, oncologists, and pathologists. To date there has been no standardized approach or guideline for the submission, trimming, margin evaluation, or reporting of neoplastic biopsy specimens in veterinary medicine. To address this issue, a committee consisting of veterinary pathologists and oncologists was established under the auspices of the American College of Veterinary Pathologists Oncology Committee. These consensus guidelines were subsequently reviewed and endorsed by a large international group of veterinary pathologists. These recommended guidelines are not mandated but rather exist to help clinicians and veterinary pathologists optimally handle neoplastic biopsy samples. Many of these guidelines represent the collective experience of the committee members and consensus group when assessing neoplastic lesions from veterinary patients but have not met the rigors of definitive scientific study and investigation. These questions of technique, analysis, and evaluation should be put through formal scrutiny in rigorous clinical studies in the near future so that more definitive guidelines can be derived.

We investigate the evolution of random positive linear maps with various type of disorder by analytic perturbation and direct simulation. Our theoretical result indicates that the statistics of a random linear map can be successfully described for long time by the mean-value vector state. The growth rate can be characterized by an effective Perron-Frobenius eigenvalue that strongly depends on the type of correlation between the elements of the projection matrix. We apply this approach to an age-structured population dynamics model. We show that the asymptotic mean-value vector state characterizes the population growth rate when the age-structured model has random vital parameters. In this case our approach reveals the nontrivial dependence of the effective growth rate with cross correlations. The problem was reduced to the calculation of the smallest positive root of a secular polynomial, which can be obtained by perturbations in terms of Green's function diagrammatic technique built with noncommutative cumulants for arbitrary n -point correlations.

Objective: To compare macrostructural and microstructural features of proximal sesamoid bones (PSBs) from horses with and without PSB midbody fracture to gain insight into the pathogenesis of PSB fracture., Sample Population: PSBs from 16 Thoroughbred racehorses (8 with and 8 without a PSB midbody fracture)., Procedures: Parasagittal sections of fractured and contralateral intact PSBs from horses with a PSB fracture and an intact PSB from age- and sex-matched control horses without a PSB fracture were evaluated for visual, radiographic, microradiographic, histologic, and his-tomorphometric differences in bone porosity, vascular channels, heme pigment, trabecular anisotropy, and pathological findings., Results: Fractured PSBs and their contralateral intact PSBs had more compacted trabecular bone than did control PSBs. Focal repair or remodeling was evident in the palmar aspect of many fractured and contralateral intact PSBs. Fracture coincided with microstructural features and propagated from the flexor to the articular surface., Conclusions and Clinical Relevance: Fractured PSBs had adapted to high loading but had focal evidence of excessive remodeling and porosity that likely predisposed the horses to complete fracture and catastrophic injury. Detection of focal injury before complete fracture provides an opportunity for prevention of catastrophic injury. Development of diagnostic imaging methods to assess porosity of PSBs may help to identify at-risk horses and allow for modifications of training and racing schedules to reduce the incidence of PSB fracture in Thoroughbred racehorses.

Neurons in the nervous system display a wide variety of plasticity processes. Among them are covariance-based rules and homeostatic plasticity. By themselves, the first ones tend to generate instabilities because of the unbounded potentiation of synapses. The second ones tend to stabilize the system by setting a target for the postsynaptic firing rate. In this work, we analyze the combined effect of these two mechanisms in a simple model of hypercolumn of the visual cortex. We find that the presence of homeostatic plasticity together with nonplastic uniform inhibition stabilizes the effect of Hebbian plasticity. The system can reach nontrivial solutions, where the recurrent intracortical connections are strongly modulated. The modulation is strong enough to generate contrast invariance. Moreover, this state can be reached even beginning from a weakly modulated initial condition.

Articular cartilage regeneration is limited. Embryonic stem (ES) cell lines provide a source of totipotent cells for regenerating cartilage. Anatomical, biomechanical, physiological and immunological similarities between humans and sheep make this animal an optimal experimental model. This study examines the repair process of articular cartilage in sheep after transplantation of ES-like cells isolated from inner cell masses (ICMs) derived from in vitro-produced (IVP) vitrified embryos. Thirty-five ES-like colonies from 40 IVP embryos, positive for stage-specific embryonic antigens (SSEAs), were pooled in groups of two or three, embedded in fibrin glue and transplanted into osteochondral defects in the medial femoral condyles of 14 ewes. Empty defect (ED) and cell-free glue (G) in the controlateral stifle joint served as controls. The Y gene sequence was used to detect ES-like cells in the repair tissue by in situ hybridization (ISH). Two ewes were euthanized at 1 month post-operatively, three each at 2 and 6 months and four at 12 months. Repairing tissue was examined by biomechanical, macroscopic, histological, immunohistochemical (collagen type II) and ISH assays. Scores of all treatments showed no statistical significant differences among treatment groups at a given time period, although ES-like grafts showed a tendency toward a better healing process. ISH was positive in all ES-like specimens. This study demonstrates that ES-like cells transplanted into cartilage defects stimulate the repair process to promote better organization and tissue bulk. However, the small number of cells applied and the short interval between surgery and euthanasia might have negatively affected the results.

Objective: To determine the short- and long-term changes in the biomechanical properties and metabolic activity of articular cartilage following the remote application of bipolar radiofrequency (bRF) and monopolar radiofrequency (mRF) energy within the rabbit stifle joint., Methods: The rabbits were randomly assigned to either Group-1 (normal rabbit food), or they were assigned to Group-2 (2% Cosequin in the diet). Each rabbit underwent bilateral stifle arthroscopy with either bRF or mRF applied to the infrapatellar fat pad for 45 seconds. Cartilage samples were collected at zero, four, and 14 weeks after surgery. Data were analyzed with a mixed model analysis of variance (ANOVA) for chondrocyte death, amount of GAG synthesis, and the equilibrium compressive modulus., Results: A significant increase in histological damage was noted at weeks four and 14 compared to week zero. Most of the chondrocyte death noted with confocal laser microscopy (49 of 56 samples) was noted in the superficial region (outer 25%) of the articular cartilage. GAG synthesis was not significantly different between groups or devices at any time point. A significant difference was not noted in equilibrium compressive modulus throughout the study., Conclusions: Remote application of bRF and mRF energy lead to immediate chondrocyte death. Most of the damage was superficial hence the metabolic activity and biomechanical properties of the extracellular matrix were maintained throughout this study. Treatment with Cosequin did not prevent superficial chondrocyte death caused by the application of radiofrequency (RF) energy with in the joint.

Objectives: To (1) determine bone contact with the outer surface and ingrowth into the perforated outer shell of the Kyon acetabular component at 2, 6, and 12 months after total hip replacement (THR) and (2) determine correlation between radiographic lucency surrounding the cup-bone interface and bone contact and ingrowth., Study Design: Experimental study., Animals: Large breed dogs (n=11) with and without hip dysplasia., Methods: Force platform gait analysis was performed preoperatively and 2, 6, and 12 months after THR. Curvilinear length of lucency (CLL) was measured on pelvic radiographs. Tissue contact with the outer cup and ingrowth into the cup were determined histomorphometrically at 2, 6, and 12 months., Results: Peak vertical force and vertical impulse of the treated and control hind limb were not significantly different at any time. Median bone contact with the outer cup surface was 77%, 48%, and 76% at 2, 6, and 12 months, respectively. Median bone ingrowth into the cup perforations was 50%, 20%, and 44% at 2, 6, and 12 months, respectively. Median bone ingrowth to the inner cup surface was minimal at any time. CLL did not correlate with bone ingrowth., Conclusions: Bone ingrowth into cup perforations occurred in each dog and was already present 2 months after THR, but most of the inner cup space remained vacant., Clinical Relevance: Radiographic lucency surrounding the cup-bone interface does not allow assessment of bone contact with the outer surface or bone ingrowth into the Kyon cup in dogs without clinical problems.

An intact male white pekin duck (Anas platyrhynchos domesticus) was presented for examination because of respiratory distress and 2- to 3-month history of lameness and lethargy. Results of radiography, ultrasonography, and cytologic examination revealed a large neoplastic mass in the coelom. The duck was euthanatized, and results of necropsy revealed 2 large, lobulated masses in the coelom and a small nodule on the liver. Histopathologic examination of the large masses revealed a collision pattern testicular tumor consisting of Sertoli, seminoma, and interstitial cell components. The hepatic nodule was a metastatic lesion consistent with a Sertoli cell testicular tumor. This is the first reported case of a mixed germ cell-sex cord-stromal tumor in a duck.

An aged mongrel dog was admitted for hemimandibulectomy as treatment for a mandibular mass that had been diagnosed as osteosarcoma. The fibro-osseous mass that surrounded the first molar tooth and replaced alveolar and cortical bone was reclassified as ossifying fibroma on the basis of anatomic location and histologic features. The tumor was composed of isomorphic fusiform cells with few mitotic figures. Tumoral stroma contained trabeculae of woven bone that were bordered by a single layer of osteoblasts. Excision was deemed complete with no evidence of extension or metastasis by computed tomography of the skull or thoracic and abdominal radiography. The dog was reportedly healthy 6 months after initial presentation. Though far less common than osteosarcoma as a primary canine bone tumor, ossifying fibroma should be included in the differential diagnosis for fibro-osseous proliferations, especially those of the jaw. Although benign, en bloc excision may be necessary for surgical cure.

Case Description: A 7-year-old domestic shorthair cat with a 2-month history of decreased appetite and weight loss was examined because of paraparesis of 1 week's duration that had progressed to paraplegia 3 days earlier., Clinical Findings: Neurologic examination revealed normo- to hyperreflexia and absence of deep pain sensation in the hind limbs and thoracolumbar spinal hyperesthesia. Neuro-anatomically, the lesion was located within the T3 through L3 spinal cord segments. Biochemical analysis and cytologic examination of CSF revealed no abnormalities. Radiography revealed narrowing of the T11-12 intervertebral disk space and intervertebral foramen suggestive of intervertebral disk disease. Myelography revealed an extradural mass centered at the T12-13 intervertebral disk space with extension over the dorsal surfaces of T11-13 and L1 vertebral bodies., Treatment and Outcome: A right-sided hemilaminectomy was performed over the T11-12, T12-13, and T13-L1 intervertebral disk spaces, and a space-occupying mass was revealed. Aerobic bacterial culture of samples of the mass yielded growth of a yeast organism after a 10-day incubation period; histologically, Histoplasma capsulatum was identified. Treatment with itraconazole was initiated. Nineteen days after surgery, superficial pain sensation and voluntary motor function were evident in both hind limbs. After approximately 3.5 months, the cat was ambulatory with sling assistance and had regained some ability to urinate voluntarily., Clinical Relevance: In cats with myelopathies that have no overt evidence of fungal dissemination, differential diagnoses should include CNS histoplasmosis. Although prognosis associated with fungal infections of the CNS is generally guarded, treatment is warranted and may have a positive outcome.

Synovial hemangioma was diagnosed in an 8-year-old castrated male Belgian Sheepdog with lameness of 3 months' duration. Pain, soft-tissue swelling, and hemarthrosis were localized to the left stifle joint. Projections of synovial membrane with reddish-purple nodules, excised via arthrotomy, were composed histologically of variably sized vascular channels that were lined by well-differentiated endothelial cells and separated by fibrous septa. Distension of some channels resulted in endothelial disruption, thrombosis, hemorrhage, necrosis, and focal spindle-cell proliferation. The limb was amputated to remove remaining neoplastic tissue. The hemangioma extended focally into the joint capsule and popliteal soft tissue but did not invade skeletal muscle or bone. The dog was free of detectable neoplasia 6 months after amputation. Synovial hemangioma is a rare benign vascular proliferation in people, most commonly in the knee, and should be included in the differential diagnosis for canine synovial tumors.

Objective: To evaluate the association between spondylosis deformans and clinical signs of intervertebral disk disease (IVDD) in dogs., Design: Retrospective case series., Animals: 210 dogs., Procedure: Records of 172 dogs with clinical signs of IVDD and 38 dogs with other neurologic disorders were reviewed. Signalment, sites of spondylosis, severity of associated osteophytosis, type of disk herniation, and duration of signs were recorded., Results: Dogs with IVDD had significantly fewer sites of involvement and lower grades of spondylosis deformans, compared with those in the non-IVDD group. When groups were adjusted for age and weight via multivariate linear regression, there were no differences in severity of osteophytosis or number of affected sites. Dogs with type II disk disease had higher numbers of affected sites and more severe changes, compared with dogs with type I disk herniation. There was no difference between groups in the rate at which IVDD was diagnosed at sites of spondylosis, compared with the rate at which IVDD was diagnosed in unaffected disk spaces. Areas of spondylosis were closer to sites of IVDD that elicited clinical signs than to randomly chosen intervertebral spaces, and distances between sites of spondylosis and sites of IVDD had a bimodal appearance., Conclusions and Clinical Relevance: An association may exist between radiographically apparent spondylosis and type II disk disease; type I disk disease was not associated with spondylosis. Spondylosis in radiographs of dogs with suspected type I disk disease is not clinically important. Spatial associations among sites of spondylosis and sites of IVDD may be coincidental or associated with vertebral column biomechanics.

Apparently synchronous, aggressive, mixed mesenchymal tumors in the right tibia, right femur, left femur, and rib cage produced multiple microscopic metastases in the lungs and macroscopic metastases in the liver, kidney, and spleen in a 1.5-year-old, neutered male, mixed-breed dog. No primary soft tissue tumor mass was present. Microscopically, the neoplasm exhibited osteosarcomatous, chondrosarcomatous, liposarcomatous, leiomyosarcomatous, fibrosarcomatous, angiosarcomatous, and leukocytic differentiation and was diagnosed as a multipotential osteosarcoma with various mesenchymal differentiation. Immunohistochemically, the neoplasm was cytoplasmically immunoreactive for vimentin, osteonectin, osteocalcin, CD 18, CD 31, desmin, and muscle-specific actin. Oil Red O staining was positive within liposarcomatous areas. Skeletal metastases from a primary bone tumor are exceedingly rare in human and veterinary medicine. However, the history, clinical signs, location, microscopic and immunohistochemical features were similar to those described in aggressive, poorly differentiated osteosarcomas of children. In addition, the wide range of mesenchymal tissue differentiation of this neoplasm was unusual, and to the authors' knowledge, an osteosarcoma with this degree of multiple differentiation has not been previously reported in the dog.