Shapes of cervical articular process joints and association with histological evidence of osteochondrosis in warmblood foals; a post-mortem study

Background: Osteochondrosis dissecans (OCD) of articular process joints (APJs) is involved in cervical vertebral compressive myelopathy (CVM). Biomechanical forces, important in development of OCD, depend on joint conformation. Oval and flat APJ surfaces are considered normal. Objectives: To identify and grade gross shape variation of cervical and cranial thoracic APJ surfaces and determine association with histological evidence of osteochondrosis. Study design: Case series. Methods: Eight hundred and four cervical and cranial thoracic APJ surfaces of 30 foals were evaluated for shape(s) and grades, and were correlated with osteochondrosis. Results: Three top view shapes (oval, pointed, elongated) and seven lateral view shapes (flat, convex, concave, stepped, bevelled, folded edge, raised edge) were regularly encountered. The oval top view shape was most common. Flat and bevelled were the most common lateral view shapes. General shape grade of caudal articular surfaces was significantly higher than of cranial surfaces. The combinations of an oval top view shape and the lateral view shapes folded edge, concave, or flat with additional raised edge and/or folded edge (flat +), were more likely to have OC than oval with convex, bevelled or flat lateral view shapes (normal vs. oval and folded, odds ratio [OR] 2.49 [95% confidence intervals (CIs) 1.13–5.67]; normal vs. oval and flat +, OR 2.77 [95% CI 1.15–6.85]; oval and convex vs. oval and folded, OR 3.20 [95% CI 1.35–8.20]; oval and convex vs. oval and flat +, OR 3.56 [95% CI 1.43–9.54]; oval and bevelled vs. oval and concave, OR 2.02 [95% CI 1.14–3.60]; oval and bevelled vs. oval and folded, OR 3.50 [95% CI 1.91–6.60]; oval and bevelled vs. oval and flat +, OR 3.90 [95% CI 2.00–7.70]). Main limitations: Most foals (21/30) were less than 1 month old. Lack of observer reliability scores for shape and shape grade. Conclusion: APJs shape might contribute to CVM by increased likelihood to have OC

Case report: Surgical treatment of an astrocytoma in the thoracic spinal cord of a cat

A 15-year-old spayed female domestic shorthaired cat was evaluated for chronic progressive paraparesis and proprioceptive ataxia. Neurological examination was consistent with a T3-L3 myelopathy. Plain thoracolumbar vertebral column radiographs and CT without intravenous contrast or myelography performed at another facility did not highlight any abnormalities. MRI of the thoracolumbar spinal cord identified an intraparenchymal space-occupying lesion extending from T10-T12. Surgery was performed to remove as much of the mass as possible, and to submit samples for histopathology. A dorsal laminectomy was performed over T9-T13. A midline myelotomy provided access to the mass, which was debrided with an intraoperative estimate of 80% removal. Histopathologic examination was consistent with a diagnosis of an astrocytoma. Post-operative treatment consisted of amoxicillin clavulanic acid, prednisolone, gabapentin, and additional analgesic medications in the direct post-operative period. Over the following 4 months, slow recovery of motor function was seen with continued physiotherapy. During the following 2 months, renal and cardiopulmonary disease were diagnosed and treated by other veterinarians. The cat was also reported to have lost voluntary movement in the pelvic limbs during this period, suggesting regression to paraplegia. Finally, 6 months post-surgery, the owner elected humane euthanasia. This is the second documentation of surgical treatment and outcome of an astrocytoma in the spinal cord of a cat

Case report: Surgical treatment and long-term successful outcome of a spinal intramedullary vascular malformation in a dog

A 3.5-year-old male intact Staffordshire terrier crossbreed dog was presented with a one-week history of progressive paraparesis with fecal and urinary incontinence. Neurological examination was consistent with a T3-L3 myelopathy. A magnetic resonance imaging study revealed the presence of a well-circumscribed hemorrhagic space-occupying lesion at the level of T12, suspected to be a vascular malformation, such as cavernoma or arteriovenous fistula, primary hematoma or hamartoma; less likely considerations included hemorrhagic inflammation or hemorrhagic primary or secondary neoplasia. A dorsal laminectomy, durotomy, and midline dorsal myelotomy were performed with a surgical microscope, and the vascular lesion was identified and removed. Histological examination of surgical samples yielded fibrin, hemorrhage, hematoidin pigment, and some neural tissue. Although a lining wall was visualized during surgery consistent with a vascular malformation, there was no histological confirmation of such a structure, hampering definitive classification of the lesion. There was no gross or histopathological evidence that would support a diagnosis of a hamartoma or benign neoplasia. The dog was paraplegic with intact nociception the day following surgery. Ambulation was recovered within 2 weeks. Progressive and complete recovery of neurological function was seen over the next 12 weeks. No recurrence of neurological dysfunction was seen over a 12-month follow-up period. Surgical treatment should be considered in dogs with spinal intramedullary vascular lesions which can have a successful long-term outcome

A recurrent somatic missense mutation in GNAS gene identified in familial thyroid follicular cell carcinomas in German longhaired pointer dogs

BACKGROUND: We previously reported a familial thyroid follicular cell carcinoma (FCC) in a large number of Dutch German longhaired pointers and identified two deleterious germline mutations in the TPO gene associated with disease predisposition. However, the somatic mutation profile of the FCC in dogs has not been investigated at a genome-wide scale. RESULTS: Herein, we comprehensively investigated the somatic mutations that potentially contribute to the inherited tumor formation and progression using high depth whole-genome sequencing. A GNAS p.A204D missense mutation was identified in 4 out of 7 FCC tumors by whole-genome sequencing and in 20 out of 32 dogs' tumors by targeted sequencing. In contrast to this, in the human TC, mutations in GNAS gene have lower prevalence. Meanwhile, the homologous somatic mutation in humans has not been reported. These findings suggest a difference in the somatic mutation landscape between TC in these dogs and human TC. Moreover, tumors with the GNAS p.A204D mutation had a significantly lower somatic mutation burden in these dogs. Somatic structural variant and copy number alterations were also investigated, but no potential driver event was identified. CONCLUSION: This study provides novel insight in the molecular mechanism of thyroid carcinoma development in dogs. German longhaired pointers carrying GNAS mutations in the tumor may be used as a disease model for the development and testing of novel therapies to kill the tumor with somatic mutations in the GNAS gene

Preductal Segmental Tubular Aortic Hypoplasia in Perinatally Died Stabyhoun Puppies

Background: A high perinatal mortality rate in the Stabyhoun breed prompted one of the Dutch breeding organizations to start an investigation. Preductal segmental tubular aortic hypoplasia is an extremely rarely documented congenital vascular anomaly in dogs, and it is suspected to be the result of constriction of ectopic ductal tissue in the aortic wall at birth. Methods: Over a period of 18 months, Stabyhoun puppies that were stillborn, died or were euthanized before 3 weeks of age were submitted to post-mortem examination at the reporting institution. Pathologic findings were documented. Results: Eight Stabyhoun puppies were submitted during the study period. In five of them, a severe preductal segmental tubular aortic hypoplasia was found. Two of the five puppies were stillborn, and three died spontaneously or were euthanized. Conclusions: Preductal tubular aortic hypoplasia was found in an unusually high frequency in the examined Stabyhoun puppies. Because the condition is believed to cause clinical signs only after birth, this anomaly cannot explain the death of the stillborn puppies. However, it might be responsible for cardiogenic pulmonary edema in the postnatal period. Routine dissection of the great vessels in perinatally deceased puppies would help to establish the prevalence of congenital anomalies of the aorta

Delayed endochondral ossification in early medial coronoid disease (MCD): a morphological and immunohistochemical evaluation in growing Labrador retrievers

Medial coronoid disease (MCD) is a common joint disease of dogs. It has a multifactorial aetiology, but the relationship between known causal factors and the disease has yet to be elucidated. As most of the published literature is clinical and it reports changes associated with advanced disease, it is not known whether the changes reflect the cause or consequences of the condition. The aim of this study was to investigate early micromorphological changes occurring in articular cartilage and to describe the postnatal development of the medial coronoid process (MCP) before MCD develops. Three litters of MCD-prone young Labrador retrievers were purpose-bred from a dam and two sires with MCD. Comparisons of the micromorphological appearance of the MCP in MCD-negative and MCD-positive joints demonstrated that MCD was initially associated with a disturbance of endochondral ossification, namely a delay in the calcification of the calcifying zone, without concurrent abnormalities in the superficial layers of the joint cartilage. Cartilage canals containing patent blood vessels were only detected in dogs <12 weeks old, but the role of these channels in impaired ossification requires further investigation. Retained hyaline cartilage might ossify as the disease progresses, but weak areas can develop into cracks between the retained cartilage and the subchondral bone, leading to cleft formation and fragmentation of the MCP

Laparoscopic vs. open adrenalectomy: perioperative data and survival analysis in 70 dogs with an adrenal tumor

Adrenalectomy is the treatment of choice in case of functional adrenal tumors and malignant adrenal incidentalomas. Laparoscopic adrenalectomy (LA) in dogs has gained popularity in recent years, however, clinical studies on large patient populations are scarce. This retrospective study describes perioperative and recurrence data, survival, and prognostic factors in 70 dogs that underwent LA or open adrenalectomy (OA) in our hospital between 2008 and 2022. Diagnosis was based on history, clinical signs, endocrine function tests and advanced diagnostic imaging. Laparoscopic adrenalectomy was performed in 42 dogs (n = 27 naturally occurring hypercortisolism, n = 4 pheochromocytoma, n = 1 pheochromocytoma with concurrent hypercortisolism, n = 10 incidentaloma) and OA in 28 dogs (n = 22 hypercortisolism, n = 3 pheochromocytoma, n = 3 incidentaloma). Bilateral adrenalectomy was performed in 8/70 dogs. Surgical duration of LA and OA did not differ significantly in unilateral and bilateral procedures (P = 0.108 and P = 0.101, respectively). Systemic hypertension occurred in 7/41 and 1/28 dogs during LA and OA, respectively (P = 0.130). Hypotension occurred in 2/41 and 4/28 dogs during LA and OA, respectively (P = 0.214). A total of 40/42 dogs in the LA group and 27/28 in the OA group survived to discharge (P = 0.810). Mean hospital stay was significantly shorter (P = 0.006) after LA (1.5 days, range 1–3) than after OA (2.2 days, range 1–4). No significant differences were demonstrated between LA and OA groups in recurrence of adrenal-dependent endocrine disease (P = 0.332), disease-free period (P = 0.733) and survival time (P = 0.353). The disease-specific 1-, 2- and 3-year survival rates were 95, 89, and 89% after LA and 92, 88, and 81% after OA. Tumor size was significantly associated with the occurrence of a recurrence. In addition, tumor size had a negative effect on the disease-free period and survival time. This study shows a favorable outcome of both LA and OA in dogs. Based on low perioperative complication rate, short hospitalization time and long-term outcomes comparable to OA in selected cases, the less invasive laparoscopic approach is considered the preferred technique

Козацькі могили у творчості Тараса Шевченка

The detoxification of ammonia occurs mainly through conversion of ammonia to urea in the liver via the urea cycle and glutamine synthesis. Congenital portosystemic shunts (CPSS) in dogs cause hyperammonemia eventually leading to hepatic encephalopathy. In this study, the gene expression of urea cycle enzymes (carbamoylphosphate synthetase (CPS1), ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS1), argininosuccinate lyase (ASL), and arginase (ARG1)), N-acetylglutamate synthase (NAGS), Glutamate dehydrogenase (GLUD1), and glutamate-ammonia ligase (GLUL) was evaluated in dogs with CPSS before and after surgical closure of the shunt. Additionally, immunohistochemistry was performed on urea cycle enzymes and GLUL on liver samples of healthy dogs and dogs with CPSS to investigate a possible zonal distribution of these enzymes within the liver lobule and to investigate possible differences in distribution in dogs with CPSS compared to healthy dogs. Furthermore, the effect of increasing ammonia concentrations on the expression of the urea cycle enzymes was investigated in primary hepatocytes in vitro. Gene-expression of CPS1, OTC, ASL, GLUD1 and NAGS was down regulated in dogs with CPSS and did not normalize after surgical closure of the shunt. In all dogs GLUL distribution was localized pericentrally. CPS1, OTC and ASS1 were localized periportally in healthy dogs, whereas in CPSS dogs, these enzymes lacked a clear zonal distribution. In primary hepatocytes higher ammonia concentrations induced mRNA levels of CPS1. We hypothesize that the reduction in expression of urea cycle enzymes, NAGS and GLUD1 as well as the alterations in zonal distribution in dogs with CPSS may be caused by a developmental arrest of these enzymes during the embryonic or early postnatal phase

Are slaughterhouse-obtained livers suitable for use in ex vivo perfusion research?

OBJECTIVES: The success of the ex vivo machine perfusion of pig livers used for preclinical research depends on organ quality and availability. In this study, we investigated whether livers obtained from slaughterhouses are suitable and equivalent to livers obtained from laboratory pigs. METHODS: Livers were obtained from slaughterhouse pigs stunned by electrocution or CO 2 inhalation and from laboratory pigs. For the latter group, 45 minutes of warm ischemia was mimicked for a subgroup, ensuring a valid comparison with slaughterhouse-derived livers. RESULTS: Livers from CO 2-stunned pigs showed lower indocyanine green clearance and bile production, higher blood lactate and potassium concentrations, and higher alanine aminotransferase activities than electrically stunned pigs. Furthermore, livers from electrically stunned pigs, and livers from laboratory pigs, subjected or not to warm ischemia, showed similar performance in terms of perfusion and metabolism. CONCLUSION: For an ex vivo liver model generated using slaughterhouse pigs, electrical stunning is preferable to CO 2 stunning. Livers from electrically stunned slaughterhouse pigs performed similarly to laboratory pig livers. These findings support the use of livers from electrically stunned slaughterhouse pigs, which may therefore provide an alternative to livers obtained from laboratory pigs, consistent with the principle of the 3Rs

Gene Expression Profiling of Histiocytic Sarcomas in a Canine Model: The Predisposed Flatcoated Retriever Dog

Background:The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors have value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed.Methods:Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS) and disseminated, visceral histiocytic sarcomas (VHS) and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR) analyses.Results:QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated), and GTSF1, Col3a1, CD90 and LUM (up-regulated) in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process.Conclusions:This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Exploration of the downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human