Surgical repair of Salter-Harris type II fracture of the distal humerus: short and long-term outcomes in a case series of three dogs and one cat.

CASE HISTORIES: Three dogs and one cat sustained forelimb trauma and were presented to a university veterinary clinic (Liège, Belgium) and a private veterinary hospital (Beacouzé, France). All four animals were referred for surgery. CLINICAL FINDINGS: Two dogs and the cat were ambulatory on admission but unable to bear weight on the affected limb. One dog was non-ambulatory and lacked voluntary movement and sensation in one forelimb. Salter-Harris type II fractures of the distal humerus were diagnosed by radiography in all cases; avulsion of the brachial plexus and pelvic fractures were also present in the non-ambulatory dog. TREATMENT AND OUTCOME: All Salter-Harris type II fractures were stabilised by open reduction and internal fixation with cross pins. One minor complication (seroma) and three major complications (implant migration) developed after surgery. The pins were completely removed in one case and partially removed in two cases to resolve these complications. At the final follow-up examination (12-31 months after surgery), owners reported no lameness in three of the four cases and grade 2/5 left forelimb lameness in one case. CLINICAL RELEVANCE: This type of fracture is rarely described in the literature; however, it should be included in the differential diagnoses of traumatic humeral fractures in growing dogs and cats. In this case series, we achieved fair-to-excellent short-term and long-term outcomes after osteosynthesis of Salter-Harris type II fractures by cross pinning.

Laryngeal paralysis secondary to cervical bite injuries in five dogs.

CASE HISTORIES: Medical records of a veterinary hospital in Belgium were reviewed for dogs (n = 5) that presented between 2016 and 2019 with laryngeal paralysis secondary to bite wounds to the cervical region received while fighting with other dogs. The time elapsed between the trauma and presentation was from a few hours up to 5 days. CLINICAL FINDINGS AND TREATMENT: Bilateral laryngeal paralysis was identified in three dogs and unilateral laryngeal paralysis in two dogs via endoscopic assessment of laryngeal function. The primary concomitant lesions included tracheal injury in 3/5 dogs and oesophageal injury in 1/5 dogs. One dog with bilateral laryngeal paralysis was treated medically as no signs of dyspnoea were present. Surgical management was elected in 4/5 dogs based on evaluation of their clinical status and lesions revealed by endoscopic examination of upper gastrointestinal and respiratory tracts. Dogs underwent surgical procedures that were determined to be appropriate for treatment of the lesions identified on clinical examination, diagnostic imaging, and endoscopy. The cervical region was explored through a ventral midline approach in 2/4 cases, to close tracheal perforations. Temporary tracheostomy was performed in 2/4 cases. Procedures to correct brachycephalic airway obstructive syndrome were performed in 2/4 cases. Cricoarytenoid lateralisation was performed in 2/4 dogs. Dogs were hospitalised for 2-10 days and received antimicrobial therapy before surgery and for 2-3 weeks after surgery. Physical examination and respiratory function were normal in 3/5 dogs 4-6 months after discharge. Information regarding outcomes for two cases was obtained from the owners by telephone assessment 1-6 months after surgery. The owner of each dog reported the respiratory function to be excellent. DIAGNOSIS: Uni- or bilateral, transient or permanent laryngeal paralysis with concomitant oesophageal, tracheal, or laryngeal lesions following cervical dog bite injuries diagnosed by endoscopic examination of upper gastrointestinal and respiratory tracts. CLINICAL RELEVANCE: This case series describes the diagnosis and management of dogs with laryngeal paralysis secondary to cervical dog bite injuries. To the authors' knowledge, this is the first published report documenting bilateral laryngeal paralysis secondary to cervical dog bite injuries. Clinicians should be aware of this pathology and the importance of investigating laryngeal function in dogs presenting with cervical bites, particularly those with inspiratory dyspnoea. Upper airway and digestive endoscopy are recommended for complete assessment of cervical traumatic injuries.

Ethanol-induced epigenetic regulations at the Bdnf gene in C57BL/6J mice.

High ethanol intake is well known to induce both anxiolytic and anxiogenic effects, in correlation with chromatin remodeling in the amygdaloid brain region and deficits in cell proliferation and survival in the hippocampus of rodents. Whether only moderate but chronic ethanol intake in C57BL/6J mice could also have an impact on chromatin remodeling and neuroplasticity was addressed here. Chronic ethanol consumption in a free choice paradigm was found to induce marked changes in the expression of genes implicated in neural development and histone post-translational modifications in the mouse hippocampus. Transcripts encoding neural bHLH activators and those from Bdnf exons II, III and VI were upregulated, whereas those from Bdnf exon VIII and Hdacs were downregulated by ethanol compared with water consumption. These ethanol-induced changes were associated with enrichment in both acetylated H3 at Bdnf promoter PVI and trimethylated H3 at PII and PIII. Conversely, acetylated H3 at PIII and PVIII and trimethylated H3 at PVIII were decreased in ethanol-exposed mice. In parallel, hippocampal brain-derived neurotrophic factor (BDNF) levels and TrkB-mediated neurogenesis in the dentate gyrus were significantly enhanced by ethanol consumption. These results suggest that, in C57BL/6J mice, chronic and moderate ethanol intake produces marked epigenetic changes underlying BDNF overexpression and downstream hippocampal neurogenesis.

RNA splicing and editing modulation of 5-HT(2C) receptor function: relevance to anxiety and aggression in VGV mice.

Changes in serotonin(2C) receptor (5-HTR2c) editing, splicing and density were found in conditions such as depression and suicide, but mechanisms explaining the changes in 5-HTR2c function are unknown. Thus, mice expressing only the fully edited VGV isoform of 5-HTR2c, in which clinically relevant behavioral changes are associated with alterations in splicing and receptor density, were studied. VGV mice displayed enhanced anxiety-like behavior in response to a preferential 5-HTR2c agonist in the social interaction test. Nearly half of interactions between pairs of VGV congeners consisted of fighting behaviors, whereas no fighting occurred in wild-type (WT) mice. VGV mice also exhibited a striking increase in freezing behaviors in reaction to an innately aversive ultrasonic stimulus. This behavioral phenotype occurred in conjunction with decreased brain 5-HT turnover during stress. These functional data were put in relation with the 5-HTR2c mRNA splicing process generating a truncated protein (5-HTR2c-Tr) in addition to the full-length receptor (5-HTR2c-Fl). 5-HTR2c-Tr mRNA was less abundant in many brain regions of VGV mice, which concomitantly had more 5-HTR2c than WT mice. Fluorescence resonance energy transfer and bioluminescence resonance energy transfer studies in transfected living HEK293T cells showed that 5-HTR2c-Tr interacts with 5-HTR2c-Fl. The 5-HTR2c-Tr was localized in the endoplasmic reticulum where it retained 5-HTR2c-Fl, preventing the latter to reach the plasma membrane. Consequently, 5-HTR2c-Tr decreased (3)H-mesulergine binding to 5-HTR2c-Fl at the plasma membrane in a concentration-dependent manner and more strongly with edited 5-HTR2c-Fl. These results suggest that 5-HTR2c pre-mRNA editing and splicing are entwined processes determining increased 5-HTR2c levels in pathological conditions through a deficit in 5-HTR2c-Tr.

Epigenetic regulation of the BDNF gene: implications for psychiatric disorders.

Abnormal brain-derived neurotrophic factor (BDNF) signaling seems to have a central role in the course and development of various neurological and psychiatric disorders. In addition, positive effects of psychotropic drugs are known to activate BDNF-mediated signaling. Although the BDNF gene has been associated with several diseases, molecular mechanisms other than functional genetic variations can impact on the regulation of BDNF gene expression and lead to disturbed BDNF signaling and associated pathology. Thus, epigenetic modifications, representing key mechanisms by which environmental factors induce enduring changes in gene expression, are suspected to participate in the onset of various psychiatric disorders. More specifically, various environmental factors, particularly when occurring during development, have been claimed to produce long-lasting epigenetic changes at the BDNF gene, thereby affecting availability and function of the BDNF protein. Such stabile imprints on the BDNF gene might explain, at least in part, the delayed efficacy of treatments as well as the high degree of relapses observed in psychiatric disorders. Moreover, BDNF gene has a complex structure displaying differential exon regulation and usage, suggesting a subcellular- and brain region-specific distribution. As such, developing drugs that modify epigenetic regulation at specific BDNF exons represents a promising strategy for the treatment of psychiatric disorders. Here, we present an overview of the current literature on epigenetic modifications at the BDNF locus in psychiatric disorders and related animal models.

Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response.

High-affinity transporters for norepinephrine (NE) and serotonin (5-HT), which ensure neurotransmitter clearance at the synapse, are the principal targets of widely used antidepressant drugs. Antidepressants targeting these high-affinity transporters, however, do not provide positive treatment outcomes for all patients. Other monoamine transport systems, with lower affinity, have been detected in the brain, but their role is largely unknown. Here we report that OCT2, a member of the polyspecific organic cation transporter (OCT) family, is expressed notably in the limbic system and implicated in anxiety and depression-related behaviors in the mouse. Genetic deletion of OCT2 in mice produced a significant reduction in brain tissue concentrations of NE and 5-HT and in ex vivo uptake of both these neurotransmitters in the presence of the dual 5-HT-NE transport blocker, venlafaxine. In vivo clearance of NE and 5-HT evaluated using microiontophoretic electrophysiology was diminished in the hippocampus of OCT2(-/-) mice in the presence of venlafaxine, thereby affecting postsynaptic neuronal activity. OCT2(-/-) mice displayed an altered sensitivity to acute treatments with NE- and/or 5-HT-selective transport blockers in the forced-swim test. Moreover, the mutant mice were insensitive to long-term venlafaxine treatment in a more realistic, corticosterone-induced, chronic depression model. Our findings identify OCT2 as an important postsynaptic determinant of aminergic tonus and mood-related behaviors and a potential pharmacological target for mood disorders therapy.

Aspergillus vertebral osteomyelitis in immunocompetent subjects: case report and review of the literature.

Aspergillus spondylodiscitis (AS) is rare in immunocompetent (IC) patients. A 65-year-old diabetic IC male subject presented with cervical AS 18 months after otomycosis. Two serological tests, mastoidectomy and biopsy of the sphenoid bone, were negative. A prevertebral biopsy identified A. flavus. The patient was successfully treated with voriconazole. Forty-three cases of AS in IC patients have been published. A predisposition was found in 84 % of cases. Fever was reported in 20 % of cases, whereas neurological defects were present in 41 %. Serology was inconsistently positive (5/7) and diagnosis was confirmed by biopsy or surgery. A. fumigatus was the most frequently isolated species (74 %). All episodes were medically treated, associated with surgery in 57 % of cases, and 73 % of patients fully recovered. AS must be discussed in IC patients presenting with risk factors, including diabetes mellitus. Biopsy is necessary to confirm diagnosis, since serology offers low sensitivity. Nevertheless, the prognosis is good.

Osteochondritis dissecans of the vertebral endplate of C5 with concomitant C4-C5 disc protrusion in a French Bulldog.

A 4-year-old French bulldog was presented with neck pain and left forelimb lameness. CT scan revealed a bony defect in the craniodorsal rim of the endplate of C5 with a concomitant disc protrusion leading to ventral spinal cord compression. Ventral slot at C4-C5 was performed to remove the protruding material and the fragment. Based on CT and histological findings, this bone defect was consistent with osteochondritis dissecans. Neck pain was absent immediately after the operation and the dog recovered without complication. Only a slight proprioceptive deficit of the left forelimb persisted during the 6-month of follow-up. Based on our search of the veterinary literature, this is the first published report of an osteochondritis dissecans of cervical endplate treated surgically.

Description of the first recorded major occurrence of equine viral arteritis in France.

REASONS FOR PERFORMING STUDY: The vast majority of equine arteritis virus (EAV) infections are inapparent or relatively mild, but may occasionally cause outbreaks of equine viral arteritis. The event observed in France during the summer of 2007 was the most important seen in the country, with mortality and disruption of economic activity. OBJECTIVES: To describe the different stages seen during the outbreak and to show how molecular tools were used for both the detection and management of the crisis. METHODS: EAV detection was performed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in blood, nasal swabs, semen or organ samples. Characterisation of EAV strains was performed by sequencing the ORF5 fragment. RESULTS: The outbreak affected 18 premises in 5 counties in western France, which represented the index, 8 primary and 9 secondary premises. Artificial insemination in draught horses was responsible for the virus spread. Eight mortality cases were observed, including one fetus, 5 young foals and 2 mature horses. Forty-three individuals had positive results by real-time RT-PCR. The range of measured cycle threshold (Ct) values varied from 19.8 to 40.4 depending on the biological samples. Phylogenetic analysis revealed that the 33 isolated strains all clustered within the EU-2 subgroup. CONCLUSIONS: The mortality rate attests to the virulence of the strain involved in this outbreak. Real-time RT-PCR was used for the first time in order to follow-up an epidemic disease in horses. POTENTIAL RELEVANCE: The early detection of 3 signals with high Ct values attest the importance of taking low signals into account in field conditions.

Repeated social defeat-induced depression-like behavioral and biological alterations in rats: involvement of cholecystokinin.

Cholecystokinin (CCK) involvement in depression-like disorders is poorly documented. Here, we investigated whether CCKergic neurotransmission is relevant to depressive-like symptoms and antidepressant therapy using a novel preclinical model based on repeated social defeat over 4 weeks in rats. Repeated social defeat triggers changes that could be considered as behavioral and biological correlates of depressive symptoms in humans, such as a hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis (increase of serum corticosterone levels and of adrenal gland weight), increased immobility time in the forced swimming test (FST), decrease of body weight and of sweet water consumption and reduction of hippocampal volume associated with a decreased cell proliferation in the dentate gyrus. In addition, in vivo microdialysis showed that cortical CCK release was tonically increased in defeated rats. Chronic imipramine treatment (16 mg kg(-1) per day for 25 days) prevented both the repeated social defeat-induced alterations of biological and behavioral parameters and the associated increase of cortical CCK release. Chronic blockade of CCK2 receptors by the specific antagonist CI-988 (1 mg kg(-1) per day for 25 days) also normalized immobility time in the FST and prevented HPA axis hyperactivity, reduction of hippocampal volume and cell proliferation and decreased sweet water intake normally evoked by repeated social defeat. These data showed that the repeated social-defeat paradigm can be considered as a suitable model of 'depression' in rats. The causal link between social defeat-evoked (1) increase in cortical CCKergic neurotransmission and (2) depression-like symptoms that we highlighted here strongly suggests that CCKergic systems may be a relevant target for novel antidepressant therapy.

[Diagnostic accuracy of 64 row multidetector computed tomography for coronary artery disease assessment]. / Performances diagnostiques des scanners 64 coupes dans l'évaluation de la maladie coronaire.

Due to technical advances, multidetector computed tomography (MDCT) allows evaluation of the coronary arteries and could in specific clinical indications provide a minimally invasive alternative to coronary angiography (CA). Recent technical advances combined with the availability of 64 row MDCT have significantly improved the evaluation of the native coronary arteries. However limitations remain for the evaluation of bypass grafts and stents. In this paper, we present a review the current literature on the diagnostic accuracy of 64 row MDCT in the assessment of coronary artery disease, and discuss the clinical implications and proposed indications of coronary CTA.

[Current indications for cardiac CT]. / Les indications actuelles du scanner cardiaque.

There is a need to define the current indications for coronary CT angiography (CCTA) even as technology continuously evolves. CCTA using 64 MDCT units has shown to be highly accurate for diagnosis of stenoses >or=50% on selected populations. It is currently used for its negative predictive value (96-98%). Stenosis quantification remains inferior to conventional coronary angiography with tendency to overestimate stenoses <70%. For diagnosis of coronary artery disease, CCTA is considered based on clinical findings (pre-test probability of coronary artery disease) and presence of myocardial ischemia on other functional studies. The main appropriate indications include: In the setting of acute coronary syndrome, CCTA excludes coronary artery disease with excellent NPV and good negative likelihood ratio (0.05) when ECG is non-contributory, 2 consecutive troponin levels at 6 hours are negative in a patient with low risk of coronary artery disease. In the setting of stable angina or atypical precordial chest pain, CCTA is indicated in patient with low to medium risk when functional test are non-contributory or unavailable, or ECG is non-interpretable. CCTA is a complement to coronary angiography for morphological evaluation of some lesions prior to angioplasty and stent placement (long segment occlusion, proximal lesions involving LAD and circumflex arteries). In selected patients, CCTA may replace coronary angiography prior to valvular surgery.

[Technological advances in cardiac CT]. / Evolutions technologiques en tomodensitométrie cardiaque.

The SFR-SFC presents guidelines dedicated to cardiac and coronary imaging using CT in the area of indications, technological requirement including both hardware and software, patient conditioning, CT protocols and related results concerning radiation dose, image quality and diagnostic value. These guidelines are based either on up-dated medical literature proofs and/or on expert consensus.

Orbital apex syndrome following inferior turbinate radiofrequency.

INTRODUCTION: We report a case of orbital apex syndrome following turbinate radiofrequency. METHODS: The clinical features, investigations (nasofibroscopy, supra-aortic and trans-cranial vessels ultrasounds, CT- and MRI-scans) are described. RESULTS: A forty-year-old man underwent radiofrequency volumetric tissue reduction (RFVTR) for bilateral inferior turbinate hypertrophy. No particular problems were reported during the procedure under general anaesthesia. Immediately after the general anaesthesia, the patient complained of right eyelid ptosis with right monocular blindness. The patient also had ophthalmoplegia and suffered from right corneal anaesthesia and right hypoaesthesia of the cheek. The CT-scan showed right ethmoidal and maxillary sinusitis with no bone or tissue lesions. MRI-scan showed an enlarged aspect of the subarachnoid membrane of the right optic nerve. Corticosteroid treatment was prescribed but did not produce any satisfactory result. No improvement in visual acuity was observed. CONCLUSION: Turbinate radiofrequency may result in a definitive orbital apex syndrome.

Leiomyoma in the nasal cavity of a dog.

A 7-year-old, 34-kg, neutered male Labrador retriever was presented with a 1-year history of intermittent sneezing with occasional left-sided epistaxis. CT revealed a mass in the left nasal cavity. Histopathological analysis of rhinoscopy-guided tissue biopsies was consistent with chronic necrotic and ulcerative rhinitis. Surgical debridement by ventral rhinotomy was subsequently performed and histopathological diagnosis was leiomyoma. Complete resolution of the nasal discharge and reduced sneezing frequency were observed after surgery. Fourteen months postoperatively, CT detected no regrowth of the mass.

PET/CT for assessing mandibular invasion by intraoral squamous cell carcinomas.

Evaluation of mandible invasion in cancer of the oral cavity and oropharynx is a major challenge. Today, CT scans are the most frequent imaging technique used, with sensitivity of 53 to 92% and specificity of 83 to 96%. Positron emission tomography is known as one of the most sensitive imaging techniques for head and neck cancer, but has poor anatomical resolution. Our study associates positron emission tomography with CT scans, fusioning both images to maximise data information. Positron emission tomography/CT fusion shows sensitivity of 100% with specificity of 85%. This result encourages the use of positron emission tomography/CT when assessing mandibular invasion.

Deficiency of the 5-hydroxytryptamine transporter gene leads to cardiac fibrosis and valvulopathy in mice.

BACKGROUND: Serotonin (5-hydroxytryptamine; 5-HT) overproduction is responsible for cardiac valvular disease in patients with carcinoid tumors. Reduced 5-HT inactivation is one proposed mechanism of the valvulopathy observed in individuals treated with the appetite suppressants fenfluramine and phentermine. One key protein limiting systemic availability of 5-HT is the 5-HT transporter (5-HTT) expressed by platelets and pulmonary vascular cells; 5-HTT is responsible for 5-HT uptake and subsequent inactivation of the amine passing through the lung. Here we investigated whether 5-HTT-deficient (5-HTT-KO) mice developed structural and/or functional cardiac abnormalities and valvulopathy. METHODS AND RESULTS: Cardiac endothelial cells expressed large amounts of 5-HTT in wild-type mice. 5-HTT deficiency appeared to be associated with marked interstitial, perivascular, and valvular fibrosis as evidenced by staining of cardiac collagen in 5-HTT-KO mice. Histological analysis provided evidence for valvulopathy characterized by valvular hyperplasia and prominent fibrosis at the attachment site and base of the leaflets. Echocardiography revealed an increase in left ventricular lumen diameter and a decrease in left ventricular diameter fractional shortening. Although 5-HT1B receptors mediated the 5-HT-induced collagen secretion by human cardiac myofibroblasts, the contribution of this receptor type to valvulopathy was ruled out because double-KO mice deficient in both 5-HTT and 5-HT1B receptors showed the same cardiac alterations as 5-HTT-KO mice. CONCLUSIONS: The present results establish a link between 5-HTT and the development of cardiac fibrosis and valvulopathy in vivo. 5-HTT-KO mice represent an especially relevant model for studying the mechanisms by which 5-HT induces valvulopathy.

Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene.

Hypoxia is a well-recognized stimulus for pulmonary blood vessel remodeling and pulmonary hypertension development. One mechanism that may account for these effects is the direct action of hypoxia on the expression of specific genes involved in vascular smooth muscle cell (SMC) proliferation. Previous studies demonstrated that the serotonin (5-hydroxytryptamine; 5-HT) transporter (5-HTT) mediates the mitogenic activity of 5-HT in pulmonary vascular SMCs and is overexpressed during hypoxia. Thus, 5-HT-related mitogenic activity is increased during hypoxia. Here, we report that mice deficient for 5-HTT (5-HTT(-/-)) developed less hypoxic pulmonary hypertension and vascular remodeling than paired 5-HTT(+/+) controls. When maintained under normoxia, 5-HTT(-/-)-mutant mice had normal hemodynamic parameters, low blood 5-HT levels, deficient platelet 5-HT uptake, and unchanged blood levels of 5-hydroxyindoleacetic acid, a metabolite of 5-HT. After exposure to 10% O(2) for 2 or 5 weeks, the number and medial wall thickness of muscular pulmonary vessels were reduced in hypoxic 5-HTT(-/-) mice as compared with wild-type paired controls. Concomitantly, right ventricular systolic pressure was lower and right ventricle hypertrophy less marked in the mutant mice. This occurred despite potentiation of acute hypoxic pulmonary vasoconstriction in the 5-HTT(-/-) mice. These data further support a key role of 5-HTT in hypoxia-induced pulmonary vascular SMC proliferation and pulmonary hypertension.