Calcium antagonists,diltiazem and nifedipine,protect broilers against low temperature‐induced pulmonary hypertension and pulmonary vascular remodeling

This study was designed to determine whether calcium antagonists, diltiazem and nifedipine, can depress low temperature‐induced pulmonary hypertension (PH) in broilers (also known as ascites) and to characterize their efficacy on hemodynamics and pulmonary artery function. Chicks were randomly allocated into six experimental groups and orally administered with vehicle, 5.0 mg/kg body weight (BW)/12 h nifedipine or 15.0 mg/kg BW/12 h diltiazem from 16 to 43 days of age under low temperature. The mean pulmonary arterial pressure (mPAP), the ascites heart index (AHI), the erythrocyte packed cell volume (PCV) and the relative percentage of medial pulmonary artery thickness were examined on days 29, 36 and 43. The data showed that administration of diltiazem protected broilers from low temperature‐induced pulmonary hypertension and vascular remodeling. Although nifedipine prevented mPAP from increasing during the early stage, it did not suppress the development of PH during the late stage and did not keep heart rate (HR), PCV, AHI and the thickness of pulmonary small artery smooth muscle layer at the normal levels. Taken together, our results showed that diltiazem can effectively prevent low temperature‐induced pulmonary hypertension in broilers with fewer side‐effects and may be a potential compound for the prevention of this disease in poultry industry.     

Clinical outcomes,ultrastructure and immunohistochemical features of canine high‐grade olfactory neuroblastoma

Olfactory neuroblastoma (ONB) is a rare intranasal neoplasm in both dogs and humans. Similar clinical presentation and overlapping histologic and immunohistochemical features of ONB with other intranasal neoplasms can make diagnosis and treatment of intranasal neoplasia challenging. Furthermore, in part because of their rarity, there is a lack of reporting on therapeutic regimen for these neoplasms. In humans, initial debulking surgery is usually followed by radiation therapy. Here we report on the histologic, immunohistochemical, and ultrastructural characteristics of canine ONB and report on the clinical progression of cases treated with radiation therapy. In all nine canine ONB examined here, neoplastic cells were arranged in a lobular manner amidst a prominent neurofibrillary matrix and had features consistent with Grade III (high grade) ONB. The neoplastic cells demonstrated positive immunohistochemical staining for TuJ‐1, a Class III beta‐tubulin neuronal cytoskeletal protein, and variable staining for other markers, including chromogranin, synaptophysin, AE1/AE3 and MAP2. The longest surviving case was treated with a regimen similar to that used in humans, consisting of debulking surgery followed by definitive radiation therapy. Our study found that TuJ‐1 is a useful marker for ONB and that radiation therapy, even in cases of advanced disease, may result in prolonged survival.     

Clinicopathologic features of lingual canine T‐zone lymphoma

Canine T‐zone lymphoma (TZL) is a subtype of T‐cell lymphoma characterized by unique histologic pattern and cytomorphology, immunophenotypic loss of CD45 expression, and an indolent clinical behaviour. Dogs with TZL typically present with 1 or more enlarged lymph nodes and/or lymphocytosis. We describe a novel extranodal presentation of TZL involving the tongue. Twelve dogs with tongue masses were diagnosed with lingual TZL based on a variable combination of immunophenotyping via flow cytometry, cytology, histopathology, immunohistochemistry and/or PCR for antigen receptor rearrangement (PARR) assay. Eleven dogs exhibited concurrent lymphocytosis and/or lymph node enlargement. Three cases were initially diagnosed as plasma cell tumours based on histology alone, thereby revealing a potential diagnostic challenge. Seven dogs achieved clinical remission and 4 achieved stable disease following variable treatment, consistent with the indolent nature of typical TZL involving the lymph nodes and peripheral blood. In 1 case the TZL resulted in progressive disease and failure to respond to treatment. In this case, the TZL exhibited histologic features of a higher grade neoplasm. This case series highlights a unique presentation of TZL and identifies a new differential diagnosis for lingual neoplasia. In this study, we characterize the clinical presentation, diagnostic features and patient outcomes of 12 dogs with lingual TZL.     

Pilot study utilizing Fluorine‐18 fluorodeoxyglucose‐positron emission tomography/computed tomography for glycolytic phenotyping of canine mast cell tumors

The goal of this prospective pilot study was to use naturally occurring canine mast cell tumors of various grades and stages as a model for attempting to determine how glucose uptake and markers of biologic behavior are correlated. It was hypothesized that enhanced glucose uptake, as measured by 2‐[fluorine‐18]fluoro‐d ‐glucose‐positron emission tomography/computed tomography (F18 FDG PET‐CT), would correlate with histologic grade. Dogs were recruited for this study from a population referred for treatment of cytologically or histologically confirmed mast cell tumors. Patients were staged utilizing standard of care methods (abdominal ultrasound and three view thoracic radiographs), followed by a whole body F18 FDG PET‐CT. Results of the F18 FDG PET‐CT were analyzed for possible metastasis and standard uptake value maximum (SUV_max) of identified lesions. Incisional or excisional biopsies of the accessible mast cell tumors were obtained and histology performed. Results were then analyzed to look for a possible correlation between the grade of mast cell tumors and SUV_max. A total of nine animals were included in the sample. Findings indicated that there was a correlation between grade of mast cell tumors and SUV_max as determined by F18 FDG PET‐CT (p‐value = 0.073, significance ≤ 0.1). Based on the limited power of this study, it is felt that further research to examine the relationship between glucose utilization and biologic aggressiveness in canine mast cell tumors is warranted. This study was unable to show that F18 FDG PET‐CT was a better staging tool than standard of care methods.     

Differences between µCT‐imaging and conventional CT for the diagnosis of possible diseases of the middle and inner cat ear

The aim of this study was to check the relevance of using in‐vivo micro computed tomography (µCT) for the diagnosis of possible diseases of the middle and inner ear of the cat. Therefore, on the one hand, differences of the detail detectability between the two imaging methods conventional computed tomography (cCT) and in‐vivo µCT were analyzed. Six healthy cat ears were dissected and scanned several times and the obtained images were compared with each other. On the other hand, histological slices of all ears were prepared and pictures of defined anatomical structures were taken and compared with the identical sectional plane of the µCT‐images. This way it was possible to evaluate the quality and clinical limitations of the in‐vivo µCT. The results show that an in‐vivo µCT is suitable to analyze even the smallest osseous structures, such as the semicircular ducts, the spiral osseous lamina or the ossicles whereas with the help of cCT it is not possible to identify such small osseous structures because of their blurred and less detailed representation. Delicate soft tissue structures as the membranous labyrinth including hearing and vestibular organ cannot be differentiated with as well in‐vivo µCT‐ as with cCT‐images. In‐vivo µCT represent a good possibility for more detailed diagnosis of extremely fine structures which cannot be detected with cCT. Histological slices can nonetheless not be replaced by in‐vivo µCT due to a too low spatial resolution and the limitations of the in‐vivo µCT with regard to the evaluation of soft tissue dense structures.     

Regional distribution of collagen and haemosiderin in the lungs of horses with exercise‐induced pulmonary haemorrhage

Reasons for performing study: Regional veno‐occlusive remodelling of pulmonary veins in EIPH‐affected horses, suggests that pulmonary veins may be central to pathogenesis. The current study quantified site‐specific changes in vein walls, collagen and haemosiderin accumulation, and pleural vascular profiles in the lungs of horses suffering EIPH. Hypothesis: In the caudodorsal lung regions of EIPH‐affected horses, there is veno‐occlusive remodelling with haemosiderosis, angiogenesis and fibrosis of the interstitium, interlobular septa and pleura. Methods: Morphometric methods were used to analyse the distribution and accumulation of pulmonary collagen and haemosiderin, and to count pleural vascular profiles in the lungs of 5 EIPH‐affected and 2 control horses. Results: Vein wall thickness was greatest in the dorsocaudal lung and significantly correlated with haemosiderin accumulation. Increased venous, interstitial, pleural and septal collagen; lung haemosiderin; and pleural vascular profiles occurred together and changes were most pronounced in the dorsocaudal lung. Further, haemosiderin accumulation colocalised with decreased pulmonary vein lumen size. Vein wall thickening, haemosiderin accumulation and histological score were highly correlated and these changes occurred only in the caudodorsal part of the lung. Conclusion: The colocalisation of these changes suggests that regional (caudodorsal) venous remodelling plays an important role in the pathogenesis of EIPH. Potential relevance: The results support the hypothesis that repeated bouts of venous hypertension during strenuous exercise cause regional vein wall remodelling and collagen accumulation, venous occlusion and pulmonary capillary hypertension. Subjected to these high pressures, there is capillary stress failure, bleeding, haemosiderin accumulation and, subsequently, lung fibrosis.     

A comparison of computed tomography, computed radiography, and film-screen radiography for the detection of canine pulmonary nodules

Computed tomography (CT) has become more widely available and computed radiography (CR) has replaced film-screen radiography for canine thoracic imaging in many veterinary practices. There are limited data comparing these modalities in a veterinary clinical setting to detect pulmonary nodules. We compared CT, CR, and film-screen radiography for detecting the presence, number, and characteristics of pulmonary nodules in dogs. Observer performance for a variety of experience levels was also evaluated. Twenty-one client-owned dogs with a primary neoplastic process underwent CT and CR; nine also received film-screen radiographs. Positive/negative classification by consensus agreed between the three modalities in 8/9 dogs and between CR and CT in the remaining 12. CT detected the greatest (P = 0.002) total number of nodules and no difference was seen between CR and films. The greatest number of nodules was seen in the right middle and both caudal regions, but only using CT (P < 0.0001). Significantly smaller nodules were detected with CT (P = 0.0007) and no difference in minimum size was detected between CR and films. Observer accuracy was high for all modalities; particularly for CT (90.5-100%) and for the senior radiologist (90.5-100%). CT was also characterized by the least interobserver variability. Although CT, CR, and film-screen performed similarly in determining the presence or absence of pulmonary nodules, a greater number of smaller nodules was detected with CT, and CT was associated with greater diagnostic confidence and observer accuracy and agreement.     

Clinicopathologic features,comorbid diseases,and prevalence of pulmonary hypertension in dogs with bronchomalacia

BackgroundReports of clinicopathologic features of bronchomalacia (BM) differ because of inconsistent definitions and frequent prevalence of comorbid cardiopulmonary disease. Pulmonary hypertension (PH) secondary to BM is poorly described.ObjectivesDogs with BM will be older but of any somatotype, and increased expiratory effort, ≥1 comorbid disease, and PH will be more common than in dogs without BM.AnimalsClient‐owned dogs (n = 210) evaluated for respiratory signs.MethodsMedical records of dogs with paired inspiratory: expiratory‐breath‐hold computed tomography, tracheobronchoscopy, or both between January 2016 and December 2019 were retrospectively reviewed. Comparisons between dogs with and without BM using Mann‐Whitney rank sum or χ ² tests (P < .05 significant were made). Because of high numbers of variables, criteria with high prevalence (>25%) were identified (n = 10) for univariate analysis (P < .005 significant). Significant variables were submitted for multivariate analysis.ResultsBronchomalacia was identified in 41% of dogs of all sizes/somatotypes; 38% were >10 kg. All dogs with BM had ≥1 comorbid cardiopulmonary disorder. Dogs with BM were significantly older (P < .001), smaller (P < .001), and were more likely diagnosed with tracheal or mainstem bronchial collapse (P < .001) or bronchiectasis (P < .001). Multivariate analysis confirmed associations with age, tracheal or mainstem bronchial collapse, and bronchiectasis. In dogs with BM, PH was more prevalent.Conclusions and Clinical ImportanceAlthough significantly more common in older, smaller dogs, BM occurs in dogs of all sizes and in all instances with comorbidities. Echocardiography should be considered in dogs with BM to identify PH.     

Clinical features of canine nodal T‐cell lymphomas classified as CD8+ or CD4−CD8− by flow cytometry

Canine T‐cell lymphoma (TCL) encompasses a heterogeneous group of diseases with variable clinical presentation, cytomorphology, immunophenotype, and biologic behaviour. The most common types of TCL in dogs involving peripheral lymph nodes include indolent T‐zone lymphoma (TZL) and biologically aggressive peripheral T‐cell lymphoma (PTCL). TCL phenotypes can be categorized by expression of the surface antigen molecules CD4 and CD8. The majority of TCL cases are CD4⁺, with far fewer cases being CD8⁺ or CD4^? CD8^?. The clinical features of CD4⁺ TCLs have been previously described. The less common TCL phenotypes, however, are poorly characterized with little to no information about prognosis. In this retrospective study, we describe and correlate the presenting clinical signs, flow cytometry, and outcomes of 119 dogs diagnosed with nodal, non‐TZL, CD8⁺ or CD4^? CD8^? TCL by flow cytometry. Skin lesions present at the time of diagnosis were more commonly observed in the CD8⁺ TCL group. Mediastinal enlargement and/or hypercalcemia were more commonly seen in the CD4^? CD8^? TCL group. Dogs with either CD8⁺ or CD4^? CD8^? TCLs had aggressive clinical disease with median overall survival (OS) times of 198 days and 145 days, respectively. In both groups, neoplastic cell size determined by flow cytometry ranged from small to large, and large cell size was associated with shorter OS times (median OS = 61 days). Cases classified as small cell had a median OS of 257 days. Expression levels of major histocompatibility complex (MHC) class II and CD5 were highly variable among cases but were not prognostically significant in this group of patients.     

Expression and functionality of TRPV1 receptor in human MCF‐7 and canine CF.41 cells

As canine mammary tumours (CMT) and human breast cancer share clinical and prognostic features, the former have been proposed as a model to study carcinogenesis and improved therapeutic treatment in human breast cancer. In recent years, it has been shown that transient receptor potential vanilloid 1 (TRPV1) is expressed in different neoplastic tissues and its activation has been associated with regulation of cancer growth and progression. The aim of the present research was to demonstrate the presence of TRPV1 in human and canine mammary cancer cells, MCF‐7 and CF.41, respectively, and to study the role of TRPV1 in regulating cell proliferation. The images obtained by Western blot showed a signal at 100 kDa corresponding to the molecular weight of TRPV1 receptor. All tested TRPV1 agonists and antagonists caused a significant decrease (P < 0.05) of cell growth rate in MCF‐7 cells. By contrast, in CF.41 cells capsaicin and capsazepine induced a significant increase (P < 0.05) in cell proliferation, whereas resiniferatoxin (RTX) and 5‐iodo‐resiniferatoxin (5‐I‐RTX) had no influence on CF.41 cell proliferation. Further studies are needed to elucidate the underlying molecular mechanism responsible for the different effects evoked by TRPV1 activation in MCF‐7 and CF.41 cells.     

Intracranial arteries of New Zealand rabbits; identification,three-dimensional modelling,and morphometry by computed tomography angiography

The aim of the study was to determine identification, three-dimensional modelling, and morphometry of intracranial arteries in New Zealand Rabbit by using computed tomography angiography. A total of 20 adult New Zealand Rabbits from both sexes were used in the study. General anaesthesia procedure was followed before computed tomography angiography imaging. Rabbits were placed in a prone position for imaging. Computed tomography angiography imaging was performed by injecting contrast agent into vena auricularis marginalis of rabbits. Morphometric measurements of the specified points were taken by MIMICS program using the computed tomography angiography images acquired. Three-dimensional intracranial artery model was prepared from the two-dimensional images on the same program. Measurements were statistically compared in terms of sex and side. It was observed in the study that arteria basilaris was generated by bilateral arteria vertebralis at the basal level of medulla oblongata. In the study, a statistically significant difference was determined only in diameter values of arteria cerebri caudalis dextra et sinistra in both female and male rabbits. On the other hand, no statistically significant difference was determined with respect to the side. Consequently, we think that the data of the present study will contribute to further studies on cerebrovascular pathology, clinicians or researchers.     

Influence of E‐cadherin genetic variation in canine mammary tumour risk,clinicopathological features and prognosis

E‐cadherin is a cell adhesion molecule that participates in several cellular processes that guarantee the maintenance of structural and functional integrity of epithelial tissues. E‐cadherin plays an important role in mammary carcinogenesis, and various studies have demonstrated the effect of CDH1 genetic variation in risk, progression and biological behaviour of human breast cancer. Although there are some recognized genetic variations in canine CDH1 gene, their influence in canine mammary tumour development and progression has not been previously evaluated. In this study, we aim to assess the influence of CDH1 SNPs rs850805755, rs852280880 and rs852639930 in the risk, clinicopathological features and clinical outcome of canine mammary tumours. A case‐control study was conducted involving 206 bitches with mammary tumours and 161 bitches free of mammary neoplasia. CDH1 SNPs rs850805755 and rs852280880 were associated with a decreased risk and a later onset of mammary tumour development. Furthermore, these SNPs were related to the development of small size carcinomas, of low histological grade and low nuclear pleomorphism. SNP rs852639930 was associated with the development of small size tumours with a non‐infiltrative, non‐invasive growth pattern. Data from the present investigation demonstrate that these CDH1 genetic variants could have a protective role in canine mammary tumours, by being associated with low risk of tumour development, delayed onset of the disease and less aggressive clinicopathological features.     

Clinical, bronchoscopic, histopathologic, diagnostic imaging, and arterial oxygenation findings in West Highland White Terriers with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, interstitial lung disease primarily affecting West Highland White Terriers (WHWTs). Objective: To describe the clinicopathological and diagnostic imaging features in WHWTs with IPF. Animals: Twelve WHWTs with IPF and 14 healthy control WHWTs. Method: Prospective study. Clinical signs and findings of physical examination, blood and arterial blood gas analyses, radiography, high‐resolution computed tomography (HRCT), bronchoscopy and bronchoalveolar lavage (BAL) of IPF dogs were obtained and compared with controls. Histopathologic changes in IPF dogs were evaluated. Results: Mean partial pressure of oxygen was significantly lower in IPF (mean ± SD, 65.5 ± 15.4 mmHg) than in controls (99.1 ± 7.8 mmHg, P<.001). The alveolar‐arterial oxygen gradient was significantly higher in IPF (50.1 ± 17.3 mmHg) than in controls (17.5 ± 4.9 mmHg, P<.001). In HRCT, ground glass opacity (GGO) was detected in all IPF dogs, traction bronchiectasis in 4, and honeycombing in 1. Bronchoscopic airway changes were noted in all IPF dogs. On BAL fluid (BALF) cytology, the total cell count (TCC) was higher in IPF dogs, and the numbers but not the percentages of macrophages, neutrophils, and mast cells were increased. On histopathology, multifocal or diffuse interstitial fibrosis, type II pneumocyte hyperplasia, prominent intraalveolar macrophages, distortion of alveolar architecture, and emphysematous change were detected. Conclusion and Clinical Importance: IPF causes substantial hypoxemia. In HRCT, GGO is a consistent finding. IPF dogs have concurrent airway changes and an increase in BALF TCC.     

Technical set‐up and radiation exposure for standing computed tomography of the equine head

The recent adaptation of human computed tomography (CT) machines to enable scanning of the equine head via standing sedation has revolutionised our ability to acquire images of this complex anatomical region. There are a small number of CT systems installed worldwide and it is to be expected that this will increase in the next few years; however, currently, there is no publication that describes the technical set‐up required to permit CT scanning of the equine head. This paper describes the technical set‐up, technique and exposures necessary to accomplish CT scanning of the horse under standing sedation to diagnose disorders of the equine head.     

Severe bilateral physitis with instability and Salter‐Harris type 1 fractures in two foals

This Case Report describes the clinical, radiographic, computed tomographic and post mortem findings in 2 foals with severe bilateral physitis of the distal third metatarsal bones (MtIII). The foals were admitted because of bilateral hindlimb lameness of several weeks' duration. Initial examination revealed that the physeal regions of the distal MtIII were enlarged, warmer than normal and painful on palpation. Case 1 was treated conservatively and discharged but was readmitted 8 weeks later because of clinical deterioration. In both foals, radiographs showed plantar dislocation of both epiphyses through the physis and a Salter‐Harris type 1 fracture. The foals were subjected to euthanasia and a post mortem examination.     

Histopathology and computed tomography of age‐associated degeneration of the equine temporohyoid joint

Reasons for performing study: The aetiology of temporohyoid osteoarthropathy (THO) is unknown; both primary infectious and degenerative causes have been suggested. Hypothesis: There is a significant association between increasing age and severity of temporohyoid joint degeneration. To examine the histopathology of the temporohyoid articulation in aged horses and to compare the appearance of the joint with computed tomography (CT) and peripheral quantitative CT (pQCT). Methods: pQCT scans of the temporohyoid articulations were obtained bilaterally from 31 horses (range age 1–44 years) post mortem and images were graded by 2 blinded observers on 2 occasions for the presence of osteophytes, irregularity of the joint surface and mineralisation. Eight heads had been examined previously by CT, with the images similarly graded for the shape and density of the proximal stylohyoid bones, bone proliferation surrounding the joint, mineralisation of the tympanohyoid cartilage and the relationship of the petrous temporal bone to the stylohyoid bone. Sixteen temporohyoid joints were then evaluated histologically. Results: There was significant association between the mean pQCT degeneration score and age (rho = 0.75; P<0.0001), between the pQCT and CT score (rho = 0.63; P = 0.01) and between the degenerative changes identified within each temporohyoid joint within each horse (rho = 0.81; P<0.0001). Age‐associated changes included the development of a club shape by the proximal stylohyoid bone, rounding of the synostosis with the petrous temporal bone and extension of osteophytes from the petrous temporal bone to envelope the stylohyoid head and bridge the joint. In no horse was there any evidence of osteomyelitis within the petrous temporal bone, stylohyoid bone or tympanohyoid cartilage. Conclusions: This study provides evidence that age is associated with increasing severity of degenerative changes in the equine temporohyoid joint and that similar changes are commonly found bilaterally. Potential relevance: The changes identified appear similar, albeit milder to the changes reported in horses with THO, suggesting that degenerative, rather than infectious causes may underlie the aetiology of THO. Future work should be directed at examining the histopathology of clinical THO cases.     

High COX‐2 expression in canine mast cell tumours is associated with proliferation,angiogenesis and decreased overall survival

COX‐2 overexpression is associated with several hallmarks of carcinogenesis such as proliferation, angiogenesis, invasion and metastasis. Fifty cases of canine mast cell tumours (MCT) were retrospectively evaluated and submitted to immunohistochemistry for COX‐2, CD31, Ki‐67, MAC‐387 and CD3. Furthermore its relationship with clinicopathological variables and overall survival (OS) was analysed. COX‐2 intensity (P = 0.016), but not COX‐2 extension nor score was associated with decreased OS and higher grades of malignancy according to Patnaik (P = 0.002) and Kiupel (P < 0.001) grading systems. Cox‐2 intensity was also associated with higher Ki‐67 scores (P = 0.009), higher mitotic index (P = 0.022) and higher microvascularization density (P = 0.045). No association was observed for COX‐2 intensity and CD3‐T lymphocyte (P = 0.377) and macrophage infiltration (P = 0.261) by MAC‐387 immunollabelling, suggesting an active role of COX‐2 in MCT oncogenesis mainly through proliferation and angiogenesis stimulation making it a potentially clinical relevant prognosis marker and therapeutic target.