Evaluating the indicators of a heart rate variability analysis in dogs using Poincaré plots.

Heart rate variability analyses using Poincaré plots can be useful for evaluating the autonomic nervous system function. However, the interpretation of the quantitative indicators of Poincaré plots remains controversial. Thus, few studies have verified the effectiveness of the quantitative indicators in veterinary medicine. This study aimed to verify the reliability of Poincaré plot indicators using pharmacological models in dogs. Four healthy beagles were used in this study. Each dog was treated with propranolol, atropine, and propranolol-atropine to block the sympathetic, parasympathetic, and sympathetic-parasympathetic functions, respectively. The quantitative indicators of the Poincaré plots were calculated based on data from 300 electrocardiogram beats collected before and after the administration of each drug and statistically analysed. The quantitative indicators of the Poincaré plots, such as the standard deviation perpendicular to the major axis (SD1), standard deviation along the major axis (SD2), and SD1 × SD2, significantly decreased after the drug administration in both the parasympathetic and sympathetic-parasympathetic blockade models. However, no significant differences were observed in SD1/SD2 between the groups. The Poincaré plots reflected the changes in the autonomic nervous system of dogs. In dogs, SD1, SD2, and SD1 × SD2 can detect a state in which parasympathetic nerve activity is suppressed.

EBSTEIN ANOMALY IN THE TSUSHIMA LEOPARD CAT (PRIONAILURUS BENGALENSIS EUPTILURUS).

Ebstein anomaly is a rare congenital heart disease that has been described in domestic dogs, a meerkat, a pygmy goat, and a lion. An 11-mo-old Tsushima leopard cat presented to Osaka Prefecture University Veterinary Hospital for diagnosis and treatment of right-sided congestive heart failure. Echocardiography showed a dilated right atrium and ventricle with an enlarged tricuspid valve annulus and apical displacement of the tricuspid valve leaflets. The cat was diagnosed with Ebstein anomaly. To the best of our knowledge, this is the first report of this type of congenital heart disease in a Tsushima leopard cat.

Epidermoid cyst of the ileum in a miniature dachshund dog.

A 13-year-old castrated male miniature dachshund dog was presented with chronic vomiting and diarrhea. Contrast radiography and surgical exploration revealed an ileal cyst, which was excised. A diagnosis of epidermoid cyst was made from a combination of the clinical findings and histological examination of the surgical specimen.

Kyste épidermoïde de l'iléon chez un chien Dachsund miniature. Un chien Dachsund miniature mâle castré âgé de 13 ans a été présenté avec des vomissements et de la diarrhée chroniques. Une radiographie à contraste et une exploration chirurgicale ont révélé un kyste iléal, qui a été excisé. Un diagnostic de kyste épidermoïde a été posé à partir d'une combinaison de constatations cliniques et de l'examen histologique du spécimen chirurgical.(Traduit par Isabelle Vallières).

A feline spinal dermoid cyst treated with surgical intervention.

A 5-year-old neutered female mixed cat presented with reduced activity and ataxia of the hind limbs. Computed tomography and magnetic resonance imaging revealed an extradural mass compressing the spinal cord on the dorsal aspects from the 7th to 8th thoracic vertebra. Dorsal laminectomy was performed on the 7-8th thoracic vertebra and the cyst was totally removed, giving full resolution of the clinical signs. The cyst was diagnosed as a dermoid cyst. To our knowledge, this is the first report of feline dermoid cyst compressing the spinal cord that was diagnosed antemortem. The prognosis is favorable when the cyst is completely resected.

Effects of trastuzumab emtansine on canine urothelial carcinoma cells in vitro and in vivo.

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract in dogs and has aggressive behaviour. Although human epidermal growth factor receptor 2 (HER2) is a known therapeutic target with evidence in canine UC, the efficacy of anti-HER2 antibody drugs remains unknown. This study aimed to investigate the effects of anti-HER2 antibody drugs including trastuzumab and trastuzumab emtansine (T-DM1) on canine UC cell lines in vitro and in vivo. Four canine UC cell lines (Nene, TCCUB, Love, and Sora) were used. In western blotting, HER2 protein expression was observed in all the cell lines. Although both trastuzumab and T-DM1 showed dose-dependent growth inhibitory activity in the cell lines, T-DM1 showed much stronger activity than that of trastuzumab. In flow cytometry analyses with the canine UC cell line (Sora), T-DM1 but not trastuzumab significantly increased the percentages of early and late apoptotic cells in annexin V apoptotic assays and the sub-G1 phase fraction in cell cycle analyses. For the in vivo experiment, the canine UC cells (Sora) were subcutaneously injected into nude mice. Four days after inoculation, trastuzumab, T-DM1, or vehicle was administered intraperitoneally once a week for three times. Tumour volumes were significantly smaller in the T-DM1 group compared to the trastuzumab and vehicle control groups. These findings indicate that T-DM1 exerts a stronger antitumour effect than that of trastuzumab on canine UC cells in vitro and in vivo, possibly by inducing apoptosis due to DM1.

Presumptive acute lung injury following multiple surgeries in a cat.

A 12-year-old, 3.5-kg spayed female domestic shorthair cat had a tracheal mass identified as malignant B-cell lymphoma. The cat had tracheal resection and subsequently developed laryngeal paralysis. Due to multiple episodes of respiratory distress the cat subsequently had tracheal surgeries. Finally, the cat had a sudden onset of severe respiratory distress and collapsed. Computed tomography imaging and arterial blood gas analysis supported a diagnosis of acute lung injury.

Blessure pulmonaire aiguë présumée après plusieurs chirurgies chez un chat. Une chatte commune domestique stérilisée âgée de 12 ans qui pesait 3,5 kg avait une masse trachéale identifiée comme un lymphome B malin. La chatte a eu une résection trachéale et a ensuite développé une paralysie laryngienne. En raison de plusieurs épisodes de détresse respiratoire, la chatte a ensuite subi des chirurgies trachéales. Enfin, la chatte a souffert soudainement d'une détresse respiratoire et s'est effondrée. Une tomographie par ordinateur et une analyse des gaz du sang artériel a appuyé un diagnostic de blessure pulmonaire aiguë.(Traduit par Isabelle Vallières).

Case Report: Detection of Transferrin in a Dog Suspected of Having Cerebrospinal Fluid Rhinorrhea.

A 12-year-old Yorkshire terrier was referred for epileptic seizures and nasal discharge. The fluid was clear and serous. Cerebrospinal fluid (CSF) rhinorrhea was suspected, based on clinical signs and MRI findings. In humans, analysis of nasal secretions to determine the concentration of glucose and brain-type transferrin has been widely used clinically in order to confirm the presence of CSF rhinorrhea. The glucose concentration in the nasal discharge was 74 mg/dL. Serum-type and brain-type isoforms of transferrin were detectable in the nasal sample. The concentration of glucose and brain-type transferrin could be useful for diagnosing CSF rhinorrhea.

Mesenteric lymph node abscesses due to Escherichia coli in a cat.

A 3-year-old, castrated male mixed-breed cat presented with an almost 2-year history of chronic loose stools. On radiography and ultrasound examination, there were two masses in the centre of the abdomen. Contrast-enhanced computed tomography revealed that the masses were enlarged mesenteric lymph nodes with fluid accumulation. Percutaneous lesion drainage yielded pus-like fluid. Fluid cytology revealed numerous neutrophils and Gram-negative rods. Pus culture identified Escherichia coli as the causative organism. Consequently, mesenteric lymph node abscesses were definitively diagnosed. Since computed tomography showed that the abscesses adhered to the surrounding tissues, it was difficult to remove them surgically. With drainage and antimicrobial therapy, the mesenteric lymph nodes gradually decreased in size. However, loose stools persisted. The cat's diet was changed to a hydrolysed diet, and the clinical symptoms improved, suggesting food-responsive enteropathy. This may be an underlying disease of lymph node abscesses. Lymph node abscesses limited to the mesenteric lymph nodes rarely occur in veterinary medicine, and this is the first report in cats.

Retrospective evaluation of nimustine use in the treatment of feline lymphoma.

BACKGROUND: Nimustine, similar to lomustine, is an alkylating agent from the nitrosourea family. There have been some reports regarding lomustine treatment for tumour-bearing cats. However, information regarding nimustine treatment for tumour-bearing cats is limited. OBJECTIVES: To retrospectively evaluate adverse events and clinical outcomes in tumour-bearing cats receiving nimustine. METHODS: Information regarding diagnosis, treatment condition, adverse events, and clinical outcomes was collected in tumour-bearing cats receiving nimustine through reviews of medical records. RESULTS: Nine cats with lymphoma were treated with nimustine in the primary therapy (n = 2) and in the rescue therapy (n = 7). Median starting dose of nimustine was 25 mg/m2 (range: 20-30 mg/m2 ) with dosing interval of three weeks and 1-11 administrations. Adverse events were mild gastrointestinal toxicity (grade 1) including diarrhoea (n = 2) and vomiting (n = 2) and mild myelosuppression (grade 1 or 2) including thrombocytopenia (n = 3) and neutropenia (n = 1). No severe adverse events were observed. Progression-free survival durations among cats receiving nimustine in the primary therapy and in the rescue therapy were 274-688 days (median: 481 days) and 9-671 days (median: 102 days), respectively. Overall survival durations among cats receiving nimustine in the primary therapy and in the rescue therapy were 275-745 days (median: 510 days) and 14-671 days (median: 109 days), respectively. CONCLUSIONS: Nimustine was well tolerated and showed clinical outcomes similar to lomustine in cats with lymphoma. These findings suggest that nimustine might be an alternative to lomustine in the treatment of feline lymphoma.

Dystrophin-deficient muscular dystrophy in a Toy Poodle with a single base pair insertion in exon 45 of the Duchenne muscular dystrophy gene.

A 10-month-old, intact male Toy Poodle was referred for a postural abnormality. Blood biochemical tests revealed a marked increase in plasma creatine phosphokinase (CPK) concentration. The isoenzyme test showed that 99% of serum CPK consisted of CPK-MM. Histopathological evaluation of muscle biopsy samples confirmed scattered degeneration and necrosis of myofibers. Immunohistochemistry for dystrophin showed an absence of staining in muscle cells. Based on these findings, the dog was diagnosed with dystrophin-deficient muscular dystrophy. Whole genome sequencing using genomic DNA extracted from blood revealed a single base pair insertion in exon 45 of the Duchenne muscular dystrophy (DMD) gene. This is the first report on muscular dystrophy in Toy Poodles and identified a novel mutation in the DMD gene.

Whole-genome analyses of extended-spectrum or AmpC ß-lactamase-producing Escherichia coli isolates from companion dogs in Japan.

The emergence and global spread of extended-spectrum or AmpC ß-lactamase (ESBL/AmpC)-producing Enterobacteriaceae in companion animals have led to the hypothesis that companion animals might be reservoirs for cross-species transmission because of their close contact with humans. However, current knowledge in this field is limited; therefore, the role of companion animals in cross-species transmission remains to be elucidated. Herein, we studied ESBL/AmpC-producing Enterobacteriaceae, Escherichia coli in particular, isolated from extraintestinal sites and feces of companion dogs. Whole-genome sequencing analysis revealed that (i) extraintestinal E. coli isolates were most closely related to those isolated from feces from the same dog, (ii) chromosomal sequences in the ST131/C1-M27 clade isolated from companion dogs were highly similar to those in the ST131/C1-M27 clade of human origin, (iii) certain plasmids, such as IncFII/pMLST F1:A2:B20/blaCTX-M-27, IncI1/pMLST16/blaCTX-M-15, or IncI1/blaCMY-2 from dog-derived E. coli isolates, shared high homology with those from several human-derived Enterobacteriaceae, (iv) chromosomal blaCTX-M-14 was identified in the ST38 isolate from a companion dog, and (v) eight out of 14 tested ESBL/AmpC-producing E. coli isolates (i.e., ST131, ST68, ST405, and ST998) belonged to the human extraintestinal pathogenic E. coli (ExPEC) group. All of the bla-coding plasmids that were sequenced genome-wide were capable of horizontal transfer. These results suggest that companion dogs can spread ESBL/AmpC-producing ExPEC via their feces. Furthermore, at least some ESBL/AmpC-producing ExPECs and bla-coding plasmids can be transmitted between humans and companion dogs. Thus, companion dogs can act as an important reservoir for ESBL/AmpC-producing E. coli in the community.

Priming effects of lipopolysaccharide and inflammatory cytokines on canine granulocytes.

Granulocytes play a pivotal role in natural immunity. Under inflammatory conditions, granulocytes are universally primed by several agents, such as endotoxins and inflammatory cytokines. Primed granulocytes exert potent adhesiveness, chemotaxis, phagocytosis and reactive oxygen species (ROS) production, effectively eliminating invading agents. Reactivity against priming agents is known to vary with species; however, there have been few reports on the effects of priming agents on canine granulocytes. In the present study, we assayed the priming effects of lipopolysaccharide (LPS), recombinant canine tumor necrosis factor-alpha (rcTNF-alpha) and recombinant canine granulocyte macrophage colony-stimulating factor (rcGM-CSF) on canine granulocyte function in vitro. Isolated recombinant canine were primed with various concentrations of LPS, rcTNF-alpha and rcGM-CSF, and CD11b expression was assayed. Furthermore, actin polymerization, phagocytosis and ROS production were then assayed at primer concentrations where enhancement of CD11b expression was observed. LPS did not enhance canine granulocyte function. Phagocytosis and actin polymerization were not enhanced by priming agents; however, rcTNF-alpha and rcGM-CSF enhanced CD11b expression and ROS production in canine granulocytes. These results suggest that priming effects are mainly reflected in CD11b expression and ROS production, with rcGM-CSF and rcTNF-alpha having a priming effect similar to that observed in humans.

Effects of lidocaine hydrochloride on canine granulocytes, granulocyte CD11b expression and reactive oxygen species production.

Lidocaine hydrochloride (Lido) is widely used for analgesia in veterinary medicine; however, in humans, it has been suggested that Lido attenuates granulocyte functions, such as adhesion and reactive oxygen species (ROS) production. Thus, Lido may affect canine granulocyte function; however, there have been no reports on the effects of Lido on canine granulocyte function. Thus, we studied the effects of Lido on canine granulocyte CD11b expression and ROS production. We further studied the effects of Lido on the priming of canine granulocyte CD11b expression and ROS production by recombinant canine granulocyte macrophage colony stimulating factor (rcGM-CSF). Isolated granulocytes were incubated with 3, 30 or 300 microg/ml Lido, or with Lido followed by priming with 5 ng/ml rcGM-CSF. CD11b was detected by the immune fluorescent antibody method, and the mean fluorescence intensity (MFI) was assayed by flow cytometry. ROS production was assessed by the peak time (PT) of ROS production and area under the luminol reaction curve (AUC), which represents total ROS production quantity against opsonized zymosan stimuli. Only 300 microg/ml Lido (tissue level observed by regional block) significantly attenuated both the MFI of CD11b and its enhancement by rcGM-CSF. Moreover, at this concentration, the AUC and its enhancement by rcGM-CSF were significantly attenuated by Lido; in contrast, Lido did not affect PT. In conclusion, Lido suppressed granulocyte adhesion to the endothelium and antiseptic capability by suppressing CD11b expression and/or ROS production. Particular care should thus be exercised when performing regional anesthesia block using Lido.

Evaluation of the function of polymorphonuclear neutrophilic leukocytes in healthy dogs given a high dose of methylprednisolone sodium succinate.

OBJECTIVE: To evaluate effects of a high dose of methylprednisolone sodium succinate (MPSS) on function of polymorphonuclear neutrophilic leukocytes (PMNs) in dogs. ANIMALS: 7 healthy male Beagles (body weight, 10.5 to 15 kg; age, 2 to 4 years). PROCEDURES: All dogs were treated by IV administration of a high dose of MPSS (30 mg/kg). Additional doses of MPSS (15 mg/kg) were administered IV at 2 and 6 hours and then at 6-hour intervals until 48 hours after the initial dose. Blood samples were collected before and 1, 2, 4, 7, and 14 days after completion of the MPSS administrations and used for evaluation of PMN functions. Isolated PMNs were used for assessment of functions, such as adhesion, migration, phagocytosis, and oxidative burst. RESULTS: On days 1, 2, and 4 after completion of MPSS administration, there was a decrease in PMN expression of adhesion markers such as CD11b and CD18. There was a decrease in the phagocytotic ability of PMNs on days 1, 2, and 7 after completion of MPSS administration, with a reduction in the oxidative burst of PMNs detected on day 7. No significant changes were identified for migration. All functional changes returned to their pretreatment values by 14 days after completion of MPSS treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with a high dose of MPSS suppressed PMN functions in dogs. Analysis of these results suggested that treatment with a high dose of MPSS can suppress some of the major functions of PMNs for at least 7 days.

Decreased serum zinc concentration in dogs with lymphocytic-plasmacytic enteritis, and its associations with disease severity and prognosis.

Human patients with inflammatory bowel disease may have poor prognosis with hypozincemia. However, there are limited data on zinc concentrations in the blood of dogs with lymphocytic-plasmacytic enteritis (LPE). The purpose of this study was to investigate the serum zinc concentration in dogs with LPE and its influence on disease severity and prognosis. Thirty-five dogs with LPE were recruited. Serum zinc concentration was measured using atomic absorption spectrometry. Hypozincemia was observed in 18/35 (51%) dogs with LPE. Serum zinc concentration was inversely correlated with histological and clinical severities. Overall survivals were significantly shorter in dogs with hypozincemia than in those without it. These findings suggest that serum zinc concentration is a useful biomarker for LPE severity and prognosis in dogs.

Diffuse leiomyomatosis with circumferential thickening of the gastrointestinal wall, resembling human diffuse leiomyomatosis, in a young miniature dachshund.

Leiomyoma is the most common mesenchymal tumor in the gastrointestinal (GI) tract. Leiomyomas usually have a single or multinodular mass of various sizes, and affected animals can develop alimentary symptoms depending on the location and size. A 3-year old female miniature dachshund died after a history of refractory rectal prolapse, esophagectasis and aspiration pneumonia. At necropsy, the GI wall at the gastroesophageal and anorectal junctions was circumferentially thickened. Histologically, both GI lesions were composed of bundles of well-differentiated smooth muscles without mass formation or invasive growth. The neoplastic cells had little cellular atypia and low proliferative activity, and were positive for α-smooth muscle actin. The lesions were diagnosed as diffuse leiomyomatosis with circumferential thickening of the GI wall and has not been described in the veterinary literature.

An aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia in a French Bulldog.

An 11-year-old female French Bulldog was presented with a mass at the base of the heart, detected by X-ray and echocardiography. Clinical abnormality included abdominal retention by ascites. Radiation therapy was performed for 5 weeks. The mass volume didn't change during the radiotherapy. The condition became worse and the dog died 6 months after the initial presentation and necropsy was performed. Grossly, the mass, 12.5 × 6.5 × 6.0 cm in size, was found at the base of the heart. Histopathological examination revealed that cardiac mass was composed of alveolar, bundle and diffuse proliferation of neoplastic cells. Most of the neoplastic cells showed a spindle morphology; in some areas small round or polyhedral neoplastic cells were observed. Occasional cartilage metaplasia was seen multifocal in the mass, and it was surrounded by the sarcomatoid proliferation. Electron microscopy revealed a few neuroendocrine granules in the cytoplasm of spindle and polyhedral neoplastic cells. Metastatic cells in the lungs which had not irradiated demonstrated typical morphology of aortic body tumors. Based on these findings, the case was diagnosed as an aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia.

Prognostic significance of midline shift of the olfactory or frontal lobes of the brain in canine nasal carcinomas treated by palliative radiotherapy: a pilot study.

Canine nasal carcinomas are often treated with radiotherapy. Presence of lysis of the cribriform plate by tumor invasion (stage 4 by modified Adams's staging system) is a well-known prognostic factor. In this study, dogs with stage 4 disease were divided into two subgroups based on the presence or absence of midline shift of the olfactory or frontal lobes of the brain (Stage 4a: without presence of midline shift. Stage 4b: with midline shift). The median survival time of dogs with midline shift was significantly shorter than that of dogs without midline shift (64 vs. 208 days). Our results indicate that the finding of a midline shift might have a prognostic significance in dogs with nasal carcinoma treated with radiotherapy.

Effect of Angiotensin II Type 1 receptor blocker on cardiac angiotensin-converting enzyme and chymase-like activities, and cardiac fibrosis in cardiomyopathic hamsters.

It has been reported that cardiac chymase has an effect on cardiac fibrosis through the Angiotensin (Ang) II formation and an Ang II-independent mechanism. In the present study, Ang II type 1 (AT1) receptor blocker (candesartan cilexetil) was administered to dilated cardiomyopathic (DCM; Bio TO2) hamsters for 4 weeks to study the effect of AT1 receptor blocker on cardiac chymase-like activity and cardiac fibrosis. Echocardiography, histological examination, and assessment of cardiac angiotensin-converting enzyme (ACE)/chymase-like activities were conducted. Hamsters showed cardiac dysfunction due to increased left ventricular dimensions and decreased ventricular wall thickness, significant increase in cardiac chymase-like activity, and fibrosis. This result indicates that the cardiac chymase-like activity is responsible for cardiac fibrosis. When candesartan cilexetil was administered to Bio TO2 hamsters, cardiac chymase-like activity increased significantly, whereas cardiac fibrosis decreased significantly. Cardiac ACE and chymase-like activities were unchanged in non-DCM hamsters with candesartan cilexetil. This suggests that the cardiac Ang II formation mechanism was stimulated by suppressing the effect of cardiac Ang II, and cardiac chymase-like activity could be increased. Moreover, this mechanism may be more highly activated if cardiac Ang II is activated in the heart. In conclusion, we demonstrated that AT1 receptor blocker reduced cardiac fibrosis, although cardiac chymase-like activity increased. Because the Ang II-forming pathway and the effect of chymase in hamsters is similar to that in dogs, the results of the present study may supplement the available information for dogs.

Effect of intermittent administration of sustained release isosorbide dinitrate (sr-ISDN) in rats with pressure-overload heart.

Recent studies have demonstrated the benefits of nitric oxide (NO) on myocardial hypertrophy and myocardial fibrosis. It was suggested that NO has a protective effect on myocardial cell through the neurohormonal system. This effect serves to highlight the important role of NO in maintaining the function and form of heart with chronic heart failure. However, there are no known reports about on the effect of prolonged administration of nitrate on pressure over-load heart. This study was conducted to examine the long-term effect of oral nitrate therapy in rats with pressure-overloaded heart. An abdominal aorta constricted (AC) model of pressure-overloaded heart was created in male Wistar rats. Sustained release isosorbide dinitrate (sr-ISDN) (5 mg/kg once a daily) was administered to the rats once a daily for 12 weeks. The animals were euthanized during the study period, and the heart was collected and weighed. Histopathological examination was performed to evaluate the effect of sr-ISDN on myocardial hypertrophy and fibrosis. The ratio of heart to body weight increased significantly in AC rat and this increase was significantly prevented by sr-ISDN treatment. Histopathological examination showed significant increase in fibrotic area of AC rat compared to sham rat, this increase was inhibited by sr-ISDN treatment. Cardiomyocyte transverse diameter was significantly increased in AC rat compared with sham rat, but this increase tended to decrease by sr-ISDN treatment. In conclusion, intermittent administration with sr-ISDN has mild effect in inhibiting cardiac hypertrophy and marked effect in inhibiting fibrosis due to pressure-overload.