Fentanyl sparing effect of ultrasound-guided proximal radial, ulnar, median, and musculocutaneous nerve (RUMM) block for radial and ulnar fracture repair in dogs: a retrospective case-control study.

This study retrospectively evaluated the fentanyl-sparing effect of ultrasound-guided proximal radial, ulnar, median, and musculocutaneous nerve (RUMM) block for radial and ulnar fracture repair in dogs. Fentanyl was prepared for intraoperative analgesia in dogs, although proximal RUMM block was performed using 0.5% or 0.25% bupivacaine before surgery in the block group. Dogs without a nerve block were assigned to the control group. The fentanyl dose in the block group [0.8 (0-1.9) µg/kg/hr] [median (interquartile range)] was significantly lower than in the control group [8.4 (7.2-10) µg/kg/hr]. Surgery was performed without fentanyl in >50% of the dogs (5/7), using 0.5% bupivacaine. Ultrasound-guided proximal RUMM block can be useful as an intraoperative analgesic for radial and ulnar fracture repair in dogs.

Establishment and characterization of urothelial carcinoma cell lines with and without BRAF mutation (V595E) in dogs.

Each 5 urothelial carcinoma (UC) cell lines with and without the v-Raf murine sarcoma virus oncogene homolog B (BRAF) gene mutation (V595E) were established and examined V595E-related tumorigenic characteristics in dogs. No typical morphological features were observed in cloned cells with and without V595E. The cell proliferation of both cloned cells showed logarithmic growth curve and those doubling time were 24.9 ± 4.1 h in V595E ( +) and 29.3 ± 11.3 h in V595E ( -). On the growth curve of xenotransplanted tumor in severe combined immunodeficiency mice, 3 out of 5 V595E ( +) and 2 out of 5 V595E ( -) cloned cells revealed gradually and remarkably increasing curve, indicating clearly tumorigenicity. The xenotransplanted tumors with V595E ( +) showed typical features of UC, such as solid proliferation of pleomorphic tumor cells, formation of papillary structure, and glandular structure. Additionally, various vascular formation was observed, probably indicating an advanced growth phase of UC. In mitogen-activated protein kinase (MAPK) signaling pathway, cytoplasmic phosphorylated-BRAF (pBRAF) and cytoplasmic and nuclear phosphorylated-ERK1/2 (pERK1/2) were detected in all 4 tumors with V595E ( +), whereas only cytoplasmic and nuclear pERK1/2 was detected in tumors with V595E ( -). Since V595E can directly activate MAPK signaling pathway, coincidence of V595E with pBRAF (phosphor Thr598/Ser601) indicates acquired resistance to BRAF inhibitors. These established UC cell lines, especially V595E ( +) cell lines, are useful tool for understanding pathophysiological states and controlling therapeutic manners of UC in dogs.

Coincidence of v-raf murine sarcoma viral oncogene homolog B mutation (V595E) with phosphorylated v-raf murine sarcoma viral oncogene homolog B in urothelial carcinoma in dogs.

Expression of phosphorylated v-raf murine sarcoma viral oncogene homolog B (pBRAF) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) were investigated in urothelial carcinoma (UC) in dogs with or without the BRAF gene mutation (V595E). Among the 10 cases of UC with V595E (-), cytoplasmic immunoreactivity against pBRAF of neoplastic cells was reported in 8, with 7 displaying moderate reactivity and 1 displaying intense reactivity. Nuclear immunoreactivity against pBRAF was detected in 5 cases; however, these reactivities were non-specific, due to pBRAF being limited in the cytoplasm. In addition, positive cytoplasmic immunoreactivity against pERK1/2 of neoplastic cells was detected in 7 cases and nuclear immunoreactivity against ERK1/2 was detected in 6 cases. Among the 13 cases of UC with V595E (+), cytoplasmic immunoreactivity against pBRAF of neoplastic cells was detected in all 13 cases and nuclear immunoreactivity against pBRAF was detected in 10 cases; however, the nuclear immunoreactivity was non-specific. Cytoplasmic immunoreactivity against pERK1/2 of neoplastic cells was detected in all 13 cases and nuclear immunoreactivity against pERK1/2 was also detected in all cases. As nuclear pERK1/2 indicates a progressive signaling process in the mitogen-activated protein kinase pathway, V595E (+) UC might be in its growing stage. Probable phosphorylated sites of pBRAF at Thr598/Ser601, detected in this study, are major and essential sites of the upstream rat sarcoma viral oncogene homolog (RAS) signaling pathway. In human cancers, the BRAF mutation never coincides with oncogenic RAS. To our knowledge, this is the first report on the simultaneous occurrence of the BRAF mutation (V595E) and pBRAF expression (at Thr598/Ser601) in dogs with UC with V595E (+).

L'expression de l'homologue B de l'oncogène viral du sarcome murin phosphorylé v raf (pBRAF) et de la kinase1/2 régulée par le signal extracellulaire phosphorylé (pERK1/2) ont été étudiées dans le carcinome urothélial (CU) chez des chiens avec ou sans la mutation du gène BRAF (V595E). Parmi les 10 cas de CU avec V595E (−), une immunoréactivité cytoplasmique contre pBRAF de cellules néoplasiques a été rapportée chez huit, sept présentant une réactivité modérée et un présentant une réactivité intense. L'immunoréactivité nucléaire contre pBRAF a été détectée dans cinq cas; cependant, ces réactivités n'étaient pas spécifiques, car pBRAF était limité dans le cytoplasme. De plus, une immunoréactivité cytoplasmique positive contre pERK1/2 des cellules néoplasiques a été détectée dans sept cas et une immunoréactivité nucléaire contre ERK1/2 a été détectée dans six cas. Parmi les 13 cas de CU avec V595E (+), une immunoréactivité cytoplasmique contre pBRAF de cellules néoplasiques a été détectée dans les 13 cas et une immunoréactivité nucléaire contre pBRAF a été détectée dans 10 cas; cependant, l'immunoréactivité nucléaire était non spécifique. L'immunoréactivité cytoplasmique contre pERK1/2 des cellules néoplasiques a été détectée dans les 13 cas et l'immunoréactivité nucléaire contre pERK1/2 a également été détectée dans tous les cas. Comme le pERK1/2 nucléaire indique un processus de signalisation progressif dans la voie de la protéine kinase activée par les mitogènes, V595E (+) UC pourrait être dans sa phase de croissance. Les sites phosphorylés probables de pBRAF à Thr598/Ser601, détectés dans cette étude, sont des sites majeurs et essentiels de la voie de signalisation de l'oncogène viral (RAS) du sarcome de rat en amont. Dans les cancers humains, la mutation BRAF ne coïncide jamais avec le RAS oncogène. À notre connaissance, il s'agit du premier rapport sur la survenue simultanée de la mutation BRAF (V595E) et de l'expression de pBRAF (à Thr598/Ser601) chez des chiens atteints de CU avec V595E (+).(Traduit par Docteur Serge Messier).

Silicone allergy associated with intraocular silicone ball prosthesis in a dog.

A 13-year-old, male Pomeranian dog was presented for scleral rupture with intraocular hemorrhage and retinal detachment in the right eye. After intrascleral silicone ball prosthesis, recurrent swelling and granulomatous blepharitis were observed for 140 d and finally melting keratitis developed. Although an intraorbital prosthesis was implanted, recurrent, serious, erosive, and ulcerative blepharitis developed with high plasma C-reactive protein concentrations. Since the blepharitis could not be controlled, the silicone ball was removed and the affected orbit was debrided. The blepharitis resolved rapidly, and the orbit healed routinely. Positive allergic reactions to silicone were discovered through a patch test. Key clinical message: To the authors' knowledge, this is the first report on silicone allergy in a dog with positive allergic reactions to silicone in the patch test.

Allergie au silicone associée à une prothèse intraoculaire en boule de silicone chez un chien. Un chien poméranien mâle de 13 ans a été présenté pour rupture sclérale avec hémorragie intraoculaire et décollement de la rétine de l'oeil droit. Après l'implantation intrasclérale d'une boule de silicone comme prothèse, un gonflement récurrent et une blépharite granulomateuse ont été observés pendant 140 jours et une kératite fondante s'est finalement développée. Bien qu'une prothèse intra-orbitaire ait été implantée, une blépharite récurrente, grave, érosive et ulcéreuse s'est développée, avec des concentrations plasmatiques élevées de protéine C réactive. Comme la blépharite ne pouvait pas être contrôlée, la boule de silicone a été retirée et l'orbite affectée a été débridée. La blépharite s'est résolue rapidement et l'orbite a guéri normalement. Des réactions allergiques positives au silicone ont été découvertes grâce à un test cutané.Message clinique clé :À la connaissance des auteurs, il s'agit du premier rapport sur une allergie au silicone chez un chien ayant des réactions allergiques positives au silicone lors du test cutané.(Traduit par Dr Serge Messier).

Utility of a novel activity monitor assessing physical activities and sleep quality in cats.

Osteoarthritis in cats is more prevalent because cats are living longer with advancement in veterinary medicine. Objective evaluation of behavioral changes in cats with osteoarthritis can facilitate an early diagnosis. The objective of this study was to investigate the utility of a novel activity monitor for analyzing physical activities and sleep quality in cats. First, a novel activity monitor (Plus Cycle®; JARMeC, Kanagawa, Japan), with a built-in three-directional accelerometer and an air pressure sensor specifically designed for cats, was compared to a human activity monitor (Actical®; Philips Respironics, OR, USA) previously used in cats (n = 10). Second, the validity of the measurement accuracy of the amount of physical activity, the number of vibrations, the number of jumps, and the resting and sleeping time was evaluated using Plus Cycle® in healthy cats (n = 6). Finally, the effects of gender and age of cats and time of day on the amount of physical activity, the number of vibrations, the number of jumps, and the resting and sleeping time were investigated in client-owned cats (n = 61). There were strong correlations between Plus Cycle® and Actical® in total activity (p < 0.05) and activity intensity (p < 0.05). When the physical activities were measured using Plus Cycle® in healthy cats, those data were quantified with high accuracy. In addition, it was also found to be very accurate in discriminating the resting and sleeping conditions of cats. In client-owned cats, there were no significant differences with respect to gender in any measured traits. The amount of physical activity and the number of jumps significantly decreased with the age of the cat. In contrast, the resting and sleeping times significantly increased with the age of the cat. In conclusion, Plus Cycle® can accurately and objectively assess physical activities and sleep quality with age of the cat, suggesting that this novel activity monitor can be used to manage the feline musculoskeletal health.

Establishment and characterization of a novel cell line of medullary thyroid carcinoma from a dog.

A novel cell line of canine medullary thyroid carcinoma (MTC) was established from the neck mass, diagnosed histopathologically and immunohistochemically as ectopic MTC. The neoplastic cells arranging trabecular structures were characterized as pleomorphic cells with eosinophilic cytoplasm and nucleus, containing often clear nucleolus. These tumor cells were immuno-positive for calcitonin gene-related protein (CGRP), somatostatin, and chromogranin A. In addition, 8th passaged cultured cells were also immuno-positive for CGRP, somatostatin, and chromogranin A. The cloned tumor cells showed logarithmic cell growth with a doubling time of 33.3 h. From the results of DNA sequencing of rearranged during transfection (RET) proto-oncogene, the cloned tumor cells had four single base substitution, including exon 5 codon 82, exon 16 codon 750, exon 17 codon 777, and exon 24 codon 1085, all of which were single nucleotide polymorphism reported in RET gene of dogs. After the xenotransplantation into severe combined immunodeficiency (SCID) mice, the cloned cells showed tumorigenicity potentials. The morphological and immunohistochemical features of the xenotransplanted tumor were almost in conformity with those of the original tumor, including positive immunoreactivity for calcitonin, CGRP, and chromogranin A. To our knowledge, this is the first report of canine MTC cell line, which provides useful in vitro tool for understanding oncogenic mechanism and pathophysiological state of MTC in dogs.

Malignant peripheral nerve sheath tumor originating from the adrenal gland in a dog.

A large abdominal mass was found in a dog. Histopathologically, the surface of the mass was covered with compressed adrenal gland tissue. The neoplastic cells showed typical features of malignant peripheral nerve sheath tumor (MPNST), including Antoni type A and type B pattern, and nuclear palisading. Immunohistochemically, these cells were positive for S100 protein, nerve growth factor receptor, nestin and claudin-1. The dog was euthanized because of the developing multiple metastatic lesions. The metastatic cells showed quite similar histopathological and immunohistochemical features as those in the original tumor. Although MPNST can develop at many body sites, this is the first report of MPNST originating from the adrenal gland in a dog.

Comparison of right atrium incision and right ventricular outflow incision for surgical repair of membranous ventricular septal defect using cardiopulmonary bypass in dogs.

OBJECTIVE: To compare right atrium incision (RAI) and right ventricular outflow incisions (RVI) for surgical repair of membranous ventricular septal defect (VSD) facilitated by cardiopulmonary bypass (CPB). STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n=10) with VSD. METHODS: Medical records of dogs that had VSD repair were reviewed. Membranous VSD without any malformation and abnormality was confirmed on several clinical examinations and by angiocardiography. RAI (5 dogs) and RVI (5 dogs) was used for VSD access and repair facilitated by CPB. Procedure comparison was by surgical duration, postoperative recovery period, and occurrence of postoperative arrhythmia. RESULTS: Duration of surgery was similar for RAI and RVI; however, postoperative recovery time was significantly reduced with RAI. Significant moderate operative damage occurred with right atrium incision. CONCLUSIONS: Right atrium incision was more effective than RVI for repair of membranous VSD using CPB. CLINICAL RELEVANCE: RAI should be considered in preference to RVI for repair of membranous VSD using CPB.

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.

The effect of intermittent administration of sustained release isosorbide dinitrate (sr-ISDN) in rats with volume overload heart.

Recently, it has been reported that intermittent administration of nitrate, with a nitrate-free interval of 10 to 12 hr eliminated expression of tolerance, and maintained its hypotensive effect. In the present study, we evaluated whether nitrate tolerance developed or not with an intermittent administration of sr-ISDN (5 mg/kg/ once a day) in Wistar rats. The effect of this administration protocol for sr-ISDN on the volume overload heart model, aortovenous fistula, was also examined. Furthermore, blood pressure was monitored by radio telemetry during sr-ISDN (5 mg/kg/once a day) administration. Nitrate tolerance did not develop, and eccentric hypertrophy due to volume overload was moderated by sr-ISDN administration. Sr-ISDN administration maintained blood pressure lower level than the placebo group. In conclusion, prolonged intermittent administration of sr-ISDN maintained its hypotensive effect during the entire experiment period, without developing tolerance, and moderated efferent hypertrophy with attenuated volume overload.

Megaesophagus was complicated with Billroth I gastroduodenostomy in a cat.

A seven-year-old, female, domestic short hair cat was presented with a history of chronic anorexia. Radiographic examination revealed a large space-occupying calcified mass in the abdominal cavity. The mass was located in pylorus and did not extend into the duodenum and surrounding tissues. Billroth I gastroduodenostomy was conducted to remove the mass. Histopathological examination of the mass showed a lymphoma. Although Recovery following the operation was excellent, the patient showed intermittent vomiting unrelated to feeding. Radiographical examination revealed a megaesophagus, which was assumed to be a complication of the Billroth I procedure, since the condition was not observed before the procedure.

An experimental study of apico-aortic valved conduit (AAVC) for surgical treatment of aortic stenosis in dogs.

A new valved conduit was developed using a canine aortic valve. The bioprosthetic valve was fixed with glutaraldehyde and epoxy compound (Denacol-EX313/810). A vascular graft composed of ultra-fine polyester fiber (10 mm in diameter, 200 mm in length) was used. Four dogs underwent apico-aortic valved conduit (AAVC) implantation and aortic banding (bypass group, BG), while another 4 dogs underwent aortic banding without AAVC implantation (control group, CG). Cardiac catheterization and angiocardiography were performed for assessment of hemodynamics 2 weeks and 6 months after surgery. Left ventricular systolic pressure, left ventricular end-diastolic pressure and the left ventricular-aortic pressure gradient differed significantly (P<0.01) between the BG and CG dogs. Left ventricular angiocardiography showed patency of the valved conduit in all the BG dogs. Echocardiography was performed before and 2, 4 and 6 months after surgery, and showed that while pressure overload caused concentric myocardial hypertrophy in the CG dogs, the left ventricle dilated eccentrically in the BG dogs. Furthermore, relief of left ventricular pressure overload by AAVC was maintained.

Percutaneous transcatheter coil embolization of a ventricular septal defect in a dog.

A 4-month-old male French Bulldog weighing 5.0 kg (11 lb) was referred for a heart murmur. A grade 3/6 systolic murmur was detected at the left heart base and a grade 4/6 systolic murmur was detected at the right heart base. By use of color-flow Doppler ultrasonography and cardiac catheterization, a diagnosis of supracristal ventricular septal defect (VSD) with accompanying aortic regurgitation was made. Percutaneous transcatheter coil embolization was used to close the VSD. Because residual shunt was detected via echocardiography after coil implantation, the residual shunt was followed periodically via echocardiography to detect spontaneous closure of the VSD. Volume overload in the left ventricle was detected in the dog 131 days after admission. Additional coils were placed 137 days after admission. Hemolysis resulting in hemoglobinuria was detected, but this complication was mild. In the dog of this report, results of coil occlusion for correction of VSD were promising. Thus, coil occlusion should be considered as an alternative treatment for VSD in dogs.

Surgical correction of subvalvular aortic stenosis using cardiopulmonary bypass in a dog.

A three-month-old male Golden Retriever had symptoms including exercise intolerance, dyspnea and syncope and was diagnosed with subvalvular aortic stenosis. Cardiac catheterization revealed a left ventricular-aortic systolic pressure gradient of 90 mm Hg. Surgical correction of the condition was achieved using cardiopulmonary bypass. The subvalvular fibrous lesion was resected through an aortotomy. The stenosis was dilated from 8.5 mm to 12.0 mm in diameter. Postoperatively the dog was asymptomatic. Seven months after surgery, the pressure gradient decreased to 44 mm Hg. However, after another three months, the dog died suddenly without any premonitory signs. Postmortem examination revealed that pathologic changes caused by increased left ventricular pressure overload were not severe.

Implantation of permanent transvenous endocardial pacemaker in a dog with atrioventricular block.

A 10-year old male mongrel dog was presented to the University Veterinary Teaching Hospital with a two-month history of episodic syncope. Twenty-four hr Holter electrocardiographic (ECG) recording revealed frequent episodes of advanced atrioventriculer block with long periods of ventricular asystole. The cause of syncope was determined to be Adams-Stokes syndrome exhibited bradyarrhythmia. After the animal failed to respond to medical therapy, permanent transvenous pacemaker implantation was performed. Postoperative Holter ECG showed 100 beat per min programmed pacemaker rhythm, which indicated successful capture of the artificial pacing. The dog recovered smoothly from the operation and syncopal episodes completely disappeared. Six months after the surgery, no complications were observed and the dog's quality of life has dramatically improved.

Comparison of extracapillary and endocapillary blood flow oxygenators for open heart surgery in dogs: efficiency of gas exchange and platelet conservation.

The goal of the current study was to compare the efficiency of gas exchange and platelet conservation of a new extracapillary blood flow oxygenator versus an endocapillary blood flow oxygenator during open heart surgery with extracorporeal circulation in dogs. Dilation and remodeling of the right ventricular outflow tract of dogs was performed using a patch graft technique to simulate pulmonary stenosis. Sequential pre- and post-operative blood analysis revealed that gas exchange efficiency and platelet conservation was significantly greater with the extracapillary blood flow oxygenator than with the endocapillary blood flow oxygenator. However, the priming volume of the extracapillary blood flow oxygenator was significantly greater, leading to hemodilution. We conclude that while the extracapillary blood flow oxygenator provided benefits in terms of gas exchange and platelet conservation, development of a smaller extracapillary blood flow type oxygenator to reduce hemodilution effects would be beneficial.

Effects of dopamine infusion on cardiac and renal blood flows in dogs.

In veterinary medicine, dopamine is currently being administered clinically by infusion for treatment of kidney disorders at low doses (< or = 3 microg/kg/min) and for assessment of hemodynamics at high doses (> or = 5 microg/kg/min). However, since high doses of dopamine cause peripheral vasoconstriction due to its effect on alpha adrenoceptors, high doses have no longer been recommended. The present study was conducted to explore possible regimens for the use of dopamine infusion in dogs. The regional (renal and cardiac) blood flow for 60 min was measured by using colored microspheres at three doses (3, 10 and 20 microg/kg/min) of dopamine infusion in healthy anesthetized mongrel dogs. The effects on kidney and peripheral hemodynamics at each dose and the resultant cardiac output, mean arterial blood pressure and total peripheral resistance were determined. Renal blood flow increased markedly at 3 microg/kg/min dopamine. Improvement in hemodynamics indicated by marked increase in cardiac blood flow, cardiac output and mean arterial blood pressure and decreased total peripheral resistance was observed at higher doses (10 and 20 microg/kg/min). At 10 microg/kg/min, in addition to the satisfactory increase in cardiac blood flow, there was also a stable satisfactory increase in renal blood flow. However, at 20 microg/kg/min, increased myocardial oxygen consumption (manifested by marked increased in cardiac output), arrythmia and irregular increase in renal blood flow were detected. This study suggests that the clinical use of dopamine infusion in dogs could be safely expanded to moderately higher doses.