Pedigree study of the heredity of copper-associated hepatitis in Dalmatians in Japan.

The pedigrees of 3 Dalmatian dogs afflicted with copper-associated hepatitis were investigated to discover the mode of inheritance. A composite family pedigree showed that the 3 affected Dalmatians were related. None of the parents of the affected dogs showed clinical symptoms of liver disease, and the disease had no sex predisposition. The estimated segregation ratio was approximately 3:1 based on surviving littermates. These findings suggested that the copper-associated hepatitis in these Dalmatians was an autosomal recessive mode of inheritance. In addition, some male Dalmatians imported from abroad might have been involved in the occurrence of this disease in Japan.

Étude généalogique de l'hérédité de l'hépatite associée au cuivre chez des Dalmatiens au Japon. Les pedigrees de trois chiens dalmatiens atteints d'hépatite associée au cuivre ont été étudiés pour découvrir le mode de transmission. Un pedigree familial composite a montré que les trois Dalmatiens affectés étaient apparentés. Aucun des parents des chiens affectés n'a présenté de symptômes cliniques de maladie du foie et la maladie n'avait aucune prédisposition associée au genre. Le ratio de ségrégation estimé était d'environ 3:1 sur la base des compagnons de portée survivants. Ces résultats suggèrent que l'hépatite associée au cuivre chez ces Dalmatiens était un mode de transmission autosomique récessif. De plus, certains dalmatiens mâles importés de l'étranger pourraient avoir été impliqués dans l'apparition de cette maladie au Japon.(Traduit par Dr Serge Messier).

Relationship between clinical parameters and malformations in dogs diagnosed with atlanto-axial instability.

Atlanto-axial instability is a common disease that affects toy-breed dogs. Most cases of atlanto-axial instability are congenital. Furthermore, patients with atlanto-axial instability are predisposed to other concurrent diseases. Therefore, this study aimed to retrospectively determine the presence of concurrent diseases in cases with atlanto-axial instability using imaging data and analyze the relationship between clinical parameters and the incidence of complex malformations. The clinical data and imaging findings of 41 toy-breed dogs diagnosed with atlanto-axial instability were analyzed using their medical records and imaging data. Occipital dysplasia (17/27), atlanto-occipital overlapping (22/34), dens dysplasia (27/41), Chiari-like malformation (8/34), syringomyelia (5/34), lateral ventricular enlargement (20/36), and intracranial arachnoid cyst (5/35) were observed in patients with atlanto-axial instability. The body weight of the patients in the groups with atlanto-occipital overlapping and lateral ventricular enlargement was lower than that of those in the groups without these diseases (1.78 ± 0.71 vs 2.71 ± 1.15 kg, P = 0.0269, 1.60 ± 0.40 vs 2.75 ± 1.08 kg, P = 0.001, respectively). Furthermore, when the correlation between the total number of concurrent diseases and the age at onset and body weight was examined, it became clear that lower body weight was associated with the incidence of a greater number of concurrent diseases. Thus, the findings of this study suggest that toy-breed dogs are more likely to present with complex malformations and should be evaluated carefully with additional examinations and treatment methods.

Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral malignant melanoma solid tumors.

BACKGROUND: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. OBJECTIVE: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. METHODS: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. RESULTS: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. CONCLUSIONS: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

Sulfasalazine, a potent cystine-glutamate transporter inhibitor, enhances osteogenic differentiation of canine adipose-derived stem cells.

Cystine-glutamate transporter (xCT) is a plasma membrane transporter that imports cystine and indirectly contributes to the oxidative stress resistance associated with increased intracellular glutathione levels. Canine adipose-derived stem cells (CADSCs) include an xCT-positive subpopulation and show relatively low expression of osteogenic markers during in vitro osteogenic differentiation. Sulfasalazine (SSZ), a drug used to treat rheumatoid arthritis, suppresses xCT expression in cancer cells. In this study, we found that the SSZ treatment at 100 µM significantly suppressed xCT mRNA expression in CADSCs but did not significantly affect cell proliferation under the same conditions. Additionally, this treatment decreased the intracellular glutathione concentration. During in vitro osteogenic differentiation, the SSZ treatment at 50 µM and 100 µM significantly increased alizarin red staining and its quantification, as well as the concentration-dependent osteogenic differentiation markers (BMP1 and SPP) mRNA expression. Our results suggested that SSZ enhances the osteogenic differentiation potential of CADSCs and can potentially exhibit a superior therapeutic profile in canine bone regenerative medicine.

Comparison of surgical invasiveness between micro-endoscopic discectomy/microscopic discectomy and conventional hemilaminectomy in dogs.

Micro-endoscopic discectomy (MED) or microscopic discectomy (MD) have been performed for disc herniation in humans. The purpose of this study was to compare the invasiveness of the hemilaminectomy in dogs between the approach using a cylindrical retractor for the MED/MD and a conventional open surgical approaches in dogs. First, as preliminary studies, we analyzed the suitability of the cylindrical retractor for the vertebral body of small to medium-sized dogs on the X-ray computed tomographic images using the three-dimensional analysis software, and confirmed that it was possible to open a bone window of an approximate length of 1.72 clto the spinal canal with the cylindrical retractor with a diameter 17 mm using two medium-sized canine cadavers. Next, to determine difference in the invasiveness of hemilaminectomy, the magnitude of tissue damage, surgical stress and postoperative pain were compared between the conventional open approach (hemilaminectomy group: HL group, n=6) and the surgical approach using the cylindrical retractor (MD group, n=6) in 12 beagle dogs. The plasma creatine phosphokinase, C-reactive protein and cortisol concentrations, incision length and University of Melbourne Pain Scale scores after the hemilaminectomy were significantly lower in the MD group than in the HL group. There were no significant differences between the durations of surgery and the other evaluated indices. The approach using the MD can provide a less invasive hemilaminectomy than the conventional approach in dogs.

Effect of tolvaptan on hyponatremia in a dog with syndrome of inappropriate secretion of antidiuretic hormone.

A 1-year-old spayed female Miniature Schnauzer had chronic hyponatremia, accompanied by polyuria and polydipsia. Blood tests and urinalysis revealed severe hyponatremia, low plasma osmolality with euvolemia, and increased sodium excretion in urine. Hypothyroidism and hypoadrenocorticism were ruled out as causes. These findings led to the diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Magnetic resonance imaging (MRI) showed dilation of the lateral ventricles, indicating severe hydrocephalus. Tolvaptan, a vasopressin V2 receptor antagonist commonly used in human SIADH, was administered along with water restriction. This treatment resulted in a consistent increase in plasma sodium levels without any adverse effects. This case report represents the first documented evidence of the therapeutic efficacy of tolvaptan in treating SIADH in a dog.

A Monte Carlo study on dose distribution of an orthovoltage radiation therapy system.

It is important to plan radiotherapy treatment and establish optimal dose distribution to reduce the chances of side effects and injury. Because there are no commercially available tools for calculating dose distribution in orthovoltage radiotherapy in companion animals, we developed an algorithm to accomplish this and verified its characteristics using tumor disease cases. First, we used the Monte Carlo method to develop an algorithm to calculate the dose distribution of orthovoltage radiotherapy (280 kVp; MBR-320, Hitachi Medical Corporation, Tokyo, Japan) using BEAMnrc at our clinic. Using development of Monte Carlo method, dose distribution for tumor and normal organs were evaluated in brain tumors, squamous cell carcinomas of the head, and feline nasal lymphomas. In all cases of brain tumors, the mean dose delivered to the GTV ranged from 36.2 to 76.1% of the prescribed dose due to the decrease through the skull. In the nasal lymphoma in cats, the eyes with covered a 2 mm-thick lead plate, the respective average dose to the eyes was 71.8% and 89.9% less than that to the uncovered eyes. The findings may be useful for informed decision making in orthovoltage radiotherapy with more effective and targeted irradiation and data collection allowing detailed informed consent.

Histiocytic sarcoma with spinal necrosis in a dog with progressing non-ambulatory tetraparesis.

Background: Histiocytic sarcoma (HS) is an aggressive malignant neoplasm, and widespread metastasis occurs with a fatal outcome. HS involving the central nervous system is relatively uncommon. Spinal cord necrosis, a very rare condition, could be induced by ischemia or infarction. Here, we report a dog progressing non-ambulatory tetraparesis with spinal cord necrosis caused by HS. Case Description: A 9-year-old male Labrador Retriever was presented with a progressing non-ambulatory tetraparesis. CT imaging revealed lysis of the spinous process of T7 and a ring-shaped lesion surrounding the soft tissue of lung fields. T2-weighted MRI showed the spinous processes of T6 to T8 as hyperintense, and the lesion infiltrated into the T7 vertebra and the spinal cord. After euthanasia, the final diagnosis upon necropsy was HS, which was observed in the lung, spinous process, thoracic cord, and the pulmonary hilar lymph node. Moreover, necrotic spots were spread widely through the thoracic spinal cord. Conclusion: This report outlines a case of canine HS in the lung, spinous process, thoracic cord, and pulmonary hilar lymph node. Ischemic deficit and necrosis of the thoracic spinal cord resulted from the compression of perivascular tumor cells, which rapidly led to progressive tetraparesis. Although the diagnosis was difficult, MRI and CT images helped determine the prognosis. To our knowledge, this is the first case report of canine HS with direct spinal cord involvement associated with spinal necrosis.

A long survival case of spinal nephroblastoma in a dog.

Background: Dogs' nephroblastoma of the spinal cord is a rare neoplastic disease, with few reports of long-term survival after surgery. We experienced that surgical treatment with postoperative radiation therapy for spinal nephroblastoma in a dog resulted in the long-term survival of 11 years. Case Description: The patient presented to our veterinary hospital because of progressive hindlimb paralysis. Based on diagnostic imaging, she was diagnosed with a thoracolumbar spinal cord tumor and was treated with surgery. The gross tumor tissue was removed after laminectomy, followed by postoperative radiation therapy using orthovoltage equipment. The histopathological features of the surgical specimen were consistent with those of previously reported spinal nephroblastoma, although infrequent mitotic figures were observed. The dog recovered well after treatment and resumed her normal walking condition. No tumor recurrence was observed on periodic follow-up magnetic resonance imaging performed 10 and 21 months after surgery. Imaging evaluation for the gradual development of hindlimb weakness was performed 9 years after surgery; however, no recurrence of tumor tissue was observed, and spondylosis deformans, probably induced after laminectomy, were identified as a possible cause. The dog died of aspiration pneumonia 11 years after surgery, independent of spinal nephroblastoma. Conclusion: To date, no clinical cases of canine spinal cord primary nephroblastoma that survived for 11 years after surgery have been reported. This case strongly suggests that providing intensive treatment for canine spinal nephroblastoma is very important.

Effect of drug-eluting bead transarterial chemoembolization loaded with cisplatin on normal dogs.

Transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE) are standard treatments for advanced hepatocellular carcinoma (HCC) and particularly for unresectable tumors or liver metastases in humans. However, reports on TACE used in veterinary medicine are few. This study aimed to evaluate the feasibility and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE). We performed DEB-TACE in four clinically normal dogs and pharmacokinetically compared the results against hepatic arterial infusion (HAI) of cisplatin in two dogs. Drug-eluting beads (DEB) loaded with cisplatin were injected through a microcatheter for selective embolization of the left hepatic artery. After embolization, computed tomography (CT) images and histological examination findings were obtained during a 4-week observation period. Serum platinum concentrations were measured to evaluate cisplatin after each procedure. Biochemical analysis was performed during a 12-week observation period. Embolization was successful in all dogs, and there were no clinically apparent abnormalities. Embolization was confirmed up to 4 weeks after DEB-TACE in two of the four dogs and up to 1 week in the other two dogs using postoperative CT images. Cisplatin was not detected in peripheral veins in all dogs after DEB-TACE, but it was detected in trace amounts after HAI. DEB-TACE using cisplatin was safe and well tolerated by normal dogs. DEB-TACE may be useful in terms of determining systemic toxicity and drug concentration within tumors.

Outcomes of megavoltage radiotherapy for canine intranasal tumors and its relationship to clinical stages.

Background: Radiation therapy is considered important for the treatment of intranasal tumors in dogs and is believed to be essential for prolonging their survival. Aim: To investigate the contribution of clinical staging to improve outcomes of megavoltage radiotherapy for canine intranasal tumors. Methods: A total of 123 dogs with intranasal tumors were included in the study. Forty-eight dogs received orthovoltage radiotherapy after cytoreductive surgery (Group I), 21 received orthovoltage radiotherapy without surgery (Group II), and 54 received megavoltage radiotherapy without surgery (Group III). All cases in each group were classified into clinical stages 1-4, and the median survival time (MST) was compared for each stage in all groups. Results: The overall MST was not significantly difference among Group I (325 days), Group II (317 days), and Group III (488 days); however, Group III was prolonged than Groups I and II. The MSTs for stages 1, 2, 3, and 4 were 597, 361, 267, and 325 days in Group I; 633, 260, 233, and 329 days in Group II; and 931, 860, 368, and 176 days in Group III, respectively. The MST for stage 2 cases in Group III was significantly prolonged when compared with that in Groups I and II; no significant difference was observed at other stages; however, the MST in Group III was longer in stage 1. These results showed that megavoltage radiotherapy prolonged the MST in dogs with intranasal tumors when compared to orthovoltage radiation with or without cytoreductive surgery, and that improvements in MST at stage 2 contributed significantly to this. Conclusion: The improvement in the MST in dogs with stages 1 and 2 intranasal tumors highlights the importance of starting megavoltage radiotherapy in the early stages.

Adjustment of multi-leaf collimator parameters in 4-MV and 6-MV IMRT: A study of veterinary clinical cases.

Background: For optimal treatment, it is important to maintain optimal multi-leaf collimator (MLC) transmission in intensity-modulated radiation therapy (IMRT). However, adjustment of transmissions has not been reported in veterinary medicine. Aim: To demonstrate that appropriate MLC parameter adjustment for IMRT using 4- and 6-MV energy can reduce the need for quality assurance revalidation in real companion animal clinical cases. Methods: The MLC parameters (leaf transmission and leaf offset) of the treatment planning system were adjusted by evaluating seven plans (10 × 10 cm, 3ABUT, DMLC, 7segA, FOURL, HDMLC, and HIMRT) and 20 preclinical cases (10 cases each in 4- and 6-MV groups). Subsequently, 101 IMRT plans of 88 cases (77 dogs and 11 cats) were evaluated for absolute dose of plan target volume (PTV) and organs at risk (OAR) and were analyzed for the relative dose distribution by gamma analysis (3%/3 mm, >10%) using EBT3 film. Results: After adjustment of the MLC parameters (leaf transmission and leaf offset, 4 MV: 0.008 and 0, 6 MV: 0.005 and 0, respectively), the data from 101 plans (4 MV: 64 plans and 6 MV: 37 plans) treated with IMRT showed PTV <3%, OAR <5%, and gamma analysis pass rates ≥95% in all cases. Conclusion: Clinically meaningful dose distributions can be created even with a limited validation device if the treatment parameters are adjusted appropriately, even for tumors in canines and felines, where the irradiation field is small, the target is adjacent to the OAR, and the target is often superficial.

Relationship of microsatellite instability to mismatch repair deficiency in malignant tumors of dogs.

BACKGROUND: Microsatellite instability (MSI) is a type of genomic instability caused by mismatch repair deficiency (dMMR) in tumors. Studies on dMMR/MSI are limited, and the relationship between dMMR and MSI is unknown in tumors of dogs. OBJECTIVES: We aimed to identify the frequency of dMMR/MSI by tumor type and evaluate the relationship between dMMR and MSI in tumors of dogs. ANIMALS: In total, 101 dogs with 11 types of malignant tumors were included. METHODS: We extracted DNA from fresh normal and tumor tissues. Twelve microsatellite loci from both normal and tumor DNA were amplified by PCR and detected by capillary electrophoresis. Each microsatellite (MS) was defined as MSI if a difference in product size between the tumor and normal DNA was detected. The dMMR was evaluated by immunohistochemistry with formalin-fixed paraffin-embedded tumor tissues. Next, we confirmed whether dMMR induces MSI by serial passaging of MMR gene knockout cell lines for 3 months. RESULTS: Microsatellite instability was detected frequently in oral malignant melanoma. The number of MSI-positive markers was higher in cases with dMMR than in those with proficient MMR (P < .0001). Statistical analysis indicated that the occurrence of MSI in FH2305 might have relevance to dMMR. Furthermore, MSI occurred in dMMR cell lines 3 months after passaging. CONCLUSIONS AND CLINICAL IMPORTANCE: Microsatellite instability and dMMR more frequently were found in oral malignant melanoma than in other tumors, and dMMR has relevance to MSI in both clinical cases and cell lines.

Evaluation of setup errors of immobilization device for radiation therapy in companion animals.

Background: Intensity-modulated radiotherapy (IMRT), which allows generating steep dose gradients, is a beneficial treatment for companion animals with adjacent target and risk organs. IMRT is essential for high setup accuracy for avoiding overdose to risk organs, and optimal radiotherapy is important for evaluating the setup accuracy of companion animals. Aim: To use an immobilization device to evaluate setup errors in radiotherapy for companion animals. Methods: We calculated setup errors in radiotherapy for 386 animals (dogs and cats; 3,261 registration images) that underwent radiotherapy between 2016 and 2022. The companion animals were immobilized with a customized bite block and vacuum lock device. A quantile-quantile plot with 95% confidence interval (CI) was used to evaluate the histogram of the setup errors, and the systematic and random setup errors were calculated for each region (brain, head and neck, chest and abdomen, pelvis, and spine). Results: The setup error in each direction presented an extremely narrow-interval histogram, with the following lower and upper 95% CIs: cranial-caudal (-0.08, -0.06 cm); left-right (-0.04, -0.02 cm); and dorsal-ventral (-0.13, -0.11 cm). The mean systematic setup error was 0.16 cm (range: 0.12-0.36 cm), and the random error was 0.15 cm (range: 0.08-0.34 cm). The pelvis showed the highest systematic and random setup errors (mean: 0.36 and 0.23 cm, respectively). Conclusion: The use of an immobilization device enables highly accurate radiotherapy for companion animals (95% CI < 0.15 cm).

Serum vascular endothelial growth factor in dogs with various proliferative diseases.

Angiogenesis plays an important role in the proliferation and metastasis mechanisms of malignant tumors. Vascular endothelial growth factor (VEGF), a group of cytokines that contribute to angiogenesis and vasculogenesis. This study aimed to investigate the serum VEGF-A concentrations in dogs with various proliferative diseases. A total of 202 dogs that were histopathologically diagnosed with proliferative diseases were included in the study. Serum VEGF-A concentrations were measured using enzyme-linked immunosorbent assay. Median serum VEGF-A concentrations in dogs were as follows: healthy dogs, 4 pg/ml [0-21 pg/ml]; hepatocellular carcinoma, 30 pg/ml [0-158 pg/ml, P=<0.001]; hepatocellular adenoma, 32 pg/ml [0-49 pg/ml, P=0.003]; hepatic nodular hyperplasia, 18 pg/ml [0-51 pg/ml, P=0.595]; adrenal pheochromocytoma, 32 pg/ml [0-187 pg/ml, P=<0.001]; adrenocortical carcinoma, 32 pg/ml [3-161 pg/ml, P=0.002]; adrenocortical adenoma, 27 pg/ml [0-106 pg/ml, P=0.005]; colorectal adenocarcinoma, 36 pg/ml [0-75 pg/ml, P=0.002]; colorectal adenoma, 43 pg/ml [0-48 pg/ml, P=0.144]; inflammatory colorectal polyps, 37 pg/ml [0-111 pg/ml, P=<0.001]; pulmonary adenocarcinoma, 35 pg/ml [4-107 pg/ml, P=0.002]; pulmonary histiocytic sarcoma, 35 pg/ml [0-131 pg/ml, P=0.016]; and follicular thyroid carcinoma, 35 pg/ml [0-106 pg/ml, P=0.009]. The serum VEGF-A concentrations were significantly higher in dogs with neoplastic lesions compared to healthy dogs, except for colorectal adenoma. High serum VEGF-A concentrations were observed in dogs with proliferative diseases. The present study suggests that angiogenesis-inhibiting therapy, which targets VEGF-A, may be useful for canine neoplastic diseases.

Establishment of a New Canine Inflammatory Mammary Carcinoma Cell Line and Analysis of its Cystine-glutamate Transporter Subunit Expression.

Introduction: Inflammatory mammary carcinoma (IMC) is a rare disease with a poor prognosis and one affecting dogs. Inflammatory breast carcinoma (IBC) is a subtype of malignant breast cancer in humans with a high degree of malignancy and a similarly poor prognosis. Since the clinical symptoms and prognoses of both are similar, canine IMC has been considered as a model of human IBC. In this study, we newly established a stable IMC-derived cell line from a patient at the Yamaguchi University Animal Medical Center in Japan. Material and Methods: The patient was a female toy poodle presenting with an inflamed mammary gland, which was diagnosed as IMC. The cell line was established from a tissue biopsy. Surface antigen marker (CD24 and CD44) expression was determined. Cystine/glutamate antiporter (xCT) expression was determined by Western blotting, flow cytometry and fluorescence immunostaining, and sulfasalazine was administered to ascertain if it suppressed xCT expression. Stem cell marker (Nanog, Sox2, Myc and Klf4) expression and aldehyde dehydrogenase (ALDH) activity were also investigated. Results: The cultured cells showed xCT, and its suppression showed downregulation of stem cell markers and ALDH activity. Stable cell proliferation was verified. Conclusion: A new canine IMC-derived cell line was established. In the future, we aim to study the effect of xCT on the maintenance of cancer stem cell properties in canine tumours, and propose a new therapeutic method for the treatment of canine IMC by targeting xCT.

Sphere-forming cells display stem cell-like characteristics and increased xCT expression in a canine hepatocellular carcinoma cell line.

Hepatocellular carcinoma (HCC) is the most common type of canine primary liver tumor; however, most chemotherapies against HCC are ineffective due to resistance to anticancer agents. Sphere-forming cells are considered to act as cancer stem cells for various types of solid tumors and have been established for many canine tumor cell lines, yet no studies have reported sphere-forming cells for canine HCC. In this study, we established sphere-forming cells from a canine HCC cell line (AZACH). These cells displayed increased stem cell marker mRNA expression (Nanog, Sox2, c-Myc, and Klf4), aldehyde dehydrogenase activity, and chemoresistance against mitoxantrone, gemcitabine, and doxorubicin. In addition, sphere-forming cells exhibited higher xCT expression and lower intracellular reactive oxygen species levels than adherent cells. Treatment with sulfasalazine, a xCT-specific inhibitor, reduced sphere formation efficiency. Together, these results indicate that sphere-forming cells derived from a canine HCC cell line have similar characteristics to cancer stem cells and that their increased xCT expression and associated resistance to oxidative stress contribute toward sphere formation.

Copper-associated hepatitis in a young Dalmatian dog in Japan.

A male 25-month-old Dalmatian dog attended our veterinary hospital because of anorexia and high circulating liver enzyme activities. Abdominal computed tomography showed a slightly small liver with rounded edges, and laparoscopic examination showed that the liver was yellowish. Histopathological examination revealed multifocal necrosis of hepatocytes and severe chronic hepatitis. Rhodanine staining showed severe copper accumulation in hepatocytes and a quantitative analysis of the copper content of the liver showed substantial accumulation (10.3 mg/g dry mass), suggesting a diagnosis of copper-associated hepatitis. Previously reported canine mutation in the COMMD1, the gene responsible for the copper-associated hepatitis in the Bedlington terrier, was not identified. To our knowledge, this is the first report of copper-associated hepatitis in a Dalmatian in Japan.

Transient third-degree atrioventricular block during anesthesia in a cat.

BACKGROUND: Third-degree atrioventricular block (AVB) is usually permanent, with transient cases being rare. Cats with transient third-degree AVB. It had been not reported in detail. CASE DESCRIPTION: A 9.3-year-old, male shorthair cat was evaluated for possible nervous disease resulting from otitis interna. Under propofol and isoflurane anesthesia, this cat developed a third-degree AVB. Isoproterenol was administered by continuous infusion to increase its heart rate. During recovery, heart rate returned to sinus bradycardia together with first-degree AVB without medical treatment. The cause of transient AVB was not observed at the examination. CONCLUSION: The case of this cat suggests that anesthesia can result in a transient third-degree AVB.

Clinical features and their course of pituitary carcinoma with distant metastasis in a dog.

An 11-year-old male toy poodle with neurological symptoms was diagnosed with a macroscopic pituitary tumor, which produced adrenocorticotropic hormone. Radiation therapy with a linear accelerator was performed for the pituitary tumor, and resulted in good local tumor control. However, serum endogenous adrenocorticotropic hormone concentrations were uncontrollable even after the tumor disappeared. Abdominal computed tomography revealed splenic masses, and splenectomy was performed. Histopathological examination of the surgical specimen showed tumor cells with eosinophilic and finely granular cytoplasm suggestive of endocrine origin. Since these cells were positive for adrenocorticotropic hormone, the case was diagnosed as a pituitary carcinoma with distant metastasis. Necropsy revealed multiple metastases to the abdominal organs. This is the first case report describing canine pituitary carcinoma with distant metastasis.