藤田 道郎

BACKGROUND: Few epidemiological studies on respiratory medicine and the relationship between clinical signs and various respiratory diseases in cats have been reported. OBJECTIVES: This retrospective study aimed to investigate the prevalence and breed predisposition to feline respiratory diseases in Japan and determine the association between clinical signs, duration and type of respiratory diseases. METHODS: The medical records of cats with feline respiratory diseases were examined to obtain information on age, sex, breed, final diagnosis, clinical signs and duration. The odds ratios (ORs) and 95% confidence intervals were calculated to evaluate breed predispositions. Mann-Whitney U, Kruskal-Wallis and Dunn's tests were used to assess the duration of clinical signs. RESULTS: This study included 540 cats with 615 respiratory diagnoses. The American Shorthair breed was predisposed to bronchopneumonia (BP; OR: 5.0) and pulmonary tumour (PT; OR: 3.6), while the Russian Blue breed exhibited a predisposition to inflammatory lower airway diseases (OR: 3.4), BP (OR: 6.1) and interstitial lung diseases (OR: 11.1). Similarly, the Scottish Fold breed displayed predisposition to PTs (OR: 5.8). The duration of clinical signs among nasal diseases, nasopharyngeal diseases and lower tracheal/bronchial and pulmonary diseases differed significantly (p = 0.001, p = 0.012, p < 0.0001, respectively). CONCLUSIONS: The results suggest that some popular breeds in Japan are predisposed to feline respiratory diseases, especially the American Shorthair, Russian Blue and Scottish Fold breeds. The characteristics of occurrence, clinical signs and duration of each disease will aid in diagnosing, treating, preventing and elucidating the pathophysiology of feline respiratory disease.

BACKGROUND: Few studies have investigated the incidence of respiratory diseases based on anatomical sites or the relationship between breed and these diseases. OBJECTIVE: The objective of this study was to investigate the prevalence of canine respiratory diseases among dogs in Japan, with relationship to the breed. METHODS: We retrospectively reviewed the medical records of dogs with respiratory symptoms and calculated the odds ratio (OR) to evaluate the relationship between breed and disease. RESULTS: A total of 1050 dogs with respiratory symptoms were included in this study. Miniature dachshunds were the most common breed affected by respiratory diseases. Among tracheobronchial diseases, there was a significant association between some small breeds and tracheobronchial collapse, miniature dachshunds (OR: 4.44, 8.43, 95% confidence interval [CI]: 3.17-6.22, 4.33-16.0) and chronic bronchitis and bronchiectasis. Among nasal diseases, miniature dachshunds (OR: 27.2, 95% CI: 16.8-44.8) and golden retrievers (OR: 21.0, 95% CI: 6.43-69.3) were the most affected by non-infectious rhinitis and nasal aspergillosis, respectively. Brachycephalic obstructive airway syndrome was the most common disease among pharyngeal and laryngeal diseases, with a relationship with breed being found in some brachycephalic breeds, and Pomeranians (OR: 2.7, 95% CI: 1.42-5.17). CONCLUSIONS: Respiratory diseases in dogs are strongly correlated with popular breeds in Japan. Miniature dachshunds, in particular, are associated with many respiratory diseases, which may differ from international reports. Thus, this result may help in the early detection, prevention, treatment, and elucidation of the pathophysiology of canine respiratory diseases.

<sec><title>Case summary</title> A 4-year-old castrated male domestic shorthair cat with a continuous cough was brought to a private veterinary clinic for detailed examination. Radiography of the thoracic cavity revealed a severe radiopaque region in the caudal lobe of the right lung. At 108 days after the initial visit, CT showed a mass of 27 × 23 × 18 mm in the caudal lobe of the right lung. At that time, no abnormalities in other organs except for the lung were detected on CT and peripheral blood and blood biochemistry tests. The mass in the caudal lobe of the right lung was resected by lobectomy; it had a white surface and was firm. Histopathologically, the mass was non-encapsulated, showing an unclear boundary with surrounding tissues. The mass comprised large, round or polygonal neoplastic cells arranged in a diffuse pattern. Immunohistochemically, neoplastic cells were diffusely positive for CD20, feline leukaemia virus (FeLV) p27 and FeLV glycoprotein 70 but negative for CD3, CD204 and E-cadherin. Based on these findings, diffuse large B-cell lymphoma associated with FeLV infection was diagnosed. Although the cat showed no clinical signs of gastrointestinal or respiratory injury, a routine ultrasonography revealed thickening in the jejunum wall 196 days after lobectomy, and subsequent fine-needle aspiration examination confirmed high-grade lymphoma. </sec><sec><title>Relevance and novel information</title> This is the first report of primary pulmonary diffuse large B-cell lymphoma associated with FeLV infection in a young cat. </sec>

Nasal lymphoma (NL) is the most common nasal tumor in cats, and radiotherapy, chemotherapy, or a combination of these treatments have been described as the treatment for this disease. However, the previous studies included various machines and protocols of radiotherapy. Therefore, we aimed to retrospectively compare the prognosis among cases treated with palliative hypofractionated radiotherapy, chemotherapy, and a combination of them with united machine and protocol of radiotherapy. When compared overall survival and progression free survival, there was no significant difference among these three groups. The data of this study suggested that similar efficacy could be achieved by palliative hypofractionated radiotherapy, chemotherapy, or a combination of them.

Meningiomas are the most common intracranial tumor in dogs and cats, and their surgical resection is often performed because they are present on the brain surface. Typical meningiomas show comparatively characteristic magnetic resonance imaging findings that lead to clinical diagnosis; however, it is necessary to capture not only macroscopic changes but also microstructural changes to devise a strategy for surgical resection and/or quality of removal. To visualize such microstructural changes, diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) have been used in human medicine. The aim of this retrospective study was to investigate the different characteristics of the apparent diffusion coefficient (ADC) from DWI and fractional anisotropy (FA) from DTI of meningioma between dogs and cats. Statistical analyses were performed to compare ADC and FA values between the intratumoral or peritumoral regions and normal-appearing white matter (NAWM) among 13 dogs (13 lesions, but 12 each in ADC and FA analysis) and six cats (seven lesions). The NAWM of cats had a significantly lower ADC and higher FA compared to dogs. Therefore, for a comparison between dogs and cats, we used ADC and FA ratios that were calculated by dividing the subject (intra- or peritumoral) ADC and FA values by those of NAWM on the contralateral side. Regarding the intratumoral region, feline meningiomas showed a significantly lower ADC ratio and higher FA ratio than canine meningiomas. This study suggested that ADC and FA may be able to distinguish a meningioma that is solid and easy to detach, like as typical feline meningiomas.

OBJECTIVE To investigate epilepsy-related neuropathologic changes in cats of a familial spontaneous epileptic strain (ie, familial spontaneous epileptic cats [FSECs]). ANIMALS 6 FSECs, 9 age-matched unrelated healthy control cats, and 2 nonaffected (without clinical seizures)dams and 1 nonaffected sire of FSECs. PROCEDURES Immunohistochemical analyses were used to evaluate hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes. Values were compared between FSECs and control cats. RESULTS Significantly fewer neurons without gliosis were detected in the third subregion of the cornu ammonis (CA) of the dorsal and ventral aspects of the hippocampus as well as the central nucleus of the amygdala in FSECs versus control cats. Gliosis without neuronal loss was also observed in the CA4 subregion of the ventral aspect of the hippocampus. No changes in mossy fiber sprouting and granule cell pathological changes were detected. Moreover, similar changes were observed in the dams and sire without clinical seizures, although to a lesser extent. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that the lower numbers of neurons in the CA3 subregion of the hippocampus and the central nucleus of the amygdala were endophenotypes of familial spontaneous epilepsy in cats. In contrast to results of other veterinary medicine reports, severe epilepsy-related neuropathologic changes (eg, hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes) were not detected in FSECs. Despite the use of a small number of cats with infrequent seizures, these findings contributed new insights on the pathophysiologic mechanisms of genetic-related epilepsy in cats.

Background: Leucine-rich glioma-inactivated (LGI) proteins play a critical role in synaptic transmission. Dysfunction of these genes and encoded proteins is associated with neurological disorders such as genetic epilepsy or autoimmune limbic encephalitis in animals and human. Familial spontaneous epileptic cats (FSECs) are the only feline strain and animal model of familial temporal lobe epilepsy. The seizure semiology of FSECs comprises recurrent limbic seizures with or without evolution into generalized epileptic seizures, while cats with antibodies against voltage-gated potassium channel complexed/ LGI1 show limbic encephalitis and recurrent limbic seizures. However, it remains unclear whether the genetics underlying FSECs are associated with LGI family genes. In the present study, we cloned and characterized the feline LGI1-4 genes and examined their association with FSECs. Conventional PCR techniques were performed for cloning and mutational analysis. Characterization was predicted using bioinformatics software. Results: The cDNAs of feline LGI1-4 contained 1674-bp, 1650-bp, 1647-bp, and 1617-bp open reading frames, respectively, and encoded proteins comprising 557, 549, 548, and 538 amino acid residues, respectively. The feline LGI1-4 putative protein sequences showed high homology with Homo sapiens, Canis familiaris, Bos taurus, Sus scrofa, and Equus caballus (92%-100%). Mutational analysis in 8 FSECs and 8 controls for LGI family genes revealed 3 non-synonymous and 14 synonymous single nucleotide polymorphisms in the coding region. Only one non-synonymous single nucleotide polymorphism in LGI4 was found in 3 out of 8 FSECs. Using three separate computational tools, this mutation was not predicted to be disease causing. No co-segregation of the disease was found with any variant. Conclusions: We cloned the cDNAs of the four feline LGI genes, analyzed the amino acid sequences, and revealed that epilepsy in FSEC is not a monogenic disorder associated with LGI genes.

Although MRI has become widely used in small animal practice, little is known about the validity of advanced MRI techniques such as diffusion-weighted imaging and diffusion tensor imaging. The aim of this retrospective analytical observational study was to investigate the characteristics of diffusion parameters, that is the apparent diffusion coefficient and fractional anisotropy, in dogs with a solitary intracranial meningioma or histiocytic sarcoma. Dogs were included based on the performance of diffusion MRI and histological confirmation. Statistical analyses were performed to compare apparent diffusion coefficient and fractional anisotropy for the two types of tumor in the intra- and peritumoral regions. Eleven cases with meningioma and six with histiocytic sarcoma satisfied the inclusion criteria. Significant differences in apparent diffusion coefficient value (x 10(-3) mm(2)/s) between meningioma vs. histiocytic sarcoma were recognized in intratumoral small (1.07 vs. 0.76) and large (1.04 vs. 0.77) regions of interest, in the peritumoral margin (0.93 vs. 1.08), and in the T2 high region (1.21 vs. 1.41). Significant differences in fractional anisotropy values were found in the peritumoral margin (0.29 vs. 0.24) and the T2 high region (0.24 vs. 0.17). The current study identified differences in measurements of apparent diffusion coefficient and fractional anisotropy for meningioma and histiocytic sarcoma in a small sample of dogs. In addition, we observed that all cases of intracranial histiocytic sarcoma showed leptomeningeal enhancement and/or mass formation invading into the sulci in the contrast study. Future studies are needed to determine the sensitivity of these imaging characteristics for differentiating between these tumor types.

Objective: The familial spontaneous epileptic cat (FSEC) is thought to be a good genetic model of mesial temporal lobe epilepsy. In the current study, cerebral diffusion and perfusion magnetic resonance imaging (MRI) were used to confirm the functional deficit zone in the FSEC and evaluate the effect of a single seizure on different brain regions. Methods: Six FSECs and six healthy control cats were used in this study. MRI was performed in the interictal state (resting state for control) and postictal state immediately after the vestibular stimulation-induced generalized epileptic seizure (control cats received the same stimulation as the FSECs). The apparent diffusion coefficient (ADC), fractional anisotropy and perfusion parameters (i.e., relative regional cerebral blood volume (rCBV), relative regional cerebral blood flow (rCBF), and relative regional mean transit time (rMTT)) were measured in the hippocampus, amygdala, thalamus, and gray and white matter. Results: In the interictal state, the rCBV and rMTT in the hippocampus was significantly decreased in FSECs, compared to the control. In the postictal state, FSECs had a significantly decreased ADC and an increased rCBV, rCBF, and rMTT in the hippocampus, and an increased rMTT in the amygdala, compared to the interictal state. Conclusion: This study showed that FSECs had interictal hypoperfusion in the hippocampus, and postictal hypodiffusion and hyperperfusion in the hippocampus and/or amygdala. These findings suggested that the hippocampus and/or amygdala act as the functional deficit and expanded seizure-onset zones in FSECs.

OBJECTIVE To evaluate the usefulness of diffusion and perfusion MRI of the cerebrum in cats with familial spontaneous epilepsy (FSECs) and identify microstructural and functional deficit zones in affected cats. ANIMALS 19 FSECs and 12 healthy cats. PROCEDURES Diffusion-weighted, diffusion tensor, and perfusion-weighted MRI of the cerebrum were performed during interictal periods in FSECs. Imaging findings were compared between FSECs and control cats. Diffusion (apparent diffusion coefficient and fractional anisotropy) and perfusion (relative cerebral blood volume [rCBV], relative cerebral blood flow [rCBF], and mean transit time) variables were measured bilaterally in the hippocampus, amygdala, thalamus, parietal cortex gray matter, and subcortical white matter. Asymmetry of these variables in each region was also evaluated and compared between FSECs and control cats. RESULTS The apparent diffusion coefficient of the total amygdala of FSECs was significantly higher, compared with that of control cats. The fractional anisotropy of the right side and total hippocampus of FSECs was significantly lower, compared with that of control cats. The left and right sides and total hippocampal rCBV and rCBF were significantly lower in FSECs than in control cats. The rCBV and rCBF of the parietal cortex gray matter in FSECs were significantly lower than in control cats. CONCLUSIONS AND CLINICAL RELEVANCE In FSECs, diffusion and perfusion MRI detected microstructural changes and hypoperfusion (lowered function) in the cerebrum during interictal periods from that of healthy cats. These findings indicated that diffusion and perfusion MRI may be useful for noninvasive evaluation of epileptogenic foci in cats.

A 16-year-old castrated male mongrel cat presented with swelling under the left pinna and a 3 -month history of voice change. Laryngeal endoscopy revealed circumferential oedema around the arytenoid cartilages and hypersecretion of saliva. Histopathological examination of the mass around the left ear canal was considered the primary lesion that originated from cutaneous apocrine adenocarcinoma or parotid gland adenocarcinoma, and it metastasized to the larynx, lung and medial retropharyngeal lymph nodes. This report provides new insights into feline laryngeal diseases which could result in laryngeal metastasis with slight mucosal irregularity alone and without obvious radiographic abnormalities. Therefore, histopathological examination should be performed when a cat presents clinical signs such as stridor, dysphonia or voice change without any mass-forming laryngeal lesion.

Background: Epilepsy is the most common neurological disease in veterinary practice. However, contrary to human medicine, epilepsy classification in veterinary medicine had not been clearly defined until recently. A number of reports on canine epilepsy have been published, reflecting in part updated proposals from the human epilepsy organization, the International League Against Epilepsy. In 2015, the International Veterinary Epilepsy Task Force (IVETF) published a consensus report on the classification and definition of canine epilepsy. The purpose of this retrospective study was to investigate the etiological distribution, survival time of dogs with idiopathic epilepsy (IdE) and structural epilepsy (StE), and risk factors for survival time, according to the recently published IVETF classification. We investigated canine cases with epilepsy that were referred to our teaching hospital in Japan during the past 10 years, and which encompassed a different breed population from Western countries. Results: A total of 358 dogs with epilepsy satisfied our etiological study criteria. Of these, 172 dogs (48 %) were classified as IdE and 76 dogs (21 %) as StE. Of these dogs, 100 dogs (consisting of 65 with IdE and 35 with StE) were included in our survival study. Median survival time from the initial epileptic seizure in dogs with IdE and StE was 10.4 and 4.5 years, respectively. Median lifespan of dogs with IdE and StE was 13.5 and 10.9 years, respectively. Multivariable analysis demonstrated that risk factors for survival time in IdE were high seizure frequency (&gt;= 0.3 seizures/month) and focal epileptic seizures. Conclusions: Focal epileptic seizures were identified as a risk factor for survival time in IdE. Clinicians should carefully differentiate seizure type as it is difficult to identify focal epileptic seizures. With good seizure control, dogs with IdE can survive for nearly the same lifespan as the general dog population. Our results using the IVETF classification are similar to previous studies, although some features were noted in our Japanese canine population (which was composed of mainly small-breed dogs), including a longer lifespan in dogs with epilepsy and a larger percentage of meningoencephalomyelitis of unknown origin in dogs with StE.

A 12-year-old spayed female Labrador retriever was presented with forebrain signs. Brain MRI revealed a huge cystic lesion with the thickened falx in the frontal region. The brain parenchyma surrounding the lesion showed significant signs of a mass effect and also increased intracranial pressure. However, the dog suddenly became lucid after about two weeks, and an MRI scan one month after the initial study revealed a dramatically shrunken cystic lesion. The dog survived for over a year until it was euthanized for other reasons, and the brain lesion was diagnosed as a cystic meningioma histologically. To the authors' knowledge, this is the first report that described the reduction of the cystic lesion of a cystic meningioma in dogs.

GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of beta-galactosidase activity. Effective therapies need to be developed to treat the disease. In Shiba Inu dogs, one of the canine GM1 gangliosidosis models, neurological signs of the disease, including ataxia, start at approximately 5 months of age and progress until the terminal stage at 12 to 15 months of age. In the present study, serial MR images were taken of an affected dog from a model colony of GM1 gangliosidosis and 4 sporadic clinical cases demonstrating the same mutation in order to characterize the MRI features of this canine GM1 gangliosidosis. By 2 months of age at the latest and persisting until the terminal stage of the disease, the MR findings consistently displayed diffuse hyperintensity in the white matter of the entire cerebrum on T2-weighted images. In addition, brain atrophy manifested at 9 months of age and progressed thereafter. Although a definitive diagnosis depends on biochemical and genetic analyses, these MR characteristics could serve as a diagnostic marker in suspect animals with or without neurological signs. Furthermore, serial changes in MR images could be used as a biomarker to noninvasively monitor the efficacy of newly developed therapeutic strategies.

犬の四肢軟部組織肉腫14症例に対して術後低分割放射線治療を行い、治療成績や放射線障害について回顧的研究を行った。再発率は7.1%、放射線障害は85.7%で何らかの障害が認められたが、現在まで重篤な障害は認められず、再発に対する影響もなかった。一、二および三年生存率はそれぞれ100、92.9および66.7%あった。また一、二および三年腫瘍コントロール率はそれぞれ85.7、71.4、57.1%であった。以上のことから、犬の四肢の軟部組織肉腫に対する術後低分割放射線治療は従来の根治目的の放射線治療スケジュールと比較して治療効果に大きな差はなく、麻酔のリスクや動物への負担、オーナーへの負担を軽減する上で有用な照射方法の1つと考えられた。

Duchenne muscular dystrophy (DMID) is a devastating muscle disorder that is characterized by progressive muscle necrosis, fibrosis, and fatty infiltration. To examine the temporospatial pathological changes, a noninvasive evaluation method such as magnetic resonance imaging (MRI) is needed. The aim of this study was to precisely assess muscle necrosis and inflammation based on a sequence of T2-weighted imaging (T2WI), gadolinium-enhanced imaging, and selective fat suppression, chemical shift selective T2-weighted imaging (CHESS-T2WI), on a 3.0-Tesla MRI unit in 3-month-old and 7-year-old dogs with canine X-linked muscular dystrophy (CXMDJ), a suitable animal model for DMD. The results show that CHESS-T2WI was more sensitive and useful from the early to late stages of CXMDJ than T2WI or contrast enhancement imaging in the evaluation of muscle necrosis, because these latter sequences can be influenced by fatty infiltration or interstitial connective tissues. Muscle Nerve 40: 815-826, 2009

SART-1, a squamous cell carcinoma (SCC) antigen recognized by cytotoxic T lymphocytes, has been useful in human cancer therapy. The SART-1259 peptide is a potential candidate for vaccine. The present study examined an orthologue of the mRNA coding this peptide in canine SCCs. Specimens were obtained from seven canine patients with SCC, and the mRNA was isolated from the samples. The SART-1 and beta-actin genes were amplified by reverse-transcription polymerase chain reaction, using the isolated mRNA as a template. Canine SART-1 was amplified in six of the seven specimens, while beta-actin was detected in all the samples. In dogs, carcinomas expressing SART-1 could be a target for cytotoxic T lymphocyte mediated immunotherapy.

Magnetic resonance (MR) was conducted for an 8-year-old, intact male Spitz with sneezing, serous discharge and epistaxis from the left nasal cavity. MR imaging showed a nasal cavity-occupied mass of iso-intensity on T1WI , high-intensity on T2WI and markedly enhanced on contrast-enhanced T1WI at parts of rostal to medial ocular angle in the left cavity. After Surgery and intraoperative radiation, the mass was diagnosed intranasal hemangiosarcoma by histopathology. Although the dog showed the finding, which suggested recurrence after the treatment ending, about 30 months later, it maintained good conditions without evidence of metastasis.<br>

慢性の努力呼吸と喘鳴音などの上部気道症状を示す8歳,不妊雌の猫に対しX線検査を実施したところ,頭蓋部,頚部および胸部X線像において骨の不透過性の増大が見られた.さらに鼻腔内のMR検査では,TIおよびT2強調画像においで鼻甲介領域が無信号,X線CT検査では鼻甲介の肥厚および鼻道狭窄が見られた.これらより,本疾患の呼吸器症状は鼻甲介の肥厚に伴う鼻道狭窄が原因の大理石骨様疾患と考えられた.