Histopathologic changes of the ear in canine models of mucopolysaccharidosis types I and VII.

Mucopolysaccharidosis (MPS) types I and VII are inborn errors of metabolism caused by mutation of enzymes involved in glycosaminoglycan catabolism, which leads to intralysosomal accumulation of glycosaminoglycans. In children, severe forms of MPS I and VII are characterized by somatic and neurologic manifestations, including a poorly understood hearing loss. The purpose of this study is to describe the age-related histopathologic changes of the ear in spontaneous canine models of MPS I and VII. Pathologic changes in the ear were assessed in MPS I and VII dogs ranging from 1.6 to 9.3 months of age. Paraffin-embedded sections of the whole ear and Epon-embedded semithin sections of the cochlea were examined. The following lesions were blindly scored in the middle and inner ear: inflammation, cells vacuolization, thickening of osseous and membranous structures, perivascular vacuolated macrophages infiltration, and bone resorption. All dogs had lysosomal storage within cells of tympanic membrane, ossicles, tympanic bone and mucosa, cochlear bone, spiral ligament, limbus, and stria vascularis. The MPS I dogs mainly had progressive cochlear lesions. The MPS VII dogs had severe and early middle ear lesions, including chronic otitis media and bone resorption. The MPS I dog only partially recapitulates the pathology seen in humans; specifically, the dog model lacks inflammatory middle ear disease. In contrast, the MPS VII dog has severe inflammatory middle ear disease similar to that reported in the human. In conclusion, the canine MPS VII model appears to be a good model to study MPS VII-related deafness.

Histopathological changes caused by Enteromyxum leei infection in farmed sea bream Sparus aurata.

Histological examinations were carried out on the stomach, pyloric caeca and 4 different parts of the intestine, as well as the rectum, hepatopancreas, gall bladder and spleen of 52 sea bream Sparus aurata spontaneously infected by Enteromyxum leei. Fifteen fish from a non-infected farm were included as a control. Clinical signs appeared only in extensively and severely infected fish. We observed Enteromyxum leei almost exclusively in the intestinal tract, and very rarely in the intrahepatic biliary ducts or gall bladder. We observed heavily infected intestinal villi adjacent to parasite-free villi. Histological changes indicated a parasite infection gradually extending from villus to villus, originating from an initial limited infected area probably located in the rectum. The parasite forms were exclusively pansporoblasts located along the epithelial basement membrane. Periodic acid-Schiff (PAS)-Alcian blue was the most useful histological stain for identifying the parasite and characterising the degree of intestinal infection. We observed severe enteritis in infected fish, with inflammatory cell infiltration and sclerosis of the lamina propria. The number of goblet cells was considerably and significantly decreased in heavily infected fish. The intestines of 4 of the 5 survivor fish were totally free of parasites and showed severe chronic enteritis with a regenerative epithelium, suggesting that an acquired immune process may spontaneously eliminate parasites.

Spinal cryptococcoma in an immunocompetent cat.

This report describes an unusual case of primary cryptococcoma in the proximal thoracic spinal cord of an 11-year-old immunocompetent cat from a farm on which there were large numbers of pigeons. This animal was referred for examination with progressive paralysis and shown to be free from feline immunodeficiency virus, feline leukaemia virus, feline coronavirus and Toxoplasma gondii. It died 2 months later. At necropsy, the only lesion detected was a malacic area, 4cm in length, in the spinal cord. Histopathological examination of the spinal cord revealed severe granulomatous inflammation associated with large numbers of encapsulated yeast cells. In addition to the granulomatous host response, necrosis, digestion chambers, Gitter cells, spheroids and lymphocytic perivascular cuffs were features of the malacic areas. Immunohistochemistry confirmed the presence of Cryptococcus neoformans var. grubii yeast cells.

Providing high-quality research training for veterinary pathologists in Europe.

Despite their key role in a wide range of fields relating to animal and public health, there is currently a lack of veterinary pathologists in Europe. In 1999, to help address the problem, the European College of Veterinary Pathologists (ECVP) and the European Society of Veterinary Pathology (ESVP) established a joint Education Committee. In this Special Article, Professor Anja Kipar and colleagues, all members of the committee, describe the ECVP/ESVP Summer Schools in Veterinary Pathology programme, which aims to provide high-quality research training for veterinary pathologists from all over Europe and beyond.

Lymphocytic insulitis in a juvenile dog with diabetes mellitus.

Autoimmune diabetes has never been described in a juvenile dog, whereas serological evidence has established its development in adult dogs. Diabetes mellitus was diagnosed in a 3-mo-old Donge de Bordeaux dog suffering from persistent hyperglycemia and concurrent insulinopenia. Histological analysis of the pancreas revealed inflammatory lesions in 40% of the islets of Langerhans, with infiltration predominantly by T lymphocytes (more than 90%), either at the edge (peri-insulitis: 10%) or in the islets (insulitis: 30%). The remaining 60% of the islets showed a marked atrophy due to massive beta cell loss with no loss of alpha cells. This pattern is quite similar to that observed in humans in which a characteristic insulitis containing high numbers of T lymphocytes is found in 20% of the islets at diabetes diagnosis. By contrast, in rodent models, nearly 70% of the islets of Langerhans show inflammation at diagnosis and macrophages and dendritic cells predominate in the inflammatory lesions. This is the first report of lymphocytic insulitis in a juvenile dog exhibiting diabetes mellitus. Our observations suggest an autoimmune origin for the disease in this dog that is similar to human type 1 diabetes mellitus, for which there is no accurate spontaneous large animal model.

Persistent left cranial vena cava causing oesophageal obstruction and consequent megaoesophagus in a dog.

A 2-month-old Brittany spaniel dog was presented for persistent regurgitation, first observed soon after weaning. Clinical examination and diagnostic imaging suggested megaoesophagus associated with a vascular ring anomaly. The normal location of the trachea on the X-ray was not consistent with a persistent right aortic arch. Post-mortem examination revealed a persistent left cranial vena cava that formed a non-elastic fibrous band enclosing the oesophagus and trachea, and causing constriction of the oesophagus. This uncommon congenital vascular defect has never previously been associated with megaoesophagus in the dog.

Microcystic meningioma in a dolphin (Delphinus delphis): immunohistochemical and ultrastructural study.

A wild common dolphin was found stranded on the French Atlantic coast. At necropsy, an intracranial grey- to tan-coloured mass (7 x 5 x 4 cm) was found at the right cerebellopontine angle, compressing the right cerebellar hemisphere, the brainstem and the occipital lobe of the right cerebral hemisphere. Microscopically, the tumour was composed of small lobules of polygonal to elongated neoplastic cells with multifocal areas of stellate and vacuolated cells. Neoplastic cells strongly expressed vimentin, S-100 protein and neuron-specific enolase. They were rarely positive for cytokeratin. Ultrastructurally, the neoplastic cells displayed all the diagnostic features of meningiomas and in some areas showed long cytoplasmic processes delimiting extracellular spaces. The immunohistochemical and ultrastructural features were consistent with the histopathological diagnosis of a microcystic meningioma. This is the first report of a meningioma in dolphins or in any other cetacean species.

In vivo assessment of a novel dacron surface with covalently bound recombinant hirudin.

Prosthetic arterial graft surfaces are relatively thrombogenic and fail to heal with a cellular neointima. The goal of this study was to characterize the in vivo antithrombin properties of a novel Dacron surface with covalently linked recombinant hirudin (rHir) implanted in a canine thoracic aorta with high flow and shear rates. rHir was bound to a knitted Dacron patch using crosslinker-modified bovine serum albumin (BSA) as a basecoat protein. BSA was first reacted with the heterobifunctional crosslinker, sulfo-SMCC. This BSA-SMCC complex was then bound to the carboxylic acid groups of hydrolyzed Dacron patches using the carbodiimide crosslinker, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. Iodinated, Traut's-modified rHir (125I-rHir-SH) was then reacted with the Dacron-BSA-SMCC surface, thereby covalently binding 125I-rHir. Graft segments were washed and sonicated to remove any nonspecifically bound 125I-rHir. Dacron-BSA-SMCC-S-125I-rHir patches (n = 5) and control Dacron-BSA patches (n = 5) were implanted in series in the thoracic aortas of canines. These patches were exposed to nonheparinized, arterial blood flow for 2 hours. Patches were explanted and assessed for 125I-rHir loss. Antithrombin activity of explanted 1-cm2 patch segments was evaluated using a chromogenic assay with 1, 5, 10, 15 units of added thrombin. Light microscopy was performed to qualitatively examine the pseudointima. Two animals were excluded from the study owing to excessive bleeding through the knitted 125I-rHir patch. Comparison of preoperative and postoperative 125I-rHir gamma counts revealed an overall decrease of 20+/-5.4% over the period studied. Explanted 125I-rHir patch segments were able to inhibit 1, 5, and 7 NIHU of thrombin, demonstrating retained antithrombin activity. Gross and microscopic examination of the control and test Dacron surfaces showed marked differences. Dacron surfaces with covalently bound 125I-rHir had no gross thrombus and a thin pseudointima of platelets and plasma proteins. In contrast, the control patches had a thick pseudointima composed of fibrin-rich thrombus. rHir, covalently bound to Dacron patches, maintains its biologic activity as well as prevents thrombus formation on the graft surface. This novel antithrombin coating, by modifying the blood/ graft interface, may improve both short- and long-term patency in small-diameter prosthetic arterial grafts and has applications with respect to other implantable or indwelling biomaterials.

Pigeon circovirus infection: pathological observations and suggested pathogenesis.

Pigeon circovirus infection (PiCV) was diagnosed by light and transmission electron microscopy in 15 birds from five lofts in western France. Histopathological findings were suggestive of primary bursotropism of pigeon circovirus, followed by secondary systemic spread from the bursa of Fabricius, particularly to non-bursal lymphoid organs. The last stage of the disease was associated with various secondary (particularly bacterial) infections. In situ detection of apoptosis in the bursa of Fabricius indicated that PiCV was concomitant with an increase in bursal lymphocytic apoptotic events related to viral infection and leading to severe acquired immunosuppression.

Late clinical expression of lameness related to associated osteomyelitis and tibial dyschondroplasia in male breeding turkeys.

A sudden outbreak of lameness related to transport stress is described in a flock of male breeding turkeys. Most of the affected turkeys exhibited obvious unilateral leg disorders. All were affected with tibial or metatarsal dyschondroplasia with at least one lesion associated with a large focus of necrosis. By histological examinations, bone lesions showed the typical feature of osteomyelitis. The inflammatory bone lesions appeared at only single isolated sites and were always associated with obvious sequestra of dyschondroplastic retained cartilage. Osteomyelitis seems to be an unexpected acute complication of previous dyschondroplasia in relation with different breeding stress situations. The resulting pain of the associated lesions could be the main cause of clinical expression of lameness. The pathogenesis of the phenomenon remains uncertain.

Muscle lesions associated with dystrophin deficiency in neonatal golden retriever puppies.

Golden retriever muscular dystrophy (GRMD), a degenerative myopathy due to the absence of dystrophin, is genetically homologous to human Duchenne muscular dystrophy (DMD). Spontaneous death of GRMD neonates within the first 2 weeks of life occurs frequently. This report describes the microscopical muscle lesions that developed in 12 GRMD puppies aged 1-8 days of age, and makes a comparison with three normal age-matched siblings and two older GRMD dogs. Immunohistochemical methods were used to confirm dystrophin deficiency in GRMD puppies. Muscle lesions were assessed on sections stained with haematoxylin-eosin-saffron, Gomori's trichrome and alizarin red S, and their severity was graded semi-quantitatively. Muscle fibre types were determined immunohistochemically on the basis of the pattern of expression of developmental, slow and fast isoforms of myosin. Muscle lesions in the GRMD puppies were characterized by massive necrosis, affecting most muscles of the proximal limbs, trunk and neck at birth. Lingual lesions began to develop in utero, and respiratory muscles underwent terminal diffuse necrosis resulting in death from acute respiratory failure. However, GRMD puppies do not invariably die in the neonatal period. Muscle in 2-month-old GRMD dogs showed signs of regeneration (immunohistochemical immaturity of muscle tissue), which suggested that all GRMD dogs suffer from massive post-natal myonecrosis, whether fatal or not. Muscle lesions in neonates consisted mainly of hyalinization, hypertrophy, calcification and necrosis, followed by regeneration. Such "phase I" lesions due to the absence of dystrophin are found in all species in which dystrophin deficiency has been described (human beings, dogs, cats and mice), whereas the endomysial fibrosis and myofibre atrophy found in 2-month-old GRMD dogs constituted "phase II" lesions, which are specific to GRMD and human DMD.

Cerebral primitive neuroectodermal tumour in a heifer.

A primitive neuroectodermal tumour (PNET) replacing the thalamus was discovered in an 18-month-old Prim'Holstein heifer. Microscopical examination of the tumour showed large sheets of densely packed cells with occasional Homer-Wright and perivascular rosettes. Neoplastic cells were small with ill-defined borders, scant cytoplasm and ovoid, irregularly shaped nuclei. Immunolabelling was positive for vimentin and neuron-specific enolase, in agreement with previous reports of PNETs in human beings and animals. This appears to be the first report of cerebral PNET in cattle.

Chronic hepatitis associated with leptospiral infection in vaccinated beagles.

Sixteen juvenile Beagle dogs originating from a single breeding colony and regularly vaccinated against Leptospira interrogans (serogroups Canicola and Icterohaemorrhagiae) developed a clinical syndrome characterized by retarded growth, weight loss and often ascites. Over a 10-month period, post-mortem examinations were performed on all affected dogs. Gross lesions were confined to the liver which was often firm, tan-coloured and mottled. Microscopically, hepatic lesions ranged from those of severe chronic hepatitis to mild diffuse hepatocellular vacuolation, with bile stasis, occasional scattered lymphocytic aggregates and haemosiderin granulomas. Special stains and electron microscopy revealed spirochaetes within bile canaliculi. The genus Leptospira was recognized by immunohistochemical methods in nine dogs. Leptospires were isolated from six dogs, but serological tests failed to detect significant titres of antibody to L. interrogans in these animals. A serological survey of 37 kennelmates demonstrated that 20 dogs had high titres of serogroup Australis leptospiral antibody, which could not have resulted from vaccination. These findings strongly suggest a connection between the presence of leptospires and the hepatic lesions.

Capripoxvirus disease in an Arabian oryx (Oryx leucoryx) from Saudi Arabia.

Lumpy skin disease caused by a capripoxvirus was observed in a captive-bred female Arabian oryx (Oryx leucoryx) at the National Wildlife Research Center, Taif, Saudi Arabia. Clinical signs included severe general depression with fever, anorexia, greater than 1,000 nodular cutaneous lesions and gradual recovery over 2 mo. The virus was found by electron microscopy and paired sera showed an increasing virus neutralization antibody titer against capripoxvirus. A serologic survey of the herd of 90 oryx showed a low prevalence (2%) of this infection. This report describes the first case of lumpy skin disease in an Arabian oryx.

Histology and histomorphometry of the tibia growth in two turkey strains.

Qualitative and quantitative histological methods on decalcified and undecalcified specimens were used for comparing the linear and radial growth of the tibia in two turkey strains: a light strain, Betina, without leg problems and a heavy strain, Maxiboul, with leg problems. Groups of 10 clinically healthy male turkeys of each strain were studied at 2, 6, 8, 16, and 20 weeks of age. Three histomorphometric parameters of longitudinal growth were quantitated in the proximal growth plate and metaphysis. These were: height of the proliferative zone, density of ossification buds (metaphyseal sprouts), and volume of metaphyseal trabecular bone. Four histomorphometric parameters of radial growth were quantitated in the diaphysis. These were cortical thickness, active zone/total surface, density of maturing osteons in the active zone, and bone apposition rate at the maturing primary osteons level. The results showed some evidence for factors predisposing to leg problems in the Maxiboul strain. At 8 weeks, the Maxiboul strain had a lower ossification bud density (13.1/mm2 vs. 20.7/mm2; P less than .05) and a lower metaphyseal trabecular bone volume (16.4% vs. 22.0%; P less than .05) when compared to the Betina strain. No difference was detected in the cortical thickness of the diaphysis in the two strains except at 2 weeks of age (799 microns vs. 387 microns; P less than .001), despite the heavier weight of the Maxiboul strain.

Attitudes toward people with disabilities.

Attitudes toward people with disabilities are learned, emotionally toned predispositions. This study compares such attitudes held by nursing faculty, beginning nursing students, graduating nursing students, registered nurses, and people with disabilities. Results of the study indicate that persons with disabilities were significantly more positive in their attitudes. Faculty held the least positive attitude, closely followed by graduating nursing students.

Comparison of postnatal development of anterior latissimus dorsi (ALD) muscle in heavy- and light-weight strains of turkey (Meleagris gallopavo).

ALD muscle development was studied from day 2 to week 15 in males of two turkey strains. At 15 weeks, the heavy-weight (HW) strain weighted 2.2 times as much as the light-weight strain (LW). Morphometric and immunocytochemical analysis showed the presence of small fibers in HW ALD muscle which simultaneously accumulated ventricular and embryonic fast myosin heavy chain isoforms. The appearance of these nascent myofibers suggests that hyperplasia contributes to the growth of HW ALD muscle.

Retrospective study of Mycoplasma gallisepticum meningoencephalitis in six turkey flocks in western France.

Mycoplasma gallisepticum (MG) meningoencephalitis was diagnosed in six turkey flocks, from 1998 to 2005, in the western part of France. Affected birds were 8-11 weeks old and all displayed neurological signs, especially torticollis, with more than half having concomitant respiratory signs. Microscopical examination of brain samples from birds in all six flocks revealed similar lesions of acute to subacute multifocal parenchymal necrosis, perivascular cuffing, leptomeningitis and vasculitis. Birds from four of the six affected flocks were seropositive for MG and in birds from four flocks MG DNA was detected by polymerase chain reaction performed on tracheal swabs or on samples of formalin-fixed and paraffin wax-embedded brain. To our knowledge, this is the first pathological description of naturally occurring cases of turkey MG meningoencephalitis in Europe.

High-grade mucoepidermoid carcinoma of the mandibular salivary gland in a lion (Panthera leo).

A 13-year-old neutered male lion was presented with a primary neoplasm arising from the left mandibular salivary gland associated with metastases to regional lymph nodes, thoracic viscera (lungs, heart, esophagus, and diaphragm), and kidney. Histologic and immunohistochemical investigations led to a diagnosis of a high-grade mucoepidermoid carcinoma of the mandibular salivary gland. In this case report, we point out the importance of the immunohistochemical characterization for differential diagnosis between various types of carcinomas of the salivary gland.