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Background Genetic and environmental factors, including dietary copper intake, contribute to the pathogenesis of copper-associated hepatitis in Labrador retrievers. Clinical disease is preceded by a subclinical phase in which copper accumulates in the liver. Objective To investigate the effect of a low-copper, high-zinc diet on hepatic copper concentration in Labrador retrievers with increased hepatic copper concentrations. Animals Twenty-eight clinically healthy, client-owned Labrador retrievers with a mean hepatic copper concentration of 919 ± 477 mg/kg dry weight liver (dwl) that were related to dogs previously diagnosed with clinical copper-associated hepatitis. Methods Clinical trial in which dogs were fed a diet containing 1.3 ± 0.3 mg copper/Mcal and 64.3 ± 5.9 mg zinc/Mcal. Hepatic copper concentrations were determined in liver biopsy samples approximately every 6 months. Logistic regression was performed to investigate effects of sex, age, initial hepatic copper concentration and pedigree on the ability to normalize hepatic copper concentrations. Results In responders (15/28 dogs), hepatic copper concentrations decreased from a mean of 710 ± 216 mg/kg dwl copper to 343 ± 70 mg/kg dwl hepatic copper after a median of 7.1 months (range, 5.5–21.4 months). Dogs from a severely affected pedigree were at increased risk for inability to have their hepatic copper concentrations normalized with dietary treatment. Conclusions and Clinical Importance Feeding a low-copper, high-zinc diet resulted in a decrease in hepatic copper concentrations in a subset of clinically normal Labrador retrievers with previous hepatic copper accumulation. A positive response to diet may be influenced by genetic background. Determination of clinical benefit requires further study.

Background: Hydrolyzed protein diets are commonly used to manage canine chronic enteropathies (CE), but their efficacy has not yet been critically evaluated. Hypothesis: A hydrolyzed protein diet is superior to that of a highly digestible (control) diet in the management of CE in dogs. Animals: Twenty-six dogs (18 test diet, 8 control diet) referred for investigation and management of naturally occurring chronic small intestinal disease. Methods: Randomized, open-label, positively controlled trial. After a full diagnostic investigation, which included endoscopy, dogs were assigned either to the test diet or control diet on a 2 : 1 basis (test : control). Cases were re-evaluated 3 times (at approximately 3, 6–12 months, and 3 years). Outcome measures included response of clinical signs (complete, partial, none), change in severity of signs (based upon clinical disease activity index; canine inflammatory bowel disease activity index [CIBDAI]), change in body weight, and need for other therapy. Results: There were no significant differences in baseline characteristics (eg, signalment, body weight, and duration of clinical signs), and histopathologic severity between test and control diet groups. However, despite randomization, CIBDAI was significantly higher in the test diet group (P= .013). Most dogs had responded by first evaluation, with no difference between groups (P= .87). However, significantly more dogs on the test diet remained asymptomatic at both the second (P= .0012) and third (P < .001) re-evaluation, and the decrease in CIBDAI was significantly greater (P= .010). Conclusions and Clinical Importance: A hydrolyzed protein diet can be highly effective for long-term management of canine chronic small bowel enteropathy.

ummary After a short survey of the literature a serie of sixteen cats with congenital heart abnormalities is described. There were three cases of fibroelastosis and one case with an aneurysm of the septum membranaceum, two cases with a high ventricular septal defect, one in combination with an atrial septal defect and tubular hypoplasia of the aortic isthmus and one case with an atrial septal defect. Dextroposition of the aorta occurred three times and was accompanied once by a ventricular septal defect, once by a monoventricle, and once by a monoventricle and monoatrium. Also described are one case of hypoplasia of the truncus pulmonalis, one case of truncus arteriosus communis, one case with a double aortic arch and three cases with patent ductus arteriosus. Some of the anomalies described were not encountered in the literature on feline cardiac abnormalities. Zusammenfassung Angeborene Herzmisbildungen bei der Katze Eine Beschreibung von 16 Fallen Nach einer einleitenden Literaturubersicht werden 16 Falle von angeborenen Herzmisbildungen bei Katzen beschrieben. Die Falle verteilen sich auf folgende Misbildungen: Endokard-Fibroelastose (3), Aneurysma am Septum membranaceum (1), Vorhofseptumdefekt (1), Ventrikelseptumdefekt kombiniert mit Vorhofseptumdefekt und tubularer Hypoplasie des Aortenisthmus (1), Ventrikelseptumdefekt (1), Dextroposition der Aorta kombiniert mit Ventrikelseptumdefekt (1), Dextroposition der Aorta kombiniert mit Monoventrikel (1), Dextroposition der Aorta kombiniert mit Monoventrikel und Monoatrium (1), Hypoplasie des Truncus pulmonalis (1), Truncus arteriosus communis (1), doppelter Aortenbogen (1), offener Ductus arteriosus Botalli (3). Gewisse in dieser Arbeit beschriebene Anomalien sind in der entsprechenden Literatur uber Misbildungen des Katzenherzens nicht angefuhrt. Resume Anomalies cardiaques congenitales chez le chat Description de seize cas Apres un bref apercu de la litterature, on decrit seize cas d'anomalies cardiaques congenitales chez le chat. On a mis en evidence les malformations suivantes: fibro-elastose de l'endocarde (3 cas), aneurisme de la cloison membraneuse (1), defaut de la cloison interauriculaire (1), defaut de la cloison interventriculaire combine a un defaut de la cloison interauriculaire et a un defaut de la cloison interauriculaire et a une hypoplasie tubulaire de la crosse aortique (1), defaut de la cloison interventriculaire (1), dextroposition de l'aorte combinee a un defaut de la cloison interventriculaire (1), dextroposition de l'aorte combinee a un monoventricule (1), dextroposition de l'aorte combinee a un monoventricule et une mono-oreillette (1), hypoplasie du tronc pulmonaire (1), tronc arteriel commun (1), crosse aortique double (1) et canal arteriel de Botal ouvert (3). Quelques-unes des anomalies observees ne sont pas encore decrites dans la litterature sur les anomalies cardiaques des felins. Resumen Anormalidades cardiacas congenitas en el gato Descripcion de 16 casos Tras una breve revision bibliografica, se describen 16 casos de anormalidades cardiacas congenitas en gatos. Los casos se distribuyen entre las malformaciones siguientes: fibro-elastosis endocardiaca (3), aneurisma en la porcion membranosa del tabique interventricular (1), defecto del tabique atrial (1), defecto del tabique ventricular combinado con otro del tabique auricular e hipoplasia tubular del cayado aortico (1), defecto del tabique ventricular (1), dextroposicion de la aorta combinada con defecto del tabique ventricular (1), dextroposicion de la aorta combinada con monoventriculo (1), dextroposicion de la aorta combinada con monoventriculo y monoatrio (1), hipoplasia del tronco pulmonar (1), tronco arterioso comun (1), cayado aortico doble (1), conducto arterial de Botal abierto (3). Algunas de las anomalias descritas en este trabajo no se encuentran en la bibliografia correspondiente sobre anormalidades de corazones felinos.

Summary Four rabbits were infected with a Trypanosoma brucei stabilate known as EATRO 1066 and developed chronic infection. At necropsy they showed emaciation, anaemia, exudative dermatitis of the nose, ears and external genitalia, a mucopurulent rhinitis and conjunctivitis, swollen lymphnodes and an enlarged spleen. Microscopical examination revealed extensive granuloma formation in the skin of the nose, conchae, male genital system and spleen especially in the peri-arterial lymphoid sheets. The lymphnodes showed both lymphoid hyperplasia and granulomas. The glomeruli were hypercellular. The pathogenesis of the granuloma formation and the possible relation with immunosuppression are discussed. Zusammenfassung Pathologische Veranderungen nach chronischer Trypanosoma brucei-Infektion beim Kaninchen Vier Kaninchen wurden mit Trypanosoma brucei, EATRO 1066, infiziert. Es entwickelte sich eine chronische Infektion. Die pathologisch-anatomischen Untersuchungen ergaben Abmagerung, Anamie, exsudation Dermatitis an Nase, Augenlidern, Ohren und Vulva oder Skrotum, mukopurulente Rhinitis und Konjunktivitis sowie vergroserte Lymphknoten und Milz. Mikroskopisch zeigten sich granulomatose Veranderungen in den betroffenen Hautabschnitten, den Conchen, dem mannlichen Genitalsystem und der Milz. In den Lymphknoten hatten sich sowohl lymphoide Hyperplasie als auch Granulome entwickelt. Die Glomeruli waren hypercellular. Die Pathogenese der granulomatosen Veranderungen und die mogliche Beziehung zur Immunsuppression werden diskutiert. Resume Lesions pathologiques a la suite d'une infection chronique a Trypanosoma brucei chez le lapin Quatre lapins ont ete infectes avec Trypanosoma brucei, EATRO 1066. Une infection chronique s'est developpee. Les examens anatomo-pathologiques ont donne un amaigrissement, une anemie, une dermatite exsudative du nez, des paupieres, des oreilles et de la vulve ou du scrotum, une rhinite mucopurulente, une conjonctivite, la rate et des ganglions grossis. Des lesions granulomateuses sont apparues a l'histologie dans les parties atteintes et dans la rate. Une hyperplasie lymphoide aussi bien que des granulomes se sont developpes dans les ganglions. Les glomerules furent hypercellulaires. On discute la pathogenese des lesions granulomateuses et le rapport possible avec une immunosuppression. Resumen Modificaciones patologicas tras infeccion cronica con Trypanosoma brucei en conejos Se infectaron cuatro conejos con Trypanosoma brucei, EATRO 1.066. Se desarrollo una infeccion cronica. Los estudios anatomopatologicos acusaron adelgazamiento, anemia, dermatitis exudativa en la nariz, parpados, orejas y vulva o escroto, rinitis mucopurulenta y conjuntivitis, asi como hipertrofia de ganglios y bazo. Al microscopio se manifestaron modificaciones granulomatosas en los tramos cutaneos afectados, cornetes, sistema genital masculino y bazo. En los ganglios se desarrollaron tanto hiperplasia linfoide como granulomas. Los glomrulos eran hipercelulares. Se discute la patogenia de las modificaciones granulomatosas y la relacion posible con la inmunosupresion.

PURPOSE: The aim of this study is to evaluate the toxicity of holmium-166 poly(L-lactic acid) microspheres administered into the hepatic artery in pigs. METHODS: Healthy pigs (20-30 kg) were injected into the hepatic artery with holmium-165-loaded microspheres ((165)HoMS; n=5) or with holmium-166-loaded microspheres ((166)HoMS; n=13). The microspheres' biodistribution was assessed by single-photon emission computed tomography and/or MRI. The animals were monitored clinically, biochemically, and ((166)HoMS group only) hematologically over a period of 1 month ((165)HoMS group) or over 1 or 2 months ((166)HoMS group). Finally, a pathological examination was undertaken. RESULTS: After microsphere administration, some animals exhibited a slightly diminished level of consciousness and a dip in appetite, both of which were transient. Four lethal adverse events occurred in the (166)HoMS group due either to incorrect administration or comorbidity: inadvertent delivery of microspheres into the gastric wall (n=2), preexisting gastric ulceration (n=1), and endocarditis (n=1). AST levels were transitorily elevated post-(166)HoMS administration. In the other blood parameters, no abnormalities were observed. Nuclear scans were acquired from all animals from the (166)HoMS group, and MRI scans were performed if available. In pigs from the (166)HoMS group, atrophy of one or more liver lobes was frequently observed. The actual radioactivity distribution was assessed through ex vivo (166m)Ho measurements. CONCLUSION: It can be concluded that the toxicity profile of HoMS is low. In pigs, hepatic arterial embolization with (166)HoMS in amounts corresponding with liver-absorbed doses of over 100 Gy, if correctly administered, is not associated with clinically relevant side effects. This result offers a good perspective for upcoming patient trials

A nine-month-old miniature doberman was referred for the evaluation of chronic icterus. History and clinical and histopathological findings were supportive of a diagnosis of drug-induced destructive cholangitis. The main histopathological findings were canalicular, centrilobular cholestasis and ductopenia with moderate inflammatory infiltrate. The dog had received three types of treatment for demodicosis before the onset of jaundice. Amoxicillin-clavulanate, amitraz, milbemycin oxime or an interaction between two of the three drugs may have been responsible for the destructive cholangitis.

Portosystemic shunting occurs frequently either as congenital anomalies of the portal vein (PVA) or as acquired shunting (AS) due to portal hypertension secondary to parenchymal liver disease or portal vein thrombosis. The 2 most commonly used screening tests for portosystemic shunting are bile acid and plasma ammonia concentrations. The purpose of this study was to compare the 12-hour fasting plasma ammonia (AMM) and bile acid concentration (BA) as tests for diagnosing portosystemic shunting. Medical records of 337 dogs were used in which AMM and BA were measured simultaneously and in which portosystemic shunting was confirmed or excluded. These dogs were divided into 2 groups (group 1: portosystemic shunting present, n = 153, and group 2: portosystemic shunting absent, n = 184). Group 1 was subdivided into 2 subgroups (group 1a: PVA, n = 132 and group 1b: AS, n = 21). The sensitivity of AMM in detecting PVA was 100% and of BA was 92.2%. For portosystemic shunting in general (PVA or AS), the sensitivity of AMM was 98% and that of BA was 88.9%. The specificity in the total population of AMM was 89.1% and that of BA was 67.9%. If only dogs with liver diseases were included with (n = 153) or without (n = 28) shunting, the specificity of AMM to detect shunting was 89.3% and that of BA was 17.9%. In conclusion, AMM is a highly sensitive and specific parameter to detect PVA and portosystemic shunting in a general population and in dogs with liver disease, whereas BA is somewhat less sensitive and considerably less specific.

A 2-year-old, castrated, male European Shorthair cat was presented with inappetence, vomiting, and fever. Ascites and an irregularly nodular liver were observed on laparotomy; in view of the poor prognosis, the animal was euthanatized. Histopathologic examination of the liver showed a chronic hepatitis with cirrhosis associated with massive accumulation of copper in hepatocytes and macrophages, particularly in the fibrotic areas between the regenerative nodules. Electron microscopy and energy-dispersive X-ray analysis revealed lysosomal accumulation of copper in the hepatocytes. Analytical determination showed very high copper concentrations in the liver. No evidence for increased dietary or environmental copper could be found. This and the pattern of hepatic copper storage, the associated inflammation and fibrosis, strongly suggest a primary copper storage disorder.

This article describes the gross, histopathologic, and ultrastructural findings of the livers of cetaceans stranded on the coast of the Canary Islands between 1992 and 2000. A total of 135 cetaceans were included in the study, among which 25 were common dolphins ( Delphinus delphis), 23 Atlantic spotted dolphins ( Stenella frontalis), 19 striped dolphins ( Stenella coeruleoalba), and 15 other species of dolphins and whales. The most common lesion observed in these animals was a nonspecific chronic reactive hepatitis (47/135), followed by hyaline intracytoplasmic inclusions in hepatocytes (33/135). Parasitic cholangitis was detected in 8/135 animals, whereas hepatic lipidosis was presented in 7/135 animals. The ultrastructure of hyaline hepatocytic cytoplasmic inclusions is described, and possible causes of these inclusions are discussed.

In primary hyperparathyroidism, calcium homeostasis is disrupted by excessive synthesis and secretion of parathyroid hormone (PTH), which is usually caused by a solitary adenoma, or less often by nodular hyperplasia or carcinoma of the parathyroid glands. So far, the distinction between these forms of primary hyperparathyroidism has been made by histological examination. In this report clinical and histological findings, including PTH immunohistochemistry, are described in five dogs with primary hyperparathyroidism, three dogs with secondary hyperparathyroidism due to chronic renal failure, and eight control dogs. In the dogs with primary hyperparathyroidism, nodular adenomatous hyperplasia was found in two animals and parathyroid adenoma in three. The dogs with chronic renal failure had diffuse parathyroid gland hyperplasia. The parathyroid glands of the control dogs and the inactive cells surrounding the hyperplastic nodules showed slight to moderate, localized, paranuclear PTH immunolabelling. In the primary nodular and secondary diffuse hyperplasia, all parathyroid cells had a diffuse cytoplasmic PTH labelling pattern, sometimes in combination with localized paranuclear labelling. In parathyroid adenoma, areas with either paranuclear labelling or diffuse cytoplasmic labelling were observed. As both parathyroid adenoma and primary nodular parathyroid gland hyperplasia have characteristics of intrinsic autonomy (i.e., suppression of the remaining endocrine tissue), there would seem to be no functional difference between the two abnormalities. It is argued that primary (multi)nodular hyperplasia is a multiple form of parathyroid adenoma.

The study presents a morphological description of inherited microphthalmia in Texel sheep and the morphogenesis of the lesion during embryonal development. The eyes of 28 newborn and young lambs with microphthalmia were examined morphologically. Blind rams with microphthalmia were crossed with ewes known to be carriers of the "microphthalmia factor", to obtain embryos of different age with and without microphthalmia for morphogenesis studies. The microphthalmic eyes showed an anteriorly located conus-shaped mass composed of connective tissue with cartilage, smooth muscle and fat tissue, particularly in the posterior part of the conus, and often islets of lacrimal glands and cystic structures lined with squamous epithelium in the anterior part. The iris, ciliary body and ciliary processes were incorporated in the periphery of the broad base of the conus. The conus was covered by a detached and folded but normally developed retina. The morphogenetic study showed an abnormal development of the lens vesicle. In embryos aged 24 days, the lens consisted of a solid unorganized proliferation of epithelial cells without formation of a lens capsule. An extensive overgrowth of primitive mesenchymal tissue followed, with infiltration and disintegration of the lens. In a later stage (45 days) a conus-shaped mass was seen in the anterior part of the eyes, which at 56 days consisted of mesenchymal tissue with focal differentiation to cartilage and epithelial structures in the anterior part of the conus. The primary event proved to be abnormal development of the lens vesicle, with disintegration of the lens and subsequent overgrowth of mesenchymal tissue. The mesenchymal tissue later differentiated in various directions, whereas the epithelial structures found in the microphthalmic eyes at days 56 and 132 and in the newborn lambs seemed to be remnants of the epithelial lens vesicle.

Item does not contain fulltext Seven tumours that were composed of balloon (n=4) or signet-ring (n=3) cells were investigated for a putative melanocytic origin. The tumours were located in the skin or the mouth cavity. In one case a sample from inguinal lymph node metastasis was available. Two antibodies used in man for the immunohistochemical diagnosis of melanomas, namely anti-Melan-A and anti-tyrosinase, were examined for their cross-reactivity with the corresponding canine antigens. The Melan-A antibody labelled all balloon cell tumours and one signet-ring cell tumour, whereas the anti-tyrosinase antibody was not reactive in any of the tumours. The Melan-A antibody also labelled a variety of canine epithelioid and spindle cell melanomas; non-melanocytic tumours were all negative. This study confirmed the occurrence of balloon and signet-ring cell melanomas in dogs. Melan-A antibody was found to be useful in the diagnosis of pigmented and non-pigmented canine melanomas.

In a 10-year-old castrated male shorthaired German pointer polyuria was associated with slight hypokalemia, hypophosphatemia and alkalosis, as well as elevated plasma concentrations of a glucocorticoid-inducible iso-enzyme of alkaline phosphatase. Repeated measurements of urinary corticoids and normal suppressibility of the hypothalamus-pituitary-adrenocorticial axis excluded glucocorticoid excess. Urine osmolality (Uosm) did not increase during administration of the vasopressin analogue desmopressin. At the time water deprivation had caused Uosm to rise from 300 to 788 mOsm/kg, there was also plasma hypertonicity. During hypertonic saline infusion the osmotic threshold for vasopressin release was increased. The combination of elevated plasma aldosterone concentrations and unmeasurably low plasma renin activity pointed to primary hyperaldosteronism. As initially computed tomography (CT) did not reveal an adrenocortical lesion, the dog was treated with the aldosterone antagonist spironolactone. This caused Uosm to rise in a dose-dependent manner. However, well-concentrated urine was only achieved with doses that gave rise to adverse effects. Once repeated CT, using 2-mm-thick slices, had revealed a small nodule in the cranial pole of the left adrenal, unilateral adrenalectomy was performed which resolved the polyuria completely. Also the plasma concentrations of kalium, aldosterone and renin activity returned to within their respective reference ranges. The adrenocortical nodule had the histological characteristics of an aldosteronoma, with the non-affected zona glomerulosa being atrophic. In this dog with primary hyperaldosteronism the polyuria was characterized by vasopressin resistance and increased osmotic threshold of vasopressin release, similar to the polyuria of glucocorticoid excess. The possibility is discussed that the polyuria of glucocorticoid excess is actually a mineralocorticoid effect.

Item does not contain fulltext We induced prostatic enlargement in castrated dogs using either androgen alone or androgen combined with estrogen. In addition to previously reported hyperplastic changes, marked infiltration with immune effector cells was observed. This mononuclear cell infiltrate was phenotypically characterized using CD3 as pan T-lymphocyte marker, CD79 for B-lymphocytes, MAC378 for macrophages, and antibodies against kappa- and lambda-immunoglobulin (Ig) light chains for plasma cells. The majority of inflammatory cells (>80%) in the mononuclear infiltrates were T-lymphocytes and the numbers correlated with the degree of inflammation. The B-lymphocytes were found particularly in areas with marked follicular formation and diffuse infiltration, whereas there were only a few positive cells (

In the period 1993-1998, digital carcinomas in 64 cats were examined. In all animals primary complaints were painful digit(s). Eight cats had a primary squamous cell carcinoma which involved one digit or two adjacent digits of one leg. Fifty-six cats had metastases of a pulmonary carcinoma in the digits, and in general multiple digits of different legs were involved. In many of these cats metastases also occurred in other organs, including the skin and muscles. No primary sweat gland carcinomas of the digits were seen. Primary squamous cell carcinomas of the digits were characterized by cornification and the absence of PAS-positive cells, PAS-positive secretory material. Immunohistochemically, these neoplasms stained negative with the monoclonal antibody CAM 5.2 directed against Keratin 8 (K 8). The metastases of pulmonary carcinomas to the digits showed one or more of the following histological features: goblet cells, ciliated epithelial cells, PAS-positive cells or lakes, and/or a PAS-positive lining of luminal membranes and no cornification. Immunohistochemically, they showed positive staining for CAM 5.2 (K8). Thoracic radiographs from three cats with a primary squamous cell carcinoma showed no abnormalities, whereas all cases of metastases from a pulmonary carcinoma to the digits available for follow-up showed evidence of a primary pulmonary carcinoma on radiography and/or postmortem examination (25 out of 56). The conclusion of this study was that most carcinomas in the digits of cats were metastases of a primary pulmonary carcinoma (87.5%). Primary squamous cell carcinomas occurred infrequently. The prognosis of metastases of a pulmonary carcinoma in the digits is poor with an average survival time of 4.9 weeks, in contrast to 29.5 weeks in cats with a squamous cell carcinoma. These data stress the importance of taking thoracic radiographs of cats with digital tumours before surgical intervention.

A 15-year-old Dutch Warmblood mare presented with respiratory distress and anorexia. Clinical examination revealed liquothorax and an abdominal mass. At necropsy, an infiltrating tumour was found in the visceral trunk, continuing through the diaphragm into the mediastinum. Histopathology, immunohistochemistry and electronmicroscopy showed empty channels lined by atypical endothelial cells, and neoplastic cells in a disorganized pattern, consistent with the diagnosis of a lymphangiosarcoma.

Progressive lameness and leg pain were the predominant clinical signs in a 17-week-old male border collie presented for examination. On clinical investigation, extrahepatic cholestasis in association with rickets due to inadequate vitamin D resorption was diagnosed. The dog was treated parenterally with vitamin D and a cholecystoduodenostomy was performed. At 25 days postsurgery the lameness had resolved and bone structure was radiographically normal. However, at six weeks postsurgery, the dog's condition deteriorated rapidly and euthanasia was finally performed at eight weeks postsurgery. At postmortem examination, Toxocara canis nematodes were found to have invaded the biliary system via the anastomosis between the gallbladder and duodenum, causing biliary and hepatic toxocariasis. The cause of the primary extrahepatic cholestasis was atresia of the common bile duct at the hepatic end. The liver tissue showed microscopic lesions of chronic extrahepatic cholestasis as well as acute inflammation associated with the nematode invasion. There was no postmortem evidence of bone lesions. Extrahepatic biliary atresia is extremely rare in animals and has not been described before in dogs. In contrast, it represents the most common cause of congenital cholestasis in children, occurring in approximately one per 10,000 to 15,000 live births.

A 10-year-old uncastrated male Dalmatian dog was referred for gait abnormalities consisting of chronic progressive stiffness and rigidity. Other symptoms were polyphagia associated with weight gain, polyuria and polydipsia, excessive panting, and an inspiratory stridor. The owner had noticed progressive thickening of the skin and enlargement of the tongue over the last 3 years. Physical examination revealed thickening of the skin, redundant skin folds, and enlargement of the tongue. The only remarkable abnormalities found on routine laboratory examination were mild anaemia and an increased serum fructosamine concentration. Circulating concentrations of total thyroxine, free thyroxine, and cTSH, and the results of an ACTH stimulation test were all within reference ranges. The basal serum growth hormone (GH) concentration was markedly elevated (23microg/l) and did not decrease during a glucose tolerance test or after somatostatin administration. The serum insulin-like growth factor-1 concentration was also markedly elevated (1254microg/l). Basal serum insulin concentration was high (95mU/l) and insulin concentrations increased considerably after glucose loading, consistent with insulin resistance. Abdominal ultrasonography showed no abnormalities. Survey radiographs of the vertebral column showed severe spondylosis deformans extending from the cervical to the lumbosacral spine. CT scanning of the skull showed an enlarged pituitary gland with normal enhancement pattern. On post-mortem examination, the entire vertebral column appeared as a single and inflexible structure due to the presence of multiple fused osteophytes. The pituitary gland contained an acidophilic adenoma that immunostained positively for GH (and negatively for ACTH and alpha-MSH). In conclusion, this Dalmatian dog with acromegaly and insulin resistance represents the first case of GH hypersecretion proven to be due to a somatotroph adenoma.

A miniature schnauzer with a history of apathy, anorexia and jaundice was presented to the Utrecht University Clinic for Companion Animals. Abnormal laboratory findings included highly increased levels of total bile acids and alkaline phosphatase, and hyponatraemia. Abdominal ultrasonography revealed that the right side of the liver was enlarged and the left side was small, together with a thrombus in the portal vein. Biopsies from the right side of the liver demonstrated subacute to chronic active hepatitis, for which the dog was treated with prednisolone (1 mg/kg/day for four weeks). No improvement was observed and the owner requested euthanasia. At necropsy the left lobes of the liver were found to be small and firm, while the right lobes were large and soft. There were two thrombi in the portal vein. Microscopic examination revealed chronic active hepatitis and cirrhosis.

Recently, linkage of a DNA microsatellite marker to inherited copper toxicosis has been reported in American Bedlington terrier families. Due to the fact that there is little exchange of breeding stock between the USA and Europe, it remains to be investigated whether in Europe the marker is informative and is linked with the disease. We have therefore examined the diagnostic value of the microsatellite marker in the European Bedlington. In 130 dogs at least one year of age (62 from The Netherlands, 35 from Belgium, and 33 from Germany) histo- or cytochemical staining of copper was done in liver biopsies. Based on liver histo- or cytochemistry, 51 dogs were obligate carriers, and 25 dogs had copper toxicosis. The inferred genotypes of these 76 dogs were compared with the marker genotypes. All dogs with the disease were homozygous for the 167 bp marker allele. All obligate carriers were heterozygotes with the 167 bp and a 163-bp alleles. All phenotypically healthy dogs were either homozygous for the 163 bp allele or heterozygous. Thus, the marker was in complete linkage disequilibrium with the putative copper toxicosis gene with the 167 bp allele in phase with the disease allele. The frequencies of the 167 bp and the 163 bp allele, respectively, were 0.33 and 0.67 in Dutch dogs, 0.31 and 0.69 in German dogs, and 0.57 and 0.43 in Belgian dogs. We have confirmed the utility of this marker for diagnosis of inherited copper toxicosis in European Bedlington terriers.

Clinical, macroscopic, and histologic features of 12 lymphangiosarcomas in cats are described. Nine tumors were located in the subcutaneous tissue at the caudoventral abdominal wall (eight cats) or in the neck (one cat). The remaining three cats had lymphangiosarcomas around the cranial mesenteric artery (two cats) or precardial in the mediastinum (one cat). Macroscopically, the tumors were noncircumscribed, white, edematous, and intermixed with fat tissue. Histologic features varied from cleft-forming and cavernous growth to papilliform and solid patterns. Follow-up data were available for seven cats with subcutaneous lymphangiosarcomas. All these cats died or were euthanatized within 6 months after surgery because of poor wound healing, local recurrence, or distant metastases. The cats with abdominal or thoracic masses were either euthanatized at surgery or within 6 months after the first surgery because of recurrent chylothorax, chyloperitoneum, or distant metastases.

This paper reviews 27 cases of polycystic disease of the kidneys and/or liver in cats. The multiple cysts in the kidneys were rounded in all but one case, as described in adult polycystic kidney disease in humans. In 68% of the cats presented with polycystic kidneys, there were also cystic changes of the liver (uni- or multilocular cysts and/or congenital hepatic fibrosis (CHF)). In 1 cat polycystic changes of kidneys and liver were accompanied by cysts in the pancreas. In 5 cases there was severe pancreas fibrosis. Twenty-one of the 27 cats were Persian or Persian-crossbred.

Effects of trypanosome infection and feed quality on the metabolism of trypanotolerant West African Dwarf goats were measured. Goats were allotted to either a diet of lucerne pellets (Crude protein level=172 g/kg DM; n=14) or a diet of chopped grass straw (Crude protein level=68 g/kg DM; n=15). Five animals per feed group served as controls, and the other animals were infected with Trypanosoma vivax parasites. Before and after infection, blood samples were taken weekly, and analyzed for packed cell volume and parasitaemia, and for serum metabolites and hormone concentrations. Six weeks after infection, the goats were killed and post mortem analysis was carried out to study the pathology of disease. Infected animals showed reduced feed intake, increased plasma nonesterified fatty acids concentration, and decreased serum insulin concentration. Liver triacylglycerol concentration was increased in all grass straw fed animals, and some infected goats fed the lucerne feed. Infection drastically reduced serum concentration of thyroxine and triiodothyronine. Infection caused an increased weight of the liver and prescapular lymph nodes in animals from both feed treatments, but lymph nodes were more enlarged in infected animals fed lucerne. Pathological findings were typical for T. vivax infection in goats, irrespective of feed type. Packed cell volume was reduced by infection in both feed groups to values below 20 percentage points. Serum γ-globulin concentration was increased more in infected animals, fed lucerne than those fed grass straw. It was concluded, that by maintaining a feed with a higher protein level, the nutritional status of infected West African Dwarf goats was improved. This was reflected in the serum concentrations of some metabolites and hormones. However, in general, no indications of an interaction between infection and feed type with respect to nutritional status were found. Differences in feed quality did not change the nature and severity of pathological variables, measured at autopsy after 6 weeks of infection.

BACKGROUND: American Cocker Spaniels are predisposed to chronic hepatitis. OBJECTIVE: To describe the clinical and histological features of chronic hepatitis in Japanese American Cocker Spaniels. ANIMALS: Thirteen cases examined from 2003 to 2009. METHODS: Retrospective study. Medical records were searched for American Cocker Spaniels with chronic liver diseases. History, physical examination, clinicopathologic features, hepatic ultrasonographic findings, hepatic histopathology, and immunohistochemistry were evaluated. RESULTS: The median age was 4.6 (1.9-10.7) years. Clinical signs included inappetence (11/13), ascites (11/13), lethargy (9/13), diarrhea (7/13), and melena (2/13). Only 1/13 dogs was jaundiced. Clinicopathological abnormalities were increased liver enzymes (gamma-glutamyl transpeptidase: 9/12, aspartate aminotransferase: 7/10, alanine aminotransferase: 6/13, alkaline phosphatase: 6/13), increased total serum bile acid concentrations (10/12), and hypoalbuminemia (10/13). The liver had an irregular surface in all dogs and acquired portosystemic collaterals were verified in 11/13 dogs by abdominal ultrasound (2), laparoscopy (4), or both (5). Liver histology revealed severe fibrosis and cirrhosis in all cases, subdivided in lobular dissecting hepatitis (7), periportal fibrosis (1), micronodular cirrhosis (3), and macronocular cirrhosis (2). Inflammatory activity was low to mild. Immunohistochemical stains showed ductular proliferation. The median survival time was 913 (range: 63-1981) days. CONCLUSION AND CLINICAL IMPORTANCE: Hepatitis in Japanese American Cocker Spaniels is clinically silent until an advanced stage and is associated with severe hepatic fibrosis leading to cirrhosis, extensive ductular/putative hepatic progenitor cell proliferation, portal hypertension, and acquired portosystemic collateral shunting, but relatively long survival times. Lobular dissecting hepatitis seems more prevalent than in previously reported cases from other countries. Copyright © 2013 by the American College of Veterinary Internal Medicine. KEYWORDS: Breed-related hepatitis, Liver progenitor cells, Portal hypertension

Three cases of carcinoid tumor in horses are described. The tumors originated from the maxillary sinuses and the retrobulbar region and caused exophthalmos. Histologically, they had a characteristic endocrine pattern and were argyrophilic with the Grimelius stain. All tumors contained reactivity for neuron-specific enolase and synaptophysin. Two of three tumors were reactive for both bovine and porcine chromogranin A. These immunohistochemical results confirm the neuroendocrine nature of these tumors. Neuroendocrine cells could not be detected in the nasal mucosa and maxillary sinuses of a normal horse; therefore, the origin of these carcinoid tumors remains obscure.

Portal hypertension caused by primary hypoplasia of the portal vein was diagnosed in 42 dogs. The portal hypertension was manifested by the presence of multiple portosystemic collateral vessels. The main clinical signs were retarded growth or weight loss, apathy, intermittent diarrhoea and vomiting, anorexia, abdominal distension and polydipsia. Major findings at physical examination were ascites in 23 dogs and neurological signs in 16 dogs. The dogs had increased activities of liver enzymes in plasma and increased fasting levels of total bile acids and ammonia; in many of the dogs the packed red cell volume, total serum protein and albumin were low. Gross inspection of the portal vein revealed a patent but underdeveloped extrahepatic vein in 13 of the dogs. Microscopic examination of the liver revealed hypoplasia of the intrahepatic portal veins in all the dogs, and this was associated with minor arteriolar proliferation and absence of fibrosis in 12 of them, with moderate to marked arteriolar proliferation often combined with ductular proliferation in 13, and with marked portal fibrosis (formerly described as hepatoportal fibrosis) with a varying number of arteriolar and bile ductular structures in 17 of the dogs. The disease affected mainly young dogs, and was most likely to have been of congenital origin.

This paper presents a review of the literature on hepatic circulation and circulatory disorders of the liver in the dog and cat, and also includes a number of our own not previously published data. Circulatory disorders of the liver are frequently observed in dogs and cats. These disorders can be divided into congenital portosystemic shunts, disorders associated with outflow disturbances, and disorders associated with portal hypertension. Outflow disturbances result in passive congestion of the liver and in both species are mainly due to cardiac failure. Portal hypertension with resultant portosystemic collateral circulation and ascites mainly results from chronic liver disease, particularly cirrhosis. The main vascular disorder resulting in portal hypertension and ascites in the dog is primary hypoplasia of the portal vein.

The behaviour, growth rate, feed intake, health and slaughter quality of group-housed veal calves fed automatically with milk replacer were compared with those of veal calves kept in individual crates and bucket-fed the same milk replacer. The growth rate and feed intakes of the group-housed calves were lower than those of the calves in individual crates. Their feed conversion rates were similar and there were no significant differences in carcase conformation. The meat of the group-housed calves was paler in colour. The feeding behaviour of the group-housed calves was studied to see whether sick animals could be identified at an early stage but behaviour alone provided an inadequate detection system. Intensive health controls in one of the trials showed that infectious respiratory and digestive diseases may be a greater problem in group-housed veal calves than in veal calves kept in crates.

Eight canine tumors originating from specific glandular structures in the anal region, as well as metastatic tumor tissue of two of these cases (case Nos. 7, 8), were immunohistochemically analyzed using various monoclonal antibodies (MoAbs) directed against human keratin types, vimentin, neurofilament proteins, and α-smooth muscle actin. These tumors also were stained for the broad-spectrum neuroendocrine markers neuron-specific enolase (NSE) and synaptophysin. In histologically normal canine anal structures, α-smooth muscle actin and NSE antibodies stained basally localized (probably myoepithelial) cells in the anal glands and the anal sac glands. NSE staining also was present in a limited number of luminal cells in both anal glands and anal sac glands. Synaptophysin labeling was not observed in any of these glandular structures. Histologically, the tumors were differentiated into well- and moderately differentiated perianal gland tumors ( n = 5) and carcinomas without perianal gland differentiation (n = 3), corresponding to the so-called apocrine carcinomas of the anal region. Immunohistochemically, the perianal gland tumors could be differentiated from the carcinomas by marked differences in staining pattern with the various keratin MoAbs, particularly MoAbs directed against human keratin types 7 and 18. The keratin-staining characteristics of the carcinomas suggest a glandular luminal cell origin. Metastases of the carcinomas showed loss of some keratin-staining characteristics as compared with the primary tumor. Staining for NSE was only observed in solitary cells and small cell clusters in the carcinomas and their metastases, whereas the α-smooth muscle actin antibody did not react with the carcinoma cells. None of the tumors stained for neurofilament proteins or synaptophysin. An unequivocal neuroendocrine nature of the carcinomas could not be substantiated by our immunohistochemical study, although the presence of a population of neuroendocrine cells within these neoplasms seems likely. Because the immunohistochemical features of the carcinomas with respect to various keratin MoAbs and NSE are similar to those of the anal glands and the anal sac glands, both these glands might be considered as site of origin of these carcinomas.

Within a 6-month-period, solitary or multiple tumors were observed in 25 young pigs in their first weeks of life in a swine breeding farm. The herd comprised approximately 100 animals, and affected pigs were observed in several litters. The number of affected littermates varied from one to three. Five animals, all from different litters and with a total of 11 tumors, were studied. Histologically the tumors were classified as undifferentiated sarcomas. Electron microscopic examination of the tumors ( n = 3) revealed myogenic differentiation, characterized by the presence of numerous cytoplasmic filaments with longitudinal densities and cytoplasmic dense bodies. Immunohistochemically, all 11 tumors were labeled by vimentin and desmin antibodies. Two tumors from which frozen material was available were additionally labeled by a titin antibody but did not show immunoreactivity with antibodies directed against myosin and α-sarcomeric actin. The tumors were finally diagnosed as undifferentiated rhabdomyosarcomas. The high incidence of these tumors within a short period of time in multiple young animals in different litters indicates a common causative event. The clinical history suggests a genetic cause.

Nine calves between three and 18 weeks old with serologically confirmed natural bovine respiratory syncytial virus infection were examined clinically, radiographically and by radionuclide lung perfusion imaging. The results were compared with those from seven healthy calves. The diseased calves were euthanased and examined pathologically, virologically and bacteriologically. The clinical signs indicated that the disease was in an acute stage. Radiography of the diseased animals revealed cysts, corresponding morphologically with bullous emphysema, and infiltrations roughly corresponding in distribution with atelectatic and, or, pneumonic areas. Radionuclide lung perfusion imaging revealed no perfusion shifts between the left and right lungs and a normal perfusion pattern in five of the nine diseased calves. The abnormalities in the perfusion patterns of three calves were probably caused by anatomical disorders such as cysts and pleural adhesions, but no cause of the abnormality could be found in one calf. These findings suggest that in calves infected with bovine respiratory syncytial virus, the normal perfusion pattern is maintained until anatomical disorders occur. The pathological examination and radiography revealed that the cranioventral lung fields were particularly poorly ventilated. This finding and the normal perfusion pattern indicate that these parts of the lungs are probably the sites where shuntings and perfusion-ventilation mismatchings occur.

Egberink, ~I.F., Berrocal, A., Bax, H.A.D., van den Ingh, T.S.G.A.M., Walter, J.H. and Horzinek, M.C., 1992. Papillomavirus induced skin lesions in a cat seropositive for feline immunodeficiency virus. Vet. Microbiol., 31:117-125. A cat was presented with skin lesions consisting of slightly raised pigmented plaques, 2-7 mm in diameter with a rough slightly verrucous surface. Histologically these lesions were identified as papillomas. A papillomavirus infection was demonstrated: virus-like particles were present in the nuclei of cells within the lesions, and staining with an anti-bovine papillomavirus (BPV-1) antibody was obtained. An infection with feline immunodeficiency virus was diagnosed in this cat; this condition had probably enhanced the development of papillomas. This is the first report of a papillomavirus infection in a cat in Europe.

Two products that contain CaCl2 and that are intended for oral administration were tested for safety aspects. One product contained CaCl2 as a gel, the other contained CaCl2 in an oil emulsion. Oral administration of the CaCl2-containing products caused minor to severe damage to the mucosa of the forestomach and abomasum. The gel solution especially proved to be highly caustic, while the oil emulsion appeared to be relatively safe.

Summary The canine digestive system and its extramural glands (parotid gland, liver, pancreas) were immunohistochemically studied using a panel of twelve monoclonal antibodies (MoAbs) specific for human keratin proteins and for α-smooth muscle actin. Various epithelial tissues and cells were characterized by different keratin staining patterns. So, the epithelial lining of the upper alimentary tract was characterized by staining with the MoAb 6B10, specific for keratin-type (K) 4, and the absence of staining with the MoAbs directed against K8 and 18 (CAM 5.2 and RGE 53, DE-K18 respectively), whereas the lower alimentary tract epithelium was not labeled by 6B10, but stained by the latter MoAbs. In the salivary glands the luminal and basal cells of the adenomeres as well as the different ductal structures could be immunohistochemically differentiated. The duct epithelium in liver and pancreas showed next to keratin staining characteristics in common with hepatocytes and exocrine pancreatic cells, additional staining by several keratin MoAbs. The keratin staining patterns in the canine tissues showed, in addition to similarities also distinct discrepancies when compared to the staining patterns in corresponding human tissues. Myoepithelial cells in salivary and oesophageal glands could be differentiated from other basally located epithelial cells by their exclusive immunoreactivity for α-smooth muscle actin. Canine pancreatic endocrine cells were not labeled by any of the keratin MoAbs. It is concluded that immunohistochemistry with polypeptide specific MoAbs specific for human keratin-types can be used to differentiate between different types of canine epithelial tissues and epithelial cells in the digestive tract. As a result such reagents may find their application in developmental biology and pathology of this species.

This study describes the occurrence of fibrocartilaginous embolism of the spinal cord (FCE) in eight juvenile Irish Wolfhounds that were presented within a period of 16 months (1996-1997). The dogs, seven males and one female between eight and 13 weeks of age, were presented because of an acute onset of abnormal locomotion. Five dogs were euthanized and FCE was diagnosed by the histomorphological presence of focal myelomalacia and Alcian blue-positive-nucleus-pulposus material in the spinal cord vasculature. Three dogs, which were thought to have FCE because of their clinical symptoms, improved with partial or almost complete return to normal locomotion. Although the observed high incidence may be a coincidence, oral information from breeders and lay reports of similar cases in journals for dog breeders from various countries suggest that FCE is a common disorder in young Irish Wolfhounds.

Summary Cerebellar cortical abiotrophy in two Portuguese Podenco littermates is reported and discussed. The disease is characterized by progressive cerebellar ataxia with an early onset of two to three weeks. Extensive loss, degeneration, and necrosis of Purkinje cells particularly involved the cerebellar hemispheres. An autosomal recessive pattern of inheritance is suspected.

Background: Little is known about etiology, disease progression, treatment outcome, survival time, and factors affecting prognosis in dogs with primary hepatitis (PH). Objectives: To review retrospectively different forms of hepatitis in a referral population, by the World Small Animal Veterinary Association Standardization criteria. Animals: One-hundred and one dogs examined for histologically confirmed PH between 2002 and 2006. Dogs with nonspecific reactive hepatitis were excluded. Methods: Retrospective study. Medical records were reviewed for prevalence, signalment, clinical and clinicopathologic manifestation, outcome, survival time, and prognostic factors for shortened survival. Results: PH occurred in 0.5% of dogs in this referral population. Acute (AH) and chronic hepatitis (CH) were diagnosed in 21 and 67 dogs, respectively. Progression from AH to CH occurred in 5/12 of the repeatedly sampled dogs. CH was idiopathic in 43 (64%) dogs, and was associated with copper accumulation in 24 (36%) dogs. Median survival time was longer in dogs with AH than in dogs with CH (either idiopathic or copper associated), and dogs with lobular dissecting hepatitis had the shortest survival time. Prognostic factors predicting shortened survival were associated with decompensated liver function and cirrhosis at initial examination. Conclusions and Clinical Importance: The majority of PH in dogs is CH. Previous studies appear to have underestimated the etiologic role of copper in both AH and CH. Prognosis is reduced in dogs with hepatic cirrhosis or cirrhosis-related clinical findings. Further research into etiology and treatment effectiveness in all PH forms is needed.

J Vet Intern Med. 2009 Sep-Oct;23(5):957-63. Epub 2009 Jul 14. Dietary management of hepatic copper accumulation in Labrador Retrievers. Hoffmann G, Jones PG, Biourge V, van den Ingh TS, Mesu SJ, Bode P, Rothuizen J. Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, P.O. box 80.154, 3508 TD, The Netherlands. g.hoffmann@uu.nl BACKGROUND: Copper-associated chronic hepatitis (CACH) recently has been recognized in the Labrador Retriever as an inherited disorder with a late onset of clinical signs. No studies have investigated dietary management for the long-term treatment of this disease or for its potential in delaying the onset of clinical signs in subclinical cases. OBJECTIVES: To investigate the effects of a low-copper diet and zinc gluconate on hepatic copper concentrations in Labrador Retrievers with abnormal hepatic copper concentrations. ANIMALS: Twenty-four client-owned Labradors that were related to patients affected with CACH and that had been diagnosed with increased hepatic copper concentrations. METHODS: Hepatic copper concentrations were assessed before and after an average of 8 and 16 months of treatment. During this time, all dogs were fed exclusively a low-copper diet. In addition, dogs were assigned to 1 of 2 groups in a randomized double-blind manner to receive a supplement of zinc gluconate or placebo. RESULTS: Twenty-one dogs completed the study. Hepatic copper concentrations decreased in both groups at recheck 1 (n = 21; group 1, P

The morphology of the proximal and distal intestine of Atlantic salmon (Salmo salar) was studied after prolonged feeding with diets containing full-fat soybean meal (FFSB) or soybean protein concentrate (SBPC) and compared with fish fed a standard herring meal (HM) diet. To avoid possible changes due to decreased food intake, dietary inclusions of FFSB and SBPC were chosen at such levels that weight gain, and protein and lipid digestibility values were similar for all three groups. The proximal intestine showed no differences among the groups, except for an increased number of goblet cells in the fish fed SBPC. In the distal intestine, the SBPC group showed no abnormalities and was identical to the HM group. In the FFSB group, the epithelium had an increased number of goblet cells and a marked decrease or even absence of absorptive vacuoles. The microvilli of the enterocytes were shortened, with increased microvillar vesicle formation. These changes may be due to the presence of antinutritional factors in the FFSB diet. The possible role of the various antinutritional factors in soybeans for the development of the intestinal lesions, and their effect on growth and performance are discussed.

Eight hours fasting in Yorkshire terrier pups resulted in marked variation of blood glucose, showing both hypo- en hyperglycaemia. Prolonged fasting in three Yorkshire terrier pups resulted in hypoglycaemia with concomitant ketosis and steatosis of the liver. The hypoglycaemia was associated with decreasing insulin and increasing glucagon and cortisol levels. This is in contrast to fasting adult dogs, which maintain glucohomeostasis and show only slightly decreased insulin levels, normal glucagon levels and a moderate increase of plasma ketone bodies. The reaction to an eight hour fasting period in the Yorkshire terrier pups is thought to be related to inadequate gluconeogenesis and diminished insulin production and/or release. The different reaction to prolonged fasting, compared to adult dogs and pups of larger breeds, seems related to inadequate gluconeogenesis and results in hypoglycaemia, a ketogenic hormonal setting and steatosis of the liver. Frequent feeding of a high-energy, protein-rich diet to both mother and pups may prevent toy-breed pups from developing hypoglycaemia and may help them to overcome periods with a decreased intake of energy.

To test for possible toxicity of soybean lectin for salmon, the location of soybean agglutinin binding sites in the small intestinal brush border membranes (BBM) was determined quantitatively by an enzyme-linked lectin sorbent assay (ELLSA). The assay revealed substantial binding in both the proximal (Bmax 1764±170 nM per mg BBM protein; Kd 2.16±0.23·10−5) and distal (Bmax 2096±79 nM per mg BBM protein; Kd 1.58±0.11·10−5) small intestine. The higher maximum binding and the lower dissociation constant for the distal small intestine might indicate a greater sensitivity to the toxic effect of soybean lectin in this region. Enzyme activities for alkaline phosphatase (EC 3.1.3.1) and sucrase isomaltase (EC 3.2.1.48) in brush border membrane preparations were very low in both the proximal and distal small intestine. A high enzyme activity was found for aminopeptidase (EC 3.4.11.2). Activities of sucrase isomaltase and aminopeptidase were lower in the distal than in the proximal small intestine.

Summary A horse with neurological signs and severe meningoencephalitis caused by Aujeszky's disease is described. The diagnosis was established by immunohistochemistry, DNA-in situ hybridization and serological tests. Aujeszky's disease virus antigen and Aujeszky's disease viral DNA were detected in neurons of the cerebrum. In the serum of the horse antibodies against Aujeszky's disease virus were detected in a virus neutralization test, in a blocking ELISA which specifically detects antibodies against the glycoprotein I (gI) of the virus, in an indirect double sandwich ELISA and with colloidal gold immunoelectron microscopy which detects antibodies directed against the envelope and nucleocapsid of the virus. Intranasal infection of two ponies with a high dose of Aujeszky's disease virus caused very mild and transient signs. Although the experimental infection induced virus neutralizing antibodies, it failed to induce gI specific antibodies.

Summary Intrabronchial instillation of a Pasteurella haemolytica type A***1 crude cytotoxin preparation in calves resulted in pulmonary gross and microscopic lesions comparable to spontaneous and experimental pasteurellosis. In the acute stage of the lesion electronmicroscopy revealed intravascular accumulation, degeneration and fragmentation of leukocytes in the interalveolar septa. Secondary thrombus formation and increased vascular permeability resulted in alveolar flooding, fibrin deposition, extravasation of erythrocytes and loss of alveolar epithelium. No cytotoxicity was observed for the tracheal (in vitro) and bronchial epithelium (in vivo). The pathogenesis of the vascular lesions and their significance for the development of the typical lesions of pneumonic pasteurellosis is discussed. Zusammenfassung Lungenveranderungen bei Kalbern, hervorgerufen durch ein Zytotoxin aus Pasteurella haemolytica Die intrabronchiale Gabe eines rohen Pasteurella haemolytica A1-Zytotoxins verursachte bei Kalbern in der Lunge grose und mikroskopische Schaden, die mit denen bei naturlich auftretender und experimentell hervorgerufener Pasteurellosis vergleichbar sind. Im akuten Stadium treten intravaskulare Ansammlungen, Degeneration und Zerstorung von Leukozyten in den interalveolaren Septen auf. Sekundare Thrombusbildung und erhohte Gefaswanddurchlassigkeit fuhren zur Flussigkeitsan-sammlung in den Alveolen, Fibrinablagerung, Erythrozytenaustritt und Verlust des Alveolarepithels. Am trachealen Epithel (in vitro) und bronchialen Epithel (in vivo) konnte keine Zytotoxinwirkung beobachtet werden. Auf die Bedeutung der Pathogenese dieser Gefasveranderungen als Ursache fur die typischen Lungenveranderungen bei der Pasteurellose wird eingegangen.

Skin reaction patterns to the intradermal injection of a whole-body flea extract were examined in five physically healthy dogs and in 24 dogs with German Shepherd dog Pyoderma (GSP) at 15 and 30 minutes and at 1, 2, 4, 8, 24, 48 and 72 hours after the injection. In 10 out of 24 GSP dogs a positive skin reaction was observed macroscopically after 15 minutes. Delayed reactions at 24 or 48 hours were not observed. In the control group neither immediate nor delayed reactions were observed. The histopathologic skin changes were basically the same in both groups: an initial polymorphonuclear reaction followed by a mononuclear cell reaction. In the GSP dogs, however, these changes occurred earlier and were more prolonged than in the normal dogs. No flea-antigen-specific IgGd antibodies could be demonstrated by enzyme-linked immunosorbent assay. It is concluded that delayed type hypersensitivity to flea antigen does not play a role in the pathogenesis of GSP. Immediate type hypersensitivity may contribute to the disease in some cases.

A cystic mass in the anterior mediastinum of a 9-year-old female European Shorthair cat was classified as a lymphocytic thymoma based on its histopathological features which were in accordance with those reported in the literature concerning feline thymomas. The application of a polyclonal keratin antiserum and monoclonal keratin antisera RCK 102, RKSE 60 and RGE 53 resulted in staining of foetal feline thymic cells, oesophageal epithelial cells as well as numerous stellate tumour cells and Hassall's corpuscles. As a result, the epithelial origin of the neoplastic cells could be established and the classification of thymoma confirmed. The results indicate the value of keratin antisera in the differentiation of thymoma and non-epithelial tumours in the anterior mediastinum.

Summary Skin reaction patterns to intradermal injections of a Staphylococcus intermedius antigen were examined in physically healthy dogs and in dogs with German Shepherd dog Pyoderma (GSP) at 15 and 30 minutes and at 1, 2, 4, 6, 8, 24, 48 and 72 hours after the injection. In both groups the skin histopathology revealed an aspecific inflammatory response of an early polymorphonuclear reaction, followed by a mononuclear cell reaction at 24 and 48 hours. It is concluded that hyper sensitivity to staphylococcal antigens does not play a role in the pathogenesis of GSP.

From case studies in humans it is known that primary hypothyroidism (PH) may be associated with morphological and functional changes of the pituitary. There is no insight into the time scale of these changes. In this study, seven beagle dogs were followed up for 3 years after the induction of primary hypothyroidism. Three of these dogs were followed up for another 1.5 years while receiving l-thyroxine. Adenohypophyseal function was investigated at 2-month intervals with the combined intravenous injection of CRH, GHRH, GnRH, and TRH, and measurement of the plasma concentrations of ACTH, GH, LH, PRL, and TSH. In addition, after 2 years of hypothyroidism a single TRH-stimulation test and a somatostatin test were performed, with measurements of the same pituitary hormones. Every 6 months the pituitary gland was visualized by computed tomography (CT). Induction of PH led to high plasma TSH concentrations for a few months, where after concentrations gradually declined to values no longer significantly different from pre-PH values. A blunted response to stimulation of TSH release preceded this decline. Basal plasma GH concentrations increased during PH and there was a paradoxical hyperresponsiveness to TRH stimulation. Basal GH concentrations remained elevated and returned only to low values during l-thyroxine treatment. Basal PRL concentrations decreased significantly during PH and normalized after several months of l-thyroxine treatment. The pituitary gland became enlarged in all dogs. Histomorphology and immunohistochemical studies in 4 dogs, after 3 years of PH, revealed thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and decreased numbers of mammotrophs. Several cells stained for both GH and TSH. In conclusion, with time PH led to a loss of the TSH response to low T4 concentrations, hypersecretion of GH, and hyposecretion of PRL. The enlarged pituitaries were characterized by thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and double-staining cells, which are indicative of transdifferentiation.

Further inquiries revealed that for many years the dog had been eating significant quantities of a commercial dry calf feed, with an added content of 13 mg copper/kg DM. The recommended copper content for normal commercial dry food is 7·3 mg/kg DM (AAFCO 2000). A similar history and comparable clinical signs, laboratory findings and clinical course had been seen in an unrelated six year-old female border collie from the same farm in autumn 2003. This dog died as a result of a car accident in August 2004, and was not available for further investigations. Inherited or familial copper-associated chronic hepatitis has been recognised in several dog breeds (van den Ingh and others 2006), but has not been described in border collies. The continuous long-term exposure to the high-copper calf feed must have contributed substantially to the development of hepatitis in these dogs. Although the inclusion of the female dog in this discussion remains speculative without a definitive diagnosis, the absence of a direct familial relationship between the two dogs makes an inherited background unlikely. However, the possibility of an inherited disease of copper metabolism could be evaluated only by examining family members of both dogs.