Search

Dogs provide highly valuable models of human disease due to the similarity in phenotype presentation and the ease of genetic analysis. Seven Saluki puppies were investigated for neurological abnormalities including seizures and altered behavior. Magnetic resonance imaging showed a diffuse, marked reduction in cerebral cortical thickness, and symmetrical T2 hyperintensity in specific brain regions. Cerebral cortical atrophy with vacuolation (status spongiosus) was noted on necropsy. Genome-wide association study of 7 affected and 28 normal Salukis revealed a genome-wide significantly associated region on CFA 35. Whole-genome sequencing of three confirmed cases from three different litters revealed a homozygous missense variant within the aldehyde dehydrogenase 5 family member A1 ( ALDH5A1 ) gene (XM_014110599.2: c.866G>A; XP_013966074.2: p.(Gly288Asp). ALDH5A1 encodes a succinic semialdehyde dehydrogenase (SSADH) enzyme critical in the gamma-aminobutyric acid neurotransmitter (GABA) metabolic pathway. Metabolic screening of affected dogs showed markedly elevated gamma-hydroxybutyric acid in serum, cerebrospinal fluid (CSF) and brain, and elevated succinate semialdehyde in urine, CSF and brain. SSADH activity in the brain of affected dogs was low. Affected Saluki dogs had striking similarities to SSADH deficiency in humans although hydroxybutyric aciduria was absent in affected dogs. ALDH5A1 -related SSADH deficiency in Salukis provides a unique translational large animal model for the development of novel therapeutic strategies.

Background: Grading schemes for the assessment of hepatic fibrosis and necroinflammatory activity in humans previously have been applied to dogs with chronic hepatitis. Interobserver agreement is a desirable characteristic for any histological scoring scheme., Hypothesis/objectives: To assess interobserver agreement associated with pathologists using a previously published histological scoring scheme to assess hepatic fibrosis and necroinflammatory activity in dogs and to compare fibrosis scores assigned to serial sections stained with hematoxylin & eosin (H&E) and picrosirius red., Animals: Histological sections of liver from 50 dogs with variable degrees of hepatic fibrosis and necroinflammatory activity were selected from institutional tissue archives., Methods: Six board-certified veterinary anatomic pathologists assigned fibrosis and necroinflammatory activity scores to the histological sections. The multiuser kappa statistic was calculated to assess interobserver agreement. Fibrosis stage assigned to serial sections stained with picrosirius red and H&E was compared using the Wilcoxon signed-rank test., Results: Multiuser kappa statistics for assessment of fibrosis and necroinflammatory activity from H&E-stained sections were 0.35 and 0.16, respectively. There was no difference in median fibrosis scores assigned to serial section stained with H&E and picrosirius red (P = .248)., Conclusions and Clinical Importance: There was fair interobserver agreement when pathologists assessed fibrosis and poor agreement when they assessed necroinflammatory activity. This suboptimal agreement must be taken into account by clinicians making decisions based on histology reports of the liver and in the design of studies evaluating these findings. To decrease this variability, ideally >1 pathologist should evaluate each section., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

The pathophysiology of canine diabetes remains poorly understood, in part due to enigmatic clinical features and the lack of detailed histopathology studies. Canine diabetes, similar to human type 1 diabetes, is frequently associated with diabetic ketoacidosis at onset or after insulin omission. However, notable differences exist. Whereas human type 1 diabetes often occurs in children, canine diabetes is typically described in middle age to elderly dogs. Many competing theories have been proposed regarding the underlying cause of canine diabetes, from pancreatic atrophy to chronic pancreatitis to autoimmune mediated β-cell destruction. It remains unclear to what extent β-cell loss contributes to canine diabetes, as precise quantifications of islet morphometry have not been performed. We used high-throughput microscopy and automated image processing to characterize islet histology in a large collection of pancreata of diabetic dogs. Diabetic pancreata displayed a profound reduction in β-cells and islet endocrine cells. Unlike humans, canine non-diabetic islets are largely comprised of β-cells. Very few β-cells remained in islets of diabetic dogs, even in pancreata from new onset cases. Similarly, total islet endocrine cell number was sharply reduced in diabetic dogs. No compensatory proliferation or lymphocyte infiltration was detected. The majority of pancreata had no evidence of pancreatitis. Thus, canine diabetes is associated with extreme β-cell deficiency in both new and longstanding disease. The β-cell predominant composition of canine islets and the near-total absence of β-cells in new onset elderly diabetic dogs strongly implies that similar to human type 1 diabetes, β-cell loss underlies the pathophysiology of canine diabetes.

A novel leukoencephalomyelopathy was identified in 73 mature male and female large captive felids between 1994 and 2005. While the majority of identified cases occurred in cheetahs (Acinonyx jubatus), the disease was also found in members of 2 other subfamilies of Felidae: 1 generic tiger (Panthera tigris) and 2 Florida panthers (Puma concolor coryi). The median age at time of death was 12 years, and all but 1 cheetah were housed in the United States. Characteristic clinical history included progressive loss of vision leading to blindness, disorientation, and/or difficulty eating. Neurologic deficits progressed at a variable rate over days to years. Mild to severe bilateral degenerative lesions were present in the cerebral white matter and variably and to a lesser degree in the white matter of the brain stem and spinal cord. Astrocytosis and swelling of myelin sheaths progressed to total white matter degeneration and cavitation. Large, bizarre reactive astrocytes are a consistent histopathologic feature of this condition. The cause of the severe white matter degeneration in these captive felids remains unknown; the lesions were not typical of any known neurotoxicoses, direct effects of or reactions to infectious diseases, or nutritional deficiencies. Leukoencephalomyelopathy was identified in 70 cheetahs, 1 tiger, and 2 panthers over an 11-year period, and to our knowledge, cases have ceased without planned intervention. Given what is known about the epidemiology of the disease and morphology of the lesions, an environmental or husbandry-associated source of neurotoxicity is suspected., (© The Author(s) 2013.)

Forty-four cats diagnosed with moderate to severe cholangitis at necropsy are described. The population comprised 0.86% of all feline necropsies performed during the 22-year study period. Liver specimens were classified as acute neutrophilic cholangitis (ANC), chronic neutrophilic cholangitis (CNC), lymphocytic cholangitis (LC) or chronic cholangitis associated with liver fluke infestation (CC) based on the World Small Animal Veterinary Association (WSAVA) classification scheme. ANC (seven) and CNC (33) comprised the majority of cases. In contrast to previous descriptions, overlap was seen in clinical findings between ANC and CNC subtypes. Results suggest that liver enzyme activity may not predict degree of inflammation. Severity of inflammation varied between liver sections in individual cats, underscoring the need to obtain biopsy samples from multiple sites. Inflammatory bowel disease (50%), pancreatitis (60%), or both (32%) commonly accompanied cholagitis. We conclude that cholangitis is not a common cause of feline mortality. Most cats that succumb to cholangitis have ANC or CNC, and concurrent disease contributes to death in many., (Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Protection against Mesocestoides corti, a cestode that invades vital organs, is dependent on the production of IL-4, as IL-4(-/-) mice were found to have higher parasite burdens when compared with wild-type mice. The goal of this study was to investigate the role of IL-4 in immunity to M. corti, focusing on the immunological profile and on potential mediators of pathology. IL-4(-/-) mice infected with M. corti showed 100% mortality by 32 days, whereas wild-type mice survived for approximately 1 year. Parasite burdens were significantly increased in the liver, peritoneal, and thoracic cavities of IL-4(-/-) mice, associated with impaired recruitment of inflammatory cells and a reduction in monocytes and macrophages. IL-5 production by splenocytes and expression in liver tissue was decreased in infected IL-4(-/-) mice compared with wild-type mice. In contrast, IL-4(-/-) mice produced increased amounts of IFNgamma and TNFalpha. Alternatively activated macrophages were a major feature of liver granulomas in wild-type mice evidenced by Arginase I expression, while livers from infected IL-4(-/-) mice showed impaired alternative macrophage activation without increased classical macrophage activation. Thus, lethality during M. corti infection of IL-4(-/-) mice is associated with decreased Th2 cytokines, increased Th1 cytokines and impairment of alternatively activated macrophages.

Objective: To determine the prevalence of nonneoplastic middle ear disease among cats undergoing necropsy and the prevalence of clinical abnormalities in cats in which nonneoplastic middle ear disease was identified., Design: Retrospective case series., Animals: 59 cats that underwent necropsy between January 1991 and August 2007., Procedures: Medical records were searched to identify cats in which nonneoplastic middle ear disease was identified at necropsy. For cats included in the study, data that were recorded included signalment, initial complaint, whether the cat had any clinical signs of middle or external ear disease, whether the cat had upper respiratory tract disease, necropsy diagnosis, gross appearance of the bullae, and reason for euthanasia. Signs of middle ear disease that were considered included unilateral peripheral vestibular disease without motor deficits, Horner syndrome, and facial nerve paralysis., Results: Of the 3,442 cats that underwent necropsy during the study period, 59 (1.7%) had nonneoplastic middle ear disease. Six of the 59 (10%) cats, including 1 cat that was affected bilaterally, had clinical signs of middle ear disease. Of these, 5 had signs of unilateral peripheral vestibular disease, and 1 had Horner syndrome., Conclusions and Clinical Relevance: Results suggested that most cats with nonneoplastic middle ear disease did not have associated clinical signs. Findings may be of clinical relevance for cats in which middle ear disease is identified as an incidental finding during computed tomography or magnetic resonance imaging for unrelated diseases.

Background: Polymicrogyria is a disorder of cerebrocortical migration resulting in increased numbers of small, disorganized gyri. This disorder occurs in Standard Poodles and in cattle., Objectives: To describe the clinical, electroencephalographic, imaging, and histopathologic features in poodles with polymicrogyria., Animals: Five Standard Poodles with histologically confirmed polymicrogyria., Methods: Retrospective case series. Cases were obtained by personal communication with 1 of 2 authors (TJVW, DPO)., Results: All dogs had cortical blindness and other neurologic abnormalities including gait and behavioral changes. Magnetic resonance imaging of 3 dogs showed multiple disorganized gyri, which were especially apparent on T2-weighted dorsal plane images. Electroencephalogram (EEG) of 1 dog revealed epileptiform discharges, including both spike and spike and wave discharges with voltage maximum potentials over the parietal/occipital region. The EEG supported that the repetitive behavior displayed by the dog was a complex partial motor seizure. One dog had concurrent hydrocephalus. All dogs had occipital lobe involvement and 2 dogs had involvement of other lobes., Clinical Importance: The cases presented here demonstrate a larger age range (7 weeks to 5 years) and a decreased frequency of associated hydrocephalus when compared with the previous report.

Gerbode type defects are rare left ventricular outflow tract-right atrial communications in people that may be congenital or acquired; they have been reported only once previously in dogs. Acquired forms in humans have been reported secondary to bacterial endocarditis, trauma, and valve replacement surgery, among other causes. We report a case of left ventricular outflow tract to right atrium and right ventricle communications (Gerbode type defect) in association with aortic and tricuspid valve bacterial endocarditis in a geriatric dog. The dog also developed third degree atrioventricular block and had underlying subaortic stenosis. The authors hypothesize that the Gerbode type defect in this case was acquired secondary to invasion and destruction of the membranous interventricular septum due to bacterial endocarditis.

Objective: To document clinicopathologic, histologic, and toxicologic findings in cats inadvertently exposed to pet food contaminated with melamine and cyanuric acid., Design: Case series., Animals: 70 cats from a single cattery inadvertently fed contaminated food that was the subject of a March 2007 recall., Procedures: Clinical signs, clinicopathologic and histopathologic findings, and results of toxicologic analyses were recorded., Results: Clinical signs were identified in 43 cats and included inappetence, vomiting, polyuria, polydipsia, and lethargy. Azotemia was documented in 38 of the 68 cats for which serum biochemical analyses were performed 7 to 11 days after consumption of the contaminated food. One cat died, and 13 were euthanized. Histologic examination of kidney specimens from 13 cats revealed intratubular crystalluria, tubular necrosis with regeneration, and subcapsular perivascular inflammation characterized by perivascular fibroplasia or fibrosis and inflammation with intravascular fibrin thrombi. Toxicologic analyses revealed melamine and cyanuric acid in samples of cat food, vomitus, urine, and kidneys., Conclusions and Clinical Relevance: In cats unintentionally fed pet food contaminated with melamine and cyanuric acid, the most consistent clinical and pathologic abnormalities were associated with the urinary tract, specifically tubular necrosis and crystalluria.

Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, often leads to heart failure and sudden death. While a substantial proportion of DCMs are inherited, mutations responsible for the majority of DCMs remain unidentified. A genome-wide linkage study was performed to identify the locus responsible for an autosomal recessive inherited form of juvenile DCM (JDCM) in Portuguese water dogs using 16 families segregating the disease. Results link the JDCM locus to canine chromosome 8 with two-point and multipoint lod scores of 10.8 and 14, respectively. The locus maps to a 3.9-Mb region, with complete syntenic homology to human chromosome 14, that contains no genes or loci known to be involved in the development of any type of cardiomyopathy. This discovery of a DCM locus with a previously unknown etiology will provide a new gene to examine in human DCM patients and a model for testing therapeutic approaches for heart failure.

Objective: To determine the prevalence of lymphosarcoma and other tumors affecting the spinal cord of cats and to relate specific types of tumors with signalment, history, and clinical findings., Design: Retrospective case series., Animals: 85 cats with tumors affecting the spinal cord., Procedures: Medical records of cats with histologically confirmed primary or metastatic tumors of the spinal cord or tumors causing spinal cord disease by local extension from adjacent tissues examined between 1980 and 2005 were reviewed. Data on signalment; clinical history; results of neurologic examination, diagnostic imaging, and clinical pathologic evaluation; and location of tumor within the spinal cord were obtained from medical records and analyzed by use of logistic regression models., Results: Lymphosarcoma was the most common tumor and affected the spinal cord in 33 (38.8%) cats, followed by osteosarcoma in 14 (16.5%) cats. Cats with lymphosarcoma were typically younger at initial examination, had a shorter duration of clinical signs, and had lesions in more regions of the CNS than did cats with other types of tumors. In 22 of 26 (84.6%) cats with lymphosarcoma, the tumor was also found in extraneural sites., Conclusions and Clinical Relevance: Data for spinal cord tumors in this population of cats were analyzed by logistic regression analysis, which effectively distinguished cats with lymphosarcoma from cats with other types of tumors. Additional clinical information reported here will help to increase the index of suspicion or definitive antemortem diagnosis of spinal cord tumors of cats.

Background: This study investigates the frequency, location, and clinical findings associated with 177 secondary brain tumors in dogs., Hypothesis: Secondary intracranial neoplasia is more common than primary intracranial neoplasia in dogs during the time period studied, and hemangiosarcoma (HSA) is the most common secondary intracranial tumor., Animals: One hundred and seventy-seven client-owned dogs presented to the Matthew J. Ryan Veterinary Hospital between 1986 and 2003., Methods: Medical records were searched for a diagnosis of intracranial neoplasia in dogs who underwent complete postmortem examination. Of these dogs, those with a diagnosis of primary intracranial neoplasia were excluded., Results: Of the 177 secondary brain tumors, 51 (29%) were HSAs, 44 (25%) were pituitary tumors, 21 (12%) were lymphosarcomas, and 21 (12%) were metastatic carcinomas. The average age at diagnosis was 9.6 +/- 3.0 years. Most tumors were located in the cerebrum, and a mentation change was the most common presenting clinical sign. On postmortem examination, the same tumor that was in the brain was also present in the lung in 84 cases (47%), in the kidney in 62 cases (35%), and in the heart in 55 cases (31%)., Conclusions and Clinical Importance: Secondary intracranial neoplasia in dogs was more common than primary intracranial neoplasia during the time period studied. Many of these dogs had related disease in other body systems that was apparent on diagnostic tests such as thoracic radiography.

The purpose of this retrospective study was to compare Rottweilers diagnosed with osteosarcoma (OSA) with other breeds to determine whether Rottweilers experienced a more aggressive form of the disease. Two hundred and fifty-eight dogs were evaluated (102 clinical and 156 necropsy cases). In the necropsy population, Rottweilers had a younger mean age at death (7.3 versus 9 years, P = 0.006). There were no significant differences between Rottweilers and other breeds in age at diagnosis, median disease-free interval or survival time. However, Rottweilers were more likely to have metastasis to the brain (7 versus 0%, P = 0.03). These results suggest that OSA in Rottweilers may have a different biological behaviour, but this study did not confirm that these differences were associated with a worse outcome.

Deficiency of glycogen branching enzyme (GBE) activity causes glycogen storage disease type IV (GSD IV), an autosomal recessive error of metabolism. Abnormal glycogen accumulates in myocytes, hepatocytes, and neurons, causing variably progressive, benign to lethal organ dysfunctions. A naturally occurring orthologue of human GSD IV was described previously in Norwegian forest cats (NFC). Here, we report that while most affected kittens die at or soon after birth, presumably due to hypoglycemia, survivors of the perinatal period appear clinically normal until onset of progressive neuromuscular degeneration at 5 months of age. Molecular investigation of affected cats revealed abnormally spliced GBE1 mRNA products and lack of GBE cross-reactive material in liver and muscle. Affected cats are homozygous for a complex rearrangement of genomic DNA in GBE1, constituted by a 334 bp insertion at the site of a 6.2 kb deletion that extends from intron 11 to intron 12 (g. IVS11+1552_IVS12-1339 del6.2kb ins334 bp), removing exon 12. An allele-specific, PCR-based test demonstrates that the rearrangement segregates with the disease in the GSD IV kindred and is not found in unrelated normal cats. Screening of 402 privately owned NFC revealed 58 carriers and 4 affected cats. The molecular characterization of feline GSD IV will enhance further studies of GSD IV pathophysiology and development of novel therapies in this unique animal model.

Five cats had clinical signs, radiographic findings, and cerebrospinal fluid analyses consistent with fibrocartilaginous embolic myelopathy. All cats had an acute onset of nonpainful, asymmetrical spinal cord signs (paresis or paralysis of one or more limbs). Magnetic resonance imaging was performed in three cats. On T2-weighted images, an intramedullary lesion was revealed that was hyperintense to normal spinal cord gray matter. On T1-weighted images, the lesion was isointense. Three of the cats were euthanized, and postmortem examination confirmed myelomalacia with intralesional fibrocartilaginous emboli. Two cats survived and were clinically improved within 3 weeks.

This study investigates the clinical and pathologic findings associated with 173 primary brain tumors in our hospital population of dogs that presented between the years 1986 and 2002. Of the 173 primary brain tumors, 78 (45%) were meningiomas, 29 (17%) were astrocytomas, 25 (14%) were oligodendrogliomas, 12 (7%) were choroid plexus tumors, and 7 (4%) were primary central nervous system lymphomas. Smaller numbers of glioblastomas (n = 5), primitive neuroectodermal tumors (n = 5), histiocytic sarcomas (n = 5), vascular hamartomas (n = 4), and unclassified gliomas (n = 3) were identified. One dog had both a meningioma and an astrocytoma. Most tumors were located within the telencephalon, and seizures were the most common clinical presenting complaint. Of 168 tumors for which a location in the brain was recorded at postmortem examination, 79 were found to involve more than 1 brain division. Other neoplasms unrelated to the primary brain tumor were identified on postmortem examination in 39 dogs (23%). Intrathoracic and intraabdominal neoplasms were present at necropsy in 13 and 24 cases, respectively. Based on the results of this study, thoracic radiographs and abdominal ultrasonography may be indicated to look for extracranial neoplasia prior to advanced imaging of the brain or intracranial surgery.

A retrospective review of records of 205 cats with histologically confirmed disease of the spinal cord was performed to identify the prevalence of disease in this nonrandomly selected population of cats. Clinical records were reviewed, and age, duration of neurologic illness, and clinical and histopathologic findings in cats with spinal cord disease were abstracted. Disease processes were classified into 7 categories and 23 groups. The most common diseases affecting the spinal cord of cats were feline infectious peritonitis (FIP), lymphosarcoma (LSA), and neoplasia of the vertebral column secondarily affecting the spinal cord. Information on age, onset and duration of clinical signs, and lesion localization at the postmortem examination in cats belonging to the 7 categories of disease were analyzed to create a practical list of differential diagnoses. Cats were also subcategorized into 3 groups based on their age at death. FIP was the most common disease of cats younger than 2 years of age. LSA and vertebral column neoplasia were the most common diseases affecting cats between 2 and 8 years of age. Vertebral column neoplasia was the most common disease affecting cats older than 8 years of age. Results of this histopathologic study showed that FIP and LSA were the most common disease processes affecting the spinal cord of cats. However, at least 21 other groups of diseases and their relative prevalence were identified.

The purpose of this retrospective study was to determine the magnetic resonance imaging (MRI) characteristics of feline brain tumors and to determine whether these characteristics can be used to accurately predict the histologic diagnosis. MRI scans of 46 cats with histologically confirmed brain tumors were reviewed, including 33 meningiomas, 6 lymphomas, 4 gliomas, 2 olfactory neuroblastomas, and 1 pituitary tumor. MRI features including axial origin, shape, location, signal intensity, contrast enhancement, peritumoral edema, and mass effect were reviewed and characterized for each tumor type. Tumor shape, axial origin, contrast enhancement, and degree of peritumoral edema aided in the identification of tumor type. Meningiomas were always extra-axial and were most often ovoid with marked contrast enhancement and mild peritumoral edema. Gliomas were always intra-axial with ring enhancement and generally caused more peritumoral edema than other tumors. The brain tumor was detected on MRI in 45 (98%) cats. Two blinded independent reviewers correctly identified 82% of all of the tumor types on the basis of MRI appearance alone. Thus, MRI is an excellent diagnostic tool for the detection of brain tumors in cats, and it provides important information to aid in the diagnosis of tumor type.

The purpose of this study was to determine the frequency of different tumor types within a large cohort of cats with intracranial neoplasia and to attempt to correlate signalment, tumor size and location, and survival time for each tumor. Medical records of 160 cats with confirmed intracranial neoplasia evaluated between 1985 and 2001 were reviewed. Parameters evaluated included age, sex, breed, FeLV/FIV status, clinical signs, duration of signs, number of tumors, tumor location(s), imaging results, treatment, survival times, and histopathologic diagnosis. Most of the cats were older (11.3 +/- 3.8 years). Primary tumors accounted for 70.6% of cases. Metastasis and direct extension of secondary tumors accounted for only 5.6 and 3.8% of cases, respectively. Twelve cats (7.5%) had 2 or more discrete tumors of the same type, whereas 16 cats (10.0%) had 2 different types of intracranial tumors. The most common tumor types were meningioma (n = 93, 58.1%), lymphoma (n = 23, 14.4%), pituitary tumors (n = 14, 8.8%), and gliomas (n = 12, 7.5%). The most common neurological signs were altered consciousness (n = 42, 26.2%), circling (n = 36, 22.5%), and seizures (n = 36, 22.5%). Cats without specific neurological signs were common (n = 34, 21.2%). The tumor was considered an incidental finding in 30 (18.8%) cats. In addition to expected relationships (eg, meninges and meningioma, pituitary and pituitary tumors), we found that lesion location was predictive of tumor type with diffuse cerebral or brainstem involvement predictive of lymphoma and third ventricle involvement predictive of meningioma.

Objective: To characterize clinical, clinicopathologic, radiographic, and ultrasonographic findings in cats with histologically confirmed acute necrotizing pancreatitis (ANP) or chronic nonsuppurative pancreatitis (CP) and identify features that may be useful in the antemortem differentiation of these disorders., Design: Retrospective study., Animals: 63 cats with histologically confirmed ANP (n = 30) or CP (33)., Procedure: Medical records were reviewed for signalment, clinical signs, concurrent diseases, clinicopathologic findings, and results of radiography and ultrasonography., Results: Cats in both groups had similar nonspecific clinical signs, physical examination findings, and radiographic and ultrasonographic abnormalities. Abdominal ultrasonographic abnormalities, including hypoechoic pancreas, hyperechoic mesentery, and abdominal effusion, were found in cats in both groups and, therefore, were not specific for ANP. Cats with CP were significantly more likely to have concurrent diseases than were cats with ANP (100 and 83%, respectively). Clinicopathologic abnormalities were similar between groups; however, serum alanine aminotransferase and alkaline phosphatase activities were significantly higher in cats with CP., Conclusions and Clinical Relevance: Results suggest that ANP and CP in cats cannot be distinguished from each other solely on the basis of history, physical examination findings, results of clinicopathologic testing, radiographic abnormalities, or ultrasonographic abnormalities.

The objective of this study was to determine whether dogs with atherosclerosis are more likely to have concurrent diabetes mellitus, hypothyroidism, or hyperadrenocorticism than dogs that do not have atherosclerosis. A retrospective mortality prevalence case-control study was performed. The study group included 30 dogs with histopathological evidence of atherosclerosis. The control group included 142 dogs with results of a complete postmortem examination, a final postmortem examination diagnosis of neoplasia, and no histopathological evidence of atherosclerosis. Control dogs were frequency matched for age and year in which the postmortem examination was performed. Proportionate changes in the prevalence of diabetes mellitus, hypothyroidism, and hyperadrenocorticism were calculated by exact prevalence odds ratios (POR), 95% confidence intervals (95% CI), and P values. Multiple logistic regression analysis was used to examine the combined effects of prevalence determinants while controlling for age and year of postmortem examination. Dogs with atherosclerosis were over 53 times more likely to have concurrent diabetes mellitus than dogs without atherosclerosis (POR = 53.6; 95% CI, 4.6-627.5; P = .002) and over 51 times more likely to have concurrent hypothyroidism than dogs without atherosclerosis (POR = 51.1; 95% CI, 14.5-180.1; P < .001). Dogs with atherosclerosis were not found to be more likely to have concurrent hyperadrenocorticism than dogs that did not have atherosclerosis (POR = 1.8; 95% CI, 0.2-17.6; P = .59). Diabetes mellitus and hypothyroidism, but not hyperadrenocorticism, are more prevalent in dogs with atherosclerosis compared to dogs without atherosclerosis on postmortem examination.

A 5-year-old, castrated male mixed-breed dog was presented for paraparesis, ataxia, hyperesthesia, and thrombocytopenia of 5 months' duration and recurrent seizures during the preceding 2 weeks. Multifocal neurological, ophthalmological, pulmonary, and cardiac diseases were identified. Magnetic resonance imaging and cerebrospinal fluid analysis supported a tentative diagnosis of neoplastic or inflammatory disease. A computed tomography-guided biopsy provided both cytopathological and histopathological evidence of intravascular lymphoma. The disease progressed despite chemotherapy with prednisone, L-asparginase, and vincristine. Postmortem histopathological examinations suggested intravascular lymphoma in the central and peripheral nervous systems as well as in multiple other organ systems. This is the first description of an antemortem diagnosis and treatment of intravascular lymphoma involving the central nervous system of a dog.

Intravascular lymphoma (IVL) is a rare angiotropic large-cell lymphoma in which neoplastic lymphocytes proliferate within the lumina of blood vessels in the absence of a primary extravascular mass or leukaemia. A retrospective review of veterinary medical records identified 17 cases of canine IVL. Spinal cord ataxia (seven dogs), posterior paralysis (one dog), seizures (four dogs) and vestibular disease (three dogs) dominated the clinical presentation. Haemorrhage, ischaemia, and occasional foci of vascular proliferation were found in tissue sections from affected dogs. Vessels, predominantly veins, throughout the body were frequently filled with neoplastic lymphocytes. Splenic involvement occurred in only one of 10 cases examined and bone marrow involvement was absent in four cases examined. Formalin-fixed paraffin wax-embedded tissues from 15 cases were examined immunohistochemically with streptavidin-biotin-horseradish peroxidase and a catalysed signal amplification system. The neoplastic cells were classified in eight cases as T cells (CD3+/IgG-/CD79a-), in one case as B cells (CD3-/CD79a.dim/IgG+), and in the remaining six cases as non-T, non-B (CD3-/IgG-/CD79a-). The clinical and pathological features of canine IVL closely resembled those of the human disease. In striking contrast to human cases, which are most often B-cell lymphomas, the immunophenotypes of the canine IVLs in this series were heterogeneous. The canine IVLs were derived primarily from T cells and non-T, non-B lymphocytes, B cells being found in only a single instance., (Copyright Elsevier Science Ltd. All rights reserved.)

Objective: To characterize concurrent disorders in dogs with diabetes mellitus (DM)., Design: Retrospective study., Animals: 221 dogs with DM., Procedure: Medical records were reviewed, and clinical signs, physical examination findings, and results of clinicopathologic testing, urinalysis, aerobic bacterial culture of urine samples, coagulation testing, endocrine testing, histologic evaluation, diagnostic imaging, and necropsy were recorded., Results: For most dogs, CBC results were normal. Common serum biochemical abnormalities included hypochloremia (127 dogs, 60%) and high alanine aminotransferase (163, 78%), aspartate aminotransferase (78, 71%), and alkaline phosphatase (188, 90%) activities. Venous pH and serum ionized calcium concentration were measured in 121 and 87 dogs, respectively, and were low in 56 (46%) and 41 (47%) dogs. Lipemia was observed in 92 (42%) dogs. Urine samples from 159 (72%) dogs were submitted for aerobic bacterial culture, and 34 (21%) yielded bacterial growth. Escherichia coli was the most commonly isolated organism. Thirty-six (16%) dogs had dermatitis or otitis. Hyperadrenocorticism was diagnosed in 51 (23%) dogs on the basis of clinical signs and results of a low-dose dexamethasone suppression test (41 dogs), an adrenocorticotropic hormone stimulation test (5), both tests (4), or histologic evaluation of necropsy specimens (1). Acute pancreatitis was diagnosed in 28 (13%) dogs. Eleven (5%) dogs had tumors for which a histologic diagnosis was obtained. Eight (4%) dogs were hypothyroid., Conclusions and Clinical Relevance: Results suggest that dogs with diabetes mellitus may have many concurrent disorders. The most commonly identified concurrent disorders included hyperadrenocorticism, urinary tract infection, dermatitis, otitis, acute pancreatitis, neoplasia, and hypothyroidism.

Objective: To document the clinical, clinicopathologic, and pathologic findings in cats with severe sepsis, identify abnormalities unique to this species, and identify criteria that could be used antemortem to diagnose the systemic inflammatory response syndrome in cats., Design: Retrospective study., Animals: 29 cats confirmed to have severe sepsis at necropsy., Procedure: Pertinent history, physical examination findings, and results of hematologic and biochemical testing were extracted from medical records., Results: Clinical diagnoses included pyothorax, septic peritonitis, bacteremia secondary to gastrointestinal tract disease, pneumonia, endocarditis, pyelonephritis, osteomyelitis, pyometra, and bite wounds. Physical examination findings included lethargy, pale mucous membranes, poor pulse quality, tachypnea, hypo- or hyperthermia, signs of diffuse pain on abdominal palpation, bradycardia, and icterus. Clinicopathologic abnormalities included anemia, thrombocytopenia, band neutrophilia, hypoalbuminemia, low serum alkaline phosphatase activity, and hyperbilirubinemia. Necropsy findings included multi-organ necrosis or inflammation with intralesional bacteria., Conclusions and Clinical Relevance: Results suggest that severe sepsis in cats is characterized by lethargy, pale mucous membranes, signs of diffuse abdominal pain, tachypnea, bradycardia, weak pulses, anemia, hypoalbuminemia, hypothermia, and icterus. Recognition of this combination of clinical findings should facilitate the diagnosis of severe sepsis in cats.

Objective: To identify risk factors associated with fatal acute pancreatitis in dogs., Design: Case-control study., Animals: 70 case dogs with clinical evidence and histopathologic confirmation of fatal acute pancreatitis and 104 control dogs that had trauma, underwent necropsy, and did not have histologic evidence of acute pancreatitis., Procedure: Information on signalment, weight, body condition, medical history, concurrent disease, and results of histopathologic examination was obtained by reviewing medical records. Logistic regression analysis included calculation of univariate and multivariate (adjusted) odds ratios and 95% confidence intervals. RESULTS AND CLINICAL IMPLICATIONS: Dogs with fatal acute pancreatitis were largely middle- to older-aged dogs. Risk of developing fatal acute pancreatitis was increased by overweight body condition, diabetes mellitus, hyperadrenocorticism, hypothyroidism, prior gastrointestinal tract disease, and epilepsy. Additionally, Yorkshire Terriers were at increased risk, and Labrador Retrievers and Miniature Poodles were at decreased risk, of developing fatal acute pancreatitis. Males and neutered females appeared to have an increased risk of developing fatal acute pancreatitis, compared with sexually intact females. Thrombus formation was more likely in dogs that developed fatal acute pancreatitis than in control dogs.

Objective: To determine the incidence of acute and subacute myocardial infarction on postmortem examination, identify associated diseases, and evaluate clinical or diagnostic indicators of myocardial infarction in dogs and cats., Design: Retrospective study., Animals: 32 dogs and 5 cats., Procedure: Records from the necropsy service from December 1985 through August 1994 were searched for dogs and cats in which acute or subacute myocardial infarction was diagnosed on postmortem examination. Clinical records were reviewed for signalment, initial owner complaint, medical history, results of physical examination, electrocardiography, radiography, echocardiography, CBC, serum chemistry analysis, urinalysis, and coagulation profile as well as clinical course, outcome, necropsy findings, and results of histologic evaluation., Results: Initial owner complaints and physical examination findings were consistent with associated diseases. Electrocardiographic abnormalities in dogs included ventricular tachycardia (16%), atrial fibrillation (9%), and premature ventricular contractions (6.5%). Premature ventricular contractions were noticed in 2 cats. Echocardiography revealed dilated, poorly contractile hearts (n = 3) and thickened mitral valves (2) in dogs, and ventricular hypertrophy (3) in cats. Ninety-seven percent of dogs had infarction of the left ventricle as well as other other portions of the heart. Infarctions in cats were found in all parts of the myocardium including the right ventricle (n = 3), left ventricle (3), and interventricular septum (1)., Clinical Implications: Myocardial infarction is rare in dogs and cats. It is associated with a number of common diseases and may contribute to morbidity and mortality in those dogs and cats that are critically ill.

Objective: To determine clinical, clinicopathologic, radiographic, ultrasonographic, and coagulation abnormalities in dogs in which acute pancreatitis was fatal., Design: Retrospective study., Animals: 70 dogs., Procedure: History, clinical signs, and physical examination findings at the time of initial evaluation at the veterinary teaching hospital; results of pretreatment laboratory tests, abdominal radiography, and ultrasonography; and histologic abnormalities were obtained from medical records., Results: Clinical signs included anorexia, vomiting, Weakness, diarrhea, polyuria and polydipsia, neurologic abnormalities, melena, weight loss, hematemesis, and passage of frank blood in feces. At the time of initial examination at the veterinary teaching hospital, 68 (97%) dogs were dehydrated, 18 (26%) were icteric, 22 (32%) were febrile, 40 (58%) had signs of abdominal pain, and 30 (43%) were classified as overweight or obese. Most dogs had leukocytosis, neutrophilia with a left shift, and thrombocytopenia. Various serum biochemical abnormalities were identified, including hypoglycemia, azotemia, hypercalcemia and other electrolyte abnormalities, hypoalbuminemia, high hepatic and pancreatic enzyme activities, hypercholesterolemia, and lipemia. For 17 of 28 (61%) dogs, results of coagulation function tests were abnormal. Results of abdominal ultrasonography and radiography were consistent with a diagnosis of acute pancreatitis in 23 of 34 (68%) and 10 of 41 (24%) dogs, respectively. For 2 dogs, results of abdominal ultrasonography were not suggestive of acute pancreatitis, but results of abdominal radiography were., Clinical Implications: Clinical signs and results of clinicopathologic tests are inconsistent. Abdominal ultrasonography may be valuable in the diagnostic evaluation of dogs suspected to have acute pancreatitis.

Objective: To characterize cranial vena cava thrombosis in dogs with regard to signalment, clinical manifestation, potential inciting causes, treatment, and outcome., Design: Retrospective study., Animals: 17 dogs with a cranial vena cava thrombus., Procedure: Medical and necropsy records were reviewed for signalment, potential causes of thrombus formation, diagnosis, clinicopathologic findings, treatment, and outcome., Results: A signalment predisposition was not found. Ten dogs had cranial vena cava syndrome, and 10 had a pleural effusion. Ten dogs were dyspneic, and 5 had palpable jugular thrombi. Predisposing conditions identified were presumed immune-mediated hematologic disease and corticosteroid administration (6 dogs), sepsis (6), protein-losing nephropathy (2), neoplasia (2), and cardiac disease (1). Central venous catheterization was implicated as a contributing cause. Thrombocytopenia was the most consistent clinicopathologic finding, and ultrasonography was helpful in confirming the diagnosis. Treatment varied, but 15 of the 17 dogs died or were euthanatized within 20 days of clinical manifestation of the thrombus. At necropsy, thrombi were found in other organs, mainly the right atrium, jugular veins, and pulmonary arteries., Clinical Implications: Prognosis is poor for dogs with cranial vena cava thrombosis associated with clinical signs. Use of central venous catheters should be avoided in dogs with predisposing diseases such as immune-mediated disease, sepsis, protein-losing nephropathy, neoplasia, and cardiac disease.

A distinctive renal lesion consisting of glomerulonephritis, diffuse tubular necrosis with regeneration, and interstitial inflammation was found in 49 biopsy/necropsy cases obtained from 1987 to 1992. This lesion is manifested clinically as a rapidly progressive glomerular disease that was uniformly fatal. Immune-mediated membranoproliferative glomerulonephritis predominated (43/49, 88%). Membranous glomerulonephritis (5/49, 10%) and amyloidosis (1/49, 2%) were also noted. Subendothelial deposits, IgG, IgM, and C3 were present along glomerular basement membranes. IgA was absent. The exact cause of the tubular necrosis is unknown. Affected dogs were significantly younger (5.6 +/- 2.6 years) than dogs with other forms of glomerulonephritis (7.1 +/- 3.6 years) and amyloidosis (7.8 +/- 3.5 years) both in the studied population for the same period and in the reported canine population. Labrador and Golden retrievers were 6.4 and 4.9 times more likely, respectively, to develop this lesion. This is the first report of a breed predilection for spontaneous canine glomerulonephritis. Previous reports have associated this lesion with Borrelia burgdorferi exposure. All dogs in this study were from Lyme disease-endemic areas. Of 18 dogs serologically tested, all were positive for exposure. Silver stain examination of kidneys revealed rare spirochetes, suggesting that the presence of spirochetes in the kidney is apparently unrelated to lesion development. The role of vaccination in development of the renal lesion is undetermined. The association of this histologically and clinically unique lesion, Lyme nephritis, with Borrelia burgdorferi infection is significant because it is the only fatal form of canine Lyme borreliosis.

Rationale and Objectives: Knowledge of the in vivo relaxivity of paramagnetic contrast agents is important in the accurate measurement of the permeability of the blood-brain barrier (BBB). This study was aimed at developing an animal model for the magnetic resonance (MR) imaging investigation of injuries to the BBB., Methods: MR imaging (1.9 T) was performed in 18 rats with acute, stable injuries to the brain caused by freezing. After injection of gadodiamide (0.05-0.20 mmol/kg), estimates were made of BBB permeability, leakage space, and relaxivity (also measured in saline)., Results: The BBB was always disrupted at the injured site (permeability = 0.038 min-1 +/- 0.0006). The central area of necrosis and the periphery of edema showed substantial differences in leakage space and relaxivity. The relaxivity of gadodiamide was much greater at the injured site than in saline., Conclusion: The in vivo relaxivity at a site of pathologic change in the brain may be substantially greater than that measured in aquo.

Objective: To characterize respiratory function and treatment in dogs with findings compatible with those of human adult respiratory distress syndrome (ARDS) and to evaluate the application in dogs of clinical for diagnosis of ARDS., Design: Retrospective review of medical records., Animals: 19 dogs with acute respiratory distress syndrome., Results: Arterial blood pH was 7.30 +/- 0.59 (mean +/- SD). Nine dogs had metabolic acidosis. In nonmechanically ventilated dogs, PaCO2 was 15.0 to 54.9 mm of Hg. Respiratory acidosis developed in 2 mechanically ventilated dogs. Hypoxemia was observed in 4 of 5 dogs breathing room air. In 4 mechanically ventilated dogs, oxygenation was inadequate, despite use of > 60% inspired O2 and positive end-expiratory pressure in 3 dogs. Alveolar-to-arterial oxygen tension gradients were widened in 4 dogs breathing room air and in 6 dogs ventilated with 100% O2. Ten dogs were mechanically ventilated; ventilatory rate was 18 to 60 breaths/min. Tidal volume was 12 +/- 3.8 ml/kg of body weight in 4 dogs, minute ventilation > 400 ml/kg/min in 2 dogs, and peak airway pressures > 25 cm of H2O in 6 dogs. Positive end-expiratory pressure was used in 8 dogs. Pneumothorax was detected in 5 ventilated dogs. Human clinical criteria for diagnosis of ARDS were fulfilled in 7 dogs. Fluid treatment consisted of IV crystalloids and synthetic colloids. Drugs most often administered were antibiotics and loop diuretics., Clinical Implications: Human clinical criteria for identification of ARDS may be helpful in diagnosis of acute respiratory distress syndrome in dogs.

Objective: To describe clinical and clinicopathologic findings from dogs with histologic pulmonary lesions consistent with human adult respiratory distress syndrome and to identify potential factors., Design: Retrospective study., Animals: 19 dogs with acute respiratory distress., Procedure: Medical records of dogs were reviewed. Signalment, physical examination and clinicopathologic findings at admission, and thoracic radiographic and necropsy findings were recorded., Results: The most common clinical sign was dyspnea. Respiratory rate ranged from 36 to 140 breaths/min and abnormal breathing patterns were detected. Crackles were auscultated in 7 dogs. Severe diffuse interstitial and alveolar infiltrates were observed on thoracic radiography in 9 dogs shortly after arrival and developed later in 4 dogs. Four dogs were leukopenic and neutropenic. Disseminated intravascular coagulation was diagnosed in 2 dogs, and hypoalbuminemia was found in 8 dogs. Respiratory status deteriorated rapidly in all dogs, and 10 dogs were mechanically ventilated. Death was attributed solely to respiratory failure in 8 dogs. In the other 11 dogs, severe lesions in nonpulmonary organs, sepsis, or both may have contributed to death. The most common associated conditions that may have contributed to acute respiratory failure were microbial pneumonia, sepsis, aspiration pneumonia, and shock, with more than 1 factor found in 11 of 19 dogs., Clinical Implications: The index of suspicion for acute respiratory distress syndrome should be high in dogs with bilateral pulmonary infiltrates and acute respiratory distress that rapidly progresses to failure.

The clinical and pathologic features of five young Maltese dogs with a necrotizing meningoencephalitis were studied and compared with published reports of the necrotizing meningoencephalitis of Pug dogs. The ages of the Maltese dogs ranged from 9 months to 4 years. Four dogs were male, and one was female. The dogs had a history of seizures with or without other neurologic signs for 3 days to 20 weeks prior to death. Cerebrospinal fluid examination in three dogs revealed a pleocytosis and elevated levels of protein. At necropsy, the cerebrum was asymmetrically swollen in four dogs, with a loss of distinction between the gray and white matter and mild to moderate asymmetrical dilation of the lateral ventricles. Histologically, there was extensive necrosis and nonsuppurative inflammation of the cerebral gray and white matter, overlying meninges, and adjacent thalamus and hippocampus. The 4-year-old dog had the longest duration of clinical signs and had little inflammation but extensive atrophy of affected areas, with astrocytosis. The clinical course and pathologic changes in these Maltese dogs are indistinguishable from those in reported cases of necrotizing meningoencephalitis of Pug dogs, indicating that this lesion is probably not unique to Pug dogs.

A retrospective study was conducted of all feline necropsies over a 7-year period. Of a total of 1,472 necropsies, 37 cases of endomyocarditis (EMC) and 25 cases of left ventricular endocardial fibrosis (LVEF) (previously called restrictive or intermediate cardiomyopathy) were identified. There was a subset of four cats with EMC that had histologic features of both diseases. Interstitial pneumonia was seen in 25 of 35 cats (71%) with EMC but in only seven of 25 cats (28%) with LVEF. Thrombi or thromboemboli were seen in 14 of 25 cats (56%) with LVEF but in only six of 37 of cats (16%) with EMC. In both LVEF and EMC, thromboemboli were located in the abdominal aorta, left atrium and ventricle of the heart, femoral artery, cranial mesenteric artery, liver, pulmonary artery, jugular vein, or a meningeal vessel. Each cat had a single thrombus/thromboembolus, except for four cats with LVEF that had more than one. The histologic and clinical findings suggest that EMC and LVEF represent temporally different manifestations of a single disease entity.

A putative retrovirus was isolated from a dog with a severe, acquired immunodeficiency-like syndrome. The haematological abnormalities and immunological deficiencies included anaemia, leucopenia (lymphopenia and neutropenia), thrombocytopenia, decreased humoral immunity, and ineffective T-cell responses in-vitro. The necropsy findings included generalized lymphoid depletion, severe bone marrow hypoplasia, plasmacytic infiltrates in lymphoid and non-lymphoid organs, and severe secondary infections. Supernates of peripheral blood mononuclear cell cultures from the affected dog contained an agent with manganese-dependent reverse transcriptase (RT) activity that sedimented at a density of 1.122 g/ml. RT activity was also found post-mortem in extracts prepared from the bone marrow, lymph nodes, and small intestine. The lymph nodes and small intestine expressed a 3.8 kb mRNA that was recognized by a bovine leukaemia virus (BLV) pol DNA probe by Northern blotting. DNA isolated from the lymph nodes and small intestine from the affected dog showed distinct band patterns by Southern analysis, suggesting an exogenous retrovirus. The retrovirus could be propagated in normal canine peripheral blood mononuclear cells or short-term canine lymphocyte cell lines in-vitro, and was cytopathogenic for cells of canine, but not human, origin. These results suggest the existence of a pathogenic canine retrovirus capable of producing disease of the type associated with retroviruses in other species.

A syndrome of cerebellar Purkinje's cell degeneration and coat color dilution was diagnosed in a family of Rhodesian Ridgeback dogs. One male and 1 female from the same litter and 1 female from a different litter were evaluated for growth retardation, inability to ambulate, and progressive ataxia. On physical examination, lateral recumbency, severe ataxia, tremors, and diluted coat color were identified. Littermates with nondiluted coat color were neurologically normal. Results of routine laboratory tests, urine metabolic screenings, and karyotype analyses were normal. Histopathologic abnormalities at necropsy included cerebellar Purkinje's cell degeneration, reduced granular cell layer thickness, and uneven distribution of macromelanosomes within hair shafts. Pedigree analysis suggested an autosomal recessive mode of inheritance. This is the first description of a genetic syndrome affecting the central nervous system and associated with coat color dilution in dogs.

Medical records and histologic sections of 40 cats with acute pancreatitis were reviewed. Two distinct groups of cats with pancreatitis were established by histologic analysis of tissue. Group 1 (32 cats) had acute pancreatic necrosis (APN). Group 2 (8 cats) had suppurative pancreatitis. Ages of affected cats ranged from 3 weeks to 16 years. The majority consisted of indoor cats of the Domestic Short-Haired breed but Siamese cats were over-represented relative to the general population (P < 0.05). Twenty-two percent of cats were obese and 57% were underweight. Thirty-eight percent of cats had acute disease. In the other cats, two stages in the progression of the disease were evident: (1) anorexia, weight loss, and lethargy, followed by (2) acute deterioration, development of shock, and a moribund state, despite fluid therapy. The most common clinical signs were severe lethargy (100%), reduced appetite (97%), dehydration (92%), and hypothermia (68%). The initial hemogram occasionally showed a neutrophilia (30%) and anemia (26%) but packed cell volume (PCV) decreased markedly to the extent that 55% of cats were anemic terminally. Serum biochemical abnormalities included increased activities of ALT (68%) and ALP (50%), and increased concentrations of bilirubin (64%) and cholesterol (64%). Cats with APN were hyperglycemic (64%), glycosuric (60%) and ketonuric (20%), whereas cats with suppurative pancreatitis tended to be hypoglycemic (75%). Renal failure and electrolyte abnormalities were mild or infrequent except for hypokalemia (56%). This study characterizes a severe necrotizing pancreatitis in the cat similar to that reported in other species, and a histologically distinct suppurative pancreatitis.

Case records from the small animal necropsy service of the University of Pennsylvania (Philadelphia, PA) from January 1981 through August 1990 were searched for reports of animals with grossly visible portal vein thrombi. Eleven dogs identified from their case materials as having portal vein thrombosis were used for this study. The age of the dogs ranged from 2 to 13 years, and there were five spayed females and six males--four intact and two castrated. Seven breeds were represented (Lhasa Apso, German Wire haired Pointer, Shetland Sheepdog, Dalmatian, Irish Wolfhound, Old English Sheepdog, and Siberian Husky), and the remaining four cases were identified as mixed breeds. The weight of the dogs ranged from 7.7 to 50 kg, and most of them were considered overweight. Dogs with microthrombi and tumor emboli in the portal vein were excluded. No age, sex, or breed predisposition was found. Thrombi were also detected in the pulmonary arteries in five of the dogs and both the pulmonary arteries and aorta in one dog. The portal thrombi extended into the mesenteric veins in three dogs, resulting in infarction of the jejunum. One of these dogs and two other dogs had chronic occlusion of the portal vein, with the formation of secondary portosystemic shunts. Conditions also present in dogs with portal vein thrombi included pancreatic necrosis (four dogs), peritonitis (two dogs), distant neoplasia (three dogs), and therapy with steroids (ten dogs).

Glycogen storage disease type IV due to branching enzyme deficiency was found in an inbred family of Norwegian forest cats, an uncommon breed of domestic cats. Skeletal muscle, heart, and CNS degeneration were clinically apparent and histologically evident in affected cats older than 5 mo of age, but cirrhosis and hepatic failure, hallmarks of the human disorder, were absent. Beginning at or before birth, affected cats accumulated an abnormal glycogen in many tissues that was determined by histochemical, enzymatic, and spectral analysis to be a poorly branched alpha-1,4-D-glucan. Branching enzyme activity was less than 0.1 of normal in liver and muscle of affected cats and partially deficient (0.17-0.75 of normal) in muscle and leukocytes of the parents of affected cats. These data and pedigree analysis indicate that branching enzyme deficiency is a simple autosomal recessive trait in this family. This is the first reported animal model of human glycogen storage disease type IV. A breeding colony derived from a relative of the affected cats has been established.

Experimental hypophysectomies were performed in 7 clinically normal dogs, using a new modification of the transsphenoidal approach. This approach facilitated centering of the sphenoid bone trephination and allowed safe exposure of the hypophysis regardless of the size or shape of a dog's skull. Complications did not occur during surgery and all dogs recovered well from surgery. Growth hormone secretory capacity was measured over a 3-month period to assess completeness of hypophysectomies. One dog was euthanatized 2 months after surgery, 4 dogs were euthanatized at 3 months after surgery, and 2 dogs were allowed to survive and their progress was followed for 2.5 years. Soft palate dehiscence and keratoconjunctivitis sicca developed in 2 of the dogs. The technical deficiencies responsible for these complications were corrected shortly after the beginning of the study. In 4 of the 5 necropsied dogs, minute remnants of adenohypophyseal tissue were found in the sellae turcica. Measurement of in vivo growth hormone secretory capacity revealed that these remnants had an altered stage of functional activity. Although complete hypophysectomy was not achieved consistently, the main technical obstacle of hypophysectomy, the reliable identification and the avoidance of the vascular structures surrounding the hypophysis, has seemingly been overcome. The surgical technique proved to enhance the safety of hypophysectomy, and the procedure can be recommended to treat clinical cases of canine pituitary-dependent hyperadrenocorticism. The clinical significance of potential subtotal hypophysectomy remains yet to be evaluated.

The incidence of hydronephrosis was determined in nine production colonies of Crl:CD (SD) BR rats (CD rats). Kidneys from 3909 rats were examined and 79 (2.0%) had unilateral or bilateral hydronephrosis. A colony with a relatively high incidence of hydronephrosis (4.1%) was chosen for further study. In unselected rats from this colony the incidence in females (87/1882, 4.6%) was not significantly different from that in males (79/1862, 4.2%). In the same group of rats, hydronephrosis was observed most frequently in the right kidney only (2.3%), followed by bilateral involvement (1.2%) and the left kidney only (0.8%). By selection and inbreeding, the incidence of hydronephrosis was increased dramatically (to 33.6%) in two generations. Hydronephrosis in the CD rat appears to be a highly heritable trait, most likely involving more than one gene.

A recessively inherited hypertrophic neuropathy was discovered in Tibetan Mastiff dogs. Affected pups developed a generalized weakness with hyporeflexia shortly after weaning. Diagnostic findings in 10-18-week-old pups included: moderate to severe reduction in nerve conduction velocities, infrequent denervation potentials, and inconstant elevation in CSF protein. Light- and electron-microscopic studies of peripheral nerves and roots revealed widespread demyelination and primitive onion bulb formation with relatively little degeneration of axons. Myelin changes often were most striking in the cytoplasmic regions of the sheaths and consisted of separations at the major dense lines, anomalous incisure patterns, and marked filamentous accumulations in the inner spirals and adaxonal cytoplasm. The results of these initial studies suggest an inborn defect in the Schwann cell's ability to form or maintain a stable myelin sheath.

Cryptosporidium was found in the intestinal tract of 10 blackbuck, 2 scimitar-horned oryx, 2 fringe-eared oryx, 2 addax, and 1 sable antelope that had diarrhea. Cryptosporidia were most numerous in the small intestine, but also were found in the cecum, spiral colon, and colon. The small intestine had minimal inflammation in association with the cryptosporidia. Salmonella typhimurium was isolated from 10 of the 51 animals evaluated, with extensive inflammation of the cecum, spiral colon, and colon observed in these animals.

A model of radiation injury to the brain was developed in the cat. Definite radiation changes were demonstrated at magnetic resonance (MR) imaging in four of six cats. These changes consisted of high-intensity abnormalities on images obtained with a long repetition time (TR) and a long echo time (TE), which were initially noted 208-285 days after irradiation. These changes were associated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement on short TR and inversion-recovery (IR) pulse sequences. Gd-DTPA enhancement and the high intensity on the long TR/TE images were identified at the same time and became more prominent throughout the study. Chemical-shift imaging and phosphorus spectroscopy demonstrated no notable changes despite clear-cut MR evidence of abnormalities. Sodium imaging was positive in one case. Correlation of MR and pathologic findings revealed areas of radiation necrosis and wallerian degeneration that corresponded to areas of Gd-DTPA enhancement on short TR and IR images and to areas of high intensity on long TR/TE images. Peripheral to the areas of Gd-DTPA enhancement were nonenhanced zones of high-signal-intensity abnormality on long TR/TE images, which represented regions of demyelination without necrosis. Gd-DTPA-enhanced proton imaging was the most sensitive method for detecting radiation damage in this animal model.

Corneal opacities were observed in numerous strains and stocks of laboratory mice (Mus musculus) from different microbiological environments. The opacities were characterized as acute and chronic inflammatory lesions of the corneal epithelium and anterior corneal stroma, including corneal ulcers and erosions, acute keratitis, stromal neovascularization and mineralization of the basement membrane zone. Some strains and stocks of mice from barrier-reared colonies had a high incidence of corneal opacities [DBA/2 (29.1%), C3H (16.2%), CF1 (16.2%) and BALB/c (10.0%)] while others had a lower incidence [CD-1 (4.3%) and C57BL/6 (4.1%)]. Axenic and gnotobiotic mice had a very low incidence of corneal opacities (1.6%). An experimental study demonstrated that twice weekly cage cleaning would reduce the incidence of corneal opacities to a very low level. A bacterial product, such as ammonia, is proposed as a significant factor in the pathogenesis of spontaneous corneal opacities in laboratory mice.