Peripheral nervous system (PNS) toxicity is surveyed inconsistently in nonclinical general toxicity studies. These Society of Toxicologic Pathology "best practice" recommendations are designed to ensure consistent, efficient, and effective sampling, processing, and evaluation of PNS tissues for four different situations encountered during nonclinical general toxicity (screening) and dedicated neurotoxicity studies. For toxicity studies where neurotoxicity is unknown or not anticipated (situation 1), PNS evaluation may be limited to one sensorimotor spinal nerve. If somatic PNS neurotoxicity is suspected (situation 2), analysis minimally should include three spinal nerves, multiple dorsal root ganglia, and a trigeminal ganglion. If autonomic PNS neuropathy is suspected (situation 3), parasympathetic and sympathetic ganglia should be assessed. For dedicated neurotoxicity studies where a neurotoxic effect is expected (situation 4), PNS sampling follows the strategy for situations 2 and/or 3, as dictated by functional or other compound/target-specific data. For all situations, bilateral sampling with unilateral processing is acceptable. For situations 1-3, PNS is processed conventionally (immersion in buffered formalin, paraffin embedding, and hematoxylin and eosin staining). For situation 4 (and situations 2 and 3 if resources and timing permit), perfusion fixation with methanol-free fixative is recommended. Where PNS neurotoxicity is suspected or likely, at least one (situations 2 and 3) or two (situation 4) nerve cross sections should be postfixed with glutaraldehyde and osmium before hard plastic resin embedding; soft plastic embedding is not a suitable substitute for hard plastic. Special methods may be used if warranted to further characterize PNS findings. Initial PNS analysis should be informed, not masked ("blinded"). Institutions may adapt these recommendations to fit their specific programmatic requirements but may need to explain in project documentation the rationale for their chosen PNS sampling, processing, and evaluation strategy.
A 12-year-old castrated male, domestic long-haired cat weighing 4.93 kg was evaluated for weight loss and an abdominal mass. The cat had a 3-month history of diabetes mellitus treated with 2 units of ultralente insulin a twice daily. Hypokalemia, mild azotemia, mild hyperglycemia, and glucosuria were noted on recent laboratory evaluations.Physical examination findings included a thin, greasy haircoat, dermal and epidermal atrophy, cutaneous fragility, a III/VI left peristernal systolic heart murmur, and a cranial abdominal mass. Clinicopathologic abnormalities included hyperglycemia (460 mg/dL, reference range 52-153 mg/ dL), azotemia (blood urea nitrogen 76 mg/dL, reference range 17-35 mg/dL; creatinine 3.1 mg/dL, reference range 0.50-2.20 mg/dL), hypokalemia (2.5 mmol/L, reference range 3.0-4.0 mmol/L), hypochloremia (110 mmol/L, reference range 114-122 mmol/L), hyperphosphatemia (6.1 mmol/L, reference range 2.0-5.3 mmol/L), increased total CO 2 (27 mmol/L, reference range 11-22 mmol/L), and glucosuria. Venous blood gas analysis was consistent with a metabolic alkalosis (pH 7.38, HCO 3 ϭ 28.2 mmol/L) with respiratory compensation (partial pressure of carbon dioxide [PCO 2 ] ϭ 48.7). Serum total thyroxine (T 4 ) concentration, magnesium concentration, creatine phosphokinase activity, and CBC were within reference ranges. A mass cranial to the right kidney (Fig 1) and mild cardiomegaly were noted on abdominal and thoracic radiographs, respectively. The mass, measuring 2 ϫ 2.5 cm by ultrasound, was identified as the right adrenal gland (Fig 2). Echocardiography was unremarkable. Mild hypertension was identified on an initial reading (blood pressure 170 mm Hg, systolic). However, considering the fractious nature of this cat during blood pressure measurement and a lack of ocular manifestations of hypertension, therapy was deemed unnecessary at the time.Endocrinologic testing was performed to investigate functionality of the adrenal tumor. Surgical exploration and tumor removal was planned. Potassium gluconate e supplementation was initiated (2 mEq q24h PO) and insulin therapy continued pending surgery. Serum potassium concentrations did not normalize before surgery despite supplementation. At surgery, the right adrenal gland contained a 1.5 ϫ 2.0-cm mass that appeared encapsulated but closely associated with the vena cava. Extension of tumor thrombi was evident into the phenicoabdominal vein but not into the vena cava. The phenicoabdominal vein was ligated at the level of the vena cava and tumor excision was accomplished with a combination of blunt dissection and the use of hemoclips. The left adrenal gland was grossly normal, and no evidence was found of gross metastasis to any abdominal organ. Histopathology of the right adrenal gland (Fig 3) was consistent with a cortical adrenal gland carcinoma.Initial postoperative treatment included insulin, dexamethasone f (0.25 mg/kg q24h IV), and a balanced electrolyte solution g with potassium supplementation (20 mEq/L IV). Insulin administration was discontinued after ...
In 2004, six puppies and one adult dog from a total of four premises were subjected to necropsy evaluation. For five of the seven dogs, disease caused by canine distemper virus (CDV) infection was suspected based on clinical signs. In all of the dogs, a diagnosis of CDV infection was established by the presence of compatible gross and histologic lesions, immunohistochemical labeling for CDV antigen, and detection of CDV RNA by reverse transcription-PCR. To further characterize the CDV strains detected in the four cases, complete gene sequences were determined for the hemagglutinin (H) and fusion (F) protein genes, while partial gene sequencing was performed for the phosphoprotein gene. A total of 4,508 bases were sequenced for the CDV strains detected from each of the four cases. Two cases were found to have identical sequences except for 2 bases in the intergenic region of the F and H genes. Phylogenetic analysis strongly suggested an evolutionary relationship between sequences detected in these two cases and those of phocine distemper virus 2 and two other strains of CDV not previously detected in the continental United States. Clear phylogenetic relationships were not established for viruses detected in the two additional cases; however, one strain showed similarity to CDV strains detected in a panda from China. Importantly, the three CDV strains detected were demonstrated to be genetically distinct from known vaccine strains and strains previously reported in the continental United States.Canine distemper virus (CDV) is the etiological agent of one the most important viral diseases of wild and domestic Canidae (dog, dingo, fox, coyote, jackal, and wolf) (2). It occurs worldwide and produces high morbidity and mortality in immunologically naïve populations (22,29). This virus also infects a broad range of other animals, such as Mustelidae (ferrets, minks, skunks, weasels, and badgers), Procyonidae (raccoons and pandas), Ursidae (bears), Viverridae (civets, genets, and linsangs), hyaenidae (hyenas), and Felidae (lions and tigers) (2,3,4,10,12,16,36). Canine distemper virus is classified in the genus Morbillivirus within the family Paramyxoviridae and has an unsegmented, negative-sense, single-stranded, ϳ15.7-kb RNA genome and an enveloped virus particle that is 150 to 300 nm in diameter (29). The pathogenesis of CDV infection in dogs has been well characterized (2,22,29,35). The genome of CDV encodes the following virion proteins: matrix (M), fusion (F), hemagglutinin (H), nucleocapsid (N), polymerase (L), and phosphoprotein (P). The H gene protein is responsible for viral attachment to the cell host (38) and may also play a role in induction of protective immunity (11). The H protein is one of the most variable morbillivirus proteins and thus has often been used to assess genetic changes between CDV isolates (8,9,17,18,20,21,23,26,28,30).In this study, postmortem findings, immunohistochemical labeling, and reverse transcription (RT)-PCR specific for CDV genomic RNA established a definitive diagnosis of diseas...
Abstract. Functional evaluation of the pars intermedia (PI) is required for the early diagnosis of equine pituitary PI dysfunction (PPID), yet most assays target the hypothalamic-pituitary-adrenal axis, which regulates the pars anterior. In contrast, the PI is regulated by dopaminergic tone from hypothalamic neurons. Loss of dopaminergic inhibition is hypothesized to cause the PI hypertrophy and hyperplasia that result in the clinical manifestations of PPID. Domperidone, a dopamine receptor antagonist, should exacerbate the loss of dopaminergic inhibition in horses with PPID and increase the release of endogenous adrenocorticotrophic hormone (eACTH) by PI melanotrophs. To test this, plasma eACTH concentration was determined in horses with or without clinical signs of PPID at 0, 4, and 8 hours after oral administration of 3.3 mg domperidone/kg. Pituitary glands were evaluated postmortem by histologic grading and morphometry. In the 33 horses, median age, plasma ACTH concentration 8 hours after domperidone, and PI area in median sagittal sections were associated with histologic grade as follows: pituitary grade 1 (normal), n 5 3, 7.5 years, 20.0 pg/ml, 0.16 cm 2 ; grade 2 (focal hypertrophy or hyperplasia), n 5 9, 14.5 years, 27.1 pg/ml, 0.27 cm 2 ; grade 3 (diffuse adenomatous hyperplasia), n 5 5, 21.0 years, 64.4 pg/ml, 0.48 cm 2 ; grade 4 (microadenomas), n 5 12, 23.3 years, 128.0 pg/ml, 0.87 cm 2 ; grade 5 (adenoma), n 5 4, 24.9 years, 720.5 pg/ml, 2.1 cm 2 . Results suggest that horses with pituitary histologic grade $3 respond to domperidone with increased plasma ACTH concentration.
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