Diagnostic accuracy of Wright-Giemsa and rhodanine stain protocols for detection and semi-quantitative grading of copper in canine liver aspirates.

BACKGROUND: Canine hepatic copper content has been increasing. Recognition of canine copper-associated hepatopathies is becoming more common. OBJECTIVES: The purpose of the study was to assess the diagnostic performance of Wright-Giemsa (WG) and rhodanine staining for detection of increased canine hepatic copper following a proposed cytologic protocol for semi-quantitative evaluation of liver aspirates and the effect of previous WG staining. METHODS: Retrospectively, 40 canine hepatic WG-stained cytology cases were rhodanine stained. Diagnostic performance of WG staining for increased hepatic copper was evaluated. A rhodanine-stained cytologic copper grading system was developed. Prospectively, 67 canine liver samples with quantitative copper measurement, a WG-then rhodanine-stained slide, and a non-WG rhodanine-stained slide were used to assess the performance of the grading system and the effect of previous WG staining. RESULTS: Copper was not described in 40 retrospective cases on initial cytologic evaluation; 8/40 cases had increased copper content after rhodanine staining or quantitative copper assessment. Prior WG staining and destaining significantly affected the cytologic copper grade but not the diagnostic performance as measured by receiver-operating characteristic curve analysis. Quantitative copper concentration and previously WG-stained copper grade were moderately correlated (n = 67, ρ = .79 [.68-.87]). For detection of ≥ 600 ppm, dry weight (dw) copper, sensitivity was .75 and specificity was .97. For detection of ≥ 1500 ppm, dw copper, sensitivity was 1.0 and specificity was .97. CONCLUSIONS: Wright-Giemsa staining alone does not reliably detect hepatic copper. Grading of rhodanine-stained canine hepatic cytologic samples demonstrates acceptable diagnostic performance for detection of copper content.

Safety and efficacy of high-dose fomepizole compared with ethanol as therapy for ethylene glycol intoxication in cats.

OBJECTIVE: To determine the safety and efficacy of high-dose fomepizole compared with ethanol (EtOH) in cats with ethylene glycol (EG) toxicosis. DESIGN: Prospective study. SETTING: University veterinary research laboratory. ANIMALS: Thirteen cats. INTERVENTIONS: Two cats received injections of high-dose fomepizole (Study 1). Three cats received lethal doses of EG and fomepizole treatment was initiated 1, 2, or 3 hours later (Study 2). Eight cats received a lethal dose of EG and were treated with fomepizole or EtOH (Study 3). Cats treated with fomepizole received 125 mg/kg IV initially, then 31.25 mg/kg at 12, 24, and 36 hours. Cats treated with EtOH received 5 mL of 20% EtOH/kg IV initially, then every 6 hours for 5 treatments, then every 8 hours for 4 treatments. Cats also received fluids and supportive therapy as needed. MEASUREMENTS AND MAIN RESULTS: Clinical signs were monitored and serial blood analyses performed. Cats receiving fomepizole experienced mild sedation but no biochemical evidence of toxicity. Cats receiving fomepizole for EG intoxication survived if therapy was initiated within 3 hours of EG ingestion. One of the 6 developed acute renal failure (ARF) but survived. Only 1 of the 3 cats treated with EtOH 3 hours following EG ingestion survived; 2 developed ARF and were euthanized. Cats treated 4 hours following EG ingestion developed ARF, whether treated with EtOH or fomepizole. CONCLUSIONS: Fomepizole is safe when administered to cats in high doses, prevents EG-induced fatal ARF when therapy is instituted within 3 hours of EG ingestion, and is more effective than treatment with EtOH.

Trace elements and prion diseases: a review of the interactions of copper, manganese and zinc with the prion protein.

Transmissible spongiform encephalopathies (TSEs) are a family of neurodegenerative diseases characterized by their long incubation periods, progressive neurological changes, and spongiform appearance in the brain. There is much evidence to show that TSEs are caused by an isoform of the normal cellular surface prion protein PrPC. The normal function of PrPC is still unknown, but it exhibits properties of a cupro-protein, capable of binding up to six copper ions. There are two differing views on copper's role in prion diseases. While one view looks at the PrPC copper-binding as the trigger for conversion to PrPSc, the opposing viewpoint sees a lack of PrPC copper-binding resulting in the conformational change into the disease causing isoform. Manganese and zinc have been shown to interact with PrPC as well and have been found in abnormal levels in prion diseases. This review addresses the interaction between select trace elements and the PrPC.

Inheritance of hereditary equine regional dermal asthenia in Quarter Horses.

OBJECTIVE: To assess heritability and mode of inheritance for hereditary equine regional dermal asthenia (HERDA) in Quarter Horses. ANIMALS: 1,295 horses with Quarter Horse bloodlines, including 58 horses affected with HERDA. PROCEDURE: Horses were classified as affected or unaffected or as undetermined when data were insufficient to assess phenotype. Pedigree data were analyzed to determine the probable mode of inheritance. Heritability was estimated by use of Bayesian statistical methods. RESULTS: Heritability (mean+/-SD) of HERDA was estimated to be 0.38+/-0.13, with both sexes having an equal probability of being affected. Results for evaluation of the pedigrees were consistent with a single Mendelian autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL RELEVANCE: HERDA in Quarter Horses is an inherited disease, and affected horses are more likely to produce affected offspring. An autosomal recessive mode of inheritance should be considered by people making breeding decisions involving Quarter Horses when a first-degree relative has been confirmed with HERDA or has produced affected offspring. In addition, breeders whose horses have produced affected offspring can reduce the likelihood of producing affected horses in the future by avoiding inbreeding.

Hereditary equine regional dermal asthenia ("hyperelastosis cutis") in 50 horses: clinical, histological, immunohistological and ultrastructural findings.

Data on fifty horses with hereditary equine regional dermal asthenia (HERDA; "hyperelastosis cutis") were collected on clinical, histopathological, ultrastructural and immunohistological findings. All horses were Quarter horses or of Quarter horse ancestry. Pedigree evaluation strongly supported an autosomal recessive mode of inheritance. The most common lesions were seromas/haematomas, open wounds, sloughing skin, and loose, easily tented skin that did not return to its initial position. Definitive diagnosis could not be made via histopathology, although the presence of tightly grouped thin and shortened collagen fibres arranged in clusters in the deep dermis was suggestive of the disease. Trichrome, acid orcein-Giemsa and immunohistochemical stains for collagens I and III showed no consistent abnormalities compared to control horses; an increase in elastic fibres was not a consistent finding. Electron microscopy showed no abnormalities in the periodicity of the collagen bundles; neither orientation nor variation of cross-section diameter of the collagen fibrils differentiated control from affected horses. The diagnosis of HERDA relies on clinical presentation, but may be supported by suggestive (although not pathognomonic) histopathological lesions.

Potentially hazardous sulfur conditions on beef cattle ranches in the United States.

OBJECTIVE: To analyze the sulfur content of water and forage samples from a geographically diverse sample of beef cow-calf operations in the United States and to estimate frequency and distribution of premises where forage and water resources could result in consumption of hazardous amounts of sulfur by cattle. DESIGN: Cross-sectional study. SAMPLE POPULATION: 709 forage samples from 678 beef cow-calf operations and individual water samples from 498 operations in 23 states. PROCEDURE: Sulfur content of forage samples and sulfate concentration of water samples were measured. Total sulfur intake was estimated for pairs of forage and water samples. RESULTS: Total sulfur intake was estimated for 454 pairs of forage and water samples. In general, highest forage sulfur contents did not coincide with highest water sulfate concentrations. Overall, 52 of the 454 (11.5%) sample pairs were estimated to yield total sulfur intake (as a percentage of dry matter) > or = 0.4%, assuming water intake during conditions of high ambient temperature. Most of these premises were in north-central (n = 19) or western (19) states. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that on numerous beef cow-calf operations throughout the United States, consumption of forage and water could result in excessively high sulfur intake. All water sources and dietary components should be evaluated when assessing total sulfur intake. Knowledge of total sulfur intake may be useful in reducing the risk of sulfur-associated health and performance problems in beef cattle.

Canine liver iron, copper, and zinc concentrations and association with histologic lesions.

Concentrations of iron, copper, and zinc were measured in livers of 95 dogs that were suspected of having liver disease. Iron concentrations ranged from 177 to 7,680 ppm (dry weight basis); 54 dogs had iron concentrations greater than the normal concentration of 1,200 ppm. Iron stores were present in Kupffer cells and macrophages but not hepatocytes. The dogs did not have lesions of hemochromatosis. Dogs with high liver iron tended to have high liver copper and inflammatory lesions. High liver copper concentrations usually were associated with hepatocellular necrosis and fibrosis. High liver zinc was found in only 5 animals and was accompanied by histologic inflammatory lesions in one. In humans, increased iron concentration in the liver exacerbates liver damage caused by a variety of insults, and the same may be true for dogs.