Objective—To evaluate differences in hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis.
Design—Retrospective case-control study.
Sample—Liver tissue specimens from 36 Labrador Retrievers with chronic hepatitis and 36 age- and sex-matched Labrador Retrievers without chronic hepatitis (control dogs).
Procedures—Liver tissue specimens were obtained during 2 study periods (1980 to 1997 and 1998 to 2010). For each tissue specimen, a histologic score was assigned independently by each of 2 interpreters, and the hepatic copper concentration was qualitatively determined via rhodanine staining and quantitatively determined via atomic absorption spectroscopy.
Results—Mean hepatic copper concentration was significantly higher in dogs with chronic hepatitis (614 μg/g of dry weight [range, 104 to 4,234 μg/g of dry weight]), compared with that in control dogs (299 μg/g of dry weight [range, 93 to 3,810 μg/g of dry weight]), and increased significantly over time. A higher proportion of liver tissue specimens collected during the 1998–2010 study period had hepatic copper concentrations > 400 μg/g of dry weight (the upper limit of the reference range), compared with the proportion of liver tissue specimens collected during the 1980–1997 study period. The qualitative copper score did not accurately predict quantitative hepatic copper concentration in 33% of study dogs.
Conclusions and Clinical Relevance—Results suggested that the increase in hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis over time may be the result of increased exposure of dogs to environmental copper, most likely via the diet.
Objective—To compare morphologic diagnoses determined
from needle biopsy specimens obtained from
the livers of dogs and cats with morphologic diagnoses
determined from wedge biopsy specimens.
Animals—124 dogs and cats.
Procedure—2 needle biopsy specimens were
obtained from each animal; wedge biopsy specimens
were obtained from the same liver lobe during laparotomy
or postmortem examination. Histologic features
were scored independently by 3 individuals; a morphologic
diagnosis was rendered after histologic features
were scored. Cases were included only if at least 2 of
the 3 examiners agreed on the morphologic diagnosis;
the definitive diagnosis was considered to be the morphologic
diagnosis rendered for the wedge biopsy
specimen. Physical characteristics (length, width, surface
area, degree of fragmentation, and number of portal
triads for needle biopsy specimens and surface area
for wedge biopsy specimens) were determined.
Results—Definitive diagnoses included hepatic necrosis
(n = 10), cholangitis-cholangiohepatitis (13), chronic
hepatitis-cirrhosis (12), canine vacuolar hepatopathy
(11), portosystemic vascular anomaly-microvascular
dysplasia (17), neoplasia (10), miscellaneous hepatic
disorders (18), and no hepatic disease (33). For individual
examiners, the morphologic diagnosis assigned
to needle biopsy specimens agreed with the morphologic
diagnosis assigned to wedge biopsy specimens
for 56 and 67% of the specimens. All 3 examiners
agreed on the morphologic diagnosis assigned to needle
and wedge biopsy specimens for 44 and 65% of
the specimens, respectively. Morphologic diagnoses
assigned to needle biopsy specimens concurred with
the definitive diagnosis for 59 of 124 (48%) animals.
Conclusions and Clinical Relevance—Results
suggest that needle biopsy specimens of the liver
from dogs and cats must be interpreted with caution.
(J Am Vet Med Assoc 2002;220:1483–1490)
Objective—To evaluate 3 methods for measuring
urine bile acids (UBA) and compare their diagnostic
performance with that of the serum bile acids (SBA)
test and other routine screening tests in dogs with
Animals—15 healthy dogs, 102 dogs with hepatic disorders,
and 9 dogs with clinical signs of hepatic disorders
that were found to have nonhepatic disorders.
Procedures—Blood and urine samples were collected
from sick dogs and healthy dogs for serum biochemical
analyses, and determination of concentrations
of SBA and UBA. Urine samples were obtained
from 15 healthy dogs to establish an upper cutoff
value for UBA concentrations. The UBA were measured
by use of a quantitative-linked enzymatic colorimetric
method. Three analytical modifications were
evaluated; 1 quantified only urine sulfated bile acids
(USBA), 1 only urine nonsulfated bile acids (UNSBA),
and 1 quantified both (USBA plus UNSBA). The UBA
values were standardized with the urine creatinine
Results—The UNSBA-to-creatinine ratio and USBA
plus UNSBA-to-creatinine ratio tests had the best
diagnostic performance of the UBA tests; each had a
substantially higher specificity, slightly higher positive
predictive value, slightly lower negative predictive
value, and lower sensitivity than the SBA test. These
UBA-to-creatinine values were positively correlated
with SBA values. The USBA-to-creatinine ratio had
poor sensitivity, indicating a low rate of bile acid sulfation
Conclusions and Clinical Relevance—The UBA can
be measured in dogs with sufficient repeatability and
accuracy for clinical application. The UNSBA-to-creatinine
ratio and USBA plus UNSBA-to-creatinine ratio
identified dogs with hepatic disorders nearly as well
as the SBA test. (J Am Vet Med Assoc 2003;222:
Objective—To evaluate the influence of treatment with ultralow-dose aspirin (ULDAsp) on platelet aggregation, P-selectin (CD62P) expression, and formation of platelet-leukocyte aggregates in clinically normal dogs.
Animals—18 clinically normal dogs.
Procedures—Studies were conducted before and 24 hours after ULDAsp administration (0.5 mg/kg, PO, q 24 h, for 2 days). Whole blood impedance aggregometry for the assessment of platelet function was performed with sodium citrate–anticoagulated blood and aggregation agonists (ADP at 20, 10, and 5 μmol/L; collagen at 10, 5, and 2 μg/mL). Onset, maximum response, and rate of platelet aggregation were recorded. Flow cytometric assays were configured to detect thrombin-induced CD62P expression and platelet-leukocyte aggregates in EDTA-anticoagulated whole blood. Externalized platelet CD62P and constitutive CD61 (GPIIIa) were labeled with antibodies conjugated to phycoerythrin (PE) and fluorescein isothiocyanate (FITC), respectively. Red blood cell–lysed paraformaldehyde-fixed EDTA-anticoagulated whole blood was dual labeled with CD61-FITC and a panleukocyte antibody (CD18-PE) to characterize platelet-leukocyte aggregates.
Results—ULDAsp significantly delayed platelet aggregation onset with ADP at 20 μmol/L by 54% to 104%, attenuated maximum aggregation with various concentrations of ADP and collagen by ≥ 41%, and slowed aggregation rate with the highest ADP and collagen concentrations by ≥ 39%. Depending on the parameter tested, up to 30% of dogs failed to have an ULDAsp effect. Thrombin stimulation significantly increased CD62P expression in platelets and platelet-leukocyte aggregates, but ULDAsp did not alter basal or thrombin-stimulated CD62P expression.
Conclusions and Clinical Relevance—ULDAsp treatment of clinically normal dogs impaired platelet aggregation in most dogs, but did not influence CD62P platelet membrane expression. (Am J Vet Res 2010;71:1294–1304)
Objective—To evaluate prognostic factors, survival,
and treatment protocols for immune-mediated
hemolytic anemia (IMHA) in dogs.
Animals—151 dogs with IMHA not associated with
underlying infectious or neoplastic disease.
Procedure—Information recorded from review of medical
records included signalment at the time of initial
evaluation; vaccination history; 30-, 60-, and 365-day follow-up outcomes; laboratory data; results of imaging
studies; and necropsy findings. Dogs were grouped
according to the presence of spherocytes, autoagglutination,
a regenerative erythrocyte response, and treatments
received (azathioprine, azathioprine plus ultralowdose
aspirin, azathioprine plus mixed–molecular-weight
heparin [mHEP], or azathioprine plus ultralow-dose
aspirin plus mHEP) for comparisons. All dogs received
Results—Cocker Spaniels, Miniature Schnauzers,
neutered dogs, and female dogs were overrepresented.
Alterations in certain clinicopathologic variables were
associated with increased mortality rate. Rates of survival
following treatment with azathioprine, azathioprine
plus ultralow-dose aspirin, azathioprine plus mHEP, and
azathioprine plus ultralow-dose aspirin plus mHEP were
74%, 88%, 23%, and 70%, respectively, at hospital discharge;
57%, 82%, 17%, and 67%, respectively, at 30
days; and 45%, 69%, 17%, and 64%, respectively, at 1
year. In comparison, mean survival rates at discharge
and at 30 days and 1 year after evaluation collated from
7 published reviews of canine IMHA were 57%, 58%,
and 34%, respectively.
Conclusions and Clinical Relevance—Treatment
with a combination of glucocorticoids, azathioprine,
and ultralow-dose aspirin significantly improved short-and
long-term survival in dogs with IMHA. (J Am Vet
Med Assoc 2005;226:1869–1880)
Objective—To characterize signalment, clinical features, clinicopathologic variables, hepatic ultrasonographic characteristics, endocrinologic profiles, treatment response, and age at death of Scottish Terriers with progressive vacuolar hepatopathy (VH) with or without hepatocellular carcinoma (HCC).
Design—Retrospective case series.
Animals—114 Scottish Terriers with progressive VH.
Procedures—Electronic databases from 1980 to 2013 were searched for adult (age > 1 year) Scottish Terriers with histopathologic diagnoses of diffuse glycogen-like VH. Available sections of liver specimens were histologically reevaluated to confirm diffuse VH with or without HCC; 8 dogs with HCC only had neoplastic tissue available. Physical examination, clinicopathologic, treatment, and survival data were obtained.
Results—39 of 114 (34%) dogs with VH had HCC detected at surgery or necropsy or by abdominal ultrasonography. Histologic findings indicated that HCC was seemingly preceded by dysplastic hepatocellular foci. No significant differences were found in clinicopathologic variables or age at death between VH-affected dogs with or without HCC. Fifteen of 26 (58%) dogs with high hepatic copper concentrations had histologic features consistent with copper-associated hepatopathy. Although signs consistent with hyperadrenocorticism were observed in 40% (46/114) of dogs, definitive diagnosis was inconsistently confirmed. Assessment of adrenal sex hormone concentrations before and after ACTH administration identified high progesterone and androstenedione concentrations in 88% (22/25) and 80% (20/25) of tested dogs, respectively.
Conclusions and Clinical Relevance—Results suggested that VH in Scottish Terriers may be linked to adrenal steroidogenesis and a predisposition to HCC. In dogs with VH, frequent serum biochemical analysis and ultrasonographic surveillance for early tumor detection are recommended.
Objective—To determine signalments, clinical features, clinicopathologic variables, imaging findings, treatments, and survival time of cats with presumed primary copper-associated hepatopathy (PCH) and to determine quantitative measures and histologic characteristics of the accumulation and distribution of copper in liver samples of cats with presumed PCH, extrahepatic bile duct obstruction, chronic nonsuppurative cholangitis-cholangiohepatitis, and miscellaneous other hepatobiliary disorders and liver samples of cats without hepatobiliary disease.
Design—Retrospective cross-sectional study.
Animals—100 cats with hepatobiliary disease (PCH [n = 11], extrahepatic bile duct obstruction , cholangitis-cholangiohepatitis , and miscellaneous hepatobiliary disorders ) and 14 cats without hepatobiliary disease.
Procedures—From 1980 to 2013, cats with and without hepatobiliary disease confirmed by liver biopsy and measurement of hepatic copper concentrations were identified. Clinical, clinicopathologic, and imaging data were compared between cats with and without PCH.
Results—Cats with PCH were typically young (median age, 2.0 years); clinicopathologic and imaging characteristics were similar to those of cats with other liver disorders. Copper-specific staining patterns and quantification of copper in liver samples confirmed PCH (on the basis of detection of > 700 μg/g of liver sample dry weight). Six cats with PCH underwent successful treatment with chelation (penicillamine; n = 5), antioxidants (5), low doses of elemental zinc (2), and feeding of hepatic support or high-protein, low-carbohydrate diets, and other hepatic support treatments. One cat that received penicillamine developed hemolytic anemia, which resolved after discontinuation of administration. Three cats with high hepatic copper concentrations developed hepatocellular neoplasia.
Conclusions and Clinical Relevance—Results suggested that copper accumulates in livers of cats as primary and secondary processes. Long-term management of cats with PCH was possible.