Objective—To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the cornea, eyelid, and third eyelid of healthy horses and those affected with squamous cell carcinoma (SCC) by use of immunohistochemical techniques.
Animals—15 horses with SCC involving ocular tissues and 5 unaffected control horses.
Procedures—SCC-affected tissues were obtained from the cornea (n = 5 horses), eyelid (5), and third eyelid (5). Site-matched control tissues were obtained from 5 horses unaffected with SCC. Tissue sections of affected and control cornea, eyelid, and third eyelid were stained immunohistochemically for COX-1 and COX-2 via standard techniques. Stain uptake was quantified by use of computer-assisted image analysis of digital photomicrographs.
Results—Immunoreactivity for both COX-1 and COX-2 was significantly greater in equine corneas with SCC than in control corneas. No significant differences in COX-1 or COX-2 immunoreactivity were detected in eyelid and third-eyelid SCC, compared with site-matched control tissues.
Conclusions and Clinical Relevance—Immunoreactivity for COX-1 and COX-2 is high in equine corneal SCC, possibly indicating that COX plays a role in oncogenesis or progression of this tumor type at this site. Pharmacologic inhibition of COX may represent a useful adjunctive treatment for corneal SCC in horses.
Case Description—A 13-year-old llama was examined because of lethargy, inappetence, and syncope.
Clinical Findings—Physical examination revealed muffled heart and lung sounds and peripheral edema. Clinicopathologic abnormalities included lymphopenia, hyperglycemia, prerenal azotemia, mild hyponatremia, mild hypoalbuminemia, and high γ-glutamyltransferase and creatine kinase activities. On ultrasonography, the liver appeared hyperechoic and ascites and pleural effusion were seen. Echocardiography revealed severe dilatation of the right atrium, right ventricle, and pulmonary artery; severe tricuspid regurgitation; and high right ventricular systolic pressure consistent with right-sided heart failure secondary to pulmonary hypertension.
Treatment and Outcome—Treatment with furosemide was attempted, but because of failing health, the llama was euthanized 4 weeks later. Macronodular cirrhosis of the liver, glomerulonephritis, and intimal fibrosis and medial hypertrophy of muscular pulmonary arteries were seen on histologic examination of postmortem specimens.
Clinical Relevance—Findings in this case were similar to those reported for human patients with portopulmonary hypertension secondary to hepatic cirrhosis. Pulmonary hypertension secondary to hepatic disease should be considered in the differential diagnosis of right-sided heart failure.
Objective—To develop protocols for helical computed
tomography (CT) and axial high-resolution CT
(HRCT) of lungs and correlate densitometric CT values
with morphometric and histologic data for normal
pulmonary tissue in dogs.
Animals—8 healthy adult dogs.
Procedure—2 dogs were used to establish a protocol
for helical CT and HRCT of lungs. Six dogs were used
to acquire densitometric CT data regarding normal
lungs. After the dogs were euthanatized, their lungs
were fixed and sampled for morphometric and histologic
evaluation. Four CT acquisitions were compared
by means of paired t tests.
Results—For normal lung tissue of dogs, mean densitometric
CT value obtained during helical CT scans
reconstructed in a sharp algorithm was -846
Hounsfield units. Values obtained via helical CT or
HRCT acquisitions and reconstructed with sharp or
standard algorithms did not differ significantly.
Morphometric analysis was used to determine the
proportion of lung parenchymal (82%) and nonparenchymal
tissue (18%). Alveolar size, estimated by
mean linear intercept, was approximately 172 µm,
and alveolar surface area-to-volume ratio was 0.024 to
0.026 µm–1. Histologic evaluation confirmed the presence
of normal lung tissue.
Conclusions and Clinical Relevance—Correlation of
densitometric CT data with morphometric and histologic
findings and the establishment of helical CT and
HRCT protocols were attained; clinical use of this
information may facilitate investigation of pulmonary
disease in dogs. Sharp helical CT acquisitions were
preferred because of better lung parenchyma detail
and rapid image acquisitions, compared with HRCT.
(Am J Vet Res 2003;64:935–944)
Objective—To compare quantitative densitometric
computed tomography (CT), morphometric, and histologic
data of normal lungs in dogs with similar parameters
obtained after induction of an acute inflammatory
response and determine whether CT densitometry
correlated with histopathologic changes.
Animals—6 healthy adult dogs.
Procedure—After initial CT, 1 mL of 0.1M hydrochloric
acid (HCl) and 3 mL of autologous blood were instilled
into the right middle (RM) and caudal segment of the
left cranial (LCCd) lung lobes, respectively. Immediately
and 24 hours after instillation, CT was repeated. At 24
hours, dogs were euthanatized and lungs were fixed
and sampled for morphometric and histologic evaluation.
The CT data were compared with lung morphology
and morphometry by use of unpaired t tests.
Comparison with lungs from control dogs was performed
using Spearman rank correlation coefficients.
Results—Mean Hounsfield units (HU) from control
and baseline HU from experimental dogs were identical.
Immediately after instillation of HCl or blood, there
was increased attenuation in both lobes. Autologous
blood initially induced severe changes that almost
completely resolved at 24 hours; HCl induced severe
changes at 24 hours. Significant increases in percentage
of parenchymal airspace and alveolar diameter
resulted in decreased surface area-to-volume ratio in
lobes receiving HCl. Histologic scores were significantly
higher in the RM lobe, compared with controls.
Conclusions and Clinical Relevance—Computed
tomography attenuation correlated well with histomorphometry
and histologic findings in this model.
Lung lesions after autologous blood were transient
and of limited severity. Lesions induced by HCl were
severe; alterations in morphometric and histologic
parameters were reflected in CT attenuation measurements.
(Am J Vet Res 2004;65:1114–1123)
Objective—To compare distributions of survivin among tissues from urinary bladders of dogs with cystitis, transitional cell carcinoma (TCC), or histologically normal urinary bladders.
Sample Population—24 archived and 7 fresh-frozen specimens of urinary bladders from dogs with cystitis.
Procedures—Immunohistochemical analysis of archived tissue specimens was performed to identify survivin protein in the nucleus and cytoplasm of cells by use of polyclonal rabbit anti-survivin antibody. Tissues that contained ≥ 5% immunoreactive cells were considered positive for survivin protein. Reverse-transcription PCR analysis was performed on fresh-frozen tissues to identify survivin mRNA. Data on tissues from dogs with TCC or histologically normal urinary bladders that were obtained during another study were used for statistical comparisons.
Results—Twelve of 24 (50%) cystitic tissues were positive for nuclear survivin, compared with 28 of 41 (68%) TCC tissues and 0 of 46 (0%) normal tissues. Two of 24 (8%) cystitic tissues were positive for cytoplasmic survivin, compared with 7 of 41 (17%) TCC tissues and 17 of 46 (37%) normal tissues. Proportions of specimens that contained nuclear or cytoplasmic survivin were significantly different between cystitic and normal tissues but not between cystitic and TCC tissues. Four of 7 cystitic tissues were positive for survivin mRNA, which was comparable with results for TCC and normal tissues.
Conclusions and Clinical Relevance—Nuclear survivin was detected in TCC and cystitic tissues but not in normal urinary bladder tissues. Additional studies are needed to determine whether nuclear survivin contributes to the development or progression of TCC.
Objective—To determine immunoreactivity of matrix
metalloproteinase (MMP)-1, -3, and -13 in cartilaginous
tumors of dogs, correlate expression of MMP
with histologic grade of tumors and clinical outcome
of dogs, and compare MMP immunoreactivity
between chondrosarcomas and chondromas.
Sample Population—Formalin-fixed, paraffin-embedded
tissues obtained from samples of naturally occurring
chondrosarcomas (n = 31) and chondromas (8) of
dogs that were submitted to our veterinary medical
Procedure—Histologic sections from each sample
were stained with H&E and monoclonal antibody to
MMP-1, -3, and -13 by use of an avidin-peroxidase
immunohistochemical technique. For each section, histologic
grade (I, II, or III) and immunohistochemical
expression (0, 1, 2, or 3) were evaluated. Clinical outcome
was obtained from medical records or interviews
with referring veterinarians and scored as a good outcome,
moderate outcome, or poor outcome.
Correlations among variables and differences between
chondrosarcomas and chondromas were analyzed.
Results—Samples from chondrosarcomas had significantly
higher immunoreactivity of MMP-1 and -13,
compared with immunoreactivity in samples from
chondromas. In chondrosarcomas, a significant positive
correlation (r, 0.386) was found between MMP-1
and -13 immunoreactivities, and a significant negative
correlation (r, –0.390) was detected between MMP-3
and -13 immunoreactivities.
Conclusion and Clinical Relevance—A significant
increase in expression of collagenases (MMP-1 and -
13) in chondrosarcomas, compared with expression in
chondromas, suggests that collagenases may play an
important role in tumor progression, and possibly
metastasis, in chondrosarcomas of dogs. (Am J Vet
Objective—To evaluate the clinical and pathologic
characteristics of mammary duct ectasia in dogs.
Animals—51 dogs with mammary duct ectasia.
Procedure—Information regarding body condition,
history, number and location of affected mammary
glands, appearance of lesions, surgical treatment,
nonsurgical treatment, and evidence of recurrence or
development of mammary neoplasia was obtained
from surveys sent to referring veterinarians. Results
of information from examination of histologic sections
and referring veterinarians were evaluated for all
mammary duct ectasia biopsies performed between
1992 and 1999.
Results—Duct ectasia was the primary diagnosis in
51 of 1,825 (2.8%) mammary biopsy specimens and
comprised 48% of nonneoplastic mammary diseases.
Affected dogs were evenly distributed over a range of
1 to 13 years of age, with a mean age at the time of
diagnosis of 6.1 ± 3.1 years. All dogs were female (31
sexually intact, 20 spayed); 10 of 26 had whelped.
Duct ectasia was described as nodular (26 dogs), cystic
(13), and multiglandular (11) and located in caudal
(31) more often than cranial (14) or middle glands (10).
Ectasia recurred in 3 dogs. One dog had a history of
previously excised mammary adenocarcinoma; another
subsequently developed mammary carcinoma.
Conclusions and Clinical Relevance—Duct ectasia
affected mature, sexually intact and spayed female
dogs over a wide age range. Certain breeds were
affected more commonly than expected. Increased
risk for mammary neoplasia was not evident. Duct
ectasia should be considered as a cause for mammary
enlargement, especially in young dogs or when its
cystic nature is evident. Mastectomy is usually curative,
and neoplasia should be ruled out in dogs with
ectasia. (J Am Vet Med Assoc 2001;218:1303–1307)