Case Descriptions—A 4-year-old spayed female Golden Retriever (dog 1) was examined because of acute edema and erythema in the left hind limb and an inguinal mass, and a 5-year-old female Jack Russell Terrier (dog 2) was examined because of a recurring retro-peritoneal mass.
Clinical Findings—Dog 1 had an edematous, hyperemic left hind limb with a fixed inguinal mass. Monocytic neutrophilic leukocytosis and hypoalbuminemia were detected. Diagnostic imaging revealed abnormal tissue surrounding the larger vessels and ureters and complete occlusion of the left limb veins. Surgery resulted in incomplete removal of the mass. Histologic examination revealed fibrosing pyogranulomatous inflammation. Results of a Histoplasma antigen test were positive, and reanalysis of the tissues revealed yeast cells indicative of Histoplasma capsulatum. Dog 2 had incomplete removal of a retroperitoneal mass. Histologic examination revealed fibrosing pyogranulomatous inflammation. The mass recurred 8 months later in dog 2; exploratory abdominal surgery at that time resulted in substantial hemorrhage from the adhered caudal aorta. Histologic examination of tissue sections from the second surgery revealed yeast cells consistent with Blastomyces dermatitidis.
Treatment and Outcome—Both dogs had temporary improvement after surgery. Full clinical resolution required treatment for fungal disease. Dog 1 was treated with itraconazole, then fluconazole (total treatment time, 23 weeks). Dog 2 was treated with fluconazole for 36 weeks.
Clinical Relevance—Retroperitoneal pyogranulomatous fibrosis caused by fungal infections has not been reported in veterinary medicine. There was substantial morbidity, but the prognosis can be good when this abnormality is recognized and antifungal medications are administered.
Objective—To determine proportions of cats in which
feline infectious peritonitis (FIP) was diagnosed on an
annual, monthly, and regional basis and identify
unique characteristics of cats with FIP.
Sample Population—Records of all feline accessions
to veterinary medical teaching hospitals (VMTH)
recorded in the Veterinary Medical Data Base
between January 1986 and December 1995 and of all
feline accessions for necropsy or histologic examination
at 4 veterinary diagnostic laboratories.
Procedure—Proportions of total and new feline
accessions for which a diagnosis of FIP was recorded
were calculated. To identify characteristics of cats
with FIP, cats with FIP were compared with the next
cat examined at the same institution (control cats).
Results—Approximately 1 of every 200 new feline
and 1 of every 300 total feline accessions at VMTH in
North America and approximately 1 of every 100
accessions at the diagnostic laboratories represented
cats with FIP. Cats with FIP were significantly more
likely to be young, purebred, and sexually intact males
and significantly less likely to be spayed females and
discharged alive than were control cats. The proportion
of new accessions for which a diagnosis of FIP
was recorded did not vary significantly among years,
months, or regions of the country.
Conclusions and Clinical Relevance—Results indicated
that FIP continues to be a clinically important
disease in North America and that sexually intact
male cats may be at increased risk, and spayed
females at reduced risk, for FIP. The high prevalence
of FIP and lack of effective treatment emphasizes the
importance of preventive programs, especially in catteries.
(J Am Vet Med Assoc 2001;218:1111–1115)
Objective—To assess whether dogs with blastomycosis
produce antibodies against the WI-1 and A-antigens
of Blastomyces dermatitidis and whether the
antibodies are useful in serodiagnosis.
Sample Population—359 serum samples obtained
from 245 dogs.
Procedure—233 samples from 122 dogs with blastomycosis,
and 1 sample each from 24 dogs with suspected
blastomycosis, 51 control dogs without infection,
and 48 healthy dogs from an enzootic region
were obtained. Antibodies against WI-1 antigen were
detected by radioimmunoassay (RIA). Serum samples
were tested in parallel for antibodies against the Aantigen
of B dermatitidis by commercial agar-gel
immunodiffusion (AGID) in a reference laboratory.
Results—Antibodies were detected in 92% of infected
dogs by RIA and in 41% by AGID. For 29 serum
samples that were obtained 11 to 1,545 days after
diagnosis, antibodies were detected in 92% of samples
by RIA and 7% by AGID. For 93 serial serum
samples from 29 dogs with blastomycosis, the mean
anti-WI-1 titer was 1:18,761 at the time of diagnosis,
and decreased to a mean of 1:1,338 by 210 days after
treatment was initiated. Of 24 dogs with suspected
infection, antibodies were detected in 67% by RIA
and 33% by AGID. Control dogs without blastomycosis
had no detectable antibodies in either assay. Thus,
sensitivity was 92% for RIA and 41% for AGID, and
specificity was 100% for both tests.
Conclusions and Clinical Relevance—Anti-WI-1
antibodies are readily detected by RIA in dogs with
blastomycosis. Titers become high, decline during
treatment, and persist for months. Anti-A antibodies
are sometimes detected with AGID, but these
decrease quickly. (Am J Vet Res 2000;61:554–558)
Objective—To determine the prevalence of stray
dogs in eastern Tennessee seropositive to Ehrlichia
canis and examine the correlation between results for
an ELISA, indirect immunofluorescent antibody (IFA)
test, and polymerase chain reaction (PCR) assay.
Sample Population—Blood samples obtained from
90 adult dogs admitted to an animal shelter in eastern
Procedure—Serum samples were analyzed for antibodies
against E canis by use of a commercially available
ELISA kit, 2 IFA tests, and a PCR assay; testing
was performed at the University of Tennessee (TN)
and North Carolina State University (NCSU). The PCR
amplification was performed by use of DNA extracted
from EDTA-anticoagulated blood and primers
designed to amplify DNA of Ehrlichia spp.
Results—Antibodies against E canis were detected
in only 1 dog by use of the ELISA. By IFA testing at
TN, 10 of 90 (11%) dogs were seroreactive against E
canis antigens, all of which had medium to high titers
to E canis. Only 5 of the 10 TN seroreactors were also
reactive against E canis antigens in IFA tests conducted
at NCSU, and all 5 had low to medium titers.
The DNA of Ehrlichia spp was not amplified in any
blood samples by use of PCR assays conducted at
the TN or NCSU.
Conclusions and Clinical Relevance—The discordant
ELISA, IFA, and PCR results obtained in this study
were unexpected and may have been related to exposure
of dogs to an Ehrlichia species other than E canis,
such as E ewingii. (Am J Vet Res 2004;65:1200–1203)
Objective—To evaluate the ability of small interfering RNAs (siRNAs) to inhibit in vitro viral replication and gene expression of feline coronavirus (FCoV).
Sample—Cell cultures of Crandell-Rees feline kidney cells.
Procedures—5 synthetic siRNAs that each targeted a different region of the FCoV genome were tested individually and in various combinations for their antiviral effects against 2 strains of FCoV (feline infectious peritonitis virus WSU 79-1146 and feline enteric coronavirus WSU 79-1683) in cell cultures. Tested combinations targeted the FCoV leader and 3′ untranslated region, FCoV leader region and nucleocapsid gene, and FCoV leader region, 3′ untranslated region, and nucleocapsid gene. For each test condition, assessments included relative quantification of the inhibition of intracellular viral genomic RNA synthesis by means of real-time, reverse-transcription PCR analysis; flow cytometric evaluation of the reduction of viral protein expression in infected cells; and assessment of virus replication inhibition via titration of extracellular virus with a TCID50 infectivity assay.
Results—The 5 siRNAs had variable inhibitory effects on FCoV when used singly. Combinations of siRNAs that targeted different regions of the viral genome resulted in more effective viral inhibition than did individual siRNAs that targeted a single gene. The tested siRNA combinations resulted in approximately 95% reduction in viral replication (based on virus titration results), compared with findings in negative control, nontargeting siRNA–treated, FCoV-infected cells.
Conclusions and Clinical Relevance—In vitro replication of FCoV was specifically inhibited by siRNAs that targeted coding and noncoding regions of the viral genome, suggesting a potential therapeutic application of RNA interference in treatment of feline infectious peritonitis.
Case Description—An 8-year-old domestic shorthair cat was evaluated because of signs of depression, circling, and visual deficits.
Clinical Findings—The cat had no cutaneous lesions, and results of an ophthalmologic examination and thoracic radiography were within reference limits. Computed tomography of the brain revealed a mass lesion involving the right parietal, temporal, and occipital lobes; the mass was in broad-based contact with the skull and smoothly marginated and had strong homogenous enhancement after contrast agent administration. During craniectomy, samples of the mass were collected for cytologic and histopathologic evaluations and microbial culture. A diagnosis of Blastomyces dermatitidis—associated meningoencephalitis with secondary pyogranulomatous inflammation was made.
Treatment and Outcome—Amphotericin B (0.25 mg/kg [0.11 mg/lb], IV) was administered on alternate days (cumulative dose, 1.75 mg/kg [0.8 mg/lb]). To minimize the risk of nephrotoxicosis, assessments of serum biochemical variables (urea nitrogen and creatinine concentrations) and urinalyses were performed at intervals. The third dose of amphotericin B was postponed 48 hours because the cat became azotemic. The cat subsequently received fluconazole (10 mg/kg [4.5 mg/lb], PO, q 12 h) for 5.5 months. Six months after discontinuation of that treatment, the cat appeared healthy and had no signs of relapse.
Clinical Relevance—Brain infection with B dermatitidis is typically associated with widespread disseminated disease. The cat of this report had no evidence of systemic disease. Blastomycosis of the CNS should be considered as a differential diagnosis for brain lesions in cats from areas in which B dermatitidis is endemic.
OBJECTIVE To determine the pharmacokinetics of orally administered rapamycin in healthy dogs.
ANIMALS 5 healthy purpose-bred hounds.
PROCEDURES The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography–tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses.
RESULTS Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.
Objective—To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment.
Animals—132 dogs with nonresectable grade 2 or 3 MCTs.
Procedures—Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time.
Results—In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib.
Conclusions and Clinical Relevance—Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs.