Treatment of Disseminated Aspergillosis with Posaconazole in 10 Dogs.

BACKGROUND: Few effective treatments for disseminated Aspergillus infections in dogs are available. Posaconazole has potent and broad-spectrum activity against Aspergillus spp., but its use has not yet been sufficiently evaluated in dogs. HYPOTHESIS/OBJECTIVES: The aim of this study was to determine the safety and efficacy of posaconazole for the treatment of naturally occurring disseminated Aspergillus infections in dogs. ANIMALS: Ten client-owned dogs with disseminated aspergillosis. METHODS: Prospective, nonrandomized, noncontrolled study with posaconazole administered to dogs at dosage of 5 mg/kg p.o. q12h. The primary veterinarian or the veterinary specialist caring for the dogs provided patient data. RESULTS: The treatment response for dogs with disseminated disease while receiving posaconazole was defined as clinical remission (n = 4) and clinical improvement (n = 6). There was a high rate of relapse during treatment or after cessation of treatment in both groups, and most dogs died or were euthanized due to progressive disease. Excluding 1 dog concurrently treated with terbinafine that remains alive 5 years after diagnosis, the mean survival time for dogs was 241 days (range 44-516 days). Three other dogs lived >1 year after starting treatment. No clinically relevant adverse events or increases in serum liver enzyme activity occurred during treatment with posaconazole. CONCLUSIONS AND CLINICAL IMPORTANCE: Posaconazole appears to be safe and well-tolerated for treatment of disseminated Aspergillus infections in dogs. Long-term survival >1 year is possible with prolonged treatment, but relapse is common.

Masitinib mesylate for metastatic and non-resectable canine cutaneous mast cell tumours.

Masitinib mesylate is a tyrosine kinase inhibitor approved for the treatment of gross, non-metastatic grade II and III canine mast cell tumours (MCTs). This study evaluated the use of masitinib as a frontline and rescue agent for metastatic and non-metastatic canine MCTs. Identification of toxicities and prognostic factors in these dogs was of secondary interest. Twenty-six dogs were included in this study. The overall response rate to masitinib was 50%. The median survival time for dogs that responded to masitinib was 630 days versus 137 days for dogs that did not respond (P = 0.0033). Toxicity was recorded in 61.5% of treated dogs, but the majority of adverse events were mild and self-limiting. Response to masitinib, not tumour grade, stage or location, was the most significant prognostic factor for survival in dogs with MCTs.

Review paper: Cancer chemopreventive compounds and canine cancer.

Canine cancer has become more prevalent in recent years because of increased life expectancy and greater attention to the health of pets. The range of cancers seen in dogs is as diverse as that in human patients, and despite more intensive therapeutic interventions, fatality rates remain unacceptably high in both species. Chemoprevention is therefore an important means of confronting this disease. Because domestic pets share our environment, greater cross-application and study of the protumorigenic and antitumorigenic factors in our shared environment will benefit all species, leading to the development of new families of less toxic antitumorigenic compounds based on novel and established molecular targets. Currently, the most interesting cancer preventive agents are nonsteroidal anti-inflammatory drugs, peroxisome proliferator-activated receptor-gamma ligands, and dietary compounds. This article provides an overview of what is known about how these agents affect molecular signaling in neoplastic disease, with reference to reported application and/or study in dogs where available.

Antigen and antibody testing for the diagnosis of blastomycosis in dogs.

BACKGROUND: Early diagnosis and treatment are associated with an improved prognosis in blastomycosis. The diagnosis of blastomycosis may be missed by cytology, histopathology, culture, or serology. An enzyme immunoassay (EIA) for detection of Blastomyces dermatitidis galactomannan antigen in body fluids has been used for rapid diagnosis of blastomycosis in humans. HYPOTHESIS: Measurement of Blastomyces antigen in urine or serum by the MVista Blastomyces antigen EIA is more sensitive than measurement of anti-Blastomyces antibodies for diagnosis of blastomycosis in dogs. METHODS: Serum and urine samples from 46 dogs with confirmed blastomycosis were tested for Blastomyces antigen and serum was tested for anti-Blastomyces antibodies. RESULTS: The sensitivity for the detection of antigen in urine was 93.5% and it was 87.0% in serum. The sensitivity of antibody detection by agar gel immunodiffusion (AGID) was 17.4% and it was 76.1% by EIA. Antigen and antibody decreased during itraconazole treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Antigen detection is a more sensitive test for diagnosis of blastomycosis than antibody testing by AGID, the only commercially available method. Antigen concentrations decreased with treatment.

Effects of L-asparaginase on plasma amino acid profiles and tumor burden in cats with lymphoma.

BACKGROUND: L-Asparaginase (Elspar(a)), is an Escherichia coli-derived enzyme that depletes lymphoma cells of asparagine, inhibiting protein synthesis and resulting in cell death. The single agent response rate in cats with lymphoma and impact of L-asparaginase on plasma amino acid concentrations is unknown. HYPOTHESES: L-Asparaginase significantly reduces plasma asparagine concentrations and has demonstrable efficacy against untreated lymphoma in cats. ANIMALS: Thirteen cats with confirmed lymphoma (LSA) of any anatomic site were given 1 dose 400 IU/kg IM) of L-asparaginase for initial LSA treatment. METHODS: Plasma collected at 0, 2, and 7 days after L-asparaginase therapy was assayed for ammonia, asparagine, aspartic acid, glutamine, and glutamic acid concentrations. Cats were restaged 7 days later to assess tumor response. RESULTS: Eight cats had T-cell LSA, 4 cats had B-cell LSA, and 1 cat's immunophenotype was unknown. Two complete and 2 partial responses to L-asparaginase were seen. Four cats had stable disease, and 5 cats had progressive disease. Ammonia and aspartic acid concentrations were increased from baseline at 2 and 7 days posttreatment. Asparagine concentrations were decreased from baseline at 2 days but not 7 days posttreatment. Glutamic acid concentrations were increased at day 2 compared to day 7 posttreatment but not compared to baseline. Glutamine concentrations were unchanged. CONCLUSIONS AND CLINICAL IMPORTANCE: L-asparaginase significantly reduced asparagine concentrations within 2 days of treatment, but this effect was lost within 7 days. The apparent overall response rate of feline LSA to L-asparaginase in this study was 30%.

Blastomyces dermatitidis antigen detection in urine specimens from dogs with blastomycosis using a competitive binding inhibition ELISA.

A competitive binding inhibition enzyme linked immunosorbent assay (ELISA) was used to detect Blastomyces dermatitidis antigens in urine specimens from dogs with blastomycosis. Sera from rabbits immunized with B. dermatitidis killed whole yeast cells were used as the primary antibody in the competitive ELISA. This initial study was performed to determine if B. dermatitidis antigen detection was possible and to test the efficacy of the rabbit sera as a primary antibody. An indirect ELISA was also performed to compare antigen detection in urine to antibody detection in the sera of the infected dogs. The results indicate 100% (36/36 specimens) detection of both antigen and antibody. Cross reactivity with Histoplasma capsulatum, as well as non-specific binding with the normal urine specimens, was observed with the competitive binding inhibition ELISA.

Ultrasonographic and cytopathological diagnosis of exocrine pancreatic carcinoma in the dog and cat.

This study describes the ultrasonographic and cytopathological characteristics of malignant neoplasms of the exocrine pancreas and their value in making an antemortem diagnosis. The medical records of eight dogs and five cats were reviewed. The clinical presentations were variable and at times mimicked pancreatitis. Overall, cytopathology of ultrasound or fluoroscopic-guided biopsies or fine-needle aspirates, or impressions from surgical biopsies were helpful in establishing the diagnosis in 10 of 12 animals where it was performed. Histopathology of ultrasound or fluoroscopic-guided biopsies provided a diagnosis in five of six cases where it was performed.

Epidemiology of feline infectious peritonitis among cats examined at veterinary medical teaching hospitals.

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. DESIGN: Case-control study. 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.

Canine antibody response to Blastomyces dermatitidis WI-1 antigen.

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 A-antigen 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.

Probable hypercalcemia of malignancy in a cat with bronchogenic adenocarcinoma.

An eight-year-old, neutered male, domestic shorthair cat was referred with a four-day history of acute vomiting. Hypercalcemia was identified on serum biochemical testing. Thoracic radiographs showed multiple pulmonary nodular densities. Postmortem and histopathological examination identified the nodules as bronchogenic adenocarcinoma with metastases to the tracheobronchial lymph nodes, diaphragm, and parietal pleura. To the authors' knowledge, this is the first reported case of hypercalcemia of malignancy associated with bronchogenic adenocarcinoma in a cat.

Fecal shedding of feline coronavirus in adult cats and kittens in an Abyssinian cattery.

OBJECTIVE: To determine patterns of fecal shedding of feline coronavirus (FCV) by cats, age at which kittens first began to shed FCV in their feces, and whether there was any relationship between fecal shedding of FCV and serum antibody titers in adult cats or kittens. DESIGN: Prospective observational study. ANIMALS: 15 adult cats and 18 kittens from a single cattery. PROCEDURE: Blood and fecal samples were collected from adult cats every other month for 13 months. Serum FCV antibody titers were measured by use of an indirect immunofluorescence assay. A reverse-transcriptase, nested polymerase chain reaction assay was used to detect FCV in feces. Blood and fecal samples were collected from kittens at approximately 2-week intervals from 3 weeks to 15 weeks of age. RESULTS: Adult cats shed FCV intermittently. All adult cats shed virus in their feces at least once during the year, and 4 of 15 shed virus > 75% of the time. Serum antibody titer was not significantly associated with shedding of FCV. For the kittens, median age at the time FCV was first detected in feces was 67 days (range, 33 to 78 days). All except 1 of the kittens was found to be shedding virus in their feces before or at the time of seroconversion. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that serum FCV antibody titers are not a good indicator of shedding of FCV in the feces. Kittens may shed FCV in their feces before they seroconvert, and all kittens in a cattery in which FCV infection is endemic may be infected before 12 weeks of age.

Owner experiences with home use of a gastrostomy tube in their dog or cat.

OBJECTIVE: To describe owner experiences with gastrostomy tubes used at home. DESIGN: Telephone survey. ANIMALS: 20 cats and 5 dogs. PROCEDURE: Owner's opinions obtained by phone interview. RESULTS: Although 32% (8/25) of owners were initially reluctant to feed their cat or dog through the gastrostomy tube, 92% (22/24) of owners became comfortable with the procedure. Eighty-four percent (21/25) of owners were able to feed their dog or cat unassisted; 16% (4/25) required another person to help. Median time required for feeding was 19.8 minutes. Ninety-six percent (24/25) of owners believed their dog or cat was comfortable with the procedure. Eighty-four percent (21/25) of owners experienced complications or difficulties. Most problems involved bandage maintenance, administration of food through the syringe and tube, or acquisition of syringes and special foods. Ninety-six percent (22/23) of owners would be willing to use a gastrostomy tube again. CLINICAL IMPLICATIONS: Most owners had positive experiences with the feeding experience and would be willing to use gastrostomy tube feeding again. Difficulties encountered by owners were not serious and could be avoided by specific client instruction.

Immunological and chemical characterization of glycoproteins in IEF fractions of Blastomyces dermatitidis yeast lysate antigen.

After isoelectric focusing (IEF), fractions of a Blastomyces dermatitidis yeast lysate antigen were analysed for the presence of glycoproteins that may lead to cross-reactivity in immunoassays for the diagnosis of blastomycosis. Five major glycoproteins were apparent, two of which showed cross-reactivity when used in Western blots with sera obtained from dogs with histoplasmosis and coccidioidomycosis. These five glycoproteins were characterized for linkage to the proteins using N-glycosidase F (NGF) and for their lectin binding properties. The cross-reactive 235- and 160-kDa glycoproteins were found to possess mainly O-linked, high-mannose-type carbohydrates, and periodate-mediated oxidation of these molecules eliminated cross-reactivity observed with heterologous sera. Thus, the periodate-treated IEF antigens described here may be useful in solid-phase enzyme immunoassays for the diagnosis of blastomycosis.

Effect of infusion regime on doxorubicin pharmacokinetics in the cat.

In the pharmacokinetic evaluation of a single doxorubicin dose calculated by body surface area (25 mg/m2) or body weight (1 mg/kg body weight) and given intravenously as a 10-, 15-, or 20-minute infusion, the rate of doxorubicin infusion (mg per minute per m2 or mg per minute per kg) correlated positively with clearance and the distribution rate constant alpha, and it inversely correlated with area under the plasma concentration versus time curve (AUC). These findings suggest that a slower infusion rate results in a greater AUC and longer distribution phase than a faster infusion rate and indicates the importance of normalizing dosage regimes by infusion rate rather than by infusion duration when considering dose-response phenomena in veterinary patients.

Dose response and time course of carboplatin-induced micronucleated polychromatic erythrocytes in the cat: implications for combination carboplatin chemotherapy.

The dose response and time course of micronucleated polychromatic erythrocytes (mPCE) in cat peripheral blood induced by various doses (150-250 mg/m2) of carboplatin in vivo was determined. The data indicate that carboplatin produced a significant (p < 0.05) dose-dependent increase in the number of mPCE over baseline values; however, the times following carboplatin administration when mPCE were first observed differed significantly (p < 0.05) between the three carboplatin dose groups. mPCE were present in significantly greater numbers (p < 0.05) on smears at an earlier time interval following a single carboplatin dose of 150 mg/m2 than for a dose of either 200 or 250 mg/m2. The peak number of mPCE occurred on days 7, 14 and 17.5 following administration of a carboplatin dose of 150, 200 and 250 mg/m2, respectively. The pattern of time course delay following carboplatin administration suggests that the block of erythropoietic stem cells in G2 is dose dependent. Indeed, the administration of carboplatin arrested the cell cycle in the G2 phase and, at higher doses, diminished the number of cycling erythroid precursor cells. mPCE were apparent in blood smears only after recovery from this arrest and resumption of replication. This observation has implications for the scheduling of carboplatin administration when used in combination with other anticancer drugs.

Hematologic and systemic toxicoses associated with carboplatin administration in cats.

OBJECTIVE: To determine prevalence and severity of carboplatin-induced dose-limiting toxicoses in the cat. ANIMALS: 9 healthy, 6- to 7-month-old cats weighing 4.7 (range, 3.0 to 6.5) kg. PROCEDURE: Cats were given a single i.v. bolus of carboplatin at a dosage of 150 (n = 3), 200 (n = 3), or 250 (n = 3) mg/m2 of body surface area. RESULTS: Dose-limiting neutropenia and thrombocytopenia were significant in all cats given carboplatin at 200 or 250 mg/m2. Weight loss, changes in appetite, and evidence of respiratory difficulty, as well as vomiting, diarrhea, or lethargy were not observed at any time during the 28-day period. At a highest dosage (250 mg/m2), the neutrophil nadir (560 +/- 303 neutrophils/microliters) was observed on day 17 and the platelet count nadir (96,500 +/- 11,815 platelets/microliters) was observed on day 14 after carboplatin administration. CONCLUSIONS: Carboplatin appears to be safe and clinically well-tolerated when given i.v. as a single bolus at a dosage of 200 mg/m2 to clinically normal cats. The dose-limiting toxicity of a single i.v. administered bolus is neutropenia. The nadir of a 200 mg/m2 i.v. administered dose occurs on day 17 (1,110 +/- 165 neutrophils/microliters) and neutropenia (< 2,000 neutrophils/microliters) lasts from day 14 through day 25 after carboplatin administration. CLINICAL RELEVANCE: The fatal dose-related pulmonary toxicosis observed in cisplatin-treated cats was inapparent in carboplatin-treated cats. To adequately determine the therapeutic role of carboplatin in tumor-bearing cats, a moderately tolerated dose of carboplatin of 200 mg/m2 given i.v. once every 4 weeks should be considered.

Changes in renal function in cats following treatment of hyperthyroidism using 131I.

Changes in renal function of twenty-two cats treated for hyperthyroidism using radioiodine were evaluated. Serum thyroxine (T4), serum creatinine, blood urea nitrogen (BUN) and urine specific gravity were measured before treatment and 6 and 30 days after treatment. Twenty-two cats had pretreatment and 21 cats had 6 day posttreatment measurement of glomerular filtration rate (GFR) using nuclear medicine imaging techniques. There were significant declines in serum T4 at 6 days following treatment, but the changes in GFR, serum creatinine and BUN were not significant. At 30 days following treatment, there were significant increases in BUN and serum creatinine and further significant declines in serum T4. Nine cats were in renal failure prior to treatment and 13 cats were in renal failure 30 days following treatment. Renal failure was defined as BUN greater than 30 mg/dl and/or serum creatinine greater than 1.8 mg/dl with concurrent urine specific gravity less than 1.035. These 13 cats included eight of 9 cats in renal failure prior to treatment and 5 cats not previously in renal failure. Follow up information beyond 30 days following treatment on 9 of these 13 cats indicated that all remained in renal failure. Based on receiver operating curve analysis of pretreatment glomerular filtration rate (GFR) in predicting posttreatment renal failure, a value of 2.25 ml/kg/min as a point of maximum sensitivity (100%) and specificity (78%) was derived. Fifteen of 22 cats had pretreatment GFR measurements of less than 2.25 ml/kg/min. These 15 cats included all 9 cats in renal failure and 5 cats with normal renal clinicopathologic values prior to treatment. At 30 days following treatment, 13 of these 15 cats were in renal failure. The 2 cats not in renal failure had persistently increased serum T4 values. Seven of 22 cats had pretreatment GFR measurements greater than 2.25 ml/kg/min. None of these 7 cats was in renal failure at 30 days following treatment, all cats having normal BUN, serum creatinine, and urine specific gravity values. It was concluded that significant declines in renal function occur after treatment of hyperthyroidism and this decline is clinically important in cats with renal disease. Pretreatment measurement of GFR is valuable in detecting subclinical renal disease and in predicting which cats may have clinically important declines in renal function following treatment.

Basophilic leukemia in a dog.

Basophilic leukemia with thrombocytosis was diagnosed in a 4-year-old Shih Tzu. This diagnosis was based on cytochemical staining and cytologic examination of blood and bone marrow smears. Hydroxyurea, an inhibitor of DNA synthesis, at a dose of 50 mg/kg PO bid induced hematologic remission after 7 days of treatment. Adverse effects observed included pruritus, erythema of the ventral abdomen, generalized alopecia, and possibly, diabetes mellitus. The dog remained in remission for 21 months before becoming lethargic, at which time the owners requested euthanasia but did not allow a necropsy.