Treatment of canine hypoadrenocorticism with microcrystalline desoxycorticosterone pivalate

The efficacy of a microcrystalline desoxycorticosterone pivalate (DOCP) injection in the management of canine hypoadrenocorticism (CHAC) was investigated in 21 dogs. On day 0 dogs previously diagnosed with CHAC were given a physical examination and an injection (2.2 mg/kg) of DOCP. This was repeated on days 25 and 50. On day 75 of the study a final physical examination was performed and the success of therapy was evaluated. Blood samples were obtained for serum chemical analysis (Na+, K+, Cl-, BUN & creatinine) on day 0 and day 75. Body weight increased steadily from a mean (+/- SD) of 25.5 +/- 14.2 kg on day 0 to 27.1 +/- 14.8 kg on day 75. The mean serum biochemistry values on day 0 were outside normal limits for Na+ (139.3 +/- 9.2 mEq/l), K+ (5.4 +/- 0.9 mEq/l), and Na+/K+ ratio [(26.4 +/- 4.8)/l]. On day 75, after three injections of DOCP, the values for Na+ (148.2 +/- 5.2 mEq/l), K+ (4.9 +/- 0.6 mEq/l), and Na+/K+ [(30.8 +/- 4.2)/l] were normal and significantly (P less than 0.01) different from values on day 0. All dogs in the study did well on DOCP therapy. The few side effects observed resolved with concomitant administration of prednisolone and/or adjustment of the DOCP dose. All clients elected to continue DOCP therapy after the trial ended, and the dogs continue to do well.     

Use of a point-of-care urine drug test in a dog to assist in diagnosing barbiturate toxicosis secondary to ingestion of a euthanized carcass

Objective – To describe a case of barbiturate toxicosis in a dog secondary to ingestion of a previously buried euthanized goat carcass and to discuss the utility of urine drug testing in diagnosing barbiturate toxicosis.
Case Summary – A 6-year-old neutered male Border Collie was presented to a university veterinary teaching hospital for evaluation of ataxia and acute collapse. Past pertinent history included Addison's disease that had been managed for 1 year. A companion dog was seen 12 hours earlier chewing on the partially decomposed head of a goat that had been euthanized 47 days previously and buried on the owner's property. The dog was laterally recumbent, unresponsive to stimuli, and hypothermic on physical examination. Initial blood work revealed hyponatremia and hyperkalemia, with a Na/K ratio of 18.5. The dog was volume resuscitated and received an injection of dexamethasone sodium phosphate due to a suspected Addisonian crisis. Despite this treatment, the dog remained laterally recumbent and unresponsive to stimuli. A urine drug screen was performed and was positive for barbiturates. A diagnosis of barbiturate toxicosis secondary to ingestion of a euthanized goat carcass was made. The dog was treated supportively over 12 hours with IV fluids and activated charcoal. The dog was able to walk 11 hours after presentation and was subsequently discharged from the hospital.
New or Unique Information Provided – Urine drug testing is a fast, easy, and point-of-care test that may be useful in dogs to assist in the diagnosis of barbiturate intoxication. Proper disposal of euthanized animals is necessary to prevent toxicosis and possible death of companion animals and wildlife.     

Risk factors for nuisance barking in dogs

Objective   To determine the key variables related to the environment, animal and owner that influence nuisance barking by dogs in a city with a subtropical climate.
Design and Population   A case–control survey of dog owners in Brisbane, Queensland, was conducted using a questionnaire investigating key variables connected to nuisance barking. Owners of dogs exhibiting nuisance barking were obtained from a list of dogs being treated in a Brisbane behaviour clinic, and those of control dogs were selected from a telephone directory.
Results   Univariate analysis showed that animal, owner and environmental factors all potentially influence the occurrence of nuisance barking. Multivariate analysis identified the following factors, with the relevant odds ratios (OR) as significant: age of the dog (young dog vs old dog, OR 11.2); multiple dogs in the household vs single (OR 5.6); origin of the dog (home bred vs obtained from breeder or friend, OR 4.0); type of dog, (herding vs other types, OR 3.2) and dog with access to the home vs dog without access (OR 2.5).
Conclusion   The greatest risk for nuisance barking occurs with a young dog of the herding type that is home bred and with access to the house in a multiple dog household.     

A retrospective analysis of the efficacy of Oncept vaccine for the adjunct treatment of canine oral malignant melanoma

Oral malignant melanoma (OMM) in the dog is often locally aggressive with a high metastatic potential and there are few treatment options that have been demonstrated to improve outcome of this disease. The purpose of this study was to determine whether adjunctive treatment with the Oncept melanoma vaccine affected the outcome of dogs with OMM that had achieved loco‐regional cancer control. Medical records from 45 dogs that presented to the Animal Cancer and Imaging Center were reviewed, including 30 dogs with stage II and III disease. Dogs that received the vaccine did not achieve a greater progression‐free survival, disease‐free interval or median survival time than dogs that did not receive the vaccine.     

Total observed error,total allowable error,and QC rules for canine serum and urine cortisol achievable with the Immulite 2000 Xpi cortisol immunoassay

Determining a simple quality control (QC) rule for daily performance monitoring depends on the desired total allowable error (TEa) for the measurand. When no consensus TEa exists, the classical approach of QC rule validation cannot be used. Using the results of previous canine serum and urine cortisol validation studies on the Immulite 2000 Xpi, we applied a reverse engineering approach to QC rule determination, arbitrarily imposing sigma = 5, and determining the resulting TEa for the QC material (QCM; TEa_QCM) and the resulting probability of error detection (P_ed) for each QC rule. For the simple QC rule 1_2.5S with P_ed = 0.96 and probability of false rejection (P_fr) = 0.03, the associated TEa_QCM were 20% and 35% for serum and 28% and 24% for urine QCM1 and QCM2. If these levels of TEa_QCM are acceptable for interpretation of patient sample results, then users can internally validate the 1_2.5S QC rule, provided that their QCM CVs and biases are similar to ours. Otherwise, more stringent QC rules can be validated by using a lower sigma to lower the TEa_QCM. With spiked samples (relevant cortisol concentrations in the veterinary patient matrix) at 38.6 and 552 nmol/L of cortisol, TEa_QCM at sigma = 5 were much higher (54% and 40% for serum; 90.3% and 42.8% for urine). Spiked samples generate TEa that is probably too high to be suitable for daily QC monitoring; however, it is crucial to verify spiked sample observed total error (TEo; 26% and 18% for serum, 60% and 30% for urine) < TEa_QCM, and to use spiked sample TEo for patient result interpretation. In the absence of consensus TEa for cortisol in dogs, we suggest the use of a 1_2.5S rule, provided that users accept the associated level of TEa_QCM also as clinical TEa for results interpretation.     

Radiation therapy for canine appendicular osteosarcoma

Radiation therapy (RT) for the management of canine appendicular osteosarcoma (OSA) can be described as either palliative‐ or curative intent. Palliative RT uses coarsely fractionated external beam RT or radiopharmaceuticals to provide relief of pain and lameness associated with OSA while resulting in minimal, if any, radiation‐induced acute adverse effects. Limb amputation and chemotherapy are considered (together) the standard of care for curative‐intent treatment of canine appendicular OSA. When limb amputation is not possible, RT can be used for limb sparing and is supplemented with chemotherapy for presumed micrometastatic disease. Fractionated tumour irradiation with curative intent appears to be ineffective and local disease control can more likely be achieved when stereotactic radiosurgery or intra‐operative extracorporeal irradiation is combined with strict case selection and adjunctive chemotherapy. The availability of limb‐sparing RT is limited by experience and availability of specialised equipment. When planned and administered appropriately, radiation‐associated adverse effects are often mild and self‐limiting.     

Validation study of canine serum cortisol measurement with the Immulite 2000 Xpi cortisol immunoassay

We report the results of validation of canine serum cortisol determination with the Immulite 2000 Xpi cortisol immunoassay (Siemens), with characterization of precision (CV), accuracy (spiking-recovery [SR] bias), and observed total error (TEo = bias + 2CV) across the reportable range, specifically at the most common interpretation thresholds for dynamic testing. Imprecision increased at increasing rate with decreasing serum cortisol concentration and bias was low, resulting in increasing TEo with decreasing serum cortisol concentration. Inter-laboratory comparison study allowed for determination of range-based bias (RB) and average bias (AB). At 38.6 and 552 nmol/L (1.4 and 20 μg/dL), between-run CV was 10% and 7.5%, respectively, and TEo ~30% and ~20%, respectively (TEo remained similar regardless of the considered bias: SR, RB, or AB). These analytical performance parameters should be considered in the interpretation of results and for future expert consensus discussions to determine recommendations for allowable total error (TEa). Importantly, the commonly used thresholds for interpretation of results were determined ~40 y ago with different methods of measurements and computation, hence updating is desirable. Quality control material (QCM) had between-run imprecision of 4% for QCM1 and 7% for QCM2; the bias was minimal for both levels. Acceptable QC rules are heavily dependent on the desired TEa for the QCM system (TEa_QCM), itself limited by the desired clinical TEa. At low TEa_QCM (20–33%), almost no rules were acceptable, whereas at high TEa_QCM (50%), almost all rules were acceptable; further investigation is needed to determine which TEa_QCM can be guaranteed by simple QC rules.     

Inhibition of telomerase in canine cancer cells following telomestatin treatment

Telomere shortening in normal somatic cells has been proposed as a major barrier to unlimited cellular proliferation. Telomerase is an enzyme capable of maintaining telomere length, and thus bypassing this barrier. In human beings, telomerase activity is restricted to cancer cells and cells of stem or germ cell lineages. Dogs represent a potentially useful clinical model for the development of telomerase‐based therapies because telomerase activity is also restricted to cancer cells and stem cells in this species. We examined the ability of telomestatin to inhibit telomerase activity in telomerase‐positive D17 and CMT7 canine cancer cell lines. At a concentration of 2 μM, telomestatin treatment resulted in a decrease in telomerase activity, telomere shortening, growth inhibition and apoptosis in telomerase‐positive cancer cells. These effects were not seen in telomerase‐negative skin fibroblasts or negative controls. These results confirm that telomestatin specifically inhibits telomerase activity in canine cancer cells and strengthens the usefulness of dogs as a model for testing telomerase‐based therapies.     

Validation study of canine urine cortisol measurement with the Immulite 2000 Xpi cortisol immunoassay

We report here validation of the Immulite 2000 Xpi cortisol immunoassay (Siemens; with kit lot numbers <550) for measurement of urine cortisol in dogs, with characterization of the precision (CV), accuracy (spiking-recovery [SR] bias), and observed total error (TEo = bias + 2CV) across the reportable range. Linearity assessed by simple linear regression was excellent. Imprecision, SR bias, and TEo increased markedly with decreasing urine cortisol concentration. Interlaboratory comparison studies determined range-based (RB) bias and average bias (AB). The 3 biases (SR, RB, and AB) and resulting TEo differed markedly. At 38.6 and 552 nmol/L (1.4 and 20 μg/dL), between-run CVs were 10% and 4.5%, respectively, and TEo_RB were ~30% and 20%, respectively, similar to observations in serum in another validation study. These analytical performance parameters should be considered for urine cortisol:creatinine ratio (UCCR) result interpretation, given that, for any hypothetical errorless urine creatinine measurement, the error % on UCCR mirrors the error % on urine cortisol. Importantly, there is no commonly used interpretation threshold for UCCR, given that UCCR varies greatly depending on measurement methods and threshold computation. To date, there is no manufacturer-provided quality control material (QCM) with target values for urine cortisol with an Immulite; for Liquicheck QCM (Bio-Rad), between-run imprecision was ~5% for both QCM levels. Acceptable QC rules are heavily dependent on the desired total allowable error (TEa) for the QCM system, itself limited by the desired clinical TEa.     

Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma

Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T‐lymphocyte (CD3), FOXP3+ cell, B‐lymphocyte (Pax‐5), and CD204+ macrophage infiltration. We found that T‐lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T‐ and B‐lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti‐tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.     

Toxicity and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of canine appendicular osteosarcoma following limb amputation

Objective To evaluate the safety and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of dogs with appendicular osteosarcoma following limb amputation. Design Retrospective study. Procedure Dogs diagnosed with appendicular osteosarcoma, with no evidence of metastatic disease, treated with amputation and adjuvant chemotherapy consisting of two doses of doxorubicin given 14 days apart, followed by four doses of carboplatin at 3‐weekly intervals between September 2003 and December 2009 were identified from the medical records of Perth Veterinary Oncology. Haematological and gastrointestinal toxicities were assessed based on information in the medical records and recorded complete blood count results. The efficacy of the protocol was assessed by determining the median disease‐free interval (DFI) and overall survival time (OST) using the Kaplan‐Meier product‐limit method. Results In total, 33 dogs met the inclusion criteria. The median DFI was 231.5 days and the median OST was 247 days. With regard to haematological toxicity, 56% of dogs had a grade 1–2 neutropenia recorded as their highest marrow toxicity and 9% of dogs experienced a grade 3–4 neutropenia, all subsequent to doxorubicin administration. The highest gastrointestinal toxicity was grade 1–2 in 15 dogs (47%) and 5 dogs (16%) experienced grade 3–4 gastrointestinal toxicity. Conclusion This chemotherapy protocol did not result in a longer time to disease recurrence or OST in this population of dogs. Dual‐agent protocols have failed to improve survival times and therefore we conclude that a single‐agent protocol using carboplatin may be equally effective with less toxicity.     

Use of low dose prostaglandin for the treatment of canine pyometra

Ten bitches with pyometra were treated with prostaglandin F_2α at a dose of 20 μg/kg bodyweight three times daily on consecutive days. Diagnosis was based on clinical signs and radiographic findings. Venous blood samples were collected for haematology and measurement of plasma progesterone levels. The response to treatment was monitored by repeated ultrasonic examinations. The treatment was continued for up to eight days. Seven out of 10 bitches responded well to treatment. The remaining three bitches underwent ovariohysterectomy and a cystic hyperplasia of the endometrium was diagnosed histologically. The results indicated that prostaglandin F_2α used at the low dose is sufficient for medical treatment of certain cases of pyometra. The treatment seems to be most effective in bitches without obvious hormonal imbalance. The aetiology of pyometra is discussed.     

Furosemide for prevention of cyclophosphamide‐associated sterile haemorrhagic cystitis in dogs receiving metronomic low‐dose oral cyclophosphamide

Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment. Diuresis using furosemide is effective in canines when maximally tolerated dosed cyclophosphamide is administered. This retrospective study aimed to determine whether orally administered furosemide decreased the incidence of SHC. Secondary aims were to identify predisposing factors for SHC. One‐hundred and fifteen dogs treated with metronomic cyclophosphamide were analysed retrospectively. Populations were not randomized. 25 dogs (21.7%) developed SHC. Furosemide administration significantly reduced the likelihood of SHC development (P = 0.010, where SHC was diagnosed in 30.3% of dogs administered cyclophosphamide without furosemide, and 10.2% of dogs administered cyclophosphamide with furosemide). Age, gender, breed, bodyweight, number of cyclophosphamide treatments, piroxicam use and previous or pre‐existing disease were not found to be associated with SHC development. This study demonstrates furosemide is effective in the prevention of SHC and its use may be considered when implementing metronomic cyclophosphamide therapy.     

Evaluation of the clinical efficacy of marbofloxacin (Zeniquin) tablets for the treatment of canine pyoderma: an open clinical trial

The efficacy and field safety of marbofloxacin (Zeniquin) for the treatment of superficial and deep bacterial pyoderma were evaluated. Seventy‐two dogs were treated with 2.75 mg kg^?1 of marbofloxacin orally once daily for 21 or 28 days. Sixty‐two dogs (86%) had superficial pyoderma and 10 (14%) had deep pyoderma. A history of prior pyoderma was reported in 39/72 dogs. Pretreatment aerobic bacteriologic cultures of skin lesions were performed in 47 cases and the predominant pathogen isolated was Staphylococcus intermedius. Treatment was successful in 62/72 (86.1%) dogs, improvement was noted in 6/72 (8.3%) dogs and treatment failed in 4/72 (5.6%) dogs. Adverse effects associated with treatment included listlessness, anorexia, vomiting, soft stool, flatulence and polydipsia; these adverse effects were seen in only 6/81 dogs. Marbofloxacin was safe and effective for the treatment of superficial and deep pyoderma in dogs at the dosage used in this study.