Intraarticular injection of a Tin‐117 m radiosynoviorthesis agent in normal canine elbows causes no adverse effects

This longitudinal prospective exploratory study used serial measurements in five dogs to evaluate safety and retention of a tin‐117 m (^117mSn) colloid after intra‐articular injection in normal elbow joints. Each dog was deemed healthy based on physical examination, laboratory results, and radiographic evaluation of both elbows. While anesthetized, each received an MRI of both elbows, followed by fluorine‐18 fluorodeoxyglucose positron emission tomography scans of both elbow joints and associated lymph nodes. Joint fluid (0.5‐1.0 mL) was withdrawn aseptically from the left elbow joint, followed by intra‐articular injection of ^117mSn colloid (92.5 MBq; 1‐1.5 ml). Post‐injection assessments included blood counts, serum chemistry panels, urinalyses, radiographs, joint fluid analyses, MRI/positron emission tomography scans, scintigraphy, and biodistribution scans. On day 45‐47, each dog was euthanized and a complete postmortem examination was performed. Tissue samples were submitted for histopathology and radioisotope retention studies. Left elbow joints were decalcified and sectioned for future autoradiography. Scintigraphy, 1 day after injection, indicated slight radioisotope escape from the joint to regional lymph nodes. Serial blood, urine, feces, and organ counts indicated >99.1% of the ^117mSn activity was retained in the joint for 45‐47 days. Radiation output levels were below patient release levels the day following injection. Maximum standard uptake value for the injected joint decreased. Joint fluid cytology was unchanged. No dog exhibited lameness during the study. Absence of joint damage and lack of systemic effects after injection of the ^117mSn colloid in normal canine elbow joints indicate that this agent may be safely used for radiosynoviorthesis in dogs with osteoarthritis.     

Evaluation of the oral antimitotic agent (ABT-751) in dogs with lymphoma

Background

ABT‐751 is a novel orally available antimitotic agent that targets microtubule polymerization. This mechanism may suggest potential activity in canine lymphoma.

Objective

Determine a maximum tolerated dose for ABT‐751, and assess long‐term tolerability and activity in canine lymphoma.

Animals

Thirty dogs with newly diagnosed (n = 19) or relapsed (n = 11) non‐Hodgkin's lymphoma.

Methods

Dogs (n = 11) were enrolled in a rapid dose escalation study to define the maximum tolerated dose. Upon definition of a maximally tolerated dose, a cohort expansion of 19 dogs allowed verification of long‐term tolerability and assessment of activity. Study endpoints in the cohort expansion included chronic tolerability, response rate, response duration, and time to progression. Additional endpoints included serum pharmacokinetics, lymph node drug concentrations, and changes in circulating endothelial cells.

Results

The maximum tolerated dose of ABT‐751 was 350 mg/m² PO q24h. Dose‐limiting toxicities included vomiting and diarrhea, which resolved with a schedule adjustment to 350 mg/m² PO q48h. ABT‐751 was consistently detected in lymphoma tissue samples from dogs treated at or above the maximum tolerated dose. In the cohort expansion, objective responses were seen in 3/15 (20%) dogs with a response duration ranging from 21 to 111 days. Decreases in circulating endothelial cells were seen in 10 dogs at day 7 (2 responding dogs and 8 nonresponding dogs).

Conclusion

ABT‐751 was well tolerated at 350   mg/m² PO q24h for 7 days and then q48h thereafter. Activity of ABT‐751 suggested a rationale for additional studies of ABT‐751 as part of a combination chemotherapy protocol for lymphoma or other canine cancers.     

Treatment of vascular and soft-tissue sarcomas in dogs using an alternating protocol of ifosfamide and doxorubicin

A retrospective analysis was done to assess the toxicity and efficacy associated with an alternating chemotherapy protocol of ifosfamide (375 mg m^?2) and doxorubicin (30 mg m^?2) for adjuvant treatment of 39 dogs with sarcomas. Twelve dogs had various soft‐tissue sarcomas and 27 dogs had hemangiosarcoma (HSA). Complete blood counts were evaluated 7 days after the first dose of ifosfamide and doxorubicin. One dog had grade 4 neutropenia (<500 µL^?1) after treatment with ifosfamide and one dog had grade 3 neutropenia (500–1000 µL^?1) after treatment with doxorubicin. One dog treated with doxorubicin was hospitalized for 24 h due to vomiting. The median survival time (ST) for the 27 dogs with HSA treated by surgery and with doxorubicin/ifosfamide was 149 days (mean 366 days). Although the protocol of alternating ifosfamide and doxorubicin was well tolerated, it failed to result in a statistically significant improvement in the ST when compared to a historical population of dogs with stage 2 splenic HSA treated by surgery alone.     

Prospective evaluation of the safety of compounded bulk material L‐asparaginase in dogs with lymphoma

Use of compounded L‐asparaginase became routine in veterinary oncology when manufacturing of Elspar^® was discontinued in 2012. The objective of this study was to evaluate the safety of compounded L‐asparaginase (CLASP, KRS Global Biotechnology, Boca Raton, FL, USA) in comparison with Elspar^® (Lundbeck LLC, Deerfield, IL, USA). In addition, we documented the response to CLASP in combination with a corticosteroid in this population of dogs with lymphoma. Dogs were prospectively treated with 10 000 IU/m² CLASP or Elspar^® subcutaneously. Corticosteroids were administered concurrently. Adverse events (AE) were assessed according to the Veterinary Cooperative Oncology Group Common Terminology Criteria for Adverse Events v1.1 (VCOG‐CTCAE). Response was recorded. Seventy‐three dogs received 75 treatments (CLASP, n = 47; Elspar^®, n = 28). No AE were attributed to CLASP. Grade I and II AE probably or possibly related to treatment were observed following two Elspar^® treatments. The overall response rate to the combination of CLASP and a corticosteroid was 80% (24% CR and 56% PR). In combination with a steroid, the compounded L‐asparaginase evaluated in this study is safe and demonstrates activity against canine lymphoma. In the face of the discontinuation of Elspar^®, veterinarians should seek compounded LASP products that have been tested for activity, purity, and sterility.     

Factors Associated with Dog Rabies Vaccination in Bhol,Philippines: Results of a Cross‐Sectional Cluster Survey Conducted Following the Island‐Wide Rabies Elimination Campaign

The Philippines has a long history of rabies control efforts in their dog populations; however, long‐term success of such programmes and the goal of rabies elimination have not yet been realized. The Bohol Rabies Prevention and Elimination Program was developed as an innovative approach to canine rabies control in 2007. The objective of this study was to assess canine rabies vaccination coverage in the owned‐dog population in Bohol and to describe factors associated with rabies vaccination 2 years after implementation of the programme. We utilized a cross‐sectional cluster survey based on the World Health Organization’s Expanded Programme on Immunization coverage survey technique. We sampled 460 households and collected data on 539 dogs residing within these households. Seventy‐seven per cent of surveyed households reported owning at least one dog. The human‐to‐dog ratio was approximately 4 : 1, and the mean number of dogs owned per household was 1.6. Based on this ratio, we calculated an owned‐dog population of almost 300 000. Overall, 71% of dogs were reported as having been vaccinated for rabies at some time in their lives; however, only 64% of dogs were reported as having been recently vaccinated. Dogs in our study were young (median age = 24 months). The odds of vaccination increased with increasing age. Dogs aged 12–23 months had 4.6 times the odds of vaccination compared to dogs aged 3–11 months (95% CI 1.8–12.0; P = 0.002). Confinement of the dog both day and night was also associated with increased odds of vaccination (OR = 2.1; 95% CI 0.9–4.9; P = 0.07), and this result approached statistical significance. While the programme is on track to meet its goal of 80% vaccination coverage, educational efforts should focus on the need to confine dogs and vaccinate young dogs.     

Novel contrast agent Visphere™ is feasible for contrast‐enhanced ultrasonography in dogs

Contrast‐enhanced ultrasonography provides a more functional diagnostic image than conventional ultrasonography. This prospective exploratory study compared the novel contrast agent, Visphere^?, with commercial contrast agents in five healthy Beagle dogs. Visphere^? has the smallest diameter and highest concentration compared with Sonazoid^® and SonoVue^®. Each dog received an intravenous injection of Visphere^?, Sonazoid^®, or SonoVue^®. Images were recorded for 300, 600, and 60 s in the heart, liver, and left kidney, respectively. The mean pixel values of the regions of interest for each organ were expressed as time intensity curves (TIC). The agents all improved the visualization of left ventricular endocardial border delineation in the heart, and had similar TICs and clinical useful durations. In contrast, Visphere^? expressed the highest mean pixel value in the liver parenchyma at an early observation time and maintained the intensity until 600 s, like Sonazoid^®. The renal evaluation results indicated there were no statistically significant differences in time‐to‐peak for the renal cortex or medulla among the agents. Compared with the other two agents, SonoVue^® had the lowest peak enhancement for the renal cortex and medulla. No dogs had any adverse reactions during or after the study. All three agents provided adequate results for left ventricular endocardial border delineation, and Visphere^? may have the same potential as Sonazoid^® to detect and characterize hepatic lesions. Visphere^? and Sonazoid^® may offer better visualization quality to evaluate renal function. In conclusion, the novel contrast agent, Visphere^?, is comparable with commercial agents and could be applied in different major organs in dogs.     

A dose‐finding study with a novel water‐soluble formulation of paclitaxel for the treatment of malignant high‐grade solid tumours in dogs

A new formulation of water‐soluble paclitaxel (Paccal® Vet) has been developed for canine cancer patients, without the need for pre‐medication (traditionally required in non‐water‐soluble paclitaxel formulations). The objective of the study was to determine a clinically safe and efficacious dose of Paccal Vet and to estimate progression‐free and overall survival and to evaluate single‐dose pharmacokinetics in tumour‐bearing dogs. A positive risk:benefit ratio was established for Paccal Vet administered at 150 mg m^–2 intravenous (IV) for three or more treatment cycles. Preliminary efficacy was demonstrated by best objective response rate (86%), median time to response (14 days) and median progression‐free survival (131 days). Paccal Vet was associated with expected adverse events (AE) (e.g. myelosuppression), however the majority were transient, clinically silent and manageable. This is the first clinical report of a water‐soluble formulation of paclitaxel suggesting successful administration and being safely used without pre‐medication in dogs.     

Validation of the TonoVet® rebound tonometer in normal and glaucomatous cats

Objective  To validate intraocular pressure (IOP) readings obtained in cats with the TonoVet^® tonometer. Animals studied  IOP readings obtained with the TonoVet^® were compared to IOP readings determined by manometry and by the Tono‐Pen XL^? in 1 normal cat and two glaucomatous cats. TonoVet^® and Tono‐Pen XL^? readings were also compared in a further six normal and nine glaucomatous cats. Procedures  The anterior chambers of both eyes of three anesthetized cats were cannulated and IOP was varied manometrically, first increasing from 5 to 70 mmHg in 5 mmHg increments, then decreasing from 70 to 10 mmHg in 10 mmHg decrements. At each point, two observers obtained three readings each from both eyes, with both the TonoVet^® and Tono‐Pen XL^?. IOP was measured weekly for 8 weeks with both tonometers in six normal and nine glaucomatous unsedated cats. Data were analyzed by linear regression. Comparisons between tonometers and observers were made by paired student t‐test. Results  The TonoVet^® was significantly more accurate than the Tono‐Pen XL^? (P = 0.001), correlating much more strongly with manometric IOP. In the clinical setting, the Tono‐Pen XL^? underestimated IOP when compared with the TonoVet^®. Conclusions  Both the TonoVet^® and Tono‐Pen XL^? provide reproducible IOP measurements in cats; however, the TonoVet^® provides readings much closer to the true IOP than the Tono‐Pen XL^?. The TonoVet^® is superior in accuracy to the Tono‐Pen XL^? for the detection of ocular hypertension and/or glaucoma in cats in a clinical setting.     

C-reactive protein concentrations in canine acute pancreatitis

Objective: To determine if C‐reactive protein (CRP) concentration is elevated in spontaneously occurring canine acute pancreatitis (AP), and to measure changes in CRP during the course of hospitalization. Design: Prospective study. Setting: Tufts University School of Veterinary Medicine Foster Hospital for Small Animals. Animals: Sixteen client‐owned dogs with AP and 16 healthy controls. Interventions: Blood samples were obtained from the AP group on the day of diagnosis (Day 1), and on Days 3 and 5, unless the dog died or was discharged from the hospital. Blood was obtained from the control dogs once. Measurements and main results: Serum CRP was measured using a commercial immunoassay for each dog with AP and for healthy controls. Day 1 CRP concentrations were significantly higher in the AP group (56.1±12.7 μg/mL) compared with controls (2.8±1.3 μg/mL; P<0.001). For the 7 dogs that had samples collected on all 3 days, the mean CRP concentrations decreased significantly (P=0.043) over the 5 days of measurement. Of the 16 dogs with AP, 14 were discharged from the hospital and 2 were euthanized. Conclusions: Serum CRP concentrations were elevated in this group of 16 dogs with spontaneously occurring AP. In the 7 dogs that had measurements on all 3 days, the mean CRP concentration decreased from the day of diagnosis to the measurement made 5 days later.     

Zinc–carnosine and vitamin E supplementation does not ameliorate gastrointestinal side effects associated with ciclosporin therapy of canine atopic dermatitis

Chelated zinc–carnosine and vitamin E [GastriCalm^® (GCM); Teva Animal Health] is marketed as an anti‐emetic supplement for dogs to assist the repair of damaged stomach and intestinal mucosa. The purpose of this prospective, double‐blinded, placebo‐controlled trial was to determine whether GCM reduced the frequency of vomiting, diarrhoea and appetite changes during initiation of ciclosporin (Atopica^®; Novartis Animal Health) therapy for the treatment of canine atopic dermatitis. Sixty privately owned dogs diagnosed with atopic dermatitis were randomly assigned to GCM (n = 30) or placebo (n = 30) groups. All dogs received ～5 mg/kg ciclosporin (range, 3.5–5.8 mg/kg) once daily. Dogs <13.6 kg received half a tablet of GCM or placebo; dogs ≥13.6 kg received one tablet once daily. GastriCalm^® or placebo was administered 30 min prior to eating, and the ciclosporin was administered 2 h after feeding. Owners recorded episodes of vomiting, diarrhoea and appetite changes. Dogs were examined on days 0 and 14. Forty‐one of 60 dogs (68.3%) had at least one episode of vomiting, diarrhoea or appetite change, leaving nine placebo dogs (30%) and ten GCM dogs (33.3%) free of adverse events (AE). Twenty‐seven of 60 dogs (45%) vomited, and 15 of 60 (25%) had diarrhoea. There was no significant difference in episodes of individual AEs, but the placebo group had a significantly lower total AE score (summation of episodes of appetite change, vomiting and diarrhoea; P = 0.022). Small dogs (<6.82 kg) had significantly fewer total AEs in both treatment groups and tolerated ciclosporin better than larger dogs (P < 0.05).     

Intravenous administration of 9-aminocamptothecin to dogs with lymphoma

A colloidal dispersion formulation of 9‐aminocamptothecin (9‐AC) was administered intravenously to 10 dogs with previously untreated, spontaneously occurring, multicentric lymphoma. The dogs received a 72‐h infusion of 9‐AC at a rate of 46.5–51.25 µg m^?2 h^?1 (total dose range 3.35–3.69 mg m^?2). This dose range was associated with myelosuppression, consisting principally of neutropenia with a nadir at 7 days following the start of infusion. Neutropenia and thrombocytopenia were the most common toxicoses and are most likely to be dose‐limiting toxicities; low‐grade gastrointestinal signs were rarely seen. Concentrations of 9‐AC lactone, as well as clinical toxicities, compare favourably with those found in humans. Tumour responses were seen in all treated dogs. Response to other chemotherapy, following cessation of 9‐AC treatment, was not obviously compromised even in dogs clinically resistant to 9‐AC. 9‐AC is a novel treatment drug for canine lymphoma, which appears to show great promise.     

Are transepidermal water loss and clinical signs correlated in canine atopic dermatitis? A compilation of studies

Background – Cutaneous impairment plays a crucial role in atopic dermatitis (AD). Transepidermal water loss (TEWL) measurement is an indirect assessment of skin barrier function and correlates with disease severity in humans. Skin impairment also exists in canine AD; however, concerns exist regarding variability and reliability of TEWL measurements in dogs. Hypothesis/Objectives – The purposes of this retrospective study were twofold: first, to investigate the correlation between severity of dermatitis [measured by Canine Atopic Dermatitis Extent and Severity Index (CADESI)] and TEWL; and second, to evaluate whether increased TEWL at a young age correlates with disease severity later in life. Methods – Data from atopic beagles and dogs with natural AD were analysed. Transepidermal water loss was measured in atopic beagles (n = 24) with an open chamber and in dogs with naturally occurring AD with a closed chamber device (two studies, with n = 14 and n = 18). Pearson product–moment correlation was used for analyses. Transepidermal water loss of the inguinal region, axilla, antebrachial flexure and pinna was analysed. Correlations were investigated for each study, separately first and then jointly. They included CADESI and TEWL of individual regions, total CADESI and total TEWL of all measured regions, and total CADESI and TEWL of key regions. Results – In atopic beagles, TEWL measured at 1 year of age pre‐ and post‐allergen challenge was correlated with CADESI at 1, 3 and 6 years of age. Overall, low correlation coefficients were found; therefore, a biologically relevant connection could not be demonstrated. The main significant positive correlation was found between TEWL in the pinna and total CADESI. Conclusions and clinical importance – It is concluded that TEWL does not correlate with disease severity.     

The pharmacokinetics of cytarabine administered subcutaneously,combined with prednisone,in dogs with meningoencephalomyelitis of unknown etiology

The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m² as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5–2 mg kg^?1day^?1). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed‐effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 μg/ml. The population estimate (CV%) for elimination half‐life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 μg/ml at the 30‐, 60‐, 90‐, and 120‐min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m² SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs.     

Detection of tumour necrosis factor-alpha in dogs with lymphoma(*)

Tumour necrosis factor‐alpha (TNF‐α) production by malignant lymphoblasts has been identified in vitro and in vivo in mice and humans, respectively. The goals of this study were (1) to evaluate a novel single‐sample TNF‐α assay and (2) to determine whether TNF‐α is increased in dogs with lymphoma prior to and following treatment. Canine TNF‐α was analysed concurrently using the novel Siemens Immulite^® single‐sample automated ELISA and the previously validated Quantikine^® standard ELISA. Serum from dogs with lymphoma and from breed‐, age‐ and gender‐matched control dogs was evaluated at two time points. Three of 25 (12%) dogs with lymphoma had detectable TNF‐α at diagnosis, whereas none had detectable TNF‐α following complete or partial remission. TNF‐α was not detectable in control dogs. Despite 91% homology between human and canine TNF‐α, the Immulite^® automated ELISA failed to detect canine TNF‐α. Serum TNF‐α appears to have limited value as a tumour marker in dogs with lymphoma.     

In vitro Inhibition of Canine Complement‐Mediated Hemolysis

Background

Immune‐mediated hemolytic anemia (IMHA) is the most common hematologic immune‐mediated disease in dogs. Complement fixation on erythrocytes causes hemolysis. Complement inhibition decreases hemolysis in people with the hemolytic disease and also may prove effective in treating IMHA in dogs.

Hypothesis/Objectives

Evaluate the in vitro efficacy of 2 complement inhibitors used in humans against canine complement.

Methods

The inhibitory activity of the C3‐inhibitor compstatin and recombinant human C1‐esterase inhibitor (C1‐INH) was evaluated using an in vitro hemolytic assay and spectrophotometric measurement of released hemoglobin. Dose‐response curves for each inhibitor were generated.

Results

Compstatin decreased approximately 50% of canine complement‐mediated hemolysis in initial experiments. This inhibition largely was lost when a new lot of drug was purchased. C1‐INH showed a dose‐dependent inhibition. The highest concentration of C1‐INH tested (500 μg/mL) decreased >80% of canine complement‐mediated hemolysis, and the lowest concentration tested (31.25 μg/mL) decreased hemolysis >60%.

Conclusions and Clinical Importance

Human C1‐INH is a robust inhibitor of canine complement‐mediated hemolysis, whereas compstatin was minimally and variably effective. Human C1‐INH may substantially decrease complement‐mediated hemolysis in dogs with IMHA and warrants further investigation.     

Evidence for Unapparent Brucella canis Infections among Adults with Occupational Exposure to Dogs

Human serological assays designed to detect brucellosis will miss infections caused by Brucella canis, and low levels of periodic bacteremia limit diagnosis by blood culture. Recent B. canis outbreaks in dogs and concomitant illnesses in caretakers suggest that unapparent human infections may be occurring. With more than a quarter of a million persons in occupations involving dogs, and nearly 80 million dog owners in the United States, this pathogen is an under‐recognized human health threat. To investigate occupational exposure to B. canis, we adapted a commercial canine serological assay and present the first controlled seroepidemiological study of human B. canis infections in recent years. 306 adults with occupational exposure to dogs and 101 non‐matched, non‐canine‐exposed subjects were enrolled. Antibodies were detected using the canine D‐Tec^® CB rapid slide agglutination test (RSAT) kit with a secondary 2‐mercaptoethanol (ME)‐RSAT. Results were validated on a blinded subset of sera with an additional RSAT and indirect enzyme‐linked immunoassay at the National Administration of Laboratories and Health Institutes (ANLIS) in Argentina. Seroprevalence ranged from 10.8% (RSAT) to 3.6% (ME‐RSAT) among canine‐exposed subjects. Kennel employees were more likely to test RSAT seropositive compared with other canine exposures (OR = 2.7; 95% CI, 1.3–5.8); however, low seroprevalence limited meaningful occupational risk factor analyses. Two seropositive participants reported experiencing symptoms consistent with brucellosis and having exposure to B. canis‐infected dogs; however, temporality of symptom onset with reported exposure could not be determined. D‐Tec^® CB results had substantial agreement with ANLIS assays (Cohen's kappa = 0.60–0.68). These data add to a growing body of literature suggesting that people occupationally exposed to dogs may be at risk of unapparent B. canis infection. It seems prudent to consider B. canis as an occupational public health concern and encourage the development of serological assays to detect human B. canis infections.     

The Influence of Powdered Coconut Water (ACP‐318®) in In Vitro Maturation of Canine Oocytes

The objective of this study was to determine the influence of powdered coconut water (ACP‐318^®) diluted in high glucose (11.0 mm ) TCM199 in the achievement of nuclear in vitro maturation (IVM) of canine oocytes. Cumulus oocyte complexes (COCs) (n = 632) were randomly allocated into three experimental groups named as group 1 (control group), group 2 (5% powdered coconut water) and group 3 (10% powdered coconut water). The percentage of meiotic resumption (MR) (GVBD to MII) was 39.1% (81/207), 50.2% (108/215) and 46.6% (98/210) for groups 1, 2 and 3 respectively (p < 0.05). There were no differences in MR rates among groups 2 and 3. The medium with ACP‐318^® slightly enhanced the nuclear maturation of canine oocytes when a comparison was established with rates of maturation exhibited by oocytes in the experimental group 1 without ACP‐318^® (p < 0.05). The results suggest that oocytes’ nuclear morphology integrity and meiosis achievement were positively influenced when exposed to high glucose TCM199 supplemented with 5% powdered coconut water. Further investigation must be performed for a better understanding of powdered coconut water influence in cellular events during IVM of dog oocytes.     

A Cross‐Sectional Study Examining the Prevalence and Risk Factors for Anti‐Microbial‐Resistant Generic Escherichia coli in Domestic Dogs that Frequent Dog Parks in Three Cities in South‐Western Ontario,Canada

Anti‐microbial resistance can threaten health by limiting treatment options and increasing the risk of hospitalization and severity of infection. Companion animals can shed anti‐microbial‐resistant bacteria that may result in the exposure of other dogs and humans to anti‐microbial‐resistant genes. The prevalence of anti‐microbial‐resistant generic Escherichia coli in the faeces of dogs that visited dog parks in south‐western Ontario was examined and risk factors for shedding anti‐microbial‐resistant generic E. coli identified. From May to August 2009, canine faecal samples were collected at ten dog parks in three cities in south‐western Ontario, Canada. Owners completed a questionnaire related to pet characteristics and management factors including recent treatment with antibiotics. Faecal samples were collected from 251 dogs, and 189 surveys were completed. Generic E. coli was isolated from 237 of the faecal samples, and up to three isolates per sample were tested for anti‐microbial susceptibility. Eighty‐nine percent of isolates were pan‐susceptible; 82.3% of dogs shed isolates that were pan‐susceptible. Multiclass resistance was detected in 7.2% of the isolates from 10.1% of the dogs. Based on multilevel multivariable logistic regression, a risk factor for the shedding of generic E. coli resistant to ampicillin was attending dog day care. Risk factors for the shedding of E. coli resistant to at least one anti‐microbial included attending dog day care and being a large mixed breed dog, whereas consumption of commercial dry and home cooked diets was protective factor. In a multilevel multivariable model for the shedding of multiclass‐resistant E. coli, exposure to compost and being a large mixed breed dog were risk factors, while consumption of a commercial dry diet was a sparing factor. Pet dogs are a potential reservoir of anti‐microbial‐resistant generic E. coli; some dog characteristics and management factors are associated with the prevalence of anti‐microbial‐resistant generic E. coli in dogs.     

A dose‐escalation study of combretastatin A4‐phosphate in healthy dogs

Combretastatin A4 ‐Phosphate (CA4P ) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m^?2. At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low‐grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m^?2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m^?2, low‐grade hypertension and high‐grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m^?2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m^?2, although transient, does not invite to use this dose in canine oncology patients.     

Evaluation of Liposomal Radiochemotherapy for Treatment of Cancer

Introduction: Pegylated liposomes target solid tumors by exploiting the capillary leakage properties of tumor neovasculature. The goal of the study was to investigate distribution and tumor targeting properties of the alpha‐particle emitter ²²³Ra, encapsulated in doxorubicin‐containing‐liposomes (Caelyx^®/Doxil^®). Methods: Caelyx^® was given before the injection of liposomal ²²³Ra to reduce the reticulo‐endothelial‐system uptake. A pilot study was conducted to determine the optimal time interval between the pre‐treatment/treatment. Subsequently a more extensive distribution study was performed in normal BalbC mice. In addition, distribution and tumor uptake was evaluated in a human osteosarcoma xenograft mice model and in a dog with spontaneous osteosarcoma. Results: Optimal blood‐to‐liver and blood‐to‐spleen ratios of liposomal radium was achieved in animals that received pre‐treatment with Caelyx^® 4 days in advance. Blood clearance was relatively slow, in mice t_1/2 was ～28 h (BalbC mice) and in the dog t_1/2 was ～ 39 h. In mice the liver uptake appeared to be relatively low in contrast to the spleen, where there was a significant uptake. In the dog the uptake in both liver and spleen was moderate. In the xenograft model there was generally a higher retention of activity in the tumor vs. soft tissue. In the dog the 24 h uptake was considerably higher in both calcified and non‐calcified tumor metastases of different organs, than in normal tissue. Conclusions: Liposomal ²²³Ra has a relevant biodistribution and blood clearance for tumor targeting. More extensive future studies are supported by the favourable tumor/normal‐tissue ratio in a dog with spontaneous osteosarcoma.