Complement C3 in Bernese Mountain dogs

Background: Previous research suggests that low serum concentrations of the third component of complement (C3) are associated with both the susceptibility to infectious agents such as Borrelia burgdorferi and the development of glomerular disease. We hypothesized that low levels of C3 are associated with the coincident occurrence of B. burgdorferi infection and glomerulonephritis in Bernese Mountain dogs. Objectives: The aims of this study were to evaluate the serum concentration of C3 in Bernese Mountain dogs with and without antibodies against B. burgdorferi and to compare this concentration with that of healthy control dogs. Methods: Eighty‐three clinically healthy Bernese Mountain dogs and 46 control dogs were included. Antibodies against B. burgdorferi were determined using an ELISA with a whole cell sonicate as antigen. Results were confirmed using Western blot. C3 was measured using a single radial immunodiffusion test. Results were reported as the percentage concentration of C3 compared with that in pooled preserved canine serum (100% C3 concentration). Results: Median C3 concentration was 128.5% in Bernese Mountain dogs with antibodies against B. burgdorferi, 133.5% in B. burgdorferi‐negative Bernese Mountain dogs, 87.8% in positive control dogs, and 102.2% in negative control dogs. Within Bernese Mountain and control groups, C3 was lower in dogs with antibodies against B. burgdorferi compared with those without. Percentage concentration of C3 was higher in healthy Bernese Mountain dogs compared with control dogs. Conclusion: Low C3 concentration is not an explanation for the high prevalence of B. burgdorferi infections and glomerular disease in Bernese Mountain dogs.     

Prolonged activated prothromboplastin time and breed specific variation in haemostatic analytes in healthy adult Bernese Mountain dogs

Coagulation tests are often performed in dogs suspected of haemostatic dysfunction and are interpreted according to validated laboratory reference intervals (RIs). Breed specific RIs for haematological and biochemical analytes have previously been identified in Bernese Mountain dogs, but it remains to be determined if breed specific RIs are necessary for haemostasis tests. Activated prothromboplastin time (aPTT), prothrombin time (PT), selected coagulation factors, D-dimers, fibrinogen, von Willebrand factor and thromboelastography (TEG) were analyzed in healthy Bernese Mountain dogs using the CLSI model. Three analytes (aPTT, TEG [MA] and TEG [G]) were different according to the CLSI model. For aPTT the new RI was markedly different (0-100s). Whereas the new intervals for TEG (MA) and TEG (G) may be due to breed related biological variation, the cause of the prolonged RI for aPTT is at present uncertain.     

Seroprevalence against Borrelia burgdorferi sensu lato and occurence of antibody co-expression with Anaplasma phagocytophilum in dogs in Latvia

Background

Lyme disease is commonly diagnosed in humans in Latvia, but up to date no studies have been performed to investigate its prevalence in dogs. The aim of this study was to evaluate if seroprevalence against B. burgdorferi sensu lato (B. burgdorferi s.l.) and co-expression of antibodies against B.burgdorferi s.l. and A. phagocytophilum is higher in dogs with clinical suspicion of tick-borne diseases compared to healthy dogs.

Findings

Venous blood was taken from healthy dogs (n=441) and dogs suspected to have borreliosis and/ or canine granulocytic anaplasmosis (n=29). The presence of antibodies was detected with SNAP 4Dx test (IDEXX, Westbrook, Maine, USA). The seroprevalence against B. burgdorferi s.l. in healthy dogs was 2.49% (11/441) and 36% (4/11) of seropositive dogs had antibodies against both of investigated bacteria. None of the dogs in sick dog group had detectable antibodies against B. burgdorferi s.l.

Conclusions

We conclude that seroprevalence to B. burgdorferi s.l. in dogs in Latvia is low and that dogs with suspicion of tick-borne disease do not have higher B. burgdorferi s.l. seroprevalence than healthy dogs. Dogs that express antibodies against B. burgdorferi s.l. frequently co-express antibodies against A. phagocytophilum.     

Prevalence of antibodies against Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum and their clinical relevance in dogs in Munich, Germany

Although prevalences of antibodies against Borrelia (B.) burgdorferi sensu lato (sl) and Anaplasma (A.) phagocytophilum have been reported to be high in the German dog population, the importance of the diseases caused by both agents is still not well characterized in a field situation.The aim of this study was (1) to determine the prevalence of antibodies to B. burgdorferi sl and A. phagocytophilum in dogs in Munich, Germany, and (2) to assess the clinical presentation and laboratory values of antibody-positive dogs and compare them to a negative control group. In total, 448 randomly selected dogs were screened for antibodies to B. burgdorferi sl and A. phagocytophilum with the SNAP 4Dx assay (IDEXX, Laboratories, Inc., USA). Dogs carrying antibodies against B. burgdorferi sl and/or A. phagocytophilum were classified as "positive"(n=100), the following 100 negative dogs served as control group. In both groups, physical examination and laboratory parameters were compared. 22 (4.9%) dogs had antibodies to B. burgdorferi sl, 78 (19.4%) to A. phagocytophilum, nine (2.0%) to both agents. Bernese Mountain Dogs had significantly more often antibodies against B. burgdorferi sl. Negative dogs were more often diagnosed as "healthy" compared to A. phagocytophilum antibody-positives that showed more often elevated body temperature and poor general condition; beyond that, there were no differences in clinical and laboratory abnormalities between both groups. Although dogs tested negative were more often considered healthy, there were no differences in parameters considered "specific" for both infections between dogs with and without antibodies. Hence, tests detecting antibodies against both agents are not able to detect animals with the clinical disease.     

Effects of recent Leptospira vaccination on whole blood real-time PCR testing in healthy client-owned dogs

Background

Bacterin‐based canine Leptospira vaccines could present a challenge for the use of whole blood real‐time polymerase chain reaction (PCR) as a diagnostic tool. Recent vaccination could induce positive results if the targeted DNA fragment is present within the vaccine and in the blood of the recently vaccinated dog.

Objectives

The objective of this study was to assess whether 2 available 4‐serovar vaccines induce a positive real‐time PCR reaction in the blood of healthy recently vaccinated dogs.

Animals

Twenty healthy dogs.

Methods

This was a prospective study. Dogs were assigned to 1 of 2 vaccine groups. Both vaccines were culture‐based and include Leptospira interrogans serovars Pomona, Canicola, and Icterohaemorrhagiae and Leptospira kirschneri serovar Grippotyphosa. Whole blood for real‐time PCR and serum for the microscopic agglutination test (MAT) were collected prior to and 3 and 7 days after vaccination and weekly thereafter for 8 weeks. Two real‐time PCR tests targeting 2 different genes were performed independently in a blinded fashion.

Results

Both Leptospira vaccines produced positive real‐time PCR reactions when assayed undiluted or diluted 1 : 100 in canine blood. However, blood samples drawn from all dogs at all time points after vaccination were negative on PCR. All dogs developed MAT titers.

Conclusions and Clinical Importance

Recent vaccination with 2 commercially available vaccines does not interfere with the use of real‐time PCR for the identification of acute Leptospira infection in dogs.     

Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy

Background

Previous reports associated 2 mutant SOD1 alleles (SOD1:c.118A and SOD1:c.52T) with degenerative myelopathy in 6 canine breeds. The distribution of these alleles in other breeds has not been reported.

Objective

To describe the distribution of SOD1:c.118A and SOD1:c.52T in 222 breeds.

Animals

DNA from 33,747 dogs was genotyped at SOD1:c.118,SOD1:c.52, or both. Spinal cord sections from 249 of these dogs were examined.

Methods

Retrospective analysis of 35,359 previously determined genotypes at SOD1:c.118G>A or SOD1:c.52A>T and prospective survey to update the clinical status of a subset of dogs from which samples were obtained with a relatively low ascertainment bias.

Results

The SOD1:c.118A allele was found in cross‐bred dogs and in 124 different canine breeds whereas the SOD1:c.52T allele was only found in Bernese Mountain Dogs. Most of the dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A homozygotes, but 8 dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A/G heterozygotes and had no other sequence variants in their SOD1 amino acid coding regions. The updated clinical conditions of dogs from which samples were obtained with a relatively low ascertainment bias suggest that SOD1:c.118A homozygotes are at a much higher risk of developing degenerative myelopathy than are SOD1:c.118A/G heterozygotes.

Conclusions and Clinical Importance

We conclude that the SOD1:c.118A allele is widespread and common among privately owned dogs whereas the SOD1:c.52T allele is rare and appears to be limited to Bernese Mountain Dogs. We also conclude that breeding to avoid the production of SOD1:c.118A homozygotes is a rational strategy.     

The influence of esomeprazole and cisapride on gastroesophageal reflux during anesthesia in dogs

Background

Gastroesophageal reflux (GER) is common in anesthetized dogs and can cause esophagitis, esophageal stricture, and aspiration pneumonia.

Objective

To determine whether preanesthetic IV administration of esomeprazole alone or esomeprazole and cisapride increases esophageal pH and decreases the frequency of GER in anesthetized dogs using combined multichannel impedance and pH monitoring.

Animals

Sixty‐one healthy dogs undergoing elective orthopedic surgery procedures.

Methods

Prospective, randomized, placebo‐controlled study. Dogs were randomized to receive IV saline (0.9% NaCl), esomeprazole (1 mg/kg) alone, or a combination of esomeprazole (1 mg/kg) and cisapride (1 mg/kg) 12–18 hours and 1–1.5 hours before anesthetic induction. An esophageal pH/impedance probe was utilized to measure esophageal pH and detect GER.

Results

Eight of 21 dogs in the placebo group (38.1%), 8 of 22 dogs in the esomeprazole group (36%), and 2 of 18 dogs in the combined esomeprazole and cisapride group (11%) had ≥1 episode of GER on impedance testing during anesthesia (P < .05). Esomeprazole was associated with a significant increase in gastric and esophageal pH (P = .001), but the drug did not significantly decrease the frequency of GER (P = .955). Concurrent administration of cisapride was associated with a significant decrease in the number of reflux events (RE) compared to the placebo and esomeprazole groups (P < .05).

Conclusions and Clinical Relevance

Preanesthetic administration of cisapride and esomeprazole decreases the number of RE in anesthetized dogs, but administration of esomeprazole alone was associated with nonacid and weakly acidic reflux in all but 1 dog.     

Update of a Retrospective Cohort Study of Changes in Hip Joint Phenotype of Dogs Evaluated by the OFA in the United States, 1989–2003

Objective— To determine whether there has been improvement in canine hip joint phenotype classifications of dogs whelped from 1989 to 2003 by the Orthopedic Foundation for Animals (OFA), by examining results of radiographic evaluations and identifying any trends in percentages of dogs classified as having desirable hip joint phenotypes.
Study Design— Retrospective cohort study.
Sample Population— OFA radiographic classifications (n=431,483) on dogs whelped between 1989 and 2003.
Methods— Numbers and percentages of dogs classified by hip joint phenotypes were determined for 2-year cohorts. Differences between breeds and sexes were assessed using the Fisher's exact test, and odds ratios with 95% confidence intervals were calculated to express associations. The Cochran–Armitage test for trend was calculated to identify significant trends over time.
Results— There were statistically significant ( P <.05) increases in the proportion of all breeds of dogs evaluated as excellent and good from 1993 to 2003, controlling for gender and age at evaluation. Labrador Retrievers, Bernese Mountain Dogs, and Rottweilers had the highest proportions of excellent and good scores, and the highest rates of improvement in excellent and good scores were seen in Bernese Mountain Dogs and Rottweilers.
Conclusions— Results support the contention that there have been improvements in hip joint phenotype classifications in dogs in the United States since the previous study (1989–1992), through increases in the proportion of dogs receiving excellent and good classifications.
Clinical Relevance— Hip joint phenotype classifications can be used by dog breeders to develop breeding programs to improve the hip joints of future generations of dogs.     

Hypocalcemia and hypovitaminosis D in dogs with induced endotoxemia

Background

Hypocalcemia is a documented electrolyte disturbance in people and animals with sepsis, but its mechanism is poorly understood.

Objective

To investigate mechanisms of hypocalcemia in dogs with experimentally induced endotoxemia.

Animals

Six healthy mixed breed dogs were included in this nonrandomized, placebo‐controlled, crossover study.

Methods

Dogs initially were injected with placebo (0.9% NaCl; 1 mL, IV) and then lipopolysaccharide (LPS; 2 μg/kg, IV) after a 5‐day washout period. Blood and urine samples were collected for measurement of serum total calcium (tCa), ionized calcium (iCa), total magnesium (tMg), ionized magnesium (iMg), parathyroid hormone (PTH), 25‐hydroxyvitamin D (vitamin D), venous blood gases, and fractional excretion (FE) of calcium.

Results

After LPS administration, body temperature increased and blood pressure decreased. Both iCa and tCa decreased (P < .01), but iMg was not significantly different between control and LPS treatments. PTH concentrations increased (P < .01) and vitamin D concentrations decreased (P < .01). Venous pH, bicarbonate, base excess, and blood glucose also decreased (P < .01). Urine tCa concentration was below the limit of detection for all dogs after LPS administration.

Conclusions

Hypocalcemia occurs during endotoxemia in dogs and is associated with hypovitaminosis D. Hypomagnesemia, hypoparathyroidism, alkalosis, and increased calciuresis are not associated with hypocalcemia in endotoxemic dogs.     

Prior joint disease is associated with increased risk of periarticular histiocytic sarcoma in dogs

Periarticular histiocytic sarcoma (PAHS) is the most common synovial tumour in dogs and is characterized by aggressive local disease with a high rate of distant metastasis. Previously, an association between PAHS and prior joint disease has been demonstrated in the Bernese Mountain Dog breed and suggested in the Rottweiler. We hypothesized that this association would be present in other breeds and investigated this via a retrospective, case‐controlled analysis. Cases were dogs diagnosed with PAHS of the stifle or elbow. Controls were age, breed and sex‐matched dogs without a diagnosis of histiocytic sarcoma. Diagnosis of prior joint disease was determined based on review of medical records and direct veterinarian and owner communications. Data were evaluated using logistic regression, 2‐sampled t tests, and chi‐squared analysis. Our study population consisted of 28 cases and 46 controls, including Flat‐Coated, Golden and Labrador Retrievers, Rottweilers, English Bulldogs, Shih Tzus, Australian Shepherds, Staffordshire Terriers and mixed breed dogs. Dogs with PAHS were more likely to have prior joint disease in the tumour‐affected joint compared with the control population (odds ratio [OR] = 13.42, P < .0001, 95% confidence interval [CI] = 4.33‐48.63). A total of 88.2% of dogs with stifle PAHS had prior joint disease in their tumour‐affected joint, most commonly cranial cruciate ligament rupture. This study confirms that the previously noted association between prior joint disease and PAHS in Bernese Mountain Dogs also applies to other breeds. Additional studies are needed to further investigate for a causal relationship.     

Evaluation of hemostatic derangements associated with canine anaphylaxis and the relationship to syndrome severity

Objective

To describe hemostatic derangements associated with canine anaphylaxis and to assess for association with syndrome severity.

Design

Prospective observational study.

Setting

University teaching hospital.

Animals

Twenty-seven client-owned dogs, recruited from November 2018 to January 2022, diagnosed with anaphylaxis of varying severity were included. Study inclusion required presentation <6 hours after initiation of clinical signs, no medications or history of illness within the prior 2 weeks, lack of comorbidities expected to affect hemostasis, and lack of a disease state that could alternatively explain the clinical presentation.

Interventions

Blood samples were collected within the first hour of presentation for CBC, serum biochemistry, prothrombin time (PT), activated partial thromboplastin time (aPTT), and viscoelastic coagulation testing for use with a cartridge-based point-of-care device.

Measurements and main results

Clotting time and clot formation time were prolonged, alpha angle and maximum clot firmness were decreased, PT and aPTT were prolonged, and platelet counts were lower in severe cases compared to mild and moderate cases. There were no differences for any parameter between mild and moderate cases. The presence or absence of abdominal effusion was not associated with hemostatic status.

Conclusions

Global hemostatic derangements consistent with hypocoagulability are a prominent feature of severe anaphylaxis in dogs and should be considered for routine evaluation.     

Coagulation effects of low molecular weight heparin compared with heparin in dogs considered to be at risk for clinically significant venous thrombosis

Objective – Compare the effects of 3 anticoagulation protocols on anti-factor Xa activity (AXa).
Design – Prospective, randomized, double-blind study.
Setting – University veterinary teaching hospital.
Animals – Eighteen dogs considered to be at risk for venous thrombosis.
Interventions – Each dog was randomly assigned to 1 of the following 3 groups ( n =6/group) and was treated for 24 hours: low-dose heparin (LDH), high-dose heparin (HDH), and dalteparin (DP). Dogs in the LDH group received a constant rate infusion (CRI) of unfractionated heparin (UFH) at 300 U/kg/d, the HDH group received a bolus of 100 U/kg of UFH IV, then a CRI of 900 U/kg/day, and the DP group received 100 U/kg DP SC at 0, 12, and 24 hours.
Measurements and Main Results – A total of 54 samples for activated partial thromboplastin time (aPTT) and AXa assays were collected at 0, 4, and 28 hours. Six samples had an AXa >0.1 U/mL, 5 of those were from the HDH group at hour 4. Two samples from the HDH group at hour 4 had a prolonged aPTT (93 and 200 seconds) and the highest AXa (0.6 and 1.0 U/mL, respectively). Four additional dogs in the HDH group did not complete the study due to hemorrhage; none of the dogs completing the study showed signs of hemorrhage.
Conclusions: Neither DP nor LDH increased AXa to values considered therapeutic in humans (0.5–1 and 0.35–0.75 U/mL, respectively), and both protocols appear to be inadequate to increase AXa in dogs with clinical illness. HDH increased AXa to this range in 2 of 6 dogs, but had unpredictable effects on aPTT and resulted in hemorrhage in some dogs.     

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.     

Early retinopathy in the Bernese Mountain Dog in France: preliminary observations

The objective of the study was to describe a form of early retinopathy in the Bernese Mountain Dog in France. Sixty-two Bernese Mountain Dogs (38 males and 24 females), whose ages ranged from 2 months to 9 years, were examined over a period of 3 years. Visual behavior, pupillary light reflexes, menace responses and ocular fundi were evaluated in all animals. Electroretinography (ERG) was performed on six of the affected dogs after dark adaptation. Fluorescein angiography (FA) was performed on one affected dog. Whenever possible, the pedigrees of the affected dogs were evaluated. A histological examination of the retina was performed on one of the affected dogs. Eight dogs (seven males and one female) were diagnosed with retinopathy with an early onset of clinical signs. (Four dogs were aged between 3 months and 1 year, two dogs were aged 2 and 3.5 years, and one dog was 7 years old.) Night vision was impaired in most of the dogs. Retinopathy was characterized ophthalmoscopically by a bilateral, symmetrical horizontal zone of tapetal hyper-reflectivity adjacent to and above the optic disc, and sometimes by peri-papillary hyper-reflectivity. ERG changes included a reduction in b-wave amplitude varying from one case to another. Fluoroscein angiography demonstrated an ischemic-type alteration with epitheliopathy opposite the hyper-reflective zone. Pedigree examinations suggested a familial predisposition. The histological examination indicated photoreceptor degeneration that was more pronounced in the central tapetal zone. In France, retinopathy in the Bernese Mountain Dog involves an early retinal degeneration that produces specific manifestations of the ocular fundus, night visual impairment or blindness, and has familial transmission.     

Haemostatic alterations in a group of canine cancer patients are associated with cancer type and disease progression

Background

Haemostatic alterations are commonly detected in human and canine cancer patients. Previous studies have described haemostatic dysfunction in canine patients with haemangiosarcomas and carcinomas, and haemostasis has been assessed in dogs with various malignant and benign neoplasias. Few studies have addressed the effect of cancer type and progression of disease on the presence of haemostatic alterations in canine patients. The objective of the present study was to evaluate haemostatic variables of coagulation and fibrinolysis in a group of canine cancer patients, and to compare haemostatic changes to the cancer type and progression of disease.

Methods

The study population consisted of 71 dogs with malignant neoplasia presented to the University Hospital for Companion Animals, Faculty of Life Sciences, University of Copenhagen, Denmark. The study was designed as a prospective observational study evaluating the haemostatic function in canine cancer patients stratified according to type of cancer disease and disease progression. The coagulation response was evaluated by thromboelastrography (TEG), platelet count, activated partial thromboplastin time (aPTT), prothombin time (PT), fibrinogen and antithrombin (AT); and fibrinolysis by d-dimer and plasminogen.

Results

Hypercoagulability was the most common haemostatic dysfunction found. Non mammary carcinomas had increased clot strength (TEG G), aPTT and fibrinogen compared to the other groups. When stratifying the patients according to disease progression dogs with distant metastatic disease exhibited significantly increased fibrinogen, and d-dimer compared to dogs with local invasive and local non-invasive cancers.

Conclusion

Hypercoagulability was confirmed as the most common haemostatic abnormality in canine cancer patients and haemostatic dysfunction in canine cancer patients was found related to the cancer type and progression of disease. Increase in TEG G, aPTT and fibrinogen were observed in non-mammary carcinomas and were speculated to overall represent a proinflammatory response associated with the disease. Dogs with distant metastatic disease exhibited increased fibrinogen and d-dimer. Future studies are needed to elucidate the clinical importance of these results.     

Collection of peripheral blood CD34+ progenitor cells from healthy dogs and dogs diagnosed with lymphoproliferative diseases using a Baxter-Fenwal CS-3000 Plus blood cell separator

Background

Canine peripheral blood mononuclear cell (PBMC) apheresis using a Baxter‐Fenwal CS‐3000 Plus automated blood cell separator has not been reported.

Objective

To determine the feasibility and safety of using a CS‐3000 Plus blood cell separator with a small volume separation container holder (SVSCH) and small volume collection chamber (SVCC) to harvest canine PBMCs from dogs weighing <50 kg.

Animals

Eight healthy mongrel dogs and 11 client‐owned dogs in clinical remission for lymphoproliferative diseases (LPD).

Methods

In this prospective study, aphereses were performed using a Baxter‐Fenwal CS‐3000 Plus blood cell separator, with or without recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) treatment.

Results

Aphereses from 6 healthy dogs given rhG‐CSF yielded an average of 1.1 × 10⁷ ± 8.2 × 10⁶ CD34+ cells/kg. Aphereses from LPD dogs given rhG‐CSF yielded an average of 5.4 × 10⁶ ± 3.25 × 10⁶ CD34+ cells/kg (P = .17). Higher hematocrit in both groups of dogs receiving rhG‐CSF correlated with an increased number of CD34+ cells/kg harvested (healthy, P = .04; LPD, P = .05). Apheresis was well tolerated by all dogs.

Conclusions and Clinical Importance

Canine PBMC apheresis using the Baxter‐Fenwal CS‐3000 Plus cell separator with an SVSCH and SVCC is a feasible and safe option for harvesting an adequate number of CD34+ peripheral blood progenitor cells from dogs weighing ≥17 kg for hematopoietic cell transplantation.     

Phase I study to determine the maximal tolerated dose and dose-limiting toxicities of orally administered idarubicin in dogs with lymphoma

Background

Idarubicin, a PO bioavailable anthracycline antibiotic‐class chemotherapeutic, could have substantial convenience advantages over currently available similar class agents in use that require IV delivery.

Objectives

The primary objective of this study was to determine the maximally tolerated dose (MTD), dose‐limiting toxicities (DLTs), and basic pharmacokinetic parameters of oral idarubicin exposure in dogs with lymphoma after a single oral dose. A secondary objective was to document preliminary antitumor efficacy in an expanded treatment cohort using the established MTD.

Animals

Client‐owned dogs with measurable lymphoma.

Methods

Dogs (n = 31) were enrolled in a prospective open label phase I study of oral idarubicin. By means of a 3 + 3 cohort design, dose escalations were made with 3 dogs per dose level, and the MTD was established based on the number of patients experiencing a DLT. Plasma concentrations of idarubicin and idarubicinol were determined by postdose sampling. Assessment of antitumor efficacy focused on evaluation of accessible, measurable lymph nodes and skin lesions by modified RECIST guidelines.

Results

The MTD in dogs > 15 kg body weight was 22 mg/m². Adverse hematologic events (neutropenia and thrombocytopenia) were the predominant DLT and generally correlated with higher plasma concentrations of idarubicin and idarubicinol.

Conclusions and Clinical Importance

PO administered idarubicin was generally well‐tolerated and had preliminary antitumor activity in dogs with lymphoma. Furthermore, the potential clinical advantage of a safe and efficacious oral anthracycline alternative supports further investigations of this agent in repeated‐dose, randomized clinical trials.     

Noninvasive Clinical Assessment of Systolic Torsional Motions by Two‐Dimensional Speckle‐Tracking Echocardiography in Dogs with Myxomatous Mitral Valve Disease

Background

Left ventricular torsional motion plays an important role for effective pump function. However, noninvasive clinical assessment of torsional deformations by two‐dimensional speckle‐tracking echocardiography (2D‐STE) in dogs with myxomatous mitral valve disease (MMVD) has not been reported.

Hypothesis

Left ventricular torsion is determined by the native orientation of the helical myocardial fibers, such that it might provide better assessment of myocardial function than conventional methods.

Animals

Sixty‐seven client‐owned dogs with MMVD were classified into 3 classes based on the International Small Animal Cardiac Health Council classification and 16 weight‐ and age‐matched healthy dogs.

Methods

Dogs were examined for myocardial deformations by 2D‐STE and were evaluated for peak systolic rotation and rotation rate at each basal and apical view. Dogs also were evaluated for peak systolic torsion and torsion rate.

Results

Peak systolic torsion was higher in class II than in class I (P < .001) dogs. Peak systolic torsion was lower in class III than in class II (P = .001) dogs and controls (P = .003).

Conclusions and Clinical Importance

Torsional deformations assessed by 2D‐STE differed among clinical classes of MMVD. Myocardial torsional deformations by 2D‐STE may provide more detailed assessment of contractile function in dogs with MMVD.     

The Seroprevalence of Canine Influenza Virus H3N8 in Dogs Participating in a Flyball Tournament in Pennsylvania in 2010: A Follow‐Up Study

Background

Canine influenza virus (CIV) H3N8 infection is thought to be highly contagious and potentially deadly. Low seroprevalence in dogs participating in the sport of flyball in 2009 was reported. It remains unknown if prevalence is changing in dogs at risk.

Objective

To determine seroprevalence of antibodies to CIV H3N8 in a population of pet dogs that participated in an indoor flyball tournament in Pennsylvania in November 2010.

Animals

Dogs participating in a flyball tournament.

Methods

Medical, travel, and activity histories for previous 10.5 months were obtained from consenting owners and serum samples were collected from dogs. Antibodies to CIV H3N8 were measured using hemagglutination inhibition.

Results

Of 251 competing dogs, 103 dogs were tested. Overall, seroprevalence of CIV H3N8 in dogs participating in flyball was 1.9% (95% CI, 0.05–6.8%). Thirty‐five dogs were tested in both 2009 (all titers <8) and 2010 (all titers <8). Ten of 103 dogs had been vaccinated for CIV H3N8. Two dogs had positive titers (>8) and both had been vaccinated twice in the previous month. Titers in remaining 8 vaccinated dogs were undetectable. Seroprevalence in vaccinated dogs was 20% (95% CI, 5.7–50.1%), whereas in unvaccinated dogs it was 0% (95% CI, 0–4.0%). Although 7 dogs had history of respiratory signs, only 1, which was vaccinated, was serologically positive for CIV H3N8.

Conclusions

Consistent with low prevalence of CIV H3N8 exposure previously reported in flyball dogs, unvaccinated dogs had 0% prevalence, suggesting a stable exposure rate. However, low seroprevalence may result in unprotected flyball dogs at risk for developing CIV H3N8.     

Serum Inhibin Concentration in Dogs with Adrenal Gland Disease and in Healthy Dogs

Background

Studies in humans identified the synthesis and secretion of inhibin from adrenocortical tumors, but not pheochromocytoma (PHEO). Inhibin has not been examined in dogs as a serum biomarker for adrenal gland tumors.

Objective

To determine serum inhibin concentration in dogs with adrenal gland disease and in healthy dogs.

Animals

Forty‐eight neutered dogs with adrenal disease including pituitary‐dependent hyperadrenocorticism (PDH, 17), adrenocortical tumor (18), and PHEO (13), and 41 healthy intact or neutered dogs.

Methods

Prospective observational study. Dogs were diagnosed with PDH, adrenocortical tumor (hyperadrenocorticism or noncortisol secreting), or PHEO based on clinical signs, endocrine function tests, abdominal ultrasound examination, and histopathology. Inhibin concentration was measured by radioimmunoassay in serum before and after ACTH stimulation, and before and after treatment.

Results

In neutered dogs, median inhibin concentration was significantly higher in dogs with adrenocortical tumors (0.82 ng/mL) and PDH (0.16 ng/mL) than in dogs with PHEO and healthy dogs (both undetectable). Median inhibin concentration was significantly higher in dogs with adrenocortical tumors than in those with PDH and decreased after adrenalectomy. Median inhibin concentration was significantly higher in intact than in neutered healthy dogs and was similar in pre‐ and post‐ACTH stimulation. Sensitivity, specificity, and accuracy of serum inhibin concentration for identifying an adrenal tumor as a PHEO were 100, 88.9, and 93.6%, respectively.

Conclusions and Clinical Importance

Adrenocortical tumors and PDH but not PHEOs are associated with increased serum inhibin concentration; undetectable inhibin is highly supportive of PHEO in neutered dogs with adrenal tumors.