Comparative Analysis of mRNA Expression of Surface Antigens between Histiocytic and Nonhistiocytic Sarcoma in Dogs

Background

Definitive diagnosis of histiocytic sarcoma (HS) in dogs is relatively difficult by conventional histopathological examination because objective features of HS are not well defined.

Hypothesis

Quantitative analysis of mRNA expression of selected cellular surface antigens (SAs) specific to HS in dogs can facilitate objective and rapid diagnosis.

Animals

Dogs with HS (n = 30) and dogs without HS (n = 36), including those with other forms of lymphoma (n = 4), inflammatory diseases (n = 6), and other malignant neoplasias (n = 26).

Methods

Retrospective clinical observational study. Specimens were collected by excisional biopsy, needle core biopsy, or fine needle aspiration. To determine HS detection efficacy, mRNA expression levels of selected SAs specific to HS in dogs, including MHC class IIα, CD11b, CD11c, and CD86, were quantitatively analyzed using real‐time quantitative polymerase chain reaction.

Results

Each SA mRNA expression level was significantly higher in HS dogs than in non‐HS dogs (P = .0082). Cutoff values for discriminating between HS and non‐HS dogs based on these expression levels were calculated on the basis of receiver‐operating characteristic analysis. Accuracy of the cutoff values, including MHC class IIα, CD11b, CD11c, and CD86, was 87.9, 86.4, 86.4, and 84.8%, respectively.

Conclusions and Clinical Importance

Our results suggest that quantitative analysis of mRNA expression of the selected SAs could be an adjunctive diagnostic technique with high diagnostic accuracy for HS in dogs. Substantial investigation is required for exclusion of diseases with similar cell types of origin to lymphoma.     

Detection of Clinically Relevant Pain Relief in Cats with Degenerative Joint Disease Associated Pain

Background

Detection of clinically relevant pain relief in cats with degenerative joint disease (DJD) is complicated by a lack of validated outcome measures and a placebo effect.

Hypothesis/Objectives

To evaluate a novel approach for detection of pain relief in cats with DJD.

Animals

Fifty‐eight client‐owned cats.

Methods

Prospective, double‐masked, placebo‐controlled, stratified, randomized, clinical study. Enrolled cats were 6–21 years of age, with owner‐observed mobility impairment, evidence of pain in at least 2 joints during orthopedic examination, and overlapping radiographic evidence of DJD, and underwent a 2‐week baseline period, 3‐week treatment period with placebo or meloxicam, and 3‐week masked washout period. Outcome measures were evaluated at days 0, 15, 36, and 57.

Results

Both groups significantly improved after the treatment period (day 36) on client‐specific outcome measures (CSOM) and feline musculoskeletal pain index (FMPI) (P < .0001 for both); there was no difference between the groups on CSOM or FMPI score improvement. After the masked washout period, more cats that received meloxicam during the treatment period had a clinically relevant decrease in CSOM score (P = .048) and FMPI score (P = .021) than cats that received placebo.

Conclusions and Clinical Importance

Using both a client‐specific and a general clinical metrology instrument, owners of cats with DJD were able to detect evident recurrence of clinical signs after withdrawal of active medication than after withdrawal of placebo, and that this study design might be a novel and useful way to circumvent the placebo effect and detect the efficacy of pain‐relieving medications.     

Breed Differences in Natriuretic Peptides in Healthy Dogs

Background

Measurement of plasma concentration of natriuretic peptides (NPs) is suggested to be of value in diagnosis of cardiac disease in dogs, but many factors other than cardiac status may influence their concentrations. Dog breed potentially is 1 such factor.

Objective

To investigate breed variation in plasma concentrations of pro‐atrial natriuretic peptide 31‐67 (proANP 31‐67) and N‐terminal B‐type natriuretic peptide (NT‐proBNP) in healthy dogs.

Animals

535 healthy, privately owned dogs of 9 breeds were examined at 5 centers as part of the European Union (EU) LUPA project.

Methods

Absence of cardiovascular disease or other clinically relevant organ‐related or systemic disease was ensured by thorough clinical investigation. Plasma concentrations of proANP 31‐67 and NT‐proBNP were measured by commercially available ELISA assays.

Results

Overall significant breed differences were found in proANP 31‐67 (P < .0001) and NT‐proBNP (P < .0001) concentrations. Pair‐wise comparisons between breeds differed in approximately 50% of comparisons for proANP 31‐67 as well as NT‐proBNP concentrations, both when including all centers and within each center. Interquartile range was large for many breeds, especially for NT‐proBNP. Among included breeds, Labrador Retrievers and Newfoundlands had highest median NT‐proBNP concentrations with concentrations 3 times as high as those of Dachshunds. German Shepherds and Cavalier King Charles Spaniels had the highest median proANP 31‐67 concentrations, twice the median concentration in Doberman Pinschers.

Conclusions and Clinical Importance

Considerable interbreed variation in plasma NP concentrations was found in healthy dogs. Intrabreed variation was large in several breeds, especially for NT‐proBNP. Additional studies are needed to establish breed‐specific reference ranges.     

Serum Biomarkers of Clinical and Cytologic Response in Dogs with Idiopathic Immune‐Mediated Polyarthropathy

Background

Immune‐mediated polyarthopathy (IMPA) is common in dogs, and is monitored by serial arthrocenteses.

Hypothesis/Objectives

Plasma C‐reactive protein (CRP), interleukin‐6 (IL‐6), and CXCL8 (interleukin‐8) would serve as noninvasive markers of joint inflammation in IMPA.

Animals

Nine client‐owned dogs with idiopathic IMPA; 6 healthy controls.

Methods

Prospective study. Plasma CRP, IL‐6, and CXCL8 were measured by ELISA at baseline, 2, and 4 weeks during treatment with prednisone at 50 mg/m²/day. Arthrocenteses, the canine brief pain inventory (CBPI), and accelerometry collars were used to assess joint inflammation, lameness, and mobility at all 3 time points.

Results

C‐reactive protein concentrations were higher in IMPA dogs (median 91.1 μg/mL, range 76.7–195.0) compared with controls (median <6.3 μg/mL, <6.3–13.7; P = .0035), and were significantly lower at week 2 (10.6 μg/mL, <6.3–48.8) and week 4 (<6.3 μg/mL, <6.3–24.4; P < .001).C‐reactive protein was correlated with median CBPI scores (r = 0.68; P = .0004), joint cellularity (r = 0.49, P = .011), and mobility by accelerometry (r = −0.42, P = .048). Plasma IL‐6 concentrations were also higher in IMPA dogs (median 45.9 pg/mL), compared with controls (median <15.7 pg/mL; P = .0008). IL‐6 was lower in IMPA dogs by week 4 (<15.7 pg/mL; P = .0099), and was modestly correlated with CBPI scores (r = 0.47, P = .023). CXCL8 did not differ significantly between IMPA and healthy dogs.

Conclusions

Plasma CRP and IL‐6 might be useful surrogate markers of synovial inflammation and disease activity in dogs with IMPA.     

Experimental Final Hosts of Metagonimus Hakubaensis (Trematoda: Heterophyidae) and Their Suitability to the Fluke

Seven laboratory mammal and bird species were orally inoculated with 200–1,000 encysted Metagonimus hakubaensis metacercariae that had been isolated from naturally infected lampreys (Lethenteron reissneri) captured in Aomori Prefecture. At 8 and 15 days post-infection, adult flukes were recovered from all of the laboratory animals tested, and therefore, hamster, rat, mouse, dog, cat, chicken and quail were considered as final hosts of M. hakubaensis. Recovery rates of the fluke were higher in dogs and hamsters than in cats, rats, mice, chickens and quails. The flukes recovered from dogs and hamsters showed increased body length and higher fecundity than those recovered from the other hosts. These results indicate that the suitability of dogs and hamsters for M. hakubaensis infection is higher than that of the other laboratory animals.     

Pathology and Neurotoxicity in Dogs after Repeat Dose Exposure to a Serotonin 5-HT1B Inhibitor

AZD3783, a cationic amphiphilic drug and a potent inhibitor of the 5-hydroxytryptamine (5-HT_1B) receptor, was explored as a potential treatment for depression. To support clinical trials, repeat dose toxicity studies in rats and dogs were conducted. Here we report toxicity findings in dogs after dosing from 1 to 3 months. In the 1-month study, there were minimal neuronal vacuolation in the brain, a marked increase in liver enzymes accompanied by hepatocellular degeneration/necrosis and phospholipidosis (PLD), and PLD/cholecystitis in the gallbladder of animals dosed at 47 mg/kg/day. In the 3-month study, neurotoxicity resulted in euthanasia of one animal dosed at 30 mg/kg/day after 86 days. Extensive pathologic changes were seen in all animals in retina epithelium (inclusion bodies), brain (neuronal vacuolation, degeneration, or necrosis and nerve fiber degeneration), spinal ganglia (vacuolation, degeneration, or necrosis), as well as sciatic and optic nerves (degeneration). Pigment-laden macrophages were observed in the lung, kidney, liver, gallbladder, bone marrow, gastrointestinal tract, and lymphoid tissues. Also seen were vitrel and retinal hemorrhage in the eyes. A brain concentration and pathology study showed that the concentration of AZD3783 in the brain was approximately 4 times higher than in the plasma after 4 weeks of dosing, however, they were similar in all regions examined, and did not correlate with areas with pathologic findings. Our findings with AZD3783 in dogs have not been reported previously with other CNS compounds that effect through serotonergic pharmacology.     

Prognostic Value of Left Atrial Function in Dogs with Chronic Mitral Valvular Heart Disease

Background

A strong correlation between left atrial (LA) dysfunction and the severity of cardiac disease has been described in human patients with various cardiac diseases. The role of LA dysfunction in dogs with chronic mitral valvular heart disease (CMVHD) has not been addressed.

Objectives

To investigate the correlation between LA function and the prognosis of dogs with CMVHD.

Animals

Thirty‐eight client‐owned dogs with CMVHD.

Methods

Prospective clinical cohort study. Dogs were divided into 2 groups (survivors and nonsurvivors) based on the onset of cardiac‐related death within 1 year. Physical examination and echocardiographic variables were compared between the groups. For the assessment of the comparative accuracy in identifying patients with cardiac‐related death, receiver operating characteristic (ROC) curves and multivariate logistic analysis were used.

Results

The highest accuracy was obtained for the LA active fractional area change (LA‐FAC _act), with an area under the ROC curve (AUC) of 0.95, followed by the left atrial to aortic root ratio (LA/Ao), with an AUC of 0.94; peak early diastolic mitral inflow velocity (E), with an AUC of 0.85; and LA total fractional area change (LA‐FAC _total), with an AUC of 0.85. In the multivariate logistic regression analysis, LA‐FAC _act emerged as the only independent correlate of cardiac‐related death within 1 year (odds ratio = 1.401, P = .002).

Conclusions and Clinical Importance

Regarding both the size and function, the LA has a strong correlation with the prognosis of dogs with CMVHD. The most significant independent predictor of mortality in this study was LA‐FAC _act.