d,l-Methionine in combination with amoxicillin-clavulanic acid successfully dissolves spontaneously occurring infection-induced struvite urocystoliths in dogs: a pilot study.

OBJECTIVE: To determine the efficacy and safety of a urinary acidifier (d,l-methionine [Methio-Form]) and an antimicrobial agent (amoxicillin-clavulanic acid [Clavamox]) without changing diet for dissolving infection-induced struvite urocystoliths in dogs. ANIMALS: 14 dogs were recruited for this prospective study; 11 completed it and 3 dogs withdrew due to inability of the owners to administer the treatment (n = 2) or refusal of treatment by the dog (1). PROCEDURES: All dogs were administered d,l-methionine (approx initial dose of 75 mg/kg, PO, q 12 h) and amoxicillin-clavulanic acid (22 mg/kg, PO, q 12 h) based on urine culture and sensitivity. Urine pH, urinalysis, urine culture, venous blood gas and serum biochemical analysis, and lateral survey abdominal radiographic images were evaluated initially and every 4 weeks until urolith dissolution (success) or lack of change in size and/or shape of urocystoliths on 2 consecutive reevaluation points (failure) occurred. RESULTS: Uroliths dissolved in 8 of 11 dogs in a median of 2 months (range, 1 to 4 months) with a final effective dosage of d,l-methionine of approximately 100 mg/kg, PO, every 12 hours. In 3 dogs, uroliths failed to dissolve and were removed surgically; they contained variable amounts of calcium oxalate. No adverse events occurred. CLINICAL RELEVANCE: Infection-induced struvite urolithiasis is 1 of the 2 most common minerals occurring in canine uroliths. Results of this study supported the use of d,l-methionine and amoxicillin-clavulanic acid without changing diet for dissolution of infection-induced struvite urocystoliths in dogs.

Clinicopathologic and gastrointestinal effects of administration of prednisone, prednisone with omeprazole, or prednisone with probiotics to dogs: A double-blind randomized trial.

BACKGROUND: The efffect of administering of probiotics or twice-daily omeprazole on glucocorticoid-induced gastric bleeding in dogs is unknown. HYPOTHESIS: Compare gastrointestinal bleeding among dogs administered placebo, prednisone (2 mg/kg q24h), prednisone with omeprazole (1 mg/kg q12h), or prednisone with probiotics (Visbiome, 11.2-22.5 billion CFU/kg q24h) for 28 days. ANIMALS: Twenty-four healthy research dogs. METHODS: Double-blinded, placebo-controlled randomized trial. Clinical signs and endoscopic gastrointestinal mucosal lesion scores at baseline (t1 ), day 14 (t2 ), and day 28 (t3 ) were compared using split-plot repeated-measures mixed-model ANOVAs. RESULTS: Fecal score differed by treatment-by-time (F[6,40] = 2.65, P < .03), with higher scores in groups receiving prednisone at t3 than t1 . Nineteen of thirty-three episodes of diarrhea occurred in the prednisone with omeprazole group. Gastric mucosal lesion scores differed by treatment-by-time (F[6,60] = 2.86, P = .05), among treatment groups (F[3,60] = 4.9, P = .004), and over time (F[2,60] = 16.5, P < .001). Post hoc analysis revealed lesion scores increased over time for all groups receiving prednisone. At t3 , scores for the prednisone (8.7 ± 4.9) and prednisone with probiotics (8.7 ± 4.9) groups differed significantly from placebo (1.8 ± 1.8; P ≤ .04), whereas scores for the prednisone with omeprazole (6.5 ± 5.5) group did not differ from placebo (P = .7). Ulcers occurred only in dogs receiving prednisone. CONCLUSIONS AND CLINICAL IMPORTANCE: Prednisone-induced gastric bleeding. Co-administration of omeprazole partially mitigated bleeding, but a similar protective benefit was not demonstrated by co-administration of the evaluated probiotic.

Evaluation of a pet-separating automatic feeder and high-frequency meal feeding for weight loss in multi-cat households.

OBJECTIVES: The objectives of this study were two-fold: (1) to determine if a feeder system providing individualized food access and automatic dispensing of meals makes weight-loss programs in multi-cat homes easier for cat owners; and (2) to assess if feeding six meals daily reduces food-seeking behavior and increases calorie requirements vs two meals per day. METHODS: Adult cats with body condition scores (BCSs) of 7/9 or greater underwent a weight-loss plan for up to 6 months using a traditional feeding bowl with two meals per day (B2) or an automatic feeder with two meals (A2) or six meals (A6) per day. Cats were weighed at weeks 0, 2, 4, 6, 10, 14, 18, 22 and 26 and food intake was adjusted to maintain weight-loss rates between 0.5% and 1.5% body weight per week. Owner questionnaires were completed at each study visit. RESULTS: Twenty-three cats were included in the study. Cats fed from the automatic feeders were more likely to reach ideal body condition (P = 0.006), with 83.2% of cats in A6, 40% of cats in A2 and no cats in B2 achieving a BCS of ⩽6/9. Owners of cats fed from automatic feeders reported the weight-loss plan was easier vs owners of cats fed from bowls (P = 0.01). Owners using the automatic feeders also reported fewer incidences of certain food-seeking behaviors. Neither percent body weight lost per week nor calorie intake per kg differed between groups. CONCLUSIONS AND RELEVANCE: Feeding six instead of two meals daily did not result in faster rates of weight loss or the need to increase calorie intake to maintain appropriate rates of weight loss. However, use of an automatic feeder that provided separated, portioned meal feeding made the weight-loss program easier, reduced food-seeking behaviors and improved the overall success of the weight-loss plan.

Effects of Synbiotics on the Fecal Microbiome and Metabolomic Profiles of Healthy Research Dogs Administered Antibiotics: A Randomized, Controlled Trial.

Background: Antibiotic-associated gastrointestinal signs occurred in 100% of dogs administered enrofloxacin with metronidazole in a previous study, and signs partially were mitigated by synbiotics. The objective of this randomized, double-blinded, placebo-controlled trial was to compare the fecal microbiome and metabolome of dogs administered enrofloxacin and metronidazole, followed by either a placebo or a bacterial/yeast synbiotic combination. Methods: Twenty-two healthy research dogs were randomized to two treatment groups. There were three study periods: baseline, treatment, and washout. Dogs were administered enrofloxacin (10 mg/kg qd) and metronidazole (12.5 mg/kg BID), followed 1 h later by placebo or a commercially-available synbiotic combination (BID), per os for 21 days with reevaluation 56 days thereafter. Fecal samples were collected on days 5-7 (baseline), 26-28, and 82-84. The fecal microbiome was analyzed by qPCR and sequencing of 16S rRNA genes; time-of-flight mass spectrometry was used to determine metabolomic profiles. Split plot repeated measures mixed model ANOVA was used to compare results between treatment groups. P < 0.05 was considered significant, with Benjamini and Hochberg's False Discovery Rate used to adjust for multiple comparisons. Results: Alpha diversity metrics differed significantly over time in both treatment groups, with incomplete recovery by days 82-84. Beta diversity and the dysbiosis index differed significantly over time and between treatment groups, with incomplete recovery at days 82-84 for dogs in the placebo group. Significant group-by-time interactions were noted for 15 genera, including Adlercreutzia, Bifidobacterium, Slackia, Turicibacter, Clostridium (including C. hiranonis) [Ruminococcus], Erysipelotrichaceae_g_, [Eubacterium], and Succinivibrionaceae_g_. Concurrent group and time effects were present for six genera, including Collinsella, Ruminococcaceae_g_, and Prevotella. Metabolite profiles differed significantly by group-by-time, group, and time for 28, 20, and 192 metabolites, respectively. These included short-chain fatty acid, bile acid, tryptophan, sphingolipid, benzoic acid, and cinnaminic acid metabolites, as well as fucose and ethanolamine. Changes in many taxa and metabolites persisted through days 82-84. Conclusion: Antibiotic administration causes sustained dysbiosis and dysmetabolism in dogs. Significant group-by-time interactions were noted for a number of taxa and metabolites, potentially contributing to decreased antibiotic-induced gastrointestinal effects in dogs administered synbiotics.

Randomized, controlled, crossover trial of prevention of antibiotic-induced gastrointestinal signs using a synbiotic mixture in healthy research dogs.

BACKGROUND: Synbiotics decrease antibiotic-associated gastrointestinal signs (AAGS) in cats, but data supporting synbiotic use to ameliorate AAGS in dogs are lacking. OBJECTIVES: To determine if administration of synbiotics mitigates AAGS in dogs. ANIMALS: Twenty-two healthy research dogs. METHODS: Randomized, double-blinded, placebo-controlled, 2-way, 2-period, crossover study with an 8-week washout period. Each period included a 1-week baseline and 3-week treatment phase. Dogs received enrofloxacin (10 mg/kg PO q24h) and metronidazole (12.5 mg/kg PO q12h), followed 1 hour later by a bacterial/yeast synbiotic combination or placebo. Food intake, vomiting, and fecal score were compared using repeated-measures crossover analyses, with P < .05 considered significant. RESULTS: Hyporexia, vomiting, and diarrhea occurred in 41% (95% confidence interval [CI], 21-64), 77% (95% CI, 55-92), and 100% (95% CI, 85-100) of dogs, respectively, during the first treatment period. Derangements in food intake were smaller in both periods for dogs receiving synbiotics (F-value, 5.1; P = .04) with treatment-by-period interactions (F-value, 6.0; P = .02). Days of vomiting differed over time (F-value, 4.7; P = .006). Fecal scores increased over time (F-value, 33.5; P < .001), were lower during period 2 (F-value, 14.5; P = .001), and had treatment-by-period effects (F-value, 4.8; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Enrofloxacin/metronidazole administration is associated with a high frequency of AAGS. Synbiotic administration decreases food intake derangements. The presence of milder AAGS in period 2 suggests that clinical effects of synbiotics persist >9 weeks after discontinuation, mitigating AAGS in dogs being treated with antibiotics followed by placebo.

Body composition of lean outdoor intact cats vs lean indoor neutered cats using dual-energy x-ray absorptiometry.

OBJECTIVES: The objectives for this study were to compare the body composition of adult indoor neutered domestic cats with outdoor intact cats with an ideal body condition score using dual-energy x-ray absorptiometry, and to report the body composition findings of free-roaming cats, as this has not been previously reported. Most domestic house cats differ from free-roaming cats as they are confined indoors and neutered. Indoor neutered cats have reduced activity and hormonal alterations that may result in lower muscle mass and higher body fat percentages vs outdoor intact cats, despite similar body condition scores. METHODS: Twenty-one outdoor intact cats (10 male, 11 female) were selected from a trap-neuter-return program and 16 indoor neutered domestic cats (10 male, six female) were client-owned. Inclusion criteria included an estimated age between 1 and 6 years, complete blood count, biochemistry panel, urinalysis, total thyroxine, feline leukemia virus/feline immunodeficiency virus screening and a body condition score of 4-5/9. RESULTS: Indoor neutered cats had a higher body fat percentage (22.1% [range 17.3-28.2%]) than outdoor intact cats (17.3% [range 10.0-33.6%]; P = 0.002). Indoor neutered male cats had a higher body fat percentage ( P <0.001) than outdoor intact cats. No difference in body fat percentage was observed in female cats ( P = 0.159). Indoor neutered domestic cats had a higher bone mineral density than outdoor intact cats ( P = 0.023). CONCLUSIONS AND RELEVANCE: The results of this study suggest indoor confinement and neutering increase body fat percentage and bone mineral density in cats with an ideal body condition score.

Prevalence of asymptomatic urinary tract infections in morbidly obese dogs.

Background. Obesity has reached epidemic proportions in dogs and, as in humans, cost of care has increased due to associated comorbidities. In humans, asymptomatic urinary tract infections (UTI) may be more prevalent in the obese. Asymptomatic bacteriuria (AB) is the term used when UTI are asymptomatic. We hypothesized that morbidly obese dogs are similarly more likely to have asymptomatic bacteriuria than lean, overweight, and moderately obese dogs. Methods. A retrospective study was undertaken to explore a possible association between obesity and asymptomatic bacteriuria. Records from lean, overweight, and obese dogs receiving both a dual energy absorptiometry (DXA) scan and urine culture were included. Results. Six positive urine cultures were identified among 46 dogs fulfilling search criteria. All six positive cultures were found in dogs with body fat percentage of >45%. In dogs with body fat percentage of <45%, there were no positive urine cultures. Discussion. There was an increased prevalence of asymptomatic bacteriuria in the morbidly obese dogs in this study compared to those that were lean, overweight, or moderately obese. Whether antibiotic therapy is necessary in such cases is still being debated, but because asymptomatic bacteriuria may be associated with ascending infections, uroliths, or other complications, the data reported herein support the screening of obese patients for bacteriuria.

Influence of acidifying or alkalinizing diets on bone mineral density and urine relative supersaturation with calcium oxalate and struvite in healthy cats.

OBJECTIVE: To evaluate the influence of acidifying or alkalinizing diets on bone mineral density and urine relative supersaturation (URSS) with calcium oxalate and struvite in healthy cats. ANIMALS: 6 castrated male and 6 spayed female cats. PROCEDURES: 3 groups of 4 cats each were fed diets for 12 months that differed only in acidifying or alkalinizing properties (alkalinizing, neutral, and acidifying). Body composition was estimated by use of dual energy x-ray absorptiometry, and 48-hour urine samples were collected for URSS determination. RESULTS: Urine pH differed significantly among diet groups, with the lowest urine pH values in the acidifying diet group and the highest values in the alkalinizing diet group. Differences were not observed in other variables except urinary ammonia excretion, which was significantly higher in the neutral diet group. Calcium oxalate URSS was highest in the acidifying diet group and lowest in the alkalinizing diet group; struvite URSS was not different among groups. Diet was not significantly associated with bone mineral content or density. CONCLUSIONS AND CLINICAL RELEVANCE: Urinary undersaturation with calcium oxalate was achieved by inducing alkaluria. Feeding an alkalinizing diet was not associated with URSS with struvite. Bone mineral density and calcium content were not adversely affected by diet; therefore, release of calcium from bone caused by feeding an acidifying diet may not occur in healthy cats.

Evaluation of plasma diazepam and nordiazepam concentrations following administration of diazepam intravenously or via suppository per rectum in dogs.

OBJECTIVE: To evaluate the pharmacokinetics of diazepam administered per rectum via compounded (ie, not commercially available) suppositories and determine whether a dose of 2 mg/kg in this formulation would result in plasma concentrations shown to be effective for control of status epilepticus or cluster seizures (ie, 150 to 300 ng/mL) in dogs within a clinically useful interval (10 to 15 minutes). ANIMALS: 6 healthy mixed-breed dogs. PROCEDURES: Dogs were randomly assigned to 2 groups of 3 dogs each in a crossover-design study. Diazepam (2 mg/kg) was administered IV or via suppository per rectum, and blood samples were collected at predetermined time points. Following a 6- or 7-day washout period, each group received the alternate treatment. Plasma concentrations of diazepam and nordiazepam were analyzed via reversed phase high-performance liquid chromatography. RESULTS: Plasma concentrations of diazepam and nordiazepam exceeded the targeted range ≤ 3 minutes after IV administration in all dogs. After suppository administration, targeted concentrations of diazepam were not detected in any dogs, and targeted concentrations of nordiazepam were detected after 90 minutes (n = 2 dogs) or 120 minutes (3) or were not achieved (1). CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of these results, administration of 2 mg of diazepam/kg via the compounded suppositories used in the present study cannot be recommended for emergency treatment of seizures in dogs.

Preliminary evaluation of serial (18) FDG-PET/CT to assess response to toceranib phosphate therapy in canine cancer.

Palladia(TM) (toceranib phosphate-Pfizer Animal Health) is a novel orally administered receptor tyrosine kinase inhibitor (TKI) approved for treatment of canine mast cell tumors. Receptor tyrosine kinase dysregulation leads to tumor growth, progression, and metastasis. Toceranib's targets include vascular endothelial growth factor receptor (VEGFR-2/Flk-1/KDR), platelet-derived growth factor receptor, and kit. Positron Emission Tomography/Computed Tomography (PET/CT) is used commonly to diagnose, prognosticate, and monitor response to antineoplastic therapy in human patients. In this study, serial PET/CT imaging with (18) F-fluorodeoxyglucose ((18) FDG) was used to assess response to toceranib therapy in dogs with measurable solid malignancies. Six tumor-bearing dogs underwent tumor assessment using both standard RECIST criteria and PET/CT prior to and at a median of 5 weeks postinitiation of toceranib treatment. Toceranib was prescribed initially at a target dose 3.25 mg/kg PO q48 h, with subsequent modifications based on observed toxicity. Treatment was continued in patients achieving stable disease with acceptable drug tolerance. One dog was maintained on drug despite dose modification due to toxicity; measurable clinical and image-based responses were seen after 10 weeks of therapy. All others had stable or progressive disease based on clinical restaging and PET/CT at first recheck. . Due to discordance with anatomic and metabolic imaging, further studies are needed to investigate the role of molecular imaging in assessment of drug response and identify other potential molecular targets of toceranib.

Giant platelet disorder in the Cavalier King Charles Spaniel.

OBJECTIVE: The aim of this study was to describe the clinical, functional, and morphologic characteristics of platelets in Cavalier King Charles Spaniel dogs (Cavaliers). MATERIALS AND METHODS: Blood from 69 clinically normal Cavaliers was collected and anticoagulated with ethylenediamine-tetraacetic acid (EDTA) and citrate. Automated and manual platelet counts were obtained. Percent platelet aggregation in response to ADP (2, 4, 8, 16, and 32 microM) was determined. Electron microscopy was performed to examine platelet internal morphology and dense granule distribution. A cardiologist recorded the quality of murmurs. RESULTS: Thrombocytopenia (<100,000/microL) was present in 51.43% (36/69) of Cavaliers. Macrothrombocytes (>3 microm) were present in 33.33% (22/69). Mean manual platelet count was 118,770/microL. Manual (EDTA blood) and automated (EDTA and citrated blood) methods of platelet counting were correlated. Prevalence of cardiac murmurs was 38% (26/69). There was no association between affected dogs and murmur, signalment, or coat color. Mean percent platelet aggregation was significantly higher in controls than in Cavaliers (79% vs 38%, p=0.001). Response to ADP was unaffected by thrombocytopenia, macrothrombocytes, murmur, or any combination thereof. Platelet electron microscopy showed normal and giant sized platelets with normal internal morphology. CONCLUSIONS: A benign inherited giant platelet disorder affects approximately 50% of Cavalier King Charles Spaniels. It is characterized by thrombocytopenia, macrothrombocytes, or decreased platelet aggregation in response to ADP. Platelet ultrastructure is normal. Citrated or EDTA blood provides accurate platelet counts. Further studies are indicated to determine platelet glycoprotein structure and any association with mitral endocardiosis. Cavaliers may be useful models of inherited giant platelet disorders.

Comparison of various methods for estimating body fat in dogs.

Obesity is considered one of the most common forms of malnutrition occurring in dogs. Laboratory methods of evaluation of body composition in live dogs have included dual-energy X-ray absorptiometry (DEXA) and deuterium oxide (D(2)O) dilution. Clinical methods of evaluation include assigning a body condition score (BCS) based on visual observation, palpation, and morphometric measurements. This study used these four methods to evaluate 23 healthy, adult, client-owned dogs. Good correlation (coefficient of determination [r(2)]=0.78) was found between measurements of percent body fat (%BF) determined by the D(2)O dilution method and the DEXA scan. Percent body fat can also be estimated using BCS (r(2)=0.92 comparison with DEXA) or by using morphometric measurements with simple calculations (r(2)=0.92 comparison with DEXA).

Effect of deracoxib, a new COX-2 inhibitor, on the prevention of lameness induced by chemical synovitis in dogs.

Twenty-four healthy, mixed-breed hound-type dogs were evenly and randomly assigned to a placebo control group, one of four dosages of deracoxib (0.3, 1, 3, or 10 mg/kg), or carprofen (2.2 mg/kg). Oral dosing of placebo, carprofen, or deracoxib was done 30 minutes before intraarticular injection of urate crystal suspension for induction of synovitis. Ground reaction forces, subjective clinical lameness scores, pain, joint effusion, and quantitative pain threshold responses were measured in a blinded fashion before induction of synovitis and 2, 4, 6, 8, 12, and 24 hours after injection. The medium and high dosages of deracoxib were effective in preventing lameness and pain associated with synovitis. Carprofen was also somewhat effective in attenuating the severity of urate-induced synovitis but to a lesser degree than the medium dose of deracoxib. Preemptive deracoxib treatment at dosages as low as 1 mg/kg reduced lameness and pain of synovitis associated with intraarticular administration of urate crystals.