Objective: To determine the pharmacokinetics (PK) and safety of various oral doses of a Cannabis herbal extract (CHE) containing a 1:20 ratio of Δ9-tetrahydrocannabinol (THC):cannabidiol (CBD) in 13 healthy Beagle-cross dogs. Methods: Single-dose PK was assessed after oral administration of CHE at low, medium, or high doses [2, 5, or 10 mg CBD and 0.1, 0.25, or 0.5 mg THC per kg of body weight (bw), respectively; n = 6 per group]. Dogs were monitored for adverse events for up to 48 h post-dose. Evaluations of neurological signs, clinical laboratory abnormalities, and other adverse events were performed in two separate study phases: a multiple-dose phase with 12 dogs receiving five medium doses (5 mg CBD/kg bw) at 12 h intervals, and a single low-dose (2 mg CBD/kg bw), randomized, blinded, negative controlled study with 13 dogs. Results: Cannabinoids CBD, THC, CBC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH were quantified in plasma. CBD and THC were rapidly absorbed (mean T max of 1.9–2.3 h) and initially depleted rapidly (mean CBD T 1/2β of 2.3–2.6 h). A prolonged elimination phase (mean CBD T 1/2λ of 13.3–24.4 h) was observed. CBD and THC concentrations increased in a dose-dependent (non-linear) manner, with disproportionally greater cannabinoid exposure relative to the dose increase. Neurological signs (hyperesthesia or proprioceptive deficits) were noted in five of six dogs in the high-dose group, but only occasionally or rarely in the medium- and low-dose groups, respectively. Presence and severity of clinical signs correlated with plasma cannabinoid concentrations. Dogs appeared to develop a tolerance to cannabinoid effects after multiple CHE doses, with fewer neurological signs noted after the final (fifth) vs. first dose. No clinically meaningful changes in blood count or chemistry values occurred after multiple CHE doses. Clinical Significance: Dogs tolerated the 1:20 THC:CBD formulation well at low and medium doses, but clinically meaningful neurological signs were observed at high doses. Because of non-proportional increases in plasma cannabinoid concentrations with increasing doses, as well as potential differences in CHE product composition and bioavailability, the possibility of adverse events and dose regimen consistency should be discussed with dog owners.
Background: Definitive diagnosis of feline pancreatic disease is dependent on histologic examination of biopsies. Hypothesis: Laparoscopic punch biopsy of the pancreas does not significantly affect pancreatic health or clinical status of healthy cats, and provides an adequate biopsy sample for histopathology.Animals: Eleven healthy female domestic shorthair cats. Methods: Effects of laparoscopic pancreatic visualization alone in 5 cats compared with laparoscopic pancreatic visualization and punch biopsy in 6 cats were studied. Temperature, pulse, and respiratory rate, physical examination, and daily caloric intake were evaluated for 1 week before and 1 week after the procedure. Pain scores (simple descriptive score and dynamic interactive visual assessment score) were evaluated hourly during the 1st 6 hours postprocedure. Complete blood cell counts, serum biochemical profiles, serum feline pancreatic lipase immunoreactivity, and urine specific gravity were evaluated before the procedure and at 6, 24, and 72 hours postprocedure. One month postprocedure, during sterilization, the pancreas was reassessed visually in all cats, and microscopically in the biopsy group.Results: For all variables evaluated, there were no significant differences between biopsy and control cats. Re-evaluation of the pancreatic biopsy site 1 month later documented a normal tissue response to biopsy. The laparoscopic punch biopsy forceps provided high-quality pancreatic biopsy samples with an average size of 5 mmÂ4 mm on 2-dimensional cut section.Conclusions and Clinical Importance: Laparoscopic pancreatic biopsy is a useful and safe technique in healthy cats.
BackgroundSeven male Labrador Retriever puppies from 3 different litters, born to clinically normal dams and sires, were evaluated for progressive weakness and muscle atrophy. Muscle biopsies identified a congenital myopathy with pathologic features consistent with myotubular myopathy. Further investigations identified a pathogenic mutation in the myotubularin gene, confirming that these puppies had X‐linked myotubular myopathy (XLMTM).ObjectiveTo review the clinical phenotype, electrodiagnostic and laboratory features of XLMTM in this cohort of Labrador Retrievers.ResultsMale puppies with XLMTM were small and thin compared with their normal littermates. Generalized weakness and muscle atrophy were present by 7 weeks of age in some puppies and evident to most owners by 14 weeks of age. Affected puppies stood with an arched spine and low head carriage, and walked with a short, choppy stride. Muscle atrophy was severe and progressive. Patellar reflexes were absent. Laryngeal and esophageal dysfunction, and weakness of the masticatory muscles occurred in puppies surviving beyond 4 months of age. Serum creatine kinase activity was normal or only mildly increased. EMG findings were nonspecific and included positive sharp waves and fibrillation potentials. Clinical signs progressed rapidly, with most affected puppies unable to walk within 3–4 weeks after clinical signs were first noticed.Conclusions and Clinical ImportanceAlthough initial clinical signs of XLMTM are similar to the phenotypically milder centronuclear myopathy in Labrador Retrievers, XLMTM is a rapidly progressive and fatal myopathy. Clinicians should be aware of these 2 distinct myopathies with similar clinical presentations in the Labrador retriever breed.
Objectives The first aim of this survey was to report client experiences associated with the administration of common medications, particularly glucocorticoids and bronchodilators, in managing cats with feline lower airway disease (FLAD). The second aim was to ascertain client perception of response to treatment and level of satisfaction. Methods This was a prospective cross-sectional study. An online survey was distributed worldwide to cat owners caring for cats with a chronic cough. Only cats reported to have FLAD were included. Results A total of 153 complete responses describing cats with FLAD were analyzed. Glucocorticoids and bronchodilators were the predominantly prescribed therapeutics for 140/153 (92%) and 80/153 (52%) of FLAD cats, respectively. Oral and inhalant administration routes were reported most commonly: glucocorticoids (64% oral and 75% inhalant) and bronchodilators (21% oral and 88% inhalant). A review of how air quality could be improved was conducted for 54% of cats. Almost half (43%) of owners reported adverse effects secondary to glucocorticoid administration, the most frequent being polyphagia (26%) and polydipsia (21%). Only 10% of owners reported bronchodilator-associated side effects, with restlessness (9%) being the most common. Difficulties giving glucocorticoid or bronchodilator tablets orally were reported for 33% and 71% of owners, respectively. Glucocorticoid or bronchodilator inhalant therapies were difficult to administer for 28% and 31% of owners, respectively. Frequency and severity of coughing were significantly lower after at least 2 months of treatment, with median numerical input on a slider scale (0–100) of 48 and 42 before, and 10 and 7 after treatment, respectively ( P <0.0001). Median numerical input of owner satisfaction was 83%. Conclusions and relevance Despite significant improvements in client-reported responses to treatment, challenges associated with the administration of medications and their adverse effects still exist. Promoting awareness of client experiences can facilitate appropriate follow-up, guidance and empathy to further optimize outcomes.
Objectives Alpha(α)2-agonist administration has been documented to increase blood glucose concentrations in many species. The aim of this study was to further describe the effect of dexmedetomidine on glucose and its regulatory hormones in healthy cats. Methods A randomized crossover study using eight healthy cats with a 14 day washout period was used to assess the effect of dexmedetomidine (10 μg/kg IV) and saline on glucose, cortisol, insulin, glucagon and non-esterified fatty acid (NEFA) concentrations at 0, 20, 60, 120 and 180 mins post-administration. Glucose:insulin ratios were calculated for each time point. Results Within the dexmedetomidine group, significant differences ( P <0.05) were detected: increased median (range) blood glucose concentrations at 60 mins (11.55 mmol/l [5.9–16.6 mmol/l]) and 120 mins (12.0 mmol/l [6.1–13.8 mmol/l]) compared with baseline (6.05 mmol/l [4.8–13.3 mmol/l]); decreased glucagon concentrations at 120 mins (3.8 pmol/l [2.7–8.8 pmol/l]) and 180 mins (4.7 pmol/l [2.1–8.2 pmol/l]) compared with baseline (11.85 pmol/l [8.3–17.2 pmol/l]); decreased NEFA concentrations at 60 mins (0.281 mmol/l [0.041–1.357 mmol/l]) and 120 mins (0.415 mmol/l [0.035–1.356 mmol/l]) compared with baseline (0.937 mmol/l [0.677–1.482 mmol/l]); and significantly larger ( P <0.05) glucose:insulin ratios at 60 mins compared with baseline. Insulin and cortisol concentrations were not significantly changed after dexmedetomidine administration. Conclusions and relevance Feline practitioners should be aware of the endocrine effects associated with the use of α2-agonists, particularly when interpreting blood glucose concentrations. The transient effects of dexmedetomidine on glucose homeostasis are unlikely to significantly affect clinical practice.
Objective: To evaluate clinicopathological prognostic indicators associated with survival based on hematology and serum biochemistry profile findings at presentation of dogs with canine parvoviral enteritis (CPE). Secondary objectives were to describe the signalment, history, physical examination findings, and progression of disease while in hospital and correlate them to survival. Design: Retrospective study from medical records of dogs diagnosed with CPE between 2001 and 2018. Setting: University teaching hospital. Animals: Three hundred twenty-two dogs diagnosed with CPE that received inhospital treatment. Interventions: None.Measurements and main results: Of 322 hospitalized dogs, 294 dogs (91%) survived infection with a median hospitalization time of 79 hours. Multivariable analysis showed that glucose (P = 0.04), total magnesium (P = 0.011), and the dichotomized variable of a low HCT (P = 0.033) on presentation were significantly associated with survival. For every 1 mmol/L (18 mg/dL) decrease in glucose concentration, cases had 1.85 lower odds of survival. For every 0.1 mmol/L (0.2 mEq/L) increase in total magnesium concentration, cases had 2.50 lower odds of survival. Cases with a low HCT had 10.69 lower odds of survival. On univariable analyses, non-survivors had a lower median body weight (P = 0.006) and presented more commonly for diarrhea (P = 0.015). At least 1 episode of diarrhea (P = 0.003) and hematochezia or melena (P < 0.001) in hospital were negatively associated with outcome, in addition to the persistence of diarrhea (P = 0.026) and hyporexia (P = 0.018) in hospital for 5 to 6 days. Conclusions: Survival rates of 91% were achieved with in-hospital treatment in this cohort of dogs. Negative biochemical prognostic indicators affecting survival include a low HCT, decreased blood glucose concentrations, and increased total serum magnesium concentrations at presentation.
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