Effect of Chronic Administration of Phenobarbital,or Bromide,on Pharmacokinetics of Levetiracetam in Dogs with Epilepsy

Background

Levetiracetam (LEV) is a common add‐on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs.

Hypothesis/Objectives

To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs.

Animals

Eighteen client‐owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB–BR group, n = 6).

Methods

Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area‐under‐the‐curve (AUC) calculated to the last measured time point.

Results

Compared to the PB and PB–BR groups, the BR group had significantly higher peak concentration (C _max) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028).

Conclusions and Clinical Importance

Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add‐on treatment with phenobarbital in dogs.     

Quantitative Accuracy of the Simplified Strong Ion Equation to Predict Serum pH in Dogs

Background

Electrochemical approach to the assessment of acid‐base states should provide a better mechanistic explanation of the metabolic component than methods that consider only pH and carbon dioxide.

Hypothesis/Objectives

Simplified strong ion equation (SSIE), using published dog‐specific values, would predict the measured serum pH of diseased dogs.

Animals

Ten dogs, hospitalized for various reasons.

Methods

Prospective study of a convenience sample of a consecutive series of dogs admitted to the Massey University Veterinary Teaching Hospital (MUVTH), from which serum biochemistry and blood gas analyses were performed at the same time. Serum pH was calculated (Hcal+) using the SSIE, and published values for the concentration and dissociation constant for the nonvolatile weak acids (A_tot and K _a), and subsequently Hcal+ was compared with the dog''s actual pH (Hmeasured+). To determine the source of discordance between Hcal+ and Hmeasured+, the calculations were repeated using a series of substituted values for A_tot and K _a.

Results

The Hcal+ did not approximate the Hmeasured+ for any dog (P = 0.499, r ² = 0.068), and was consistently more basic. Substituted values A_tot and K _a did not significantly improve the accuracy (r ² = 0.169 to <0.001). Substituting the effective SID (Atot−[HCO3−]) produced a strong association between Hcal+ and Hmeasured+ (r ² = 0.977).

Conclusions and clinical importance

Using the simplified strong ion equation and the published values for A_tot and K _a does not appear to provide a quantitative explanation for the acid‐base status of dogs. Efficacy of substituting the effective SID in the simplified strong ion equation suggests the error lies in calculating the SID.     

Prevalence and Prognostic Importance of Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease

Background

Pulmonary hypertension (PH) is common in dogs with myxomatous mitral valve disease (MMVD) but its effect on clinical outcome has not been investigated.

Hypothesis/objectives

The presence of PH worsens the outcome in dogs with MMVD. To compare survival times of dogs with MMVD and PH to those without PH.

Animals

Two hundred and twelve client‐owned dogs.

Methods

Case review study. Medical records of dogs diagnosed with ACVIM stage B2 and C MMVD between January 2010 and December 2011 were retrospectively reviewed. Long‐term outcome was determined by telephone interview or from the medical record. End of the observation period was March 2013. PH was identified if tricuspid regurgitation peak velocity was >3 m/s.

Results

Two hundred and twelve were identified. Eighty‐three dogs (39%) had PH. PH was more commonly identified in stage C compared to B2 (P < .0001). One hundred and five (49.5%) dogs died during the observation period. Median survival time for the entire study population was 567 days (95% CI 512–743). Stage C (P = .003), the presence of PH (P = .009), left atrial to aortic root ratio (LA/Ao) >1.7 (P = .0002), normalized left‐ventricular end‐diastolic diameter (LVEDn) >1.73 (P = .048), and tricuspid regurgitation pressure gradient (TRPG) >55 mmHg (P = .009) were associated with worse outcomes in the univariate analyses. The presence of TRPG >55 mmHg (HR 1.8 95% CI 1–2.9; P = .05) and LA/Ao > 1.7 (HR 2 95% CI 1.2–3.4; P = .01) remained significant predictors of worse outcome in the multivariate analysis.

Conclusions and Clinical Importance

In dogs with MMVD, moderate to severe PH worsens outcome.     

Urinary and Plasma Catecholamines and Metanephrines in Dogs with Pheochromocytoma,Hypercortisolism, Nonadrenal Disease and in Healthy Dogs

Background

Diagnosis of pheochromocytoma (PC) is based on a combination of clinical suspicion, finding an adrenal mass, increased plasma, and urine concentrations of catecholamine metabolites and is finally confirmed with histopathology. In human medicine, it is controversial whether biochemically testing plasma is superior to testing urine.

Objectives

To measure urinary and plasma catecholamines and metanephrines in healthy dogs, dogs with PC, hypercortisolism (HC), and nonadrenal diseases (NAD) and to determine the test with the best diagnostic performance for dogs with PC.

Animals

Seven PC dogs, 10 dogs with HC, 14 dogs with NAD, 10 healthy dogs.

Methods

Prospective diagnostic clinical study. Urine and heparin plasma samples were collected and stored at −80°C before analysis using high‐pressure liquid chromatography (HPLC) coupled to electrochemical detection or tandem mass spectrometry were performed. Urinary variables were expressed as ratios to urinary creatinine concentration.

Results

Dogs with PC had significantly higher urinary normetanephrine and metanephrine : creatinine ratios and significantly higher plasma‐total and free normetanephrine and plasma‐free metanephrine concentrations compared to the 3 other groups. There were no overlapping results of urinary normetanephrine concentrations between PC and all other groups, and only one PC dog with a plasma normetanephrine concentration in the range of the dogs with HC and NAD disease. Performances of total and free plasma variables were similar. Overlap of epinephrine and norepinephrine results between the groups was large with both urine and plasma.

Conclusion and clinical importance

Measurement of normetanephrine is the preferred biochemical test for PC and urine was superior to plasma.     

Hypercoagulability in Dogs with Blastomycosis

Background

Blastomycosis is a potentially fatal fungal disease that most commonly affects humans and dogs. The organism causes systemic inflammation and has a predilection for the lungs. The inflammation might lead to a hypercoagulable state with microemboli in the pulmonary circulation which could contribute to inadequate oxygen exchange in infected dogs.

Hypothesis/Objectives

Dogs with blastomycosis will be hypercoagulable compared with healthy case‐matched controls.

Animals

Client‐owned dogs with a diagnosis of blastomycosis (n = 23) and healthy case‐matched controls (n = 23).

Methods

Prospective case‐controlled study of client‐owned dogs presented to a veterinary teaching hospital with clinical signs compatible with blastomycosis. Complete blood counts, fibrinogen, PT, aPTT, thromboelastometry (TE), thrombin antithrombin complexes (TAT), and thrombin generation were evaluated.

Results

Cases had a leukocytosis compared with controls [mean (SD) 16.6 (7.6) × 10³/μL versus 8.2 (1.8) × 10³/μL, P < .001], hyperfibrinogenemia [median 784 mg/dL, range 329–1,443 versus median 178 mg/dL, range 82–257, P < .001], and increased TAT concentrations [mean (SD) 9.0 (5.7) μg/L versus 2.0 (2.8) μg/L, P < .001]. As compared to controls, cases were also hypercoagulable as evaluated by thromboelastometry and had increased in vitro thrombin generation on calibrated automated thrombography.

Conclusions and Clinical Importance

Hypercoagulability occurs in dogs with systemic blastomycosis. Additional studies are needed to explore a possible contribution of thrombogenicity to the clinical manifestations of systemic blastomycosis.     

Clinical Features and Outcome of Dogs with Epiglottic Retroversion With or Without Surgical Treatment: 24 Cases

Background

Published information describing the clinical features and outcome for dogs with epiglottic retroversion (ER) is limited.

Hypothesis/Objectives

To describe clinical features, comorbidities, outcome of surgical versus medical treatment and long‐term follow‐up for dogs with ER. We hypothesized that dogs with ER would have upper airway comorbidities and that surgical management (epiglottopexy or subtotal epiglottectomy) would improve long‐term outcome compared to medical management alone.

Animals

Twenty‐four client‐owned dogs.

Methods

Retrospective review of medical records to identify dogs with ER that underwent surgical or medical management of ER.

Results

Dogs with ER commonly were middle‐aged to older, small breed, spayed females with body condition score (BCS) ≥6/9. Stridor and dyspnea were the most common presenting signs. Concurrent or historical upper airway disorders were documented in 79.1% of cases. At last evaluation, 52.6% of dogs that underwent surgical management, and 60% of dogs that received medical management alone, had decreased severity of presenting clinical signs. In dogs that underwent surgical management for ER, the incidence of respiratory crisis decreased from 62.5% before surgery to 25% after surgical treatment. The overall calculated Kaplan–Meier median survival time was 875 days.

Conclusion and clinical importance

Our study indicated that a long‐term survival of at least 2 years can be expected in dogs diagnosed with epiglottic retroversion. The necessity of surgical management cannot be determined based on this data, but dogs with no concurrent upper airway disorders may benefit from a permanent epiglottopexy to alleviate negative inspiratory pressures.     

Pulmonary Vein‐to‐Pulmonary Artery Ratio is an Echocardiographic Index of Congestive Heart Failure in Dogs with Degenerative Mitral Valve Disease

Background

Early recognition of left‐sided congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD) is important because it influences medical therapy, timing of follow‐up, and outcome.

Hypothesis

Pulmonary vein diameter‐to‐pulmonary artery diameter ratio (PV/PA) measured by echocardiography can predict CHF.

Animals

Ninety‐eight client‐owned dogs, 37 controls, and 61 dogs with DMVD.

Methods

Prospective clinical cohort study. History, physical examination and Doppler‐echocardiography were performed. Dogs were classified as International Small Animal Cardiac Health Council class I, II or III. Congestive heart failure was identified in a subset of 56 dogs based on radiographic findings. The PV/PA was measured in bidimensional (2D) and M‐mode by 2 investigators blinded to the radiologists’ conclusions.

Results

Interobserver coefficients of variation for PV/PA acquisition and measurement were <10%. The PV/PA in control dogs was approximately 1 and increased with class of heart failure. The presence of CHF could be best predicted by measuring PV/PA in 2D echocardiography (cut‐off, 1.7; area under the curve, 0.98; CI, 0.97–0.98; P < .001) with a sensitivity of 96% and a specificity of 91%.

Conclusion and clinical importance

The PV/PA is a simple and reproducible echocardiographic variable that increases with class of heart failure and may help discriminate dogs in CHF from asymptomatic dogs with DMVD. Additional studies are required to determine whether PV/PA might provide additional information in the integrated interpretation of Doppler‐echocardiographic indices of left ventricular filling pressures and could be used for rapid assessment of CHF in dogs in a critical care setting.     

Geographic Information System‐Based Analysis of the Spatial and Spatio‐Temporal Distribution of Zoonotic Cutaneous Leishmaniasis in Golestan Province,North‐East of Iran

Zoonotic cutaneous leishmaniasis (ZCL), a vector‐borne disease, poses serious psychological as well as social and economic burden to many rural areas of Iran. The main objectives of this study were to analyse yearly spatial distribution and the possible spatial and spatio‐temporal clusters of the disease to better understand spatio‐temporal epidemiological aspects of ZCL in rural areas of an endemic province, located in north‐east of Iran. Cross‐sectional survey was performed on 2983 recorded cases during the period of 2010–2012 at village level throughout the study area. Global clustering methods including the average nearest‐neighbour distance, Moran's I, general G indices and Ripley's K‐function were applied to investigate the annual spatial distribution of the existing point patterns. Presence of spatial and spatio‐temporal clusters was investigated using the spatial and space–time scan statistics. For each year, semivariogram analysis and all global clustering methods indicated meaningful persistent spatial autocorrelation and highly clustered distribution of ZCL, respectively. Eight significant spatial clusters, mainly located in north and northeast of the province, and one space–time cluster, observed in northern part of the province and during the period of September 2010–November 2010, were detected. Comparison of the location of ZCL clusters with environmental conditions of the study area showed that 97.8% of cases in clusters were located at low altitudes below 725 m above sea level with predominantly arid and semi‐arid climates and poor socio‐economic conditions. The identified clusters highlight high‐risk areas requiring special plans and resources for more close monitoring and control of the disease.