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.     

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.     

Magnetic resonance imaging for the differentiation of neoplastic, inflammatory, and cerebrovascular brain disease in dogs

Background

The reliability and validity of magnetic resonance imaging (MRI) for detecting neoplastic, inflammatory, and cerebrovascular brain lesions in dogs are unknown.

Objectives

To estimate sensitivity, specificity, and inter‐rater agreement of MRI for classifying histologically confirmed neoplastic, inflammatory, and cerebrovascular brain disease in dogs.

Animals

One hundred and twenty‐one client‐owned dogs diagnosed with brain disease (n = 77) or idiopathic epilepsy (n = 44).

Methods

Retrospective, multi‐institutional case series; 3 investigators analyzed MR images for the presence of a brain lesion with and without knowledge of case clinical data. Investigators recorded most likely etiologic category (neoplastic, inflammatory, cerebrovascular) and most likely specific disease for all brain lesions. Sensitivity, specificity, and inter‐rater agreement were calculated to estimate diagnostic performance.

Results

MRI was 94.4% sensitive (95% confidence interval [CI] = 88.7, 97.4) and 95.5% specific (95% CI = 89.9, 98.1) for detecting a brain lesion with similarly high performance for classifying neoplastic and inflammatory disease, but was only 38.9% sensitive for classifying cerebrovascular disease (95% CI = 16.1, 67.0). In general, high specificity but not sensitivity was retained for MR diagnosis of specific brain diseases. Inter‐rater agreement was very good for overall detection of structural brain lesions (κ = 0.895, 95% CI = 0.792, 0.998, P < .001) and neoplastic lesions, but was only fair for cerebrovascular lesions (κ = 0.299, 95% CI = 0, 0.761, P = .21).

Conclusions and Clinical Importance

MRI is sensitive and specific for identifying brain lesions and classifying disease as inflammatory or neoplastic in dogs. Cerebrovascular disease in general and specific inflammatory, neoplastic, and cerebrovascular brain diseases were frequently misclassified.     

A randomized trial investigating the efficacy and safety of water soluble micellar paclitaxel (Paccal Vet) for treatment of nonresectable grade 2 or 3 mast cell tumors in dogs

Background

Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel [micellar]) has shown promise in early‐phase studies.

Hypothesis/Objectives

The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was μ_p = μ_L (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively).

Animals

Two hundred and fifty‐two dogs with advanced stage nonresectable grade 2 or 3 MCT.

Methods

Prospective multicenter randomized double‐blind positive‐controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate (BORR), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE).

Results

Overall CORR (7% versus 1%; P = .048) and BORR (23% versus 10%; P = .012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar)‐treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty‐seven dogs (33%) receiving lomustine were discontinued because of hepatopathy compared with 3 dogs (2%) receiving paclitaxel (micellar) (P < .0001; odds ratio 26.7).

Conclusions and Clinical Importance

Paclitaxel (micellar)'s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and, as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols.     

Renal resistive index in 55 dogs with degenerative mitral valve disease

Background

Azotemia occurs frequently in dogs with degenerative mitral valve disease (DMVD). It could indicate changes in renal hemodynamics.

Hypothesis/Objectives

To assess the renal resistive index (RI) in dogs with DMVD, and the statistical link between heart failure class, azotemia, echo‐Doppler parameters, several plasma variables, and RI.

Animals

Fifty‐five dogs with naturally occurring DVMD were used (ISACHC class 1 [n = 28], 2 [n = 19], and 3 [n = 8]).

Methods

Observational, blinded study, performed under standardized conditions. Physical examination, renal ultrasonography, and echo‐Doppler examinations were performed in awake dogs. The RI of the renal, interlobar, and arcuate arteries were measured. Plasma creatinine, urea, and N‐terminal pro‐B‐type natriuretic peptide concentrations (NT‐proBNP) were determined. Statistical links between variables and RI were tested by means of a general linear model.

Results

Although the RI of renal and arcuate arteries were unaffected by ISACHC class, the left interlobar RI increased (P < .001) from 0.62 ± 0.05 (mean ± SD) in class 1 to 0.76 ± 0.08 in class 3. It was also higher (P < .001) in azotemic (0.74 ± 0.08) than in non‐azotemic (0.62 ± 0.05) dogs. Similar findings were observed for right interlobar RI. Univariate analysis showed a positive statistical link between NT‐proBNP (P = .002), urea (P < .001), creatinine (P = .002), urea‐to‐creatinine ratio (P < .001), left atrium‐to‐aorta ratio (P < .001), regurgitation fraction (P < .001), systolic pulmonary arterial pressure (P < .001), shortening fraction (P = .035), and RI.

Conclusion and Clinical Importance

In dogs with DMVD, interlobar RI increases with heart failure severity and azotemia but a cause and effect relationship remains to be established.     

Effect of Weight Loss in Obese Dogs on Indicators of Renal Function or Disease

Background

Obesity is a common medical disorder in dogs, and can predispose to a number of diseases. Human obesity is a risk factor for the development and progression of chronic kidney disease.

Objectives

To investigate the possible association of weight loss on plasma and renal biomarkers of kidney health.

Animals

Thirty‐seven obese dogs that lost weight were included in the study.

Methods

Prospective observational study. Three novel biomarkers of renal functional impairment, disease, or both (homocysteine, cystatin C, and clusterin), in addition to traditional markers of chronic renal failure (serum urea and creatinine, urine specific gravity [USG], urine protein‐creatinine ratio [UPCR], and urine albumin corrected by creatinine [UAC]) before and after weight loss in dogs with naturally occurring obesity were investigated.

Results

Urea (P = .043) and USG (P = .012) were both greater after weight loss than before loss, whilst UPCR, UAC, and creatinine were less after weight loss (P = .032, P = .006, and P = .026, respectively). Homocysteine (P < .001), cystatin C (P < .001) and clusterin (P < .001) all decreased upon weight loss. Multiple linear regression analysis revealed associations between percentage weight loss (greater weight loss, more lean tissue loss; r = ?0.67, r² = 0.45, P < .001) and before‐loss plasma clusterin concentration (greater clusterin, more lean tissue loss; r = 0.48, r² = 0.23, P = .003).

Conclusion and Clinical Importance

These results suggest possible subclinical alterations in renal function in canine obesity, which improve with weight loss. Further work is required to determine the nature of these alterations and, most notably, the reason for the association between before loss plasma clusterin and subsequent lean tissue loss during weight management.

     

Metabolizable energy intake of client‐owned adult dogs

A post hoc analysis of the metabolizable energy (ME) intake of privately owned pet dogs from the authors' nutrition consultation practice (Years 2007–2011) was carried out to identify if current ME recommendations are suitable for pet dogs. Data on 586 adult dogs were available (median age 5.5, median deviation from ideal weight 0.0), 55 of them were healthy; the others had various diseases. For ration calculation, a standardized questionnaire and the software diet‐check Munich^? was used. ME was predicted according to NRC (2006). Data were evaluated for the factors disease, breed, size, age, gender and type of feeding. The mean ME intake of all adult dogs amounted to 0.410 ± 0.121 MJ/kg metabolic body weight (BW^0.75) (n = 586). There was no effect of size and disease. Overweight dogs ate 0.360 ± 0.121 MJ/kg BW^0.75, and underweight dogs ate 0.494 ± 0.159 MJ/kg BW^0.75. Older dogs (>7 years, n = 149, 0.389 ± 0.105 MJ/kg BW^0.75) had a lower ME intake than younger ones (n = 313, 0.419 ± 0.121 MJ/kg BW^0.75), and intact males had a higher ME intake than the others (p < 0.001). Some breeds were above average: Jack Russell Terrier, Dalmatian, small Munsterlander and Magyar Viszla, Bearded Collies, Sight Hounds, German Boxers, English foxhounds, Rhodesian Ridgebacks and Flat‐Coated Retrievers with a mean ME intake of 0.473 ± 0.121 MJ/kg BW^0.75. The following breeds were below average: Dachshunds, Bichons, West highland White Terrier, Collies except Bearded Collies, Airedale Terriers, American Staffordshire terriers and Golden Retrievers with a mean ME intake of 0.343 ± 0.096 MJ/kg BW^0.75. The mean maintenance energy requirements of pet dogs are similar to that of kennel dogs which do not exercise very much. These results suggest that opportunity and stimulus to exercise provided for pet dogs are lower than for kennel dogs. Lower activity in pet dogs may reduce part of potential effects of breed, medical history and age groups.     

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.     

Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte‐colony stimulating factor

Duffy A., Dow S., Ogilvie G., Rao S., Hackett T. Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte‐colony stimulating factor. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.01153.x. Previously, dogs with canine parvovirus‐induced neutropenia have not responded to treatment with recombinant human granulocyte‐colony stimulating factor (rhG‐CSF). However, recombinant canine G‐CSF (rcG‐CSF) has not been previously evaluated for treatment of parvovirus‐induced neutropenia in dogs. We assessed the effectiveness of rcG‐CSF in dogs with parvovirus‐induced neutropenia with a prospective, open‐label, nonrandomized clinical trial. Endpoints of our study were time to recovery of WBC and neutrophil counts, and duration of hospitalization. 28 dogs with parvovirus and neutropenia were treated with rcG‐CSF and outcomes were compared to those of 34 dogs with parvovirus and neutropenia not treated with rcG‐CSF. We found that mean WBC and neutrophil counts were significantly higher (P < 0.05) in the 28 dogs treated with rcG‐CSF compared to disease‐matched dogs not treated with rcG‐CSF. In addition, the mean duration of hospitalization was reduced (P = 0.01) in rcG‐CSF treated dogs compared to untreated dogs. However, survival times were decreased in dogs treated with rcG‐CSF compared to untreated dogs. These results suggest that treatment with rcG‐CSF was effective in stimulating neutrophil recovery and shortening the duration of hospitalization in dogs with parvovirus infection, but indicate the need for additional studies to evaluate overall safety of the treatment.     

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.     

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.     

Investigation of bacterial microorganisms in the conjunctival sac of clinically normal dogs and dogs with ulcerative keratitis in Beijing, China

Objective To determine the bacterial microorganisms in the conjunctival sac of clinically normal dogs and dogs with ulcerative keratitis in Beijing, China. The effect of breed, sex and age of dogs and season on the presence or absence of bacteria in the conjunctival sac of clinically normal dogs was evaluated. Sample population This investigation included 240 healthy dogs, 27 dogs with unilateral corneal ulcer and one dog with bilateral corneal ulcer. Procedure The 480 samples from healthy dogs and the 29 samples from dogs with ulcerative keratitis were incubated in an aerobic and 5% CO₂ environment at 37 °C for 48 h. Logistic regression analysis was performed. Statistical significance was set at P < 0.01. Results Of 480 normal eyes, Staphylococcus spp. were the most frequently isolated organisms (40.29%). Neisseria spp. (11.47%) were the next most frequently isolated organisms, followed by Corynebacterium spp. (9.4%). Of 29 eyes with ulcerative keratitis, Staphylococcus spp. were also the most frequently isolated bacteria (47.06%). Streptococcus spp. (12.94%) and Pseudomonas spp. (8.24%) were the second and third, respectively. Season (P = 0.002) was a significant factor influencing presence or absence of bacterial microorganisms in the conjunctival sac of normal dogs in Beijing, China, while the effects of breed (P = 0.095), sex (P = 0.588) and age (P = 0.866) of dogs were insignificant. Conclusion Staphylococcus spp. were the most frequently isolated organisms, and S. intermedius predominated in the conjunctival sac of clinically normal dogs and dogs with ulcerative keratitis in Beijing, China. The likelihood of detecting bacteria depends on the season.     

Infrared ocular thermography in dogs with and without keratoconjunctivitis sicca

Infrared thermography was used to measure temperature differences of the corneal surface between nasal and temporal limbus regions and central cornea of normal dogs and dogs with keratoconjunctivitis sicca (KCS), in order to establish temperature values in normal canine eyes and in patients with decreased Schirmer tear tests (STT) values. Dogs investigated were all either patients seen at the Veterinary Teaching Hospital of Federal University of Paraná or normal dogs that belonged to the same institution. STT were performed in all eyes. A total of 40 control eyes (STT ≥15 mm/min) and 20 eyes with low STT values (STT ≤14 mm/min) were examined. The mean STT value for eyes with normal STT values was 22.9 ± 3.9 mm/min (mean ± standard deviation), and the mean STT value for eyes with low STT value was 7.2 ± 4.8 mm/min. The mean corneal temperature was significantly lower in eyes with low STT values than in control eyes (P < 0.0001). The following significant correlations were found: (i) Schirmer and breakup time (BUT) (P = 0.0001, r = 0.5); (ii) STT values and corneal surface temperature (P = 0.001, r = 0.256); (iii) STT values and age (P = 0.0001, r = ?0.448); (iv) age and corneal surface temperature (P = 0.0001, r = ?0.281); and (v) BUT and corneal surface temperature (P = 0.0001, r = 0.36). Thermography is a method that can differentiate between eyes with normal and abnormal STT values. In the future, thermography might be incorporated as part of the ophthalmic examination and perhaps become a popular ancillary test for the diagnoses of ocular surface disorders.     

Comparative potential therapeutic effect of sesame oil and peanut oil against acute monocrotaline (Crotalaria) poisoning in a rat model

Background

Many Crotalaria plant species contain hepatotoxic pyrrolizidine alkaloids (such as monocrotaline) that can cause acute and chronic poisoning in cattle and other animals.

Hypothesis

Peanut oil, atropine sulfate, and antidiarrheal agents are used to treat acute monocrotaline poisoning. The effect of sesame on acute monocrotaline poisoning has never been investigated.

Animals

Fifty male Sprague‐Dawley rats were used for toxicity studies.

Methods

Experiment 1: Group I, control. Groups II–IV were given monocrotaline (205.2 mg/kg) and euthanized 6, 12, and 24 hours later. Experiment 2: Group I, control. Group II monocrotaline alone (205.2 mg/kg). Groups III–VI were given monocrotaline (205.2 mg/kg) and 1 hour later, Groups III and IV were given sesame oil (1 and 2 mL/kg) and Groups V and VI were given peanut oil (1 and 2 mL/kg).

Results

Monocrotaline significantly decreased (P < .05) serum amylase activity, but, over time, increased (P < .05) pancreatic and lung injury. AST and ALT activity and liver injury peaked at 24 hours. Sesame oil and peanut oil (P < .05) inhibited the changes in all tested parameters in acute monocrotaline poisoning. Although peanut oil inhibited acute monocrotaline poisoning, it induced steatosis, but sesame oil did not.

Conclusion and Clinical Importance

We hypothesize that early pancreatic and lung injury and late liver injury contribute to acute monocrotaline poisoning and that sesame oil is more efficacious than peanut oil against acute monocrotaline poisoning in rats. However, additional studies are needed to confirm that these oils have the same effects in cattle and other animals.     

Transpalpebral ultrasonographic measurement of the optic nerve sheath diameter in healthy dogs

Objective

To develop a reference range for ultrasonographically measured optic nerve sheath diameter (ONSD‐US) in dogs. We hypothesized that ONSD‐US can be measured reliably and is associated with weight but not age, sex, or body condition score (BCS), and that the relationship between weight and ONSD‐US in dogs is allometric due to canine size variations.

Design

Prospective, observational study.

Setting

University teaching hospital.

Animals

Seventy‐eight healthy adult dogs.

Interventions

The ONSD was measured by a standardized transpalpebral approach.

Measurements and Main Results

Regression analysis showed the relationship between weight and ONSD was better fit with a linear model (R² = 0.8510) than an allometric model (R² = 0.7917). Multiple regression analysis showed ONSD is associated with weight (P < 0.0001), age (P = 0.0021), and BCS (P = 0.0007), but not with sex. Dominance analysis showed 94.6% of the variance explained by the model was due to weight. Intraclass correlation coefficient (ICC) analysis showed excellent interobserver (ICC = 0.9338–0.9608) and intraobserver (ICC = 0.9893) reliability.

Conclusions

These results suggest that ONSD‐US may be reliably measured in dogs using our described transpalpebral approach, and we have calculated prediction intervals based on body weight. Future studies are needed to determine if ONSD‐US measurements are associated with intracranial hypertension as shown in human medicine.     

Glutathione Peroxidase Activity,Plasma Total Antioxidant Capacity,and Urinary F2‐ Isoprostanes as Markers of Oxidative Stress in Anemic Dogs

Background

Oxidative stress plays a role in the pathophysiology of several diseases and has been documented as a contributor to disease in both the human and veterinary literature. One at‐risk cell is the erythrocyte, however, the role of oxidative stress in anemia in dogs has not been widely investigated.

Hypothesis/Objective

Anemic dogs will have an alteration in the activity of glutathione peroxidase (GPx), a decrease in of total antioxidant capacity (TAC), and an increased concentration of urinary 15‐F₂‐isoprostanes (F₂‐IsoP) when compared to healthy dogs.

Animals

40 client‐owned dogs with anemia (PCV <30%) age‐matched to 40 client‐owned healthy control dogs.

Methods

Prospective, cross‐sectional study. Whole blood GPx activity, plasma TAC, and urinary F₂‐isoprostane concentrations were evaluated in each dog and compared between groups.

Results

Anemic dogs had significantly lower GPx activity (43.1 × 10³ +/‐ 1.6 × 10³ U/L) than did dogs in the control group (75.8 × 10³ +/‐ 2.0 × 10³ U/L; P < 0.0001). The GPx activity in dogs with hemolysis (10³ +/‐ 0.8 × 10³ U/L) was not significantly different (P = 0.57) than in dogs with nonhemolytic anemia (43.5 × 10³ +/‐ 1.1 × 10³ U/L). The TAC concentrations (P = 0.15) and urinary F₂‐isoprostanes (P = 0.73) did not significantly differ between groups.

Conclusions and Clinical Importance

Glutathione peroxidase activity was significantly decreased in anemic dogs indicating oxidative stress. Additional studies are warranted to determine if antioxidant supplementation would improve survival and overall outcome as part of a therapeutic regimen for anemic dogs.     

Cyclooxygenase Expression and Platelet Function in Healthy Dogs Receiving Low‐Dose Aspirin

Background

Low‐dose aspirin is used to prevent thromboembolic complications in dogs, but some animals are nonresponsive to the antiplatelet effects of aspirin (“aspirin resistance”).

Hypothesis/Objectives

That low‐dose aspirin would inhibit platelet function, decrease thromboxane synthesis, and alter platelet cyclooxygenase (COX) expression.

Animals

Twenty‐four healthy dogs.

Methods

A repeated measures study. Platelet function (PFA‐100 closure time, collagen/epinephrine), platelet COX‐1 and COX‐2 expression, and urine 11‐dehydro‐thromboxane B₂ (11‐dTXB₂) were evaluated before and during aspirin administration (1 mg/kg Q24 hours PO, 10 days). Based on prolongation of closure times after aspirin administration, dogs were divided into categories according to aspirin responsiveness: responders, nonresponders, and inconsistent responders.

Results

Low‐dose aspirin increased closure times significantly (62% by Day 10, P < .001), with an equal distribution among aspirin responsiveness categories, 8 dogs per group. Platelet COX‐1 mean fluorescent intensity (MFI) increased significantly during treatment, 13% on Day 3 (range, ?29.7–136.1%) (P = .047) and 72% on Day 10 (range, ?0.37–210%) (P < .001). Platelet COX‐2 MFI increased significantly by 34% (range, ?29.2–270%) on Day 3 (P = .003) and 74% (range, ?19.7–226%) on Day 10 (P < .001). Urinary 11‐dTXB₂ concentrations significantly (P = .005, P < .001) decreased at both time points. There was no difference between aspirin responsiveness and either platelet COX expression or thromboxane production.

Conclusions and Clinical Importance

Low‐dose aspirin consistently inhibits platelet function in approximately one‐third of healthy dogs, despite decreased thromboxane synthesis and increased platelet COX expression in most dogs. COX isoform expression before treatment did not predict aspirin resistance.

     

Comparison of three mobilization protocols for peripheral blood stem cell apheresis with Spectra Optia continuous mononuclear cell protocol in healthy dogs

Peripheral blood stem cell (PBSC) transplantation following consolidation therapy is a feasible treatment option for canine haematological malignancies. In veterinary medicine, haematopoietic stem cells are generally mobilized into peripheral circulation using a granulocyte colony‐stimulating factor (G‐CSF). This pilot study aimed to evaluate the haematopoietic stem cell mobilization effect of three different regimens for PBSC apheresis with Spectra Optia continuous mononuclear cell (CMNC) protocol in healthy dogs. Stem cell mobilization was performed using high‐dose plerixafor (CXCR‐4 inhibitor) alone, a G‐CSF alone, or a combination of the low‐dose plerixafor and G‐CSF. Three dogs were assigned to each mobilization protocol. Regardless of the mobilization protocol, the total blood volume processed was uniformly set as 270 mL/kg and many PBSCs, defined as CD34+/CD45^dim cells, within the apheresis product were compared. Changes in complete blood count, PBSC counts, and blood chemistry analysis were monitored before, during, and after apheresis. All dogs tolerated the apheresis procedure using the Spectra Optia system with minimal adverse effects. The mean PBSC counts of the apheresis products for plerixafor, G‐CSF, and the combination groups were 1.3 ± 0.24, 4.2 ± 0.47, and 6.4 ± 0.9 × 10⁶ cells/kg, respectively. The apheresis procedure using Spectra Optia CMNC protocol in dogs is safe and feasible. Furthermore, PBSC mobilization with a combination of G‐CSF and plerixafor appeared more effective than either compound alone in mobilizing PBSC to the peripheral blood in dogs.     

Safety of orally administered,USP‐compliant levothyroxine sodium tablets in dogs

The safety of synthetic levothyroxine sodium tablets (Thyro‐Tabs® Canine; LLOYD , Inc.) in dogs was evaluated in a randomized, sham‐dose controlled, parallel‐group study. Young, healthy, euthyroid Beagle dogs were randomized into four groups (four females and four males per group) and received single daily doses of 0×, 2× (0.044 mg/kg), 6× (0.132 mg/kg), or 10× (0.22 mg/kg) the labeled starting dose of 0.022 mg kg^?1 day^?1 for 182 days. Every 2 weeks, physical examinations, electrocardiology examinations, and sample collections for thyroid panel, hematology, serum biochemistry, coagulation panel, and urinalysis were performed. At the end of the study, the dogs were euthanized and full necropsies performed. The most overt finding was the expected dose‐dependent increase in serum concentrations of total and free thyroxine with dose‐dependent suppression of the hypothalamic–pituitary–thyroid axis as evidenced by decreased serum thyroid‐stimulating hormone concentrations, decreased thyroid+parathyroid/body weight ratios, and a trend for decreased pituitary weight/brain weight ratios. Clinical signs of thyrotoxicosis (excitation, tachypnea, tachycardia) in the treated dogs were sporadic with no dose–response relationship. Other findings statistically associated with levothyroxine treatment were generally mild and not clinically important. In summary, doses of levothyroxine sodium up to 10× the labeled starting dose were well tolerated in healthy dogs.     

Comparison of radioimmunoassay and chemiluminescent assay methods to estimate canine blood cortisol concentrations

Background Non‐radioactive assay methods are widely used in commercial laboratories to measure canine blood cortisol concentrations, despite a paucity of published validity data of these tests compared with the traditional ‘gold standard’ radioimmunoassay. Objectives To compare a commercial chemiluminescence assay with radioimmunoassay for blood cortisol measurement, determine the effect of storage on the radioimmunoassay, and determine the impact of any differences on clinical decisions. Methods The study included 54 client owned dogs undergoing adrenal function testing. Fresh plasma or serum samples (n = 170) were assayed for cortisol using radioimmunoassay (RIA1). Samples (n = 196) were also frozen and stored in batches, and assayed by chemiluminescence and radioimmunoassay (RIA2). Results Overall, there was a strong correlation (r² = 0.967, P < 0.001) between RIA2 and chemiluminescence concentrations without significant difference between means. Strong correlations were present for RIA2 and chemiluminescence at concentration subgroups of > 400 nmol/L (r² = 0.869, P < 0.001), < 100 nmol/L (r² = 0.790, P < 0.001), and < 40 nmol/L (r² = 0.738, P < 0.001). Significant differences between means were present for RIA2 and chemiluminescence concentrations in the < 100 nmol/L, and < 40 nmol/L (P < 0.001) groups. Despite a significant difference in RIA1 and RIA2 results overall, there was no significant difference between RIA1 and RIA2 for any of the concentration groups. In seven cases, discrepant RIA2 and chemiluminescence results may have altered clinical decisions. Conclusions Although RIA and chemiluminescence cortisol concentrations appear highly correlated, a significant difference may exist for concentrations less than 100 nmol/L in stored canine sera. Results of chemiluminescence cortisol assays should be interpreted with caution unless the specific assay method in the laboratory has been adequately validated in dogs.