Clinical Use In Dogs Research Articles

Analysis of US Marketed Artemisinin Supplements for Use in Dogs.

Oral artemisinin has antiparasitic activity and may help improve treatment success rates in dogs infected with Babesia gibsoni. However, these artemisinin products are unapproved and unregulated botanical supplements. They have not been evaluated for safety and efficacy or for strength, purity, or quality compared with a reference standard. Before considering these products for a clinical study, we evaluated the strength of four suppliers of artemisinin capsules using an high-performance liquid chromatography method validated in our laboratory. We found that the four artemisinin-labeled products that were tested had high within product and between product variability in capsule strength compared with the stated capsule strength on the product label. No products met the acceptance criteria of the United States Pharmacopeia and International Council for Harmonisation (ICH) as well as the criteria adapted by the authors. One product had no detectable artemisinin, and the other three products were much higher than the stated label strength. The results of this study reinforce the importance of testing unapproved and unregulated supplements before recommending a supplement for clinical use in dogs.

Thermal and Circulatory Changes in Diverse Body Regions in Dogs and Cats Evaluated by Infrared Thermography.

Simple SummaryInfrared thermography is a tool that measures changes in the surface temperature of the skin and has been used in companion animals to determine their health state and to diagnose inflammatory processes, neoplasia, pain, or neuropathies. Body regions such as the face, body, or hind/forelimbs are commonly used for thermography in dogs and cats. However, since there is disagreement about the differences in temperature recorded using this tool, this article analyzes the usefulness of IRT in companion animals (pets) as a complementary diagnostic method for evaluating thermal and circulatory changes. It analyzes the recent scientific evidence on the use of facial, body, and appendicular thermal windows in dogs and cats under different clinical conditions.Infrared thermography (IRT) has been proposed as a method for clinical research to detect local inflammatory processes, wounds, neoplasms, pain, and neuropathies. However, evidence of the effectiveness of the thermal windows used in dogs and cats is discrepant. This review aims to analyze and discuss the usefulness of IRT in diverse body regions in household animals (pets) related to recent scientific evidence on the use of the facial, body, and appendicular thermal windows. IRT is a diagnostic method that evaluates thermal and circulatory changes under different clinical conditions. For the face, structures such as the lacrimal caruncle, ocular area, and pinna are sensitive to assessments of stress degrees, but only the ocular window has been validated in felines. The usefulness of body and appendicular thermal windows has not been conclusively demonstrated because evidence indicates that biological and environmental factors may strongly influence thermal responses in those body regions. The above has led to proposals to evaluate specific muscles that receive high circulation, such as the biceps femoris and gracilis. The neck area, perivulvar, and perianal regions may also prove to be useful thermal windows, but their degree of statistical reliability must be established. In conclusion, IRT is a non-invasive technique that can be used to diagnose inflammatory and neoplastic conditions early. However, additional research is required to establish the sensitivity and specificity of these thermal windows and validate their clinical use in dogs and cats.

In a Randomized, Placebo-Controlled Cross-Over Study, Administration of 6 and 12 G Fortetropin® Does Not Reduce Serum Myostatin in Healthy Adult Dogs Over 72-Hours.

Objective: To evaluate the effect of a single administration of 6 and 12 g of Fortetropin compared to placebo on serum myostatin in healthy, adult dogs over a 72-h period.Methods: Prospective, placebo-controlled, randomized, double-blind, crossover study. Ten hospital-employee-owned healthy adult dogs aged 2 to 8 years old were enrolled in the study. Blood samples were collected prior to and then 12-, 24-, 36-, 48-, and 72-h following administration of the test agent (6 and 12 g) or placebo. Serum samples were processed according to manufacturer's guidelines for canine serum using GDF-8/Myostatin Quantikine ELISA kit (R&D Systems). Analysis-of-variance (ANOVA) analyses were carried out where P < 0.05 was deemed significant.Results: Mean serum myostatin was not significantly lower in treatment groups of either low or high dose compared to placebo at any time point. Baseline mean serum myostatin in low and high dose treatment groups was 29,481 (SD = 5,224) and 32,214 pg/mL (SD = 7,353), respectively. Placebo group low and high dose baseline mean serum myostatin was 30,247 (SD = 5,875) and 28,512 (SD = 5,028).Conclusion: The results of this study indicate that administration of single 6 or 12 g dose of Fortetropin does not reduce serum myostatin in healthy adult dogs over a 72-h period.Clinical Importance: Oral supplements, like Fortetropin, require further studies to determine the efficacy and bioavailability in order to guide clinical use in dogs.

Effect of phytosterols on reducing low-density lipoprotein cholesterol in dogs

Hyperlipidemia is described as an increase in serum and/or plasma levels of triglycerides, cholesterol, or both. This disturbance can be primary in some cases, or combined with other comorbidities such as endocrinopathies, liver diseases, or specific drug use. Among the various ways to control dyslipidemia are specific diets, omega-3 fatty acid supplementation, or hypolipemiant treatment. Herbal medicine has been used in the human clinical routine to reduce cholesterol circulation. With an aim to expand its application in veterinary medicine, we analyzed the use of phytosterols in dogs as a potential alternative to control hypercholesterolemia. We performed lipidogram analysis in healthy dogs to examine the possible adverse effects during the treatment. Eight Beagle dogs received orally two 650 mg capsules of phytosterols (Collestra, Aché), for 15 consecutive d, along with the 2 usual meals. All animals remained clinically stable during the trial. There were significant alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels during the trial. LDL was reduced (86.8 ± 29.89 mg/dL [D0], 74.45 ± 31.58 mg/dL [D8], and 58.91 ± 18.65 mg/dL [D15]; P = 0.0442) and HDL was elevated (83.40 ± 12.05 mg/dL [D0], 86.46 ± 13.05 mg/dL [D8], and 101.5 ± 10.52 [D15]; P = 0.0141), while total cholesterol and triglyceride concentrations remained constant and within the normal range for canine species. Thus, a 1300 mg dose of phytosterols, administrated orally and fractionated along with the 2 usual meals, was capable of reducing LDL and increasing HDL concentration in healthy nondyslipidemic dogs, which makes them candidates to be included on the list of hypolipemiant drugs for clinical use in dogs with hypercholesterolemia.

Recombinant canine basic fibroblast growth factor-induced differentiation of canine bone marrow mesenchymal stem cells into voltage- and glutamate-responsive neuron-like cells.

IntroductionBasic fibroblast growth factor (bFGF) is a promising cytokine in regenerative therapy for spinal cord injury. In this study, recombinant canine bFGF (rc-bFGF) was synthesized for clinical use in dogs, and the ability of rc-bFGF to differentiate canine bone marrow mesenchymal stem cells (BMSCs) into functional neurons was investigated.MethodsThe rc-bFGF was synthesized using a wheat germ cell-free protein synthesis system. The expression of rc-bFGF mRNA in the purification process was confirmed using a reverse transcription-polymerase chain reaction (RT-PCR). Western blotting was performed to confirm the antigenic property of the purified protein. To verify function of the purified protein, phosphorylation of extracellular signal-regulated kinase (ERK) was examined by in vitro assay using HEK293 cells. To compare the neuronal differentiation capacity of canine BMSCs in response to treatment with rc-bFGF, the cells were divided into the following four groups: control, undifferentiated, rh-bFGF, and rc-bFGF groups. After neuronal induction, the percentage of cells that had changed to a neuron-like morphology and the mRNA expression of neuronal markers were evaluated. Furthermore, to assess the function of the canine BMSCs after neuronal induction, changes in the intracellular Ca2+ concentrations after stimulation with KCl and l-glutamate were examined.ResultsThe protein synthesized in this study was rc-bFGF and functioned as bFGF, from the results of RT-PCR, western blotting, and the expression of pERK in HEK293 cells. Canine BMSCs acquired a neuron-like morphology and expressed mRNAs of neuronal markers after neuronal induction in the rh-bFGF and the rc-bFGF groups. These results were more marked in the rc-bFGF group than in the other groups. Furthermore, an increase in intracellular Ca2+ concentrations was observed after the stimulation of KCl and l-glutamate in the rc-bFGF group, same as in the rh-bFGF group.ConclusionsA functional rc-bFGF was successfully synthesized, and rc-bFGF induced the differentiation of canine BMSCs into voltage- and glutamate-responsive neuron-like cells. Our purified rc-bFGF may contribute, on its own, or in combination with canine BMSCs, to regenerative therapy for spinal cord injury in dogs.

Analytical validation of a conventional cardiac troponin I assay for dogs and cats.

Cardiac troponins are gold-standard biomarkers of myocardial injury. There is a need for validation of assays with higher availability and lower costs in veterinary medicine. The primary aim of the present study was to perform an analytical validation of the IMMULITE 2000 TnI assay for use in dogs and cats. A secondary aim was to evaluate its agreement with the previously validated and sensitive Siemens ADVIA Centaur TnI-Ultra assay. Intra- and inter-assay variation, detection limits, the linearity under dilution, and a sample addition study (modified spike-and-recovery analysis) were investigated to assess analytical performance in 15 canine and 15 feline serum samples. Agreement between the assays was evaluated by correlation and Bland-Altman analyses including an additional 99 canine serum samples. Intra-assay variation of cTnI in canine and feline serum was 3.71% and 4.68%, while inter-assay variation was 5.88% and 6.54%, respectively. The assay performed with acceptable linearity within a clinically relevant range of serum cTnI concentrations. The sample addition study revealed insufficient recovery in the range of 71.9%-81.4% for dogs and 62.6%-75.7% for cats. This was considered to be due to a negative matrix effect. A significant correlation between the assays was found, and the Bland-Altman analysis showed acceptable agreement for a wide range of concentrations, but revealed a proportional error, with the IMMULITE TnI assay consistently measuring a higher concentration than the Centaur TnI-Ultra assay. This was relevant only at high serum cTnI concentrations. The IMMULITE TnI assay is considered acceptable for clinical use in dogs and cats.

Platelet Rich Plasma Eye Drops: Preparation, Storage and Clinical Use in Dogs and Cats.Preliminary Results

Platelet Rich Plasma Eye Drops: Preparation, Storage and Clinical Use in Dogs and Cats.Preliminary Results

Platelet Rich Plasma Eye Drops: Preparation, Storage and Clinical Use in Dogs and Cats.Preliminary Results

Platelet Rich Plasma Eye Drops: Preparation, Storage and Clinical Use in Dogs and Cats.Preliminary Results

Posaconazole pharmacokinetics after administration of an intravenous solution, oral suspension, and delayed-release tablet to dogs.

To determine pharmacokinetics of posaconazole in dogs given an IV solution, oral suspension, and delayed-release tablet. 6 healthy dogs. Posaconazole was administered IV (3 mg/kg) and as an oral suspension (6 mg/kg) to dogs in a randomized crossover study. Blood samples were collected before (time 0) and for 48 hours after each dose. In an additional experiment, 5 of the dogs received posaconazole delayed-release tablets (mean dose, 6.9 mg/kg); blood samples were collected for 96 hours. Plasma concentrations were analyzed with high-performance liquid chromatography. IV solution terminal half-life (t1/2) was 29 hours (coefficient of variation [CV], 23%). Clearance and volume of distribution were 78 mL/h/kg (CV, 59%) and 3.3 L/kg (CV, 38%), respectively. Oral suspension t1/2 was 24 hours (CV, 42%). Maximum plasma concentration (Cmax) of 0.42 μg/mL (CV, 56%) was obtained at 7.7 hours (CV, 92%). Mean bioavailability was 26% (range, 7.8% to 160%). Delayed-release tablet t1/2 was 42 hours (CV, 25%), with a Cmax of 1.8 μg/mL (CV, 44%) at 9.5 hours (CV, 85%). Mean bioavailability of tablets was 159% (range, 85% to 500%). Bioavailability of delayed-release tablets was 497% (range, 140% to 1,800%) relative to that of the oral suspension. Absorption of posaconazole oral suspension in dogs was variable. Absorption of the delayed-release tablets was greater than absorption of the oral suspension, with a longer t1/2 that may favor its clinical use in dogs. Administration of delayed-release tablets at a dosage of 5 mg/kg every other day can be considered for future studies.

Evaluierung des Tonovet®-Reboundtonometers in der klinischen Anwendung bei Hund und Katze

To evaluate the Tonovet® rebound tonometer in a larger number of dogs and cats free of ocular disease and to examine the impact of handling errors of the tonometer. In 100 ophthalmologically healthy dogs (n = 80) and cats (n = 20) of different breeds (beagle, dachshund, retriever, brachycephalic dogs, domestic shorthair cats), the intraocular pressure (IOP) was measured bilaterally using the Tonovet® according to the manufacturer's instructions. Subsequently, different aspects of handling/positioning were altered (localisation and angle of impact, distance of probe to corneal surface). Finally a comparative measurement was made using the Tonopen Vet® applanation tonometer. Mean IOP ± standard deviation (SD) in the dogs (160 eyes) was 13,7 ± 2.9 mmHg for the Tonovet® and 12.9 ± 3.1 mmHg for the Tonopen Vet®. In the cats (40 eyes) a IOP value of 16.7 mmHg ± 3.0 mmHg was obtained with the Tonovet® and 17.4 mmHg ± 3.0 mmHg with the Tonopen Vet®. Deviation from the manufacturer's recommendations on handling the Tonovet® during the measurement significantly affected the results obtained. Compared to the reference measurement, directing the Tonovet® onto the peripheral cornea (approximately 1.5 mm from the limbus) as well as reducing the measuring distance to <4 mm resulted in slightly elevated IOP readings. Substantial underestimation of IOP occurred with angular deviation of the measuring axis. The Tonovet® rebound tonometer proved to be a valuable alternative to conventional tonometers for clinical use in dogs and cats. It is well tolerated by both canine and feline patients. However, the use of the Tonovet® in a clinical setting requires the examiner to consider potential sources of error when handling the tonometer to avoid false IOP readings.

DESCRIPTION AND VALIDATION OF A MAGNETIC RESONANCE IMAGING‐GUIDED STEREOTACTIC BRAIN BIOPSY DEVICE IN THE DOG

A stereotactic brain biopsy system that is magnetic resonance (MR) imaging-guided has not been validated in dogs. Our purpose was to determine the mean needle placement error in the caudate nucleus, thalamus, and midbrain of a canine cadaver brain using the modified Brainsight stereotactic system. Relocatable reference markers (fiducial markers) were attached to the cadaver head using a dental bite block. A T1-weighted gradient echo three-dimensional (3D) sequence was acquired using set parameters. Fiducial markers were used to register the head to the acquired MR images in reference to a 3D position sensor. This allowed the planning of trajectory path to brain targets in real time. Coordinates (X, Y, Z) were established for each target and 0.5 microl of diluted gadolinium was injected at each target using a 26-gauge needle to create a lesion. The center of the gadolinium deposition was identified on the postoperative MR images and coordinates (X', Y', Z') were established. The precision of this system in bringing the needle to target (needle placement error) was calculated. Seventeen sites were targeted in the brain. The mean needle placement error for all target sites was 1.79 +/- 0.87 mm. The upper bound of error for this stereotactic system was 3.31 mm. There was no statistically significant relationship between needle placement error and target depth (P = 0.23). The ease of use and precision of this stereotactic system support its development for clinical use in dogs with brain lesions > 3.31 mm.

Transient Evoked Otoacoustic Emissions Testing for Screening of Sensorineural Deafness in Puppies

Transient evoked otoacoustic emissions (TEOAE) are widely used for human neonatal deafness screening, but have not been reported for clinical use in dogs. To investigate the feasibility of TEOAE testing in conscious puppies and the ability of TEOAE testing to correctly identify deaf and hearing ears, as defined by brainstem auditory evoked response (BAER). Forty puppies from 10 litters. Prospective study on puppies presented for hearing assessment as part of a congenital deafness BAER screening program. Hearing status was determined using BAER. TEOAE testing was performed after the BAER assessment and the results of the TEOAE testing were compared with the hearing status for each ear. Parameters were tested for normality using the D'Agostino Pearson test and comparisons between the deaf and hearing ears were made using Mann-Whitney tests. TEOAE testing was readily performed in puppies presented for congenital deafness screening. Using analysis parameters based on those used in human neonatal hearing screening, TEOAE testing correctly identified all deaf ears, as defined by BAER testing, with a sensitivity of 100% (95% CI: 56-100%) for diagnosing deafness and specificity of 78% (95% CI: 66-87%). TEOAE testing is an effective screening modality for identifying congenital sensorineural deafness in dogs. In light of the simpler and less expensive equipment, TEOAE testing has the potential to improve access to hearing screening and through this reduce the prevalence of congenital deafness in the dog.

Rational use of medicines

A PHYSICIAN treating people usually has information available from randomised controlled trials to allow rational, evidence-based prescribing. Partly because of the cost of clinical trials and partly because many of...

Analgesic and motor-blocking action of epidurally administered levobupivacaine or bupivacaine in the conscious dog

ObjectiveTo compare the analgesic and motor-blocking effects of epidurally administered levobupivacaine and bupivacaine in the conscious dog. Study designProspective, randomized, cross-over study. AnimalsSix adult female Beagle dogs. MethodsEach animal received three doses of levobupivacaine or bupivacaine (0.5, 1.0 and 1.5 mg kg−1; concentrations 0.25%, 0.50%, and 0.75%, respectively) in a total volume of 0.2 mL kg−1 by means of a chronically implanted epidural catheter. Onset, duration (through pinch response in the sacral, lumbar and toe areas) and degree of analgesia and motor-blocking status was determined with a scoring system and at regular intervals over 8.5 hours before (baseline) and after drug administration. ResultsEpidurally administered levobupivacaine and bupivacaine had a similar dose-dependent analgesic action with no significant differences in onset (range: 5–8 minutes), duration (bupivacaine: 42 ± 28, 135 ± 68 and 265 ± 68 minutes, and levobupivacaine: 28 ± 33, 79 ± 55 and 292 ± 133 minutes; 0.25%, 0.50%, and 0.75%, respectively) or maximum degree of analgesia. However, levobupivacaine tended to produce a shorter duration of motor block than bupivacaine and the difference in the motor to nociceptive blockade times was significant at the highest dose. ConclusionEpidural levobupivacaine produced an analgesic action similar to that of bupivacaine. Clinical relevanceEpidural levobupivacaine is suitable for clinical use in dogs, mostly at the highest dose if a high degree of analgesia is required.

Separation of the Auricular and Annular Ear Cartilages: Surgical Repair Technique and Clinical Use in Dogs and Cats

To report a surgical technique for primary repair of separation of the annular and auricular cartilages of the ear and long-term outcome. Case series. Cats (3) and dogs (2) with ear canal separation. Medical records (1998-2007) of dogs and cats with ear canal separation were reviewed. Long-term outcome was obtained by telephone interview of owners or referring veterinarians. Three cats and 1 dog had ear canal separation after being hit by a car; there was no history of trauma in 1 dog. Successful repair was achieved by a caudal approach to the ear canal, identifying and debriding separated cartilage edges and using primary repair. A patent ear canal was confirmed in all animals by otoscopy 4-12 weeks later and by ear canalography in 3 animals. Long-term outcome was excellent with no reported complications 10-90 months later (median 24 months). Both acute and chronic separation between the annular and auricular cartilages, in the absence of middle ear disease, can be successfully treated using primary repair via a caudal approach to the ear canal, with excellent long-term outcome. Primary repair should be considered in animals with separation of the annular and auricular cartilages.

Canine Hypophysectomy Using a Ventral Paramedian Approach

To evaluate the degree of pituitary exposure, completeness of hypophysectomy, and perioperative morbidity associated with an alternative paramedian surgical approach and excisional technique for the canine pituitary gland. Experimental imaging, surgical, and endocrinologic study. Nine healthy, purpose-bred Beagle dogs. Surgical landmarks for the pituitary were determined by computed tomography (CT), and then using a ventral paramedian approach medial to the rami of the mandible, the pituitary was exposed and removed en bloc by manipulation and ultrasonic aspiration. Efficacy of the procedure was evaluated using endocrinologic and pathologic observation. CT images allowed the precise location of surgical landmarks for hypophysectomy. Statistically significant decreases in secretion of all measured pituitary hormones except adrenocorticotropic hormone (ACTH) occurred after hypophysectomy. Despite the absence of gross evidence of residual pituitary tissue, immunohistochemical staining revealed residual pituitary cells in the sella turcica of most dogs. CT imaging and a paramedian approach facilitated surgical access to the pituitary gland by a transoral technique; however, use of an ultrasonic aspirator removed all visible pituitary glands but left cellular remnants capable of ACTH secretion in the sella turcica. Although this technique did not result in complete hypophysectomy, clinical use in dogs with pituitary-dependent hyperadrenocorticism is warranted because the goal is not complete hypophysectomy but removal of a pituitary tumor.

Choosing fluids in traumatic hypovolemic shock: the role of crystalloids, colloids, and hypertonic saline.

Choosing fluids in traumatic hypovolemic shock: the role of crystalloids, colloids, and hypertonic saline.

Electrophysiologic and Hemodynamic Effects of Apomorphine in Dogs

Apomorphine is a dopamine receptor agonist used as an emetic, for Parkinson's disease, and for treating erectile dysfunction. This study was conducted to monitor cardiovascular function in dogs given the standard emetic dose (0.05 mg/kg) or 10 times that. Measurements were made during baseline and at 1, 5, 15, 30, 45, and 60 min after iv administration. There were no changes produced by the 0.05 mg/kg dose of apomorphine except for a decrease in mean systemic arterial pressure (AoPm) at the 1 through 15 min recordings. For the 0.5 mg/kg dose, there were reductions in systemic vascular resistance at the 1 and 5 min recordings and in AoPm at the 1 through 60 min recordings. Although not significant, when AoPm fell, heart rate, stroke volume, and cardiac output tended to increase. Action potentials were recorded from superfused Purkinje and endocardial ventricular fibers while exposed to 10−9 to 10−5 M apomorphine (10−10 M is considered therapeutic and 10−7 M is considered lethal). There were no changes in action potential characteristics of Purkinje fibers, but action potential duration at 90% repolarization prolonged approximately 10–12% in endocardium at concentrations of 10−6 M and greater. At the usual emetic dose (0.05 mg/kg) apomorphine resulted in no signs of cardiovascular toxicity and, at 0.5 mg/kg, cardiovascular changes were minimal. The emetic dose is higher than that for Parkinson's disease or erectile dysfunction; thus apomorphine appears to be a safe compound for clinical use in dogs and by extrapolation to man.

Development of gastroscopic food sensitivity testing in dogs.

The aims of this study were to develop a gastroscopic food sensitivity testing (GFST) technique for clinical use in dogs and to determine if the results of GFST were influenced by the feeding of a hypoallergenic diet immediately before the testing period ("unmasking"). The technical requirements for GFST were devised during a total of eight endoscopies performed in four healthy dogs. GFST was performed in anesthetized dogs in sternal recumbency. Food extracts were dripped onto the dependent aspect of the body of the stomach via plastic tubing passed through the endoscope. Changes were observed within 2 to 3 minutes of application, and included localized mucosal swelling and erythema, generalized mucosal erythema, and hyperperistalsis. The influence of "unmasking" was then examined in 6 atopic and 2 healthy dogs, which underwent GFST on three occasions, 4 weeks apart. Before the first and third testing periods, the dogs consumed a commercial dry dog food. For 5 days before the second testing period the dogs were fed a hypoallergenic elemental diet. Oral challenges were performed to identify which of the dogs had clinically overt immediate food sensitivity. Localized swelling was most frequently correlated with positive challenge PO. No positive reactions occurred in response to the negative control extract (lamb). The number of positive GFST results increased after feeding the hypoallergenic diet. In conclusion, these preliminary results indicate that GFST holds substantial promise for the diagnosis of immediate food sensitivities affecting the gastrointestinal tract. The sensitivity of the procedure appears to be enhanced by preceding testing with a hypoallergenic diet.

Lymphedema. Clinical signs, diagnosis, and treatment.

Medical management of lymphedema is warranted in all dogs with suspected congenital lymphedema, before surgical intervention. Although pharmaceutical agents, such as the benzo-pyrones, have not been investigated for clinical use in dogs, such studies appear to be justified. None of the surgical techniques discussed will cure lymphedema. The only technique reported with any frequency in the dog has been excision of affected tissues, and although some successes have been reported with this procedure, others have found it to be of no benefit or severe complications have occurred. Excisional techniques require meticulous attention to prevent infection intraoperatively and postoperatively. Staging the procedure may decrease problems associated with devascularization of remaining tissues. Evaluation of other techniques may be warranted in dogs; however, no technique has proven to be consistently beneficial in human beings with lymphedema.