Platelet Activation in Cats with Hypertrophic Cardiomyopathy

Background

Cats with hypertrophic cardiomyopathy (HCM) are at risk for development of systemic thromboembolic disease. However, the relationship between platelet activation state and cardiovascular parameters associated with HCM is not well described.

Objectives

To characterize platelet activation by flow cytometric evaluation of platelet P‐selectin and semiquantitative Western blot analysis of soluble platelet‐endothelial cell adhesion molecule‐1 (sPECAM‐1).

Animals

Eight normal healthy cats (controls) owned by staff and students of the School of Veterinary Medicine and 36 cats from the UC Davis Feline HCM Research Laboratory were studied.

Methods

Platelet‐rich plasma (PRP) was used for all flow cytometry studies. Platelet surface CD41 and P‐selectin expression were evaluated before and after ADP stimulation. sPECAM‐1 expression was evaluated by Western blot analysis of platelet‐poor plasma that had been stabilized with aprotinin. Standard echocardiographic studies were performed.

Results

Resting platelets from cats with severe HCM had increased P‐selectin expression compared to controls, and expressed higher surface density of P‐selectin reflected by their increased mean fluorescence intensities (MFI). Stimulation with ADP also resulted in significantly increased P‐selectin MFI of platelets from cats with severe HCM. Increased P‐selectin expression and MFI correlated with the presence of a heart murmur and end‐systolic cavity obliteration (ESCO). sPECAM‐1 expression from cats with moderate and severe HCM was significantly increased above those of control cats.

Conclusions and Clinical Importance

P‐selectin and sPECAM expression may be useful biomarkers indicating increased platelet activation in cats with HCM.     

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.     

Abdominal Ultrasound Examination Findings in 534 Hyperthyroid Cats Referred for Radioiodine Treatment Between 2007–2010

Background

The prevalence of concurrent disease in hyperthyroid cats is unknown.

Objectives

To identify the prevalence of concurrent intra‐abdominal disease using abdominal ultrasound examination (AUS) in hyperthyroid cats referred for radioactive iodine treatment (RIT) and to determine whether the requirement for pretreatment AUS is justified.

Animals

Five hundred and thirty‐four client‐owned cats diagnosed with hyperthyroidism and referred for RIT.

Methods

Retrospective study. Age, breed, sex, body weight, clinical signs, total serum T4 concentration, blood urea nitrogen (BUN) concentration, serum creatinine concentration, urine specific gravity (USG), AUS results, and biopsy or cytology results, or both (if obtained) were collected from the medical records.

Results

The prevalence of concurrent disease identified using AUS in hyperthyroid cats referred for RIT was 36.1%; 22.8% of the cats in the study had renal disease and 2.4% had confirmed neoplasia. Significant differences in median USG (P value 0.032) and median BUN (P value 0.028) were found between cats that had abnormal kidneys on AUS compared to those with normal‐appearing kidneys. Only 2.2% of the cats were not treated with RIT as a result of changes identified on AUS and subsequently obtained cytology or biopsy results.

Conclusions and Clinical Importance

The results indicate that pretreatment AUS in hyperthyroid cats referred for RIT is unnecessary in most patients.     

Changes in Serum and Urine SAA Concentrations and Qualitative and Quantitative Proteinuria in Abyssinian Cats with Familial Amyloidosis: A Five‐year Longitudinal Study (2009–2014)

Background

Diagnosis of familial amyloidosis (FA) in Abyssinian cats usually is made on postmortem examination.

Hypothesis/Objectives

Sequential analysis of serum SAA (sSAA), urinary SAA (uSAA), urinary protein:creatinine (UPC) ratio, or sodium‐dodecylsulfate agarose gel electrophoresis (SDS‐AGE) may facilitate early identification of cats with FA.

Animals

Twenty‐three Abyssinian cats belonging to cattery A or B (low and high prevalence of FA, respectively).

Methods

Prospective longitudinal study using 109 blood and 100 urine samples collected over 4‐year period every 4 months, if possible, or more frequently in case of illness. Cats that died during study were necropsied. Health status of live cats was checked 5 years after enrollment. Serum amyloid A (sSAA) and urinary SAA (uSAA) were measured using ELISA kit. The UPC ratio and SDS‐AGE also was performed.

Results

Familial amyloidosis was not identified in cattery A, whereas 7/14 cats from cattery B had FA. Serum amyloid A concentrations were not significantly different between cats in catteries A and B or between cats with or without FA, despite frequent peaks in cats from cattery B. Conversely, uSAA was significantly higher in cattery B, especially in the terminal phases of FA. Proteinuria occasionally was found in cats from both catteries, especially in those with FA. Urine protein electrophoresis identified mixed proteinuria only in cats with FA.

Conclusions and Clinical Importance

Serum amyloid A and UPC ratio are not helpful for early identification of Abyssinian cats with FA. Conversely, increases in uSAA with or without mixed proteinuria may be found before onset of clinical signs in cats with FA.     

Changes in Systolic Blood Pressure over Time in Healthy Cats and Cats with Chronic Kidney Disease

Background

Hypertension is a common problem in older cats, most often associated with chronic kidney disease (CKD). Cross‐sectional studies have suggested that blood pressure in cats increases with age.

Hypothesis/Objectives

To determine whether blood pressure in cats increases with age and whether this occurs independently of the presence of CKD. To investigate risk factors for developing hypertension.

Animals/Subjects

Two hundred and sixty‐five cats with CKD and 133 healthy cats ≥9 years were retrospectively identified.

Methods

Four groups were created according to status at initial evaluation (CKD or healthy) and blood pressure at the last included visit (normotensive [NT] or developed hypertension [DH]): Healthy‐NT, Healthy‐DH, CKD‐NT and CKD‐DH. Systolic blood pressure (SBP) over time slopes were compared with 0 and between groups. Risk factors for the development of hypertension were investigated, and associations of biochemical and clinical variables with SBP were examined.

Results

Cats that were hypertensive at CKD diagnosis (n = 105) were not included in further analyses. Twenty‐seven cats with CKD and 9 healthy cats developed hypertension ≥3 months after diagnosis of CKD or their first visit. Systolic blood pressure significantly increased with age in all cats (P < .001). Healthy cats were at less risk than cats with CKD to become hypertensive (hazard ratio 0.2, P < .001), with creatinine being an independent risk factor for the development of hypertension.

Conclusions and Clinical Importance

The high prevalence of hypertension in azotemic cats in this study shows the importance of monitoring of SBP in elderly cats, and in particular in cats with CKD.     

Cardiac Biomarkers in Hyperthyroid Cats

Background

Hyperthyroidism has substantial effects on the circulatory system. The cardiac biomarkers NT‐proBNP and troponin I (cTNI) have proven useful in identifying cats with myocardial disease but have not been extensively investigated in hyperthyroidism.

Hypothesis

Plasma NT‐proBNP and cTNI concentrations are higher in cats with primary myocardial disease than in cats with hyperthyroidism and higher in cats with hyperthyroidism than in healthy control cats.

Animals

Twenty‐three hyperthyroid cats, 17 cats with subclinical hypertrophic cardiomyopathy (HCM), and 19 euthyroid, normotensive healthy cats ≥8 years of age. Fourteen of the hyperthyroid cats were re‐evaluated 3 months after administration of radioiodine (¹³¹I).

Methods

Complete history, physical examination, complete blood count, serum biochemistries, urinalysis, blood pressure measurement, serum T4 concentration, plasma concentrations of NT‐proBNP and cTNI, and echocardiogram were obtained prospectively from each cat.

Results

Hyperthyroid cats and cats with HCM had plasma NT‐proBNP and cTNI concentrations that were significantly higher than those of healthy cats, but there was no significant difference between hyperthyroid cats and cats with HCM with respect to the concentration of either biomarker. In hyperthyroid cats that were re‐evaluated 3 months after ¹³¹I treatment, plasma NT‐proBNP and cTNI concentrations as well as ventricular wall thickness had decreased significantly.

Conclusions and Clinical Importance

Although there may be a role for NT‐proBNP in monitoring the cardiac response to treatment of hyperthyroidism, neither NT‐proBNP nor cTNI distinguish hypertrophy associated with hyperthyroidism from primary HCM. Therefore, the thyroid status of older cats should be ascertained before interpreting NT‐proBNP and cTNI concentrations.     

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

Background

Fibroblast growth factor‐23 (FGF‐23) and parathyroid hormone (PTH) are commonly increased in cats with azotemic chronic kidney disease (CKD). Both are predictors of survival time in human patients, but these relationships have not previously been examined in the cat.

Objectives

To investigate the relationship between plasma FGF‐23 and PTH concentrations at diagnosis of CKD in cats with survival time and with disease progression over 12 months.

Animals

214 azotemic, client‐owned cats (≥9 years).

Methods

Retrospective study: Biochemical and urinary variables at diagnosis of azotemic CKD, including plasma FGF‐23 and PTH concentrations were assessed as predictors of survival time (all‐cause mortality) using Cox regression, and as predictors of CKD progression over 12 months using logistic regression.

Results

In the final multivariable Cox regression model, survival was negatively associated with plasma creatinine (P = .002) and FGF‐23 concentrations (P = .014), urine protein‐to‐creatinine ratio (P < .001) and age (P < .001). Survival was positively associated with PCV (P = .004). In the final multivariable logistic regression model, independent predictors of CKD progression included logFGF‐23 and age. Neither plasma phosphate nor PTH was found to be an independent predictor of survival time or of CKD progression.

Conclusions and Clinical Importance

Plasma FGF‐23 concentration is a novel prognostic indicator in cats with CKD, independent of other factors including plasma creatinine and phosphate concentrations. Further work is required to assess if FGF‐23 contributes directly to CKD progression, but regardless these findings may make FGF‐23 a useful biomarker for predicting poorer outcomes in cats with CKD.     

Detection of Clinically Relevant Pain Relief in Cats with Degenerative Joint Disease Associated Pain

Background

Detection of clinically relevant pain relief in cats with degenerative joint disease (DJD) is complicated by a lack of validated outcome measures and a placebo effect.

Hypothesis/Objectives

To evaluate a novel approach for detection of pain relief in cats with DJD.

Animals

Fifty‐eight client‐owned cats.

Methods

Prospective, double‐masked, placebo‐controlled, stratified, randomized, clinical study. Enrolled cats were 6–21 years of age, with owner‐observed mobility impairment, evidence of pain in at least 2 joints during orthopedic examination, and overlapping radiographic evidence of DJD, and underwent a 2‐week baseline period, 3‐week treatment period with placebo or meloxicam, and 3‐week masked washout period. Outcome measures were evaluated at days 0, 15, 36, and 57.

Results

Both groups significantly improved after the treatment period (day 36) on client‐specific outcome measures (CSOM) and feline musculoskeletal pain index (FMPI) (P < .0001 for both); there was no difference between the groups on CSOM or FMPI score improvement. After the masked washout period, more cats that received meloxicam during the treatment period had a clinically relevant decrease in CSOM score (P = .048) and FMPI score (P = .021) than cats that received placebo.

Conclusions and Clinical Importance

Using both a client‐specific and a general clinical metrology instrument, owners of cats with DJD were able to detect evident recurrence of clinical signs after withdrawal of active medication than after withdrawal of placebo, and that this study design might be a novel and useful way to circumvent the placebo effect and detect the efficacy of pain‐relieving medications.     

Longitudinal Evaluation of Serum Pancreatic Enzymes and Ultrasonographic Findings in Diabetic Cats Without Clinically Relevant Pancreatitis at Diagnosis

Background

Cats with diabetes mellitus can have subclinical pancreatitis but prospective studies to confirm this are lacking. Metabolic control of diabetic cats with pancreatitis is difficult.

Hypothesis

Subclinical pancreatitis occurs in diabetic cats at the time diabetes is diagnosed or might develop during the follow‐up period, hampering diabetic remission.

Animals

Thirty cats with newly diagnosed diabetes without clinical signs of pancreatitis on admission.

Methods

Prospective study. On admission and 2 and 6 months later, serum Spec fPL and DGGR‐lipase were measured and the pancreas underwent ultrasonographic examination. Pancreatitis was suspected if serum markers were increased or ≥2 ultrasonographic abnormalities were detected. Cats were treated with insulin glargine and diabetic remission was defined as euglycemia ≥4 weeks after discontinuation of insulin. Nonparametric statistical tests were used for analysis.

Results

Subclinical pancreatitis at the time of diagnosis was suspected in 33, 50, and 31% of cats based on Spec fPL, DGGR‐lipase and ultrasonography, respectively; and in 60% when diagnostic criteria were combined. During the follow‐up period, suspected pancreatitis developed in additional 17–30% cats. Only 1 cat had transient clinical signs compatible with pancreatitis. Seventeen of the 30 cats (57%) achieved remission. Frequency of abnormal Spec fPL and DGGR‐lipase and abnormal ultrasonographic findings did not differ in cats achieving remission and those who did not. Cats achieving remission had significantly lower Spec fPL at 2 months (P < .001).

Conclusions and Clinical Importance

Based on laboratory and ultrasonographic measurements, many cats with diabetes might have pancreatitis, although without clinical signs. Cats with high Spec fPL might have a reduced chance of diabetic remission; however, this topic needs further studies in large cohorts of diabetic cats.     

Evaluation of Serum Thyroid‐Stimulating Hormone Concentration as a Diagnostic Test for Hyperthyroidism in Cats

Background

In humans, measurement of serum thyroid‐stimulating hormone (TSH) concentration is commonly used as a first‐line discriminatory test of thyroid function. Recent reports indicate that canine TSH (cTSH) assays can be used to measure feline TSH and results can help diagnose or exclude hyperthyroidism.

Objectives

To investigate the usefulness of cTSH measurements as a diagnostic test for cats with hyperthyroidism.

Animals

Nine hundred and seventeen cats with untreated hyperthyroidism, 32 euthyroid cats suspected of having hyperthyroidism, and 131 clinically normal cats.

Methods

Prospective study. Cats referred to the Animal Endocrine Clinic for suspected hyperthyroidism were evaluated with serum T₄, T₃, free T₄ (fT ₄), and TSH concentrations. Thyroid scintigraphy was used as the gold standard to confirm or exclude hyperthyroidism.

Results

Median serum TSH concentration in the hyperthyroid cats (<0.03 ng/mL) was significantly (P < .001) lower than concentrations in clinically normal cats (0.05 ng/mL) or euthyroid cats with suspected thyroid disease (0.06 ng/mL). Only 18 (2.0%) hyperthyroid cats had measurable TSH concentrations (≥0.03 ng/mL), whereas 114 (69.9%) of the 163 euthyroid cats had detectable concentrations. Combining serum TSH with T₄ or fT ₄ concentrations lowered the test sensitivity of TSH from 98.0 to 97.0%, but markedly increased overall test specificity (from 69.9 to 98.8%).

Conclusions and Clinical Importance

Serum TSH concentrations are suppressed in 98% of hyperthyroid cats, but concentrations are measurable in a few cats with mild‐to‐moderate hyperthyroidism. Measurement of serum TSH represents a highly sensitive but poorly specific test for diagnosis of hyperthyroidism and is best measured in combination with T₄ and fT ₄.     

Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long‐Term Follow‐Up Study

Background

Lagotto Romagnolo (LR) dogs with benign juvenile epilepsy syndrome often experience spontaneous remission of seizures. The long‐term outcome in these dogs currently is unknown. In humans, behavioral and psychiatric comorbidities have been reported in pediatric and adult‐onset epilepsies.

Hypothesis/Objectives

The objectives of this study were to investigate possible neurobehavioral comorbidities in LR with a history of benign familial juvenile epilepsy (BFJE) and to assess the occurrence of seizures after the remission of seizures in puppyhood.

Animals

A total of 25 LR with a history of BFJE and 91 control dogs of the same breed.

Methods

Owners of the LR dogs in the BFJE and control groups completed an online questionnaire about each dog''s activity, impulsivity, and inattention. Principal component analysis (PCA) served to extract behavioral factors from the data. We then compared the scores of these factors between the 2 groups in a retrospective case–control study. We also interviewed all dog owners in the BFJE group by telephone to inquire specifically about possible seizures or other neurological problems after remission of seizures as a puppy.

Results

Lagotto Romagnolo dogs with BFJE showed significantly higher scores on the factors Inattention and Excitability/Impulsivity than did the control group (P = .003; P = .021, respectively). Only 1 of the 25 BFJE LR exhibited seizures after remission of epilepsy in puppyhood.

Conclusions and Clinical Importance

Although the long‐term seizure outcome in BFJE LR seems to be good, the dogs exhibit behavioral abnormalities resembling attention deficit hyperactivity disorder (ADHD) in humans, thus suggesting neurobehavioral comorbidities with epilepsy.     

Plasma and Erythrocyte Glutathione Peroxidase Activity,Serum Selenium Concentration,and Plasma Total Antioxidant Capacity in Cats with IRIS Stages I–IV Chronic Kidney Disease

Background

Serum selenium concentrations and the activity of plasma glutathione peroxidase (GPx) decrease with the progression of chronic kidney disease (CKD) in human patients. Selenium is considered a limiting factor for plasma GPx synthesis. Plasma total antioxidant capacity (TAC) is decreased in CKD cats in comparison to healthy cats.

Hypothesis

Serum selenium concentrations and plasma and erythrocyte GPx activity in cats with CKD are lower than in healthy cats. Serum selenium concentrations, the activity of enzymes, and plasma TAC progressively decrease with the progression of kidney disease according to IRIS (International Renal Interest Society) classification.

Animals

Twenty‐six client‐owned cats in IRIS stages I–IV of CKD were compared with 19 client‐owned healthy cats.

Methods

A CBC, serum biochemical profile, urinalysis, plasma and erythrocyte GPx activity, serum selenium concentration, and plasma TAC were measured in each cat.

Results

Cats in IRIS stage IV CKD had a significantly higher (P = .025) activity of plasma GPx (23.44 ± 6.28 U/mL) than cats in the control group (17.51 ± 3.75 U/mL). There were no significant differences in erythrocyte GPx, serum selenium concentration, and plasma TAC, either among IRIS stages I–IV CKD cats or between CKD cats and healthy cats.

Conclusions and Clinical Importance

Erythrocyte GPx activity, serum selenium concentration, and plasma TAC do not change in CKD cats compared with healthy cats. Selenium is not a limiting factor in feline CKD. Increased plasma GPx activity in cats with stage IV CKD suggests induction of antioxidant defense mechanisms. Antioxidant defense systems might not be exhausted in CKD in cats.     

Prevalence of Chiari‐like Malformations in Clinically Unaffected Dogs

Background

The importance of Chiari‐like malformation (CM) in the generation of clinical signs or the formation of syringomyelia in dogs is incompletely understood, partly because the prevalence of various CM definitions in unaffected dogs is unknown.

Hypothesis/Objectives

The aims were: to estimate the prevalence of CM in dogs asymptomatic for CM or syringomyelia, according to 3 currently used definitions; and, to investigate the effect of brachycephaly and head position during magnetic resonance (MR) imaging on estimates of the prevalence of CM.

Animals

One ninety‐nine client‐owned dogs without apparent signs of CM or syringomyelia.

Methods

Blinded, retrospective analysis. Archived MR images were analyzed for evidence of cerebellar indentation and impaction into or herniation through the foramen magnum. Logistic regression analysis was used to investigate the relationship of CM diagnosis with head position and the cranial index (a measure of brachycephaly).

Results

In 185 non‐Cavalier King Charles Spaniel (CKCS) dogs, indentation was identified in 44% (95% CI, 47–51%) and impaction in 22% (95% CI, 16–28%). No asymptomatic, non‐CKCS dogs showed herniation. Regression analysis showed a significant increase in the odds of indentation and impaction in an extended head position and as the cranial index increased (became more brachycephalic).

Conclusions and Clinical Importance

The high prevalence of cerebellar indentation and impaction suggests that they may be normal anatomical variations and therefore unsuitable as definitions of CM. We suggest that future research into CM in dogs should define cases and controls more strictly so that overlap between normal and abnormal animals is minimized.     

Acute Effects of Ivabradine on Dynamic Obstruction of the Left Ventricular Outflow Tract in Cats with Preclinical Hypertrophic Cardiomyopathy

Background

Ivabradine is a negative chronotropic drug with minimal effects on central hemodynamics. Its effect on dynamic obstruction of the left ventricular outflow tract (LVOT) in cats with hypertrophic cardiomyopathy (HCM) remains unknown.

Hypothesis/Objectives

Ivabradine reduces dynamic obstruction of the LVOT in cats with HCM.

Animals

Twenty‐eight client‐owned cats with preclinical HCM and dynamic LVOT obstruction.

Methods

Randomized, double‐blind, active‐control single dose study. Cats received a single dose of either ivabradine (0.3 mg/kg PO) or atenolol (2 mg/kg PO). Heart rate, echocardiographic variables, and systolic blood pressure (SBP) were recorded before and 3 hours after drug administration. Statistical comparisons were made using ANCOVA.

Results

Peak velocity in the LVOT was significantly decreased compared to baseline for both drugs; however, the effect was more prominent with atenolol (mean reduction 2.53 m/s; 95% CI 2.07–3.13 m/s) compared to ivabradine (mean reduction 0.32 m/s; 95% CI −0.04 to 0.71 m/s; P < .0001). Echocardiographic indices of systolic function were largely unchanged by ivabradine, but significantly reduced by atenolol.

Conclusions and Clinical Importance

A single dose of ivabradine decreases dynamic LVOT obstruction in cats with HCM, but the clinical effect is negligible and inferior compared to that achieved by atenolol.     

Clinical Characterization of Epilepsy of Unknown Cause in Cats

Background

The diagnosis of feline epilepsy of unknown cause (EUC) requires a thorough diagnostic evaluation, otherwise the prevalence of EUC could be overestimated.

Hypothesis

Feline EUC is a clinically defined disease entity, which differs from feline hippocampal necrosis by the absence of magnetic resonance imaging (MRI) signal alteration of the hippocampus. The objectives of this study were (1) to evaluate the prevalence of EUC in a hospital population of cats by applying well‐defined inclusion criteria, and (2) to describe the clinical course of EUC.

Animals

Eighty‐one cats with recurrent seizures.

Methods

Retrospective study—medical records were reviewed for cats presented for evaluation of recurrent seizures (2005–2010). Inclusion criteria were a defined diagnosis based on laboratory data, and either MRI or histopathology. Final outcome was confirmed by telephone interview with the owner. Magnetic resonance images were reviewed to evaluate hippocampal morphology and signal alterations.

Results

Epilepsy of unknown cause was diagnosed in 22% of cats with epilepsy. Physical, neurologic, and laboratory examinations, and either 1.5 T MRI and cerebrospinal fluid analysis or postmortem examination failed to identify an underlying cause. Cats with EUC had a higher survival rate (P < .05) and seizure remission occurred frequently (44.4%).

Conclusion and Clinical Importance

A detailed clinical evaluation and diagnostic imaging with MRI is recommended in any cat with recurrent seizures. The prognosis of cats with normal MRI findings and a clinical diagnosis of EUC are good. Standardized imaging guidelines should be established to assess the hippocampus in cats.     

Nanoparticulate CpG Immunotherapy in RAO‐Affected Horses: Phase I and IIa Study

Background

Recurrent airway obstruction (RAO), an asthma‐like disease, is 1 of the most common allergic diseases in horses in the northern hemisphere. Hypersensitivity reactions to environmental antigens cause an allergic inflammatory response in the equine airways. Cytosine‐phosphate‐guanosine‐oligodeoxynucleotides (CpG‐ODN) are known to direct the immune system toward a Th1‐pathway, and away from the pro‐allergic Th2‐line (Th2/Th1‐shift). Gelatin nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug delivery systems that protect CpG‐ODN against nuclease degeneration. Preliminary studies on the inhalation of GNP‐bound CpG‐ODN in RAO‐affected horses have shown promising results.

Objectives

The aim of this study was to evaluate the clinical and immunological effects of GNP‐bound CpG‐ODN in a double‐blinded, placebo‐controlled, prospective, randomized clinical trial and to verify a sustained effect post‐treatment.

Animals and Methods

Twenty‐four RAO‐affected horses received 1 inhalation every 2 days for 5 consecutive administrations. Horses were examined for clinical, endoscopic, cytological, and blood biochemical variables before the inhalation regimen (I), immediately afterwards (II), and 4 weeks post‐treatment (III).

Results

At time points I and II, administration of treatment rather than placebo corresponded to a statistically significant decrease in respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO ₂ and neutrophil percentage, and an increase in arterial oxygen pressure.

Conclusion and Clinical Importance

Administration of a GNP‐bound CpG‐ODN formulation caused a potent and persistent effect on allergic and inflammatory‐induced clinical variables in RAO‐affected horses. This treatment, therefore, provides an innovative, promising, and well‐tolerated strategy beyond conventional symptomatic long‐term therapy and could serve as a model for asthma treatment in humans.     

Use of Contrast‐Enhanced Fluid‐Attenuated Inversion Recovery Sequence to Detect Brain Lesions in Dogs and Cats

Background

The diagnostic value of a contrast‐enhanced T2‐weighted FLAIR sequence (ceFLAIR) in brain imaging is unclear.

Hypothesis/Objectives

That the number of brain lesions detected with ceFLAIR would be no greater than the sum of lesions detected with nFLAIR and ceT1W sequence.

Animals

One hundred and twenty‐nine animals (108 dogs and 21 cats) undergoing magnetic resonance imaging (MRI) of the head between July 2010 and October 2011 were included in the study.

Methods

A transverse ceFLAIR was added to a standard brain MRI protocol. Presence and number of lesions were determined based on all available MRI sequences by 3 examiners in consensus and lesion visibility was evaluated for nFLAIR, ceFLAIR, and ceT1W sequences.

Results

Eighty‐three lesions (58 intra‐axial and 25 extra‐axial) were identified in 51 patients. Five lesions were detected with nFLAIR alone, 2 with ceT1W alone, and 1 with ceFLAIR alone. Significantly higher numbers of lesions were detected using ceFLAIR than nFLAIR (76 versus 67 lesions; P = 0.04), in particular for lesions also detected with ceT1W images (53 versus 40; P =.01). There was no significant difference between the number of lesions detected with combined nFLAIR and ceT1W sequences compared to those detected with ceFLAIR (82 versus 76; P =.25).

Conclusion and Clinical Importance

Use of ceFLAIR as a complementary sequence to nFLAIR and ceT1W sequences did not improve the detection of brain lesions and cannot be recommended as part of a routine brain MRI protocol in dogs and cats with suspected brain lesions.