Thrombocytosis in 158 cats (2011-2018).

OBJECTIVES: Thrombocytosis is an uncommon hematologic abnormality that is associated with various physiologic, metabolic, inflammatory and neoplastic conditions in people and dogs. Thrombocytosis is not a well-described abnormality in cats. The objective of this study was to classify thrombocytosis in cats based on underlying disease processes and severity, and to compare this with a control population of cats. METHODS: A retrospective study was conducted by reviewing the medical records of cats with increased (>600 × 103/µl; thrombocytosis group) and normal (200-600 × 103/µl; 2:1 age-matched control group) platelet counts between 2011 and 2018. Platelet counts were estimated based on blood smear assessment in all cats. Cats were classified by the severity (mild, moderate or marked) of thrombocytosis. Diagnoses were recorded for all cases, and were classified broadly into either neoplasia, endocrine or inflammatory disease. RESULTS: In total, 158 cats were identified with thrombocytosis, with 315 cats in the control group. Non-neoplastic inflammatory disease was the most common diagnosis in both groups (54.4% in cats with thrombocytosis and 56.2% in controls; P = 0.77); however, gastrointestinal diseases were more common in cats with thrombocytosis (75.6%) when compared with controls (34.5%; P <0.0001). Neoplasia was diagnosed more frequently in cats with thrombocytosis (44.3%) compared with the control group (25.4%; P <0.0001). Round cell tumor was the most common neoplasia diagnosis in both groups, but gastrointestinal and multicentric lymphoma were diagnosed more frequently in cats with thrombocytosis compared with control cats. No association between the severity of thrombocytosis and etiology was identified. CONCLUSIONS AND RELEVANCE: Thrombocytosis in cats is more commonly associated with gastrointestinal, hepatobiliary or immune-mediated diseases when compared with a control population. Neoplasia, especially multicentric and gastrointestinal lymphoma, was more commonly diagnosed in cats with thrombocytosis when compared with control cats.

Examination of Motivational Influences on Clinical-Year Veterinary Students' Career Decisions.

The purpose of this study was to identify motivations for fourth-year veterinary students to choose future career paths based on post-graduation employment or post-graduation education. Approximately 500 students from four institutions were invited to participate in an online survey. Surveys were based on the cognitive evaluation theory, a minitheory within the self-determination macrotheory framework developed by Deci and Ryan. Intrinsic motivational factors were categorized by autonomy, competence, and relatedness, and extrinsic motivators were categorized by environmental and interpersonal factors. Students pursuing post-graduation education have intrinsic motivators that aligned with competence and were extrinsically motivated by a mentor, while students interested in post-graduation employment had intrinsic motivators that were more focused on autonomy with extrinsic motivational influences of debt/finances and geographic location.

Complete Blood Counts and Blood Smear Analyses in 312 Diabetic Dogs (2007-2017).

Diabetes mellitus is a common endocrinopathy in dogs that has been associated with various biochemical changes and comorbid diseases, but hematologic abnormalities have been rarely reported. The aim of this retrospective study was to evaluate complete blood count and blood smear alterations and to describe their relationship with, and incidence of comorbid diseases in, diabetic dogs. Three-hundred twelve diabetic dogs, 286 dogs diagnosed with systemic, nondiabetic illnesses, and 506 healthy dogs were identified during the study period. Groups were compared using contingency tables and logistic regression. Associations between statistically significant complete blood count and blood smear alterations and comorbidities were evaluated using multivariable analysis. High-grade codocytosis and anisocytosis were identified more frequently in diabetic dogs, whereas high-grade reactive lymphocytosis and keratocytosis were identified less frequently (P < .001). Diabetic dogs with high-grade codocytosis had lower red blood cell, hemoglobin, hematocrit and higher white blood cell counts (P < .001). Diabetic ketoacidosis was diagnosed more frequently in diabetic dogs with high-grade codocytosis when compared with those with low-grade codocytosis (P < .001) or when compared with any other cell morphologic alterations. This study suggests that blood smear analysis should be a routine part of the evaluation of diabetic dogs.

Interleukin-6 and thrombopoietin concentrations in dogs with carcinoma with and without thrombocytosis.

BACKGROUND: Carcinoma-associated thrombocytosis involves tumor production of mediators such as interleukin-6 (IL-6) and thrombopoietin (TPO) that increase thrombopoiesis and may play a role in tumor evasion and metastasis. Carcinoma-associated thrombocytosis is described in people, but has not been described in dogs. HYPOTHESIS/OBJECTIVES: Evaluate the concentrations of IL-6 and TPO in dogs diagnosed with carcinoma with or without thrombocytosis. We hypothesized that IL-6 and TPO concentrations would be higher in dogs with carcinoma compared to healthy dogs, and that IL-6 and TPO concentrations would be higher in dogs with carcinoma and thrombocytosis when compared to dogs with carcinoma and normal platelet counts. ANIMALS: One-hundred sixteen dogs: 63 with carcinoma and 53 healthy control dogs. METHODS: Complete blood count was performed in all dogs, and they were stratified for sub-group analysis based on the presence or absence of thrombocytosis (platelet count > 500 103/µL). Serum TPO and IL-6 concentrations were measured by ELISA. Results of selected numeric variables were compared using Wilcoxon rank sum tests for pairwise comparisons. A value of P < .05 was considered significant. RESULTS: Twelve of the dogs with carcinoma (12/63, 19.0%) and none of the healthy control dogs (0%) had thrombocytosis. Thrombopoietin concentrations (median [range]) were significantly higher in dogs with carcinoma when compared to controls (87.42 pg/mL [0 to >600] vs 15.99 pg/mL [0 to >600], P < .001). Interleukin-6 concentrations (median [range]) were not different between dogs with carcinoma and healthy control dogs (9.70 pg/mL [0-181.53] vs 3.03 pg/mL [0-280.77], P = .15). In dogs with carcinoma, the TPO and IL-6 concentrations were not different between dogs with thrombocytosis and dogs with normal platelet count. CONCLUSIONS AND CLINICAL IMPORTANCE: Thrombopoietin concentrations were significantly higher in dogs with carcinoma, regardless of platelet count. Thrombopoietin is likely to be 1 of multiple factors that can impact platelet number, production, and consumption in dogs with carcinoma.

Development and validation of a flow cytometric assay for detecting reactive oxygen species in the erythrocytes of healthy dogs.

OBJECTIVE: To validate the use of a flow cytometric assay that uses 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) to measure reactive oxygen species in the erythrocytes of healthy dogs. ANIMALS: 50 healthy adult dogs. PROCEDURES: Erythrocytes were incubated with DCFH-DA or a vehicle control (dimethyl sulfoxide), then incubated with (stimulated) or without (unstimulated) hydrogen peroxide. The flow cytometric assay was evaluated for specificity with increasing concentrations of DCFH-DA and hydrogen peroxide, and a polynomial regression line was applied to determine optimal concentrations. For precision, samples were analyzed 5 consecutive times for determination of intra- and interassay variability. Stability of samples stored at 4°C for up to 48 hours after blood collection was determined with flow cytometric analysis. Coefficient of variation (CV) was considered acceptable at 20%. Baseline measurements were used to determine an expected range of median fluorescence intensity for unstimulated erythrocytes incubated with DCFH-DA. RESULTS: Erythrocytes were successfully isolated, and stimulated samples demonstrated higher median fluorescence intensity, compared with unstimulated samples. The intra-assay CV was 11.9% and 8.9% and interassay CV was 11.9% and 9.1% for unstimulated and stimulated samples, respectively. Unstimulated samples were stable for up to 24 hours, whereas stimulated samples were stable for up to 48 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Flow cytometry for the measurement of reactive oxygen species in the erythrocytes of healthy dogs by use of DCFH-DA had acceptable specificity, precision, and stability. Flow cytometry is a promising technique for evaluating intraerythrocytic oxidative stress for healthy dogs.

Effects of administration of ascorbic acid and low-dose hydrocortisone after infusion of sublethal doses of lipopolysaccharide to horses.

BACKGROUND: Sepsis is associated with ascorbic acid (AA) depletion and critical illness-related corticosteroid insufficiency (CIRCI) in humans. HYPOTHESES: Intravenous infusion of lipopolysaccharide (LPS) would (a) decrease endogneous AA concentrations, (b) induce CIRCI and (c) administration of a combination of AA and hydrocortisone (HC) would have decreased indices of inflammation compared to either drug alone. ANIMALS: Thirty-two healthy horses. METHODS: Randomized placebo-controlled experimental trial. Horses were assigned to 1 of 4 groups (saline, AA and HC, AA only, or HC only). Treatments were administered 1 hour after completion of LPS infusion. Clinical signs, clinicopathological variables, pro-inflammatory cytokine gene expression and production, and plasma AA concentrations were assessed at various time points. Serum cortisol concentrations and ACTH stimulation tests were used to detect CIRCI. RESULTS: There was no effect of drug on clinical signs or pro-inflammatory cytokine gene expression or production compared to controls at any time point. Administration of AA was associated with higher blood neutrophil counts 6 hours after LPS infusion (11.01 ± 1.02 K/µl) compared to other groups (8.99 ± 0.94 K/µL; P < .009). Adminstration of HC was associated with higher blood neutrophil counts 12 hours after LPS infusion (10.40 ± 0.75 K/µl) compared to other groups (6.88 ± 0.68 K/µl; P < .001). Serum cortisol increased from 5.11 ± 1.48 µg/dL before LPS administration to 9.59 ± 1.83 µg/dL 1 h after completion of LPS infusion (T1) without an effect of treatment (P = 0.59). CONCLUSIONS AND CLINICAL IMPORTANCE: Ascorbic acid and HC appeared to protect against LPS-induced neutrophil depletion and could be considered as adjunctive therapy in horses with endotoxemia.

Reactive oxygen species, glutathione, and vitamin E concentrations in dogs with hemolytic or nonhemolytic anemia.

BACKGROUND: Red blood cells (RBC) are uniquely susceptible to oxidative injury. Oxidative stress is both a cause for, and effect, of anemia in people but this has been minimally documented in dogs. OBJECTIVE: To describe direct and indirect markers of oxidative stress in anemic dogs. HYPOTHESIS: Anemic dogs will have oxidative stress when compared to healthy dogs. ANIMALS: Forty-seven dogs with anemia (10 with hemolytic anemia) and 70 healthy control dogs. METHODS: Prospective, cross-sectional study. Anemic dogs were identified from the patient population, and medical records were reviewed to classify the anemia as hemolytic or nonhemolytic. Flow cytometry was used to detect reactive oxygen species (ROS) in erythrocyte isolates. Reduced glutathione (GSH) concentrations were measured in both plasma and hemolysate samples, and vitamin E was measured in serum. RESULTS: Anemic dogs (both hemolytic and nonhemolytic) had significantly lower median RBC hemolysate GSH concentrations (3.1 µM [0.4-30.8]) when compared to healthy dogs (7.0 µM [0.5-29.7]; P = .03). Dogs with hemolytic anemia had significantly higher median plasma GSH (7.6 µM [0.4-17.8]) when compared to dogs with nonhemolytic anemia (1.6 µM [0.01-7.1]; P = .04) and healthy dogs (2.8 µM [0.1-29.9]; P < .0001). Reactive oxygen species were detectable in all samples, but there was no difference in ROS or vitamin E between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Oxidative stress is present in anemic dogs. Derangements in biomarkers of oxidative stress are different in dogs with hemolytic anemia and nonhemolytic anemia.

Assessment of urinary 15-F2 -isoprostanes in dogs with urothelial carcinoma of the urinary bladder and other lower urinary tract diseases.

BACKGROUND: The 15-F2 -isoprostanes are by-products of oxidative stress and are increased in the urine of people with lower urinary tract diseases (LUTD), especially urinary neoplasia. Urothelial carcinoma (UC) is the most common urinary neoplasm in dogs. Earlier detection of UC by noninvasive means could lead to improved outcomes. Urinary 15-F2 -isoprostanes potentially could provide this means, but have not been evaluated in dogs with UC. OBJECTIVE: The objective of this study was to measure urinary 15-F2 -isoprostanes in dogs with UC and dogs with other LUTD. ANIMALS: One hundred seventeen dogs: 46 dogs with UC, 30 dogs with LUTD, and 25 control dogs. METHODS: Any dog that was presented with dysuria was eligible for inclusion. Diagnosis of UC was confirmed histologically. Urinalysis was performed in each case, and 15-F2 -isoprostanes quantified by gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NICI-MS) and normalized to urinary creatinine concentration. RESULTS: Dogs with urinary diseases (UC + LUTD) had higher median urinary 15-F2 -isoprostanes when compared to control dogs (5.92 ng/mg [range, 0.46-31.03] vs 3.73 [range, 1.8-7.98]; P = .02). Urinary 15-F2 -isoprostanes were similar in dogs with UC (5.33 ng/mg [range, 0.46-31.03]) compared to dogs with LUTD (6.29 ng/mg [range, 0.54-18.93]; P = .47) and control dogs (P = .06). Dogs with UC had higher qualitative measures of proteinuria (P = .004), hematuria (P = .01), and epithelial cells on urinalysis (P = .002) compared to the other groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary F2 -isoprostanes are not useful for the detection of UC in dogs. Future research could evaluate urinary 15-F2 -isoprostanes as a marker of inflammation in disease progression and prognosis.

Feline urinary F2-isoprostanes measured by enzyme-linked immunoassay and gas chromatography-mass spectroscopy are poorly correlated.

15-F2T-isoprostanes are byproducts of lipid peroxidation and were determined to be the best marker of oxidative injury in a rodent model of oxidative stress. A previous study compared methods for measurement of urinary F2-isoprostanes (gas chromatography and negative ion chemical ionization-mass spectrometry, GC-NICI-MS; and ELISA) and found poor agreement in dogs, horses, and cows. Surprisingly, fair agreement between these methods was identified in a small population of cats. We evaluated the agreement between GC-NICI-MS and ELISA of urinary F2-isoprostanes in the urine of 50 mature cats ranging from healthy to systemically ill. All urine samples had detectable levels of F2-isoprostanes by both methods. Significant proportional bias and poor agreement were identified between the 2 methods (ρ = 0.364, p = 0.009) for all cats, and in subgroup analysis based on health status. The concentration of urinary F2-isoprostanes was significantly lower in systemically ill cats compared to healthy cats when measured by ELISA (p = 0.002) but not by GC-NICI-MS (p = 0.068). Our results indicate that GC-NICI-MS and ELISA have poor agreement when measuring urinary F2-isoprostanes in cats.

Diagnosis and management of a case of retroperitoneal eosinophilic sclerosing fibroplasia in a cat.

CASE SUMMARY: A 4-year-old neutered male cat was presented with a 2-month history of intermittent constipation that progressed to obstipation. Primary clinical findings included a large, multi lobulated mass in the caudodorsal abdomen, peripheral eosinophilia and hyperglobulinemia. Abdominal imaging revealed a multilobulated, cavitated mass in the sublumbar region. Exploratory celiotomy revealed multiple firm masses in the sublumbar retroperitoneal space causing ventral displacement and compression of the descending colon with extension of the masses into the pelvic canal. Histopathology was consistent with feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF). Aerobic culture was positive for Staphylococcus aureus. The cat was treated with prednisolone (2 mg/kg PO q24h), lactulose (0.5 g/kg PO q8h), amoxicillin/clavulanic acid (62.5 mg/cat PO q12h for 1 month) and fenbendazole (50 mg/kg PO q24h for 5 days). Six months postoperatively, the cat had no recurrence of clinical signs. Repeat evaluation and imaging at day 732 postoperatively revealed marked improvement of the abdominal mass, resolution of peripheral eosinophilia and no clinical signs with continued prednisolone therapy (0.5 mg/kg PO q24h). RELEVANCE AND NOVEL INFORMATION: This is a report of a primary extramural FGESF lesion, and the first description of characteristics of FGESF on CT. Previous evidence suggests that the most favorable outcomes require immunosuppressive therapy and complete surgical excision; however, this case demonstrates a favorable outcome with medical management alone.

Comparison of metabolomics and platelet aggregometry between Plavix and generic clopidogrel in cats: a pilot study.

OBJECTIVES: This pilot study sought to assess the metabolism of Plavix (Bristol-Myers Squibb/Sanofi) and generic clopidogrel in cats, using a novel assay for the measurement of clopidogrel, clopidogrel carboxylic acid (CCA) and clopidogrel active metabolite (CAM-D). METHODS: This was a prospective, randomized, double-blind study. Four healthy, skeletally mature cats were enrolled into the study. There were two treatment phases during which cats received either Plavix or generic clopidogrel at a dosage of 18.75 mg PO q24h for 7 days with a 2 week washout between phases. During each phase, plasma concentrations of parent drug and active and inactive metabolites were measured along with impedance platelet aggregometry in response to adenosine diphosphate (ADP). RESULTS: The ratio of CAM-D between generic clopidogrel and Plavix was 0.83 (equivalence reference 1.00, 90% confidence interval 0.80-1.25). Inhibition of ADP-induced platelet aggregation was variable, with two cats classified as non-responders in both treatment phases. The concentrations of CAM-D were not predictive of aggregometry-based responsiveness to either formulation of clopidogrel. CONCLUSIONS AND RELEVANCE: This is the first study comparing Plavix and generic clopidogrel in cats. Administration of the generic formulation resulted in comparable plasma concentrations of clopidogrel active metabolite when compared with Plavix.

Assessing Academic Self-Efficacy, Knowledge, and Attitudes in Undergraduate Physiology Students.

Academic self-efficacy affects the success of students in the sciences. Our goals were to develop an instrument to assess the self-efficacy and attitudes toward science of students in an undergraduate physiology course. We hypothesized 1) that our instrument would demonstrate that students taking this course would exhibit greater self-efficacy and more positive attitudes toward science than students in a non-science undergraduate course, and 2) that the physiology students' self-efficacy and attitudes would improve after completing the course. A 25-question survey instrument was developed with items investigating demographic information, self-efficacy, content knowledge, confidence, and attitudes regarding science. Students in either an undergraduate physiology course (Group P) or a history course (Group H) completed the survey. Forty-eight students in Group P completed both PRE- and POST-class surveys, while 50 students in Group H completed the pre-class survey. The academic self-efficacy of Group P as assessed by the PRE-survey was significantly higher than Group H (p=0.0003). Interestingly, there was no significant difference between groups in content knowledge in the PRE-survey. The self-efficacy of Group P was significantly higher as assessed by the POST-survey, when compared to the PRE-survey (p<0.0001) coincident with an improvement (p<0.001) in content knowledge for Group P in the POST-survey. This study established a survey instrument with utility in assessing self-efficacy, attitudes, and content knowledge. Our approach has applicability to studies designed to determine the impact of instructional variables on academic self-efficacy, attitudes, and confidence of students in the sciences.

Evaluation of baseline cortisol concentration to monitor efficacy of twice-daily administration of trilostane to dogs with pituitary-dependent hyperadrenocorticism: 22 cases (2008-2012).

OBJECTIVE: To evaluate use of cortisol concentration prior to ACTH stimulation (baseline) to monitor efficacy of twice-daily administration of trilostane to dogs with pituitary-dependent hyperadrenocorticism (PDH). DESIGN: Retrospective case series. ANIMALS: 22 dogs with PDH. PROCEDURES: The database of a veterinary hospital was searched to identify dogs with PDH that were treated with the FDA-approved veterinary formulation of trilostane twice daily between January 1, 2008, and December 31, 2012. For each dog, signalment and details regarding each hospital visit including comorbidities, electrolyte concentrations, and clinical signs were extracted from the record. For each ACTH stimulation test performed, the respective correlations between baseline cortisol concentration and the cortisol concentration after ACTH stimulation (ACTH-stimulated cortisol concentration) and resultant decision regarding trilostane dose adjustment were determined. Excessive suppression of cortisol production was defined as an ACTH-stimulated cortisol concentration < 2.0 µg/dL. The ability of various baseline cortisol concentrations to predict whether a dog had excessive suppression of cortisol production was determined. RESULTS: 109 ACTH stimulation tests were performed for the 22 dogs. A baseline cortisol concentration > 3.2 µg/dL predicted that ACTH-stimulated cortisol concentration would be ≥ 2.0 µg/dL with 100% certainty; however, 14 of 64 tests with a baseline cortisol concentration > 3.2 µg/dL had an ACTH-stimulated cortisol concentration ≤ 3.2 µg/dL, which was suggestive of inadequate adrenocortical cortisol reserves. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that baseline cortisol concentration should not be used as the sole monitoring tool for management of dogs with PDH treated with trilostane twice daily.

Treatment of canine meningoencephalomyelitis of unknown aetiology with mycophenolate mofetil and corticosteroids: 25 cases (2007-2012).

The use of mycophenolate mofetil (MMF) for a variety of immune-mediated diseases in veterinary medicine has been described. However, there is only a small number of cases documenting its use in dogs with meningoencephalomyelitis of unknown aetiology (MUE). We hypothesized that the use of MMF and corticosteroids in dogs with MUE results in comparable survival data to other published treatment protocols and is associated with limited adverse effects. A retrospective study of medical case records of dogs clinically diagnosed with MUE recorded signalment, neuroanatomic localization, magnetic resonance imaging findings, cerebrospinal fluid analysis results, medications administered, follow-up neurologic examinations, survival and adverse events. Variables were compared between dogs which were treated with MMF within 30 days of diagnosis (immediate group) vs. dogs in which MMF therapy was started >30 days after diagnosis (delayed group). Twenty-five cases of MUE were identified. The overall median survival time from diagnosis was 731 days (range 43-1672 days). After 1 month of MMF treatment, 92% of dogs showed improvement on a neurological examination. There was no significant effect of any recorded parameter on survival, including delayed vs. immediate initiation of MMF treatment. Dogs with delayed treatment had significantly lower clinical remission rates than dogs with immediate treatment at 6 months after starting MMF. Adverse events were identified in two cases (8%) and were characterized by mild gastrointestinal signs (vomiting and decreased appetite). Administration of MMF appears safe in dogs with MUE. The use of MMF results in comparable survival times to alternate immunosuppressive protocols.

Successful treatment of a cat with primary hypoadrenocorticism and severe hyponatremia with desoxycorticosterone pivalate (DOCP).

A 6-year-old, castrated male Siamese cat was diagnosed with primary hypoadrenocorticism, confirmed by an adrenocorticotopic hormone (ACTH) stimulation test documenting both hypocortisolism and hypoaldosteronism. The cat was successfully treated using a combination of prednisolone and desoxycorticosterone pivalate (DOCP). This case demonstrates that DOCP can be used successfully as mineralocorticoid supplementation in cats with hypoadrenocorticism and may have a longer therapeutic duration than that in dogs.

Traitement réussi d'un chat atteint d'hypoadrénocorticisme primaire et d'hyponatrémie à l'aide de pivalate de désoxycorticostérone (DOCP). Un diagnostic d'hypoadrénocorticisme primaire a été posé pour un chat Siamois castré âgé de 6 ans et confirmé par un test de stimulation de l'hormone adrénocorticotope (ACTH) qui a documenté l'hypocortisolisme et l'hypoaldostéronisme. Le chat a été traité avec succès à l'aide d'une combinaison de prednisolone et de pivalate de désoxycorticostérone (DOCP). Ce cas démontre que le DOCP peut être utilisé avec succès en tant que supplément de minéralocorticoïdes chez les chats atteints d'hypoadrénocorticisme et peut présenter une durée thérapeutique plus longue que chez les chiens.(Traduit par Isabelle Vallières).