Journal of Veterinary Internal Medicine最新文献

Background: Chronic gingivostomatitis in cats (FCGS) is a moderately to severely painful condition, potentially caused by inadequate immune response to oral antigenic stimulation. Salivary peptidome analysis can identify inflammatory protein mediators and pathways involved in oral mucosal immune activation and may indicate potential therapeutic options for FCGS.

Objective: Evaluate the diversity and abundance of salivary peptides in cats with FCGS using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and nanoscale liquid chromatography-tandem mass spectrometry (nano LC-MS/MS).

Animals: Thirty-two cats with FCGS and 18 healthy controls.

Methods: Case-control cross-sectional study. We compared the salivary peptide profiles of diseased and healthy cats. The diagnosis of FCGS was confirmed by histopathology. Saliva samples were analyzed for viral infections using polymerase chain reaction (PCR), peptide mass fingerprint (PMF) using MALDI-TOF MS, and peptide identification using nano LC-MS/MS.

Results: Distinct clusters of peptide profiles were observed between groups. In FCGS, 26 salivary peptides were altered, including apolipoprotein A1, nuclear receptor subfamily 1 group I member 3, fibrinogen alpha chain, interleukin 2 receptor gamma, interleukin 23 receptor, hemoglobin subunit alpha, and serpin peptidase inhibitor clade A (alpha-1 antiproteinase, antitrypsin) member 12, protein-tyrosine-phosphatase, and cholinergic receptor nicotinic alpha 10 subunit. Protein-anti-inflammatory drug interaction networks were observed.

Conclusions and clinical importance: Peptide mass fingerprint and peptide profiles identified distinct clusters between FCGS and healthy cats. The 9 novel salivary peptide markers were associated with the JAK/STAT and PI3K/Akt pathways and immune responses. These potentially noninvasive biomarkers may facilitate understanding of FCGS pathophysiology and guide future therapeutic research.

Background: Phenylbutazone is prescribed for laminitis-associated pain and decreases glucose and insulin responses to an oral glucose test (OGT) in horses with insulin dysregulation (ID).

Hypothesis/objectives: Investigate the effect of phenylbutazone administration on the enteroinsular axis in horses.

Animals: Sixteen horses, including 7 with ID.

Methods: Randomized cross-over study design, with horses assigned to treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). On Day 9 of treatment, an OGT was conducted, followed by a 10-day washout period, administration of the alternative treatment, and repetition of the OGT. Glucose-dependent insulinotropic polypeptide (GIP), and active glucagon-like peptide 1 and 2 (aGLP-1 and GLP-2) concentrations were determined by ELISA. The effects of ID status and treatment on peptide concentrations were assessed using t tests and analyses of variance.

Results: Horses with ID had significantly higher maximum GIP concentrations (Cmax) than controls (median, 279.1; interquartile range [IQR], 117.5-319.4 pg/mL vs median, 90.12; IQR, 74.62-116.5 pg/mL; P = .01), but no significant effect of ID was detected on aGLP-1 and GLP-2 concentrations. In horses with ID, phenylbutazone treatment significantly decreased GIP Cmax compared with placebo (168.1 ± 59.26 pg/mL vs 242.8 ± 121.8 pg/mL; P = .04), but no significant effect of phenylbutazone was detected on aGLP-1 and GLP-2 concentrations.

Conclusion and clinical importance: Glucose-dependent insulinotropic polypeptide, aGLP-1 and GLP-2 do not mediate the decrease in glucose and insulin concentrations observed after phenylbutazone administration. Only GIP was repeatedly associated with ID status, calling into question the role of the enteroinsular axis in ID.

Background: Angiotensin-converting enzyme inhibitors (ACEi) have the potential to cause worsening renal function (WRF). Therefore, reevaluation of renal function is recommended 1-2 weeks after starting ACEi therapy.

Objectives: To identify risk factors for WRF in dogs receiving ACEi for cardiac diseases, proteinuria, or systemic hypertension.

Animals: A total of 156 client-owned dogs that received ACEi were included.

Methods: Serum creatinine concentration was determined at the initial presentation and first reevaluation to detect and grade WRF (increase in sCr ≥ 0.3 mg/dL). Grade 1 (nonazotemic), 2 (mild), and 3 (moderate to severe) WRF were characterized by sCr remaining ≤1.6 mg/dL, 1.7-2.5 mg/dL increase, and 2.6-5.0 mg/dL increase, respectively. Demographic and serum chemistry data, such as total protein, albumin, blood urea nitrogen, creatinine, symmetric dimethylarginine, glucose, triglyceride, total cholesterol concentrations, and serum electrolyte concentrations at first presentation, were evaluated. Multivariable modeling was performed to identify risk factors for WRF after treatment with ACEi.

Results: Worsening renal function was identified in 27/156 (17%, 95% confidence interval [CI], 0.11-0.23) dogs after ACEi treatment. It was classified as Grades 1, 2, and 3 in 17, 2, and 8 dogs, respectively. The only significant factors associated with WRF in dogs receiving ACEi were concurrent administration of furosemide (odds ratio, 5.05; 95% CI, 2.05-12.4; P < .001) and pre-existing azotemia (odds ratio, 3.21; 95% CI, 1.28-8.03; P = .01).

Conclusions and clinical importance: Although WRF is uncommon and mild, ACEi should be cautiously prescribed in dogs receiving furosemide or those with pre-existing azotemia.

Background: Protothecosis in dogs is a rare, yet emerging disease, distinguished by its often-aggressive clinical course and high fatality rate. Our study was conducted to enhance treatment protocols for affected dogs by better understanding the genetic diversity and drug resistance patterns of Prototheca species.

Objectives: To identify species and drug susceptibility profiles of an international collection of 28 Prototheca strains isolated from cases of protothecosis in dogs.

Animals: None.

Methods: Retrospective study. Species-level identification was made for isolates from 28 dogs in 6 countries by molecular typing with the partial cytb gene as a marker. For the determination of minimum inhibitory concentrations (MICs) and minimum algicidal concentrations (MACs), the Clinical Laboratory Standards Institute (CLSI) protocol (M27-A3) was used.

Results: Prototheca bovis was the most prevalent species, accounting for 75% (21/28) of the cases, followed by P. wickerhamii (18%; 5/28) and P. ciferrii (7%; 2/28). Of the 6 drugs tested, efinaconazole (EFZ) was the most potent in vitro, with its median MIC and MAC values equal to 0.125 mg/L. The lowest activity was found for fluconazole (FLU), with MIC and MAC medians of 48 mg/L and 64 mg/L, respectively.

Conclusions and clinical importance: Our study identifies P. bovis as the species that most frequently causes protothecosis in dogs, which suggests the possibility of cross-species infection from other animals, especially cows. Additionally, it indicates that EFZ could be used in the treatment of infection in the colon.

Background: Obesity is a risk factor for diabetes mellitus, which commonly coexists with pancreatitis in cats. However, obesity has not previously been associated with pancreatitis in cats.

Objectives: To evaluate factors affecting serum concentrations of pancreatic lipase immunoreactivity (fPLI), trypsin-like immunoreactivity (fTLI), cobalamin and folate in clinically healthy lean, overweight and obese, or diabetic cats.

Animals: Seventy-nine client-owned cats (27 healthy lean [LN, BCS 4-5/9], 30 healthy overweight and obese [OW, BCS 7-9/9], and 22 diabetic [DM]) were included.

Methods: Cross-sectional study. The cats underwent physical examination, and blood tests. Linear regression models compared differences in fPLI, fTLI, cobalamin, and folate concentrations. Fisher's exact test assessed the proportions of cats with fPLI and fTLI indicative of pancreatitis, and hypocobalaminemia. A random forest algorithm identified explanatory variables for cats having fPLI levels indicative of pancreatitis.

Results: No LN cats, while 6/30 (20%) of OW and 10/22 (45%) of DM cats had fPLI concentrations indicative of pancreatitis. Body condition score (P = .02) and body weight (P = .002) were positively associated with fPLI levels in LN and OW cats. Higher fPLI, and lower cobalamin concentrations were associated with higher age across groups.

Conclusions and clinical importance: Body condition score and body weight were associated with higher fPLI levels in nondiabetic cats. A larger proportion of OW and DM cats had fPLI concentrations indicative of pancreatitis compared to LN cats. Whether this indicates subclinical pancreatitis remains to be determined. Hypocobalaminemia was less frequent in OW compared to DM cats.

Background: Gallbladder mucocele (GBM) is a common disease in the canine gallbladder. Although the pathogenesis of GBM remains unclear, we recently reported that the excessive accumulation of mucin in the gallbladder is not a result of overproduction by gallbladder epithelial cells (GBECs).

Hypothesis/objectives: Changes in the function of GBECs other than the production of mucin are associated with the pathogenesis of GBM. We performed an RNA sequencing (RNA-seq) analysis to comprehensively search for abnormalities in gene expression profiles of GBECs in dogs with GBM.

Animals: Fifteen dogs with GBM and 8 dogs euthanized for reasons other than gallbladder disease were included.

Methods: The GBECs were isolated from gallbladder tissues to extract RNA. The RNA-seq analysis was performed using the samples from 3 GBM cases and 3 dogs with normal gallbladders, and the gene expression profiles were compared between the 2 groups. Differences in mRNA expression levels of the extracted differentially expressed genes (DEGs) were validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) using samples of 15 GBM cases and 8 dogs with normal gallbladders.

Results: Comparison of gene expression profiles by RNA-seq extracted 367 DEGs, including ANO1, a chloride channel associated with changes in mucin morphology, and HTR4, which regulates the function of chloride channels. The ANO1 and HTR4 genes were confirmed to be downregulated in the GBM group by RT-qPCR.

Conclusions and clinical importance: Our results suggest that GBM may be associated with decreased function of chloride channels expressed in GBECs.

Background: Knowledge about primary hypoadrenocorticism coexisting with immune-mediated thyroiditis (Schmidt's syndrome) in dogs is limited.

Objective: To evaluate thyroid function in dogs with naturally occurring hypoadrenocorticism before and during treatment.

Animals: Sixty-six client-owned dogs.

Methods: Measurement of canine thyroid stimulating hormone (cTSH), total thyroxine (T4), free thyroxine, and autoantibodies against thyroglobulin, T4, and total triiodothyronine.

Results: Thirty-eight dogs were assessed before and 28 during treatment. Follow-up data were available for 24/38 and 17/28 dogs, with median follow-up duration of 3.8 years (range, <1.0-8.8 years) and 4 years (range, 1.1 weeks to 10.5 years), respectively. Canine thyroid stimulating hormone was above the reference range at the time of diagnosis of hypoadrenocorticism in 10 of 38 dogs but decreased into the reference range in 7 for which follow-up data was available. Hypothyroidism was confirmed in 5 dogs at a median age of 11 years (range, 7-15 years). In 4 dogs, the condition was diagnosed after a median treatment duration of 5.75 years (range, 2.6-10 years), while in 1 dog, the diagnosis was made concurrently. One dog had detectable thyroid autoantibodies.

Conclusions and clinical relevance: Hypothyroidism occurs as a rare concurrent condition in dogs with hypoadrenocorticism, potentially at any phase of treatment. Close monitoring of cTSH levels in these dogs could be beneficial, as early changes might indicate the onset of hypothyroidism. The low prevalence of detectable thyroid autoantibodies suggests that nonimmune mechanisms might contribute to thyroid dysfunction.

Understanding and incorporating evidence-based veterinary medicine (EBVM) into clinical practice and research continues to pose a challenge for our profession despite over 2 decades of increasing awareness of this concept. Reasons for this include a lack of understanding of its importance to the practice of medicine, veterinary literature that often fails to adhere to evidence-based standards, inadequate attention to teaching EBVM at the university level, and the inherent reluctance of clinicians to alter historical practice styles. For many practitioners, EBVM continues to be an abstract concept they believe requires advanced training in statistics and epidemiology resulting in them relying on less robust sources for clinical guidance. This unfortunately results in suboptimal care for our patients and delayed medical advancements for our profession. As part of the 20th anniversary of the founding of the Evidence-Based Veterinary Medicine Association (EBVMA), we are refocusing our efforts to highlight the need for dedicated teaching of EBVM at the university level, for rigorous adherence to established research reporting guidelines, for expansion of EBVM infrastructure, and for the provision of easily accessible tools that permit clinicians to incorporate EBVM into their daily practice. As the quality of veterinary literature improves, so too will development of more effective clinical practice guidelines that ultimately can be widely adopted if they are flexible enough to support the triadic relationship between veterinarians, our clients and our patients. Ultimately, EBVM is not an end unto itself, but rather a means to improve the quality of care we provide our patients.

Background: Myoclonus has been described in aging Cavalier King Charles Spaniels (CKCS), but the natural course of the disease and response to treatment have not been described.

Objectives: Report the clinical features and course of myoclonus in CKCS.

Animals: Twenty-seven caregivers provided questionnaire responses at a median of 24 months after the onset of myoclonus in their CKCS. Fifteen caregivers completed a second follow-up questionnaire at a median of 17 months after submission of the first questionnaire.

Methods: The caregivers of affected CKCS were invited to provide video footage for review. Owners of CKCS with videos demonstrating myoclonus then completed the online questionnaire for further evaluation. A second shortened questionnaire was sent to participants at least 6 months after completion of the first.

Results: Most CKCS displayed spontaneous myoclonus affecting predominantly the head (25/27). Overall, the majority had episodes that increased in frequency (20/27) and severity (17/27). Eighteen dogs had developed changes in behavior since the onset of myoclonus. These dogs were typically older and had experienced myoclonic episodes for longer than dogs without behavioral changes. Generalized epileptic seizures were reported in 4/27 dogs. Ten dogs received medical treatment. Eight were prescribed levetiracetam; all had an initial decrease in episode frequency, but a subsequent increase in both frequency and severity of episodes was common.

Conclusions and clinical importance: Myoclonus in CKCS tends to progress in frequency and severity regardless of treatment. Progressive behavioral changes suggestive of cognitive decline are common. These findings support the possibility of an underlying neurodegenerative process.