ResearchPad - standard-article https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[CRISPRi-mediated functional analysis of lung disease-associated loci at non-coding regions]]> https://www.researchpad.co/article/elastic_article_16193 Genome-wide association studies have identified lung disease-associated loci; however, the functions of such loci are not well understood in part because the majority of such loci are located at non-coding regions. Hi-C, ChIP-seq and eQTL data predict potential roles (e.g. enhancer) of such loci; however, they do not elucidate the molecular function. To determine whether these loci function as gene-regulatory regions, CRISPR interference (CRISPRi; CRISPR/dCas9-KRAB) has been recently used. Here, we applied CRISPRi along with Hi-C, ChIP-seq and eQTL to determine the functional roles of loci established as highly associated with asthma, cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Notably, Hi-C, ChIP-seq and eQTL predicted that non-coding regions located at chromosome 19q13 or chromosome 17q21 harboring single-nucleotide polymorphisms (SNPs) linked to asthma/CF/COPD and chromosome 11p15 harboring an SNP linked to IPF interact with nearby genes and function as enhancers; however, CRISPRi indicated that the regions with rs1800469, rs2241712, rs12603332 and rs35705950, but not others, regulate the expression of nearby genes (single or multiple genes). These data indicate that CRISPRi is useful to precisely determine the roles of non-coding regions harboring lung disease-associated loci as to whether they function as gene-regulatory regions at a genomic level.

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<![CDATA[Evaluation of toceranib for treatment of apocrine gland anal sac adenocarcinoma in dogs]]> https://www.researchpad.co/article/N01458150-0f51-4d25-bca9-1fe32d37f324

Abstract

Background

There is no widely accepted standard medical treatment for apocrine gland anal sac adenocarcinoma (AGASACA) in dogs. Targeted agents such as toceranib may be effective in treatment of AGASACA, but the number of clinical reports investigating its efficacy is limited.

Hypothesis/Aim

To evaluate the efficacy of toceranib treatment of AGASACA in dogs, and to assess prognostic factors in the study population. Our hypothesis was that toceranib would provide a clinical benefit in the treatment of dogs with AGASACA.

Animals

Thirty‐six client‐owned dogs with either a cytologic or histologic diagnosis of AGASACA that were treated with toceranib alone or in combination with surgery, nonconcurrent chemotherapy or both.

Methods

Retrospective study.

Result

The median progression‐free survival (PFS) and overall survival time (OST) for the study population was 313 days and 827 days, respectively. A clinical benefit from toceranib treatment was observed in 69% of dogs, with 20.7% of dogs experiencing partial response and 48.3% of dogs experiencing stable disease. Dogs that responded to toceranib treatment had significantly prolonged PFS and OST. Hypercalcemia was a negative prognostic factor for clinical outcomes.

Conclusions

Toceranib is effective in the treatment of AGASACA in dogs. Prospective, controlled clinical trials are needed to determine the efficacy of toceranib in comparison to other treatment protocols for dogs with AGASACA.

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<![CDATA[Comparison of 2 collection methods for cerebrospinal fluid analysis from standing, sedate adult horses]]> https://www.researchpad.co/article/N471b5040-d570-4ef3-87d6-927d690a7b22

Abstract

Background

Cerebrospinal fluid (CSF) analysis is an important component of the evaluation of horses with neurologic disease. Lumbosacral (LS) centesis is routine, but CSF is also collected from the space between the first and second cervical vertebrae (C1‐C2).

Objectives

To compare collection times, CSF cytology results, and equine protozoal myelitis (EPM) titers of CSF collected from the C1‐C2 and LS sites.

Animals

Fifteen university‐owned adult horses with no evidence of neurologic disease, and 9 horses with signs of neurologic disease: 3 university‐owned and 6 client‐owned.

Methods

Prospective study. Cerebrospinal fluid collection from the LS space and C1‐C2 space of each horse was performed in randomized order. Continuous data were analyzed using mixed‐effects linear models and count data using mixed‐effects negative binomial regression. Statistical significance was set at P < .05.

Results

Cerebrospinal fluid collected from the C1‐C2 site had a significantly lower mean protein concentration (49 [95% CI: 43‐55.8] mg/dL C1‐C2 versus 52.1 [95% CI: 45.7‐59.3] mg/dL LS; P = .03) and red blood cell count (6 [95% CI: 2‐16] cells/μL versus 33 [95% CI: 13‐81] cells/μL; P = .02). Collection time, total nucleated cell count, EPM titers, and serum:CSF EPM titer ratios were not significantly different between collection sites.

Conclusions and Clinical Importance

Cerebrospinal fluid from the C1‐C2 space provides an acceptable alternative to LS CSF collection with decreased likelihood of clinically important blood contamination of samples.

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<![CDATA[Agreement of stall‐side and laboratory major crossmatch tests with the reference standard method in horses]]> https://www.researchpad.co/article/Ne5c2f006-1372-403b-9633-cc73c039d7bd

Abstract

Background

Crossmatching is used to prevent life‐threatening transfusion reactions in horses. Laboratory methods are laborious and technically challenging, which is impractical during emergencies.

Hypothesis/Objectives

Evaluate agreement between a stall‐side crossmatch kit (KIT) and a laboratory method (LAB) in horses with known and unknown blood types.

Animals

Twenty‐four blood‐typed and alloantibody‐screened healthy adult horses (Aim 1) and 156 adult horses of unknown blood type (Aim 2).

Methods

Prospective, blinded study. Expected positive (n = 35) and negative (n = 36) crossmatches among 24 antibody and blood‐typed horses were used to determine sensitivity and specificity of KIT and LAB against the reference method. Agreement in 156 untyped horses was evaluated by reciprocal crossmatch (n = 156).

Results

Sensitivity (95% confidence interval [CI]) for LAB and KIT compared with expected reactions was 77.1% (59.9%‐90.0%) and 91.4% (77.0%‐98.2%), and specificity 77.8% (60.9%‐89.9%) and 73.5% (55.6%‐87.1%), respectively. The KIT was 100% sensitive for Aa reactions; LAB was 100% sensitive for Qab; and both were 100% sensitive for Ca. Cohen's κ agreement for LAB and KIT with expected positive and negative reactions (n = 71) was moderate (0.55 [0.36‐0.74]) and substantial (0.65 [0.47‐0.82]), respectively. Agreement was fair comparing LAB with KIT in Aim 1 (0.30 [0.08‐0.52]) and in untyped horses in Aim 2 (0.26 [0.11‐0.41]).

Conclusions and Clinical Importance

Agreement between KIT and LAB with expected reactions was blood type dependent. Performance of both methods depends on blood type prevalence.

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<![CDATA[Concurrent use of rabacfosadine and L‐asparaginase for relapsed or refractory multicentric lymphoma in dogs]]> https://www.researchpad.co/article/Naf5d600e-36a8-43b1-aaec-635aa5ebbb22

Abstract

Background

Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naïve and previously treated dogs. Its use in combination with L‐asparaginase (L‐ASP) has not been studied.

Hypothesis/Objectives

To evaluate the safety and efficacy of L‐ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma.

Animals

Fifty‐two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin‐based chemotherapy protocol.

Methods

Open‐label, multicenter, prospective single‐arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L‐asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB.

Results

The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression‐free survival time (MPFS) was 63 days (range 5‐428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44‐428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L‐ASP were negative prognostic factors on multivariate analysis.

Conclusions and Clinical Importance

Concurrent RAB/L‐ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed.

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<![CDATA[Comparison of cerebellomedullary and lumbar cerebrospinal fluid analysis in dogs with neurological disease]]> https://www.researchpad.co/article/Nf49dc614-4199-4281-a64f-bbf8070fbb6d

Abstract

Background

Cerebrospinal fluid (CSF) analysis aids in categorizing underlying disease processes in patients with neurologic disease. Convention suggests that CSF should be collected caudal to the lesion. However, little evidence exists to justify this assertion.

Hypothesis/Objectives

Evaluate the clinicopathologic differences between CSF collected from the cerebellomedullary (CM) and lumbar cisterns in dogs presented for evaluation of neurologic disease.

Animals

Fifty‐one client‐owned dogs undergoing magnetic resonance imaging (MRI) and CSF collection for investigation of neurologic disease.

Methods

Cerebrospinal fluid was prospectively collected from the CM and lumbar cisterns in all patients. The total protein (TP) concentration, red blood cell (RBC) count, and total nucleated cell count (TNCC) were analyzed within 30 minutes of collection. Results and cytology findings were interpreted by a single pathologist.

Results

Fifty‐one paired samples were collected. The TNCC (P < .001), RBC (P < .001), and TP (P < .001) were different between collection sites. When grouped by neurolocalization, TP (intracranial, P < .001; cervical, P < .001; thoracolumbar, P < .001) and RBC (intracranial, P < .001; cervical, P ≤ .002; thoracolumbar, P = .006) counts were significantly different. The TNCC was significantly different in the cervical (P = .04) and thoracolumbar localizations (P = .004) but not for intracranial (P = .30) localizations. The pathologist's interpretation differed between sites in 66.7% of the cases (34/51).

Conclusions

In dogs with lesions that neurolocalized to the brain or cervical spinal cord, there may be clinical benefit in collecting fluid from both the CM and lumbar cisterns. In dogs with thoracolumbar myelopathy, CSF collected from the CM cistern may not be representative of the underlying disease process.

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<![CDATA[Fecal microbiota in horses with asthma]]> https://www.researchpad.co/article/N8f164233-5f16-4ade-8e9c-e5780164c976

Abstract

Background

Gastrointestinal microbiota can be influenced by several factors, including diet and systemic inflammation, and in turn could act as a modulator of the allergic response. Fecal microbiota of horses with asthma has not been described.

Hypothesis/Objectives

Analyze the bacterial fecal microbiota of horses with and without asthma under different environment and diet conditions, during both remission and exacerbation.

Methods

Prospective observational study. Feces from 6 asthmatic and 6 healthy horses were collected under 3 different conditions: on pasture, housed indoors receiving good quality hay (“good hay”), and housed indoors receiving poor quality hay (“dusty hay”). Sequencing was performed using an Illumina MiSeq platform and data were processed using the software mothur v.1.41.3 and LEfSe.

Results

In horses with asthma, low‐abundance bacteria were more affected by changes in environment and diet (ie, when horses were experiencing an exacerbation), as shown by changes in membership and results from the LEfSe analysis. There was a significant increase in the relative abundance of Fibrobacter in healthy horses eating hay, a change that was not observed in horses with asthma.

Conclusions and Clinical Importance

The intestinal microbiota of horses with asthma does not adapt in the same way to changes in diet and environment compared to the microbiota of healthy horses. Mechanisms explaining how airway obstruction and inflammation could influence the intestinal microbiota and how in turn this microbiota could modulate systemic inflammation in asthmatic horses deserves further investigation.

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<![CDATA[Effects of arginine and ornithine supplementation to a high‐protein diet on selected cellular immune variables in adult cats]]> https://www.researchpad.co/article/N4118e4e4-0918-47cd-93d7-5b7bd3090c6a

Abstract

Background

Dietary protein and amino acid intake and composition can modulate immune function.

Objectives

To evaluate the effects of high‐protein intake and arginine and ornithine supplementation on feline immune cells.

Animals

Ten healthy cats.

Methods

Experimental study. Cats received a high‐protein basal diet as a single daily meal. A crossover design was applied with treatments being basal diet (w/o); basal diet with arginine supplementation (+50, 75, 100% compared to the arginine provision by the basal diet; Arg 1‐3); and basal diet with ornithine supplementation (+100, 150, 200% compared to the arginine provision by the basal diet; Orn 1‐3). Blood samples were collected at the end of each 11‐day treatment period.

Results

Mitogen‐stimulated proliferative activity of blood leukocytes revealed a quadratic effect for the dietary supplementation of arginine (P = .02) and ornithine (P = .03) (means for ConA‐stimulation: w/o = 6.96; Arg 1 = 9.31; Arg 2 = 11.4; Arg 3 = 8.04; Orn 1 = 15.4; Orn 2 = 9.43; Orn 3 = 9.28; pooled SEM: 0.96). The number (% gated) of phagocytic granulocytes linearly decreased with increasing dietary concentrations of arginine (P = .05) and ornithine (P = .03) (means: w/o = 95.5; Arg 1 = 93.0; Arg 2 = 92.5; Arg 3 = 92.6; Orn 1 = 92.6; Orn 2 = 92.6; Orn 3 = 91.5; pooled SEM = 0.44).

Conclusions and Clinical Importance

This study could demonstrate immunomodulating properties of dietary arginine and ornithine in cats.

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<![CDATA[Accuracy of transcranial magnetic stimulation and a Bayesian latent class model for diagnosis of spinal cord dysfunction in horses]]> https://www.researchpad.co/article/N5988fc9c-73c3-4cdc-aeed-768491f4594f

Abstract

Background

Spinal cord dysfunction/compression and ataxia are common in horses. Presumptive diagnosis is most commonly based on neurological examination and cervical radiography, but the interest into the diagnostic value of transcranial magnetic stimulation (TMS) with recording of magnetic motor evoked potentials has increased. The problem for the evaluation of diagnostic tests for spinal cord dysfunction is the absence of a gold standard in the living animal.

Objectives

To compare diagnostic accuracy of TMS, cervical radiography, and neurological examination.

Animals

One hundred seventy‐four horses admitted at the clinic for neurological examination.

Methods

Retrospective comparison of neurological examination, cervical radiography, and different TMS criteria, using Bayesian latent class modeling to account for the absence of a gold standard.

Results

The Bayesian estimate of the prevalence (95% CI) of spinal cord dysfunction was 58.1 (48.3%‐68.3%). Sensitivity and specificity of neurological examination were 97.6 (91.4%‐99.9%) and 74.7 (61.0%‐96.3%), for radiography they were 43.0 (32.3%‐54.6%) and 77.3 (67.1%‐86.1%), respectively. Transcranial magnetic stimulation reached a sensitivity and specificity of 87.5 (68.2%‐99.2%) and 97.4 (90.4%‐99.9%). For TMS, the highest accuracy was obtained using the minimum latency time for the pelvic limbs (Youden's index = 0.85). In all evaluated models, cervical radiography performed poorest.

Clinical Relevance

Transcranial magnetic stimulation‐magnetic motor evoked potential (TMS‐MMEP) was the best test to diagnose spinal cord disease, the neurological examination was the second best, but the accuracy of cervical radiography was low. Selecting animals based on neurological examination (highest sensitivity) and confirming disease by TMS‐MMEP (highest specificity) would currently be the optimal diagnostic strategy.

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<![CDATA[Renin‐angiotensin aldosterone profile before and after angiotensin‐converting enzyme‐inhibitor administration in dogs with angiotensin‐converting enzyme gene polymorphism]]> https://www.researchpad.co/article/N7b59e551-1604-4a60-af5c-743da47b756c

Abstract

Background

An angiotensin‐converting enzyme (ACE) gene polymorphism occurs in dogs; however, functional importance is not well studied.

Hypothesis

We hypothesized that dogs with the polymorphism would show alternative renin‐angiotensin aldosterone system (RAAS) pathway activation and classical RAAS pathway suppression before and after ACE‐inhibitor administration, as compared to dogs without the polymorphism that would show this pattern only after ACE‐inhibitor administration.

Animals

Twenty‐one dogs with mitral valve disease that were genotyped for the ACE gene polymorphism.

Methods

This retrospective study utilized stored samples from 8 ACE gene polymorphism‐negative (PN) dogs and 13 ACE gene polymorphism‐positive (PP) dogs before and after enalapril administration. Equilibrium analysis was performed to evaluate serum RAAS metabolites and enzyme activities. Results were compared before and after enalapril, and between groups.

Results

The classical RAAS pathway was suppressed and the alternative RAAS pathway was enhanced for both genotypes after administration of enalapril, with no differences before enalapril administration. Aldosterone breakthrough occurred in both PN (38%) and PP (54%) dogs despite angiotensin II suppression. Aldosterone was significantly higher (P = .02) in ACE gene PP dogs (median, 92.17 pM; IQR, 21.85‐184.70) compared to ACE gene PN dogs (median, 15.91 pM; IQR, <15.00‐33.92) after enalapril.

Conclusions and Clinical Importance

The ACE gene polymorphism did not alter baseline RAAS activity. Aldosterone breatkthrough in some dogs suggests nonangiotensin mediated aldosterone production that might be negatively influenced by genotype. These results support the use of aldosterone receptor antagonists with ACE‐inhibitors when RAAS inhibition is indicated for dogs, especially those positive for the ACE gene polymorphism.

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<![CDATA[Serum triglyceride and cholesterol concentrations and lipoprotein profiles in dogs with naturally occurring pancreatitis and healthy control dogs]]> https://www.researchpad.co/article/N0cee5029-1f67-418f-8dbb-a8731eb7499c

Abstract

Background

Previous studies have reported an association between hyperlipidemia and pancreatitis in dogs, but details of this association remain poorly defined.

Hypothesis/Objectives

To compare serum triglyceride and cholesterol concentrations and lipoprotein profiles between dogs with naturally occurring pancreatitis and healthy dogs.

Animals

Seventeen dogs with a clinical diagnosis of pancreatitis (Group 1) and 53 healthy control dogs (Group 2).

Methods

Prospective case‐control study.

Results

In Group 1, 3/17 dogs (18%) had hypertriglyceridemia whereas in Group 2, 4/53 dogs (7.5%) had hypertriglyceridemia (odds ratio [OR], 2.63; 95% confidence interval [CI], 0.52‐13.14; P = .35). A significant difference was found in serum triglyceride concentrations between Group 1 (median, 67 mg/dL) and Group 2 (median, 54 mg/dL; P = .002). In Group 1, 4/17 dogs (24%) had hypercholesterolemia, whereas 1/53 (1.9%) dogs in Group 2 had hypercholesterolemia (OR, 16; 95% CI, 1.64‐155.5; P = .01). No significant difference was found in serum cholesterol concentrations between Group 1 (median, 209 mg/dL) and Group 2 (median, 227 mg/dL; P = .56). Lipoprotein profiles were significantly different between Group 1 and Group 2 dogs (Eigenvalues, 0.6719; R 2 = 1.0; P = .001).

Conclusions and Clinical Importance

Most dogs with pancreatitis (>70%) had serum triglyceride and cholesterol concentrations within reference intervals. In the small percentage of dogs that had hypertriglyceridemia, hypercholesterolemia, or both, increases were mild. Important differences were identified in lipoprotein profiles between dogs with pancreatitis and healthy control dogs. Dogs with pancreatitis had higher low‐density lipoprotein fractions and lower triglyceride‐rich lipoprotein and high‐density lipoprotein fractions than healthy dogs.

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<![CDATA[Paraoxonase‐1 activity evaluation as a diagnostic and prognostic marker in horses and foals]]> https://www.researchpad.co/article/Nd5a6c708-3e5e-44cb-8d82-0b6591b89782

Abstract

Background

In several species, paraoxonase‐1 (PON‐1) decreases during inflammation, because of the presence of oxidative stress; its measurement recently has been validated in horses, but its role as a clinical biomarker is unknown.

Objectives

To evaluate sensitivity, specificity and likelihood ratio of PON‐1 activity to identify systemic inflammatory response syndrome (SIRS)‐positive horses or horses with a poor prognosis.

Animals

One hundred seventy‐two blood samples from 58 sick horses from 3 different veterinary hospitals.

Methods

In a cross‐sectional study, PON‐1 activity was measured upon admission and at 24‐hour intervals until discharge or death, and results were analyzed based on SIRS status and outcome.

Results

No statistically significant difference was found in median PON‐1 activity between SIRS and non‐SIRS cases or between survivors and non‐survivors except for mares, in which PON‐1 activity was significantly lower in SIRS‐positive horses (P = .05). The sensitivity of PON‐1 activity in identifying horses with SIRS or negative outcome was low (0.0%‐46.2% depending on the examined group) but its specificity was high (87.0%‐100.0%). However, when PON‐1 is low, the likelihood of death is 2.40‐3.89 times higher than the likelihood of survival. Repeated measurement of PON‐1 after treatment does not predict outcome.

Conclusions and Clinical Importance

Evaluation of PON‐1 activity in horses with inflammation might be advisable in the future, but only low activity at admission may be relevant in predicting SIRS or negative outcome.

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<![CDATA[Effect of radiotherapy on freedom from seizures in dogs with brain tumors]]> https://www.researchpad.co/article/N5e37fffe-ee73-4a60-9455-26233edd7b71

Abstract

Background

Seizures are a common presenting sign in dogs with brain tumors.

Hypothesis/Objectives

To investigate the effect of radiotherapy on freedom from brain tumor‐associated seizures and survival time in dogs.

Animals

Thirty‐two client‐owned dogs with brain tumor‐associated seizures; 18 received medical treatment and radiotherapy, 14 received medical treatment alone.

Methods

Multicenter retrospective study. Baseline characteristics (seizure semiology, magnetic resonance imaging [MRI] characteristics, and treatment) and duration of seizure freedom were recorded for the 2 treatment groups. Duration of seizure freedom between groups was compared (log‐rank test) using Cox's proportional hazard analysis, with baseline characteristics entered as covariates.

Results

The duration of seizure freedom and survival time were significantly longer in the radiotherapy group (P < .001), with a mean of 24 months (95% confidence interval [CI], 14.3‐33.8) versus 1.7 months in the control group (95% CI, 0.5‐2.9) and a mean of 34.6 months (95% CI: 25.2‐44.1) versus 6.2 months in the control group (95% CI, 2.6‐9.7) respectively. Baseline characteristics were not associated with duration of seizure freedom after the start of treatment. In the radiotherapy group, 5 dogs were euthanized during the study period because of causes other than seizures. In the control group, recurrence of seizures was observed before death in all dogs.

Conclusions and Clinical Importance

A longer period of seizure freedom and longer survival time was observed in dogs with brain tumors after radiotherapy compared to medical treatment only. The pathophysiological mechanisms of epileptogenesis and the effect of radiation therapy on seizure control are unclear to date. Further prospective studies are needed.

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<![CDATA[Abomasitis in calves: A retrospective cohort study of 23 cases (2006‐2016)]]> https://www.researchpad.co/article/N4f1c3d22-ec3c-4baf-bcff-ab29288ae182

Abstract

Background

Abomasitis is a syndrome affecting young milk‐fed calves. The current veterinary literature describes mainly its necropsy findings.

Objectives

To describe the clinical presentation, complementary tests, treatments, and case‐fatality rate of calves with a clinical diagnosis of abomasitis and to identify potential factors associated with outcome.

Methods

Observational retrospective cohort study (2006‐2016). Review of the medical records of calves <3 months of age presented with abdominal and abomasal distension for <7 days that were clinically diagnosed with abomasitis at the Faculty of Veterinary Medicine of the Université de Montréal. A follow‐up examination was conducted by telephone interview.

Animals

Twenty‐three calves clinically diagnosed with abomasitis.

Results

Median age of presentation was 3 days (range, 0‐62 days). The typical duration of the clinical course was <24 hours (15/23). On admission, the 2 most common clinical signs were anorexia (13/14) and positive succussion (13/14). Hyper‐l‐lactatemia (15/16) and increased γ‐glutamyl‐transferase activity (13/14) were the most common laboratory abnormalities. Hypoproteinemia (19/22) and a left shift (15/18) of the neutrophils also were observed. The short‐term case‐fatality rate was 52% (12/23). The clinical diagnosis was confirmed on all necropsied calves. Clostridium spp. and Escherichia coli were the most frequently isolated bacteria. Based on univariate statistical analysis, the surviving calves were significantly (P < .05) less hypothermic, less acidemic, less hyper‐l‐lactatemic, and had lower serum creatinine concentrations on admission than did the deceased calves.

Conclusions and Clinical Importance

In our study, abomasitis was associated with a guarded prognosis.

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<![CDATA[Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses]]> https://www.researchpad.co/article/Nc6ed3fd9-4440-4123-9313-e9287b824446

Abstract

Background

In humans, gabapentin an analgesic, undergoes non‐proportional pharmacokinetics which can alter efficacy. No information exists on the pharmacokinetics of dosages >20 mg/kg, escalating dosages or dose proportionality of gabapentin in horses.

Hypothesis and Objectives

Gabapentin exposure in plasma would not increase proportionally relative to the dose in horses receiving dosages ≥20 mg/kg. To assess the plasma pharmacokinetics of gabapentin after nasogastric administration of gabapentin at dosages of 10 to 160 mg/kg in adult horses.

Animals

Nine clinically healthy adult Arabian and Quarter Horses.

Methods

In a randomized blinded trial, gabapentin was administered by nasogastric intubation to horses at 10, 20 mg/kg (n = 3) and 60, 80, 120, 160 mg/kg (n = 6). Plasma was collected before and at regular times over 64 hours after administration of gabapentin. Gabapentin was quantified using a validated chromatographic method. Dose proportionality was estimated using a power model. Pharmacokinetic parameters were estimated using compartmental pharmacokinetic analysis.

Results

Plasma pharmacokinetics parameters of gabapentin were estimated after nasogastric administration at dosages of 10 to 160 mg/kg. Gabapentin plasma concentration increased with dose increments. However, the area under the concentration curve from zero to infinity and maximal plasma concentration did not increase proportionally relative to the dose in horses.

Conclusions and Clinical Importance

Gabapentin exposure in plasma is not proportional relative to the dose in horses receiving nasogastric dosages of 10 to 160 mg/kg.

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<![CDATA[Bacterial infection before and after stent placement in dogs with tracheal collapse syndrome]]> https://www.researchpad.co/article/N2406174a-365f-45b0-9561-17f7bfb06fd8

Abstract

Background

Dogs with tracheal stents often have positive airway bacterial cultures. The pathogenicity of these organisms and risk factors for infection have not been investigated.

Objective

Describe bacterial infection in dogs with tracheal collapse before and after tracheal stent placement.

Animals

Fifty‐three client‐owned dogs.

Methods

Retrospective review of medical records of dogs receiving tracheal stents with thoracic radiographs, tracheoscopy, and endotracheal lavage.

Results

There was no difference between the overall prevalence of dogs with positive bacterial cultures before (31/38; 82%) or after stent placement (24/31; 77%) (P = .67). An increased number of geriatric (17/28; 61%) and traditional‐type collapse (TTC) (16/26; 62%) dogs had positive pathogenic airway infections before stent placement, compared to young (8/25; 32%; P = .04) and malformation‐type collapse (MTC) dogs (9/27; 33%; P = .04). After tracheal stent placement, geriatric dogs had a 52% reduction in pathogenic bacteria infection frequency (P = .02) and dogs with TTC had a 56% reduction in pathogenic bacteria infection frequency (P = .01). Significant risk factors for pathogenic infection included a history of pneumonia (OR = 3.6; 95% CI, 0.28‐43.36) and cardiac disease (OR = 1.25; 95% CI, 0.16‐9.92) in geriatric dogs, and hepatomegaly in young dogs (OR = 1.5; 95% CI, 0.12‐19.44).

Conclusions and Clinical Importance

Tracheal stent placement does not increase the overall rate of pathogenic bacterial infection in dogs with tracheal collapse and can decrease the rate of subsequent pathogenic infections in geriatric dogs and dogs with TTC that require tracheal stenting. Airway culture and cytology should be performed in all dogs undergoing tracheal stent placement.

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<![CDATA[Tracheal microbial populations in horses with moderate asthma]]> https://www.researchpad.co/article/Ndb90ef8a-a43f-43f9-8a7d-00c3fce49e58

Abstract

Background

There are limited data on potential dysbiosis of the airway microbiota in horses with asthma.

Hypothesis/Objectives

We hypothesized that the respiratory microbiota of horses with moderate asthma is altered. Our objectives were (a) to quantify tracheal bacterial populations using culture and qPCR, (2) to compare aerobic culture and qPCR, and (c) to correlate bacterial populations with bronchoalveolar lavage fluid (BALF) cytology.

Animals

Eighteen horses with moderate asthma from a hospital population and 10 controls.

Methods

Prospective case‐control study. Aerobic culture was performed on tracheal aspirates, and streptococci, Pasteurella multocida, Chlamydophila spp., Mycoplasma spp., as well as 16S (bacterial) and 18S (fungal) rRNA subunits were quantified by qPCR.

Results

Potential pathogens such as Streptococcus spp., Actinobacillus spp., and Pasteurellaceae were isolated from 8, 5, and 6 horses with asthma and 3, 0, and 2 controls, respectively. There was a positive correlation between Streptococcus spp. DNA and 16S rRNA gene (r ≥ 0.7, P ≤ 0.02 in both groups), but the overall bacterial load (16S) was lower in asthma (1.5 ± 1.3 versus 2.5 ± 0.8 × 104 copy/μL, P < 0.05). There was no association between microbial populations and clinical signs, tracheal mucus or BALF inflammation.

Conclusions and Clinical Importance

This study does not support that bacterial overgrowth is a common feature of chronic moderate asthma in horses. Lower bacterial load could suggest dysbiosis of the lower airways, either as a consequence of chronic inflammation or previous treatments, or as a perpetuating factor of inflammation.

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<![CDATA[Detection and dynamics of anti‐platelet antibodies in thrombocytopenic dogs with and without idiopathic immune thrombocytopenia]]> https://www.researchpad.co/article/Nce62046c-90b0-47d0-8b84-b8d8fca70b4c

Abstract

Background

Antiplatelet antibodies are detected in multiple diseases including primary immune thrombocytopenia (ITP). Dynamics of how these antibodies change over time in ITP is unknown in dogs.

Hypothesis/Objectives

Antiplatelet antibodies (APA) will be detected in thrombocytopenic dogs with multiple etiologies and dynamics of APA in dogs with ITP can be used to evaluate response to treatment and relapse. Determine APA at the time of diagnosis in thrombocytopenic dogs and serially in primary ITP dogs.

Animals

Seventy‐nine thrombocytopenic dogs and 28 primary ITP dogs.

Methods

Direct flow cytometry was performed in thrombocytopenic dogs at initial evaluation and serially in suspected primary ITP dogs. In primary ITP dogs, a 2‐tailed Fisher's exact test was performed comparing survival to discharge between dogs with and without melena and to relate response to treatment and relapse to changes in APA and platelet count (repeated measures analysis, Spearman correlation).

Results

Twenty percent (16/79) of thrombocytopenic non‐ITP dogs with infectious, neoplastic, or other diseases and all primary ITP dogs were positive for APA. Melena at initial evaluation was associated with decreased survival to discharge (odds ratio 0.06; P = .01). Persistence of APA was not associated with response to treatment, but recurrence of antibodies was associated with relapse (odds ratio 205.0; P < .01). There was no difference in percentage of APA or platelet count at initial diagnosis between dogs that did or did not respond to treatment.

Conclusions and Clinical Importance

Serial monitoring of APA in dogs with primary ITP appeared beneficial for determining relapse of disease.

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<![CDATA[Associations among echocardiography, cardiac biomarkers, insulin metabolism, morphology, and inflammation in cats with asymptomatic hypertrophic cardiomyopathy]]> https://www.researchpad.co/article/N148909f4-6db2-462b-8804-14ea826c1165

Abstract

Background

Insulin, insulin‐like growth factor‐1 (IGF‐1), and inflammation possibly are involved in cats with asymptomatic hypertrophic cardiomyopathy (aHCM).

Objectives

To evaluate echocardiography, morphology, cardiac and inflammatory markers, insulin and IGF‐1 in cats with aHCM.

Animals

Fifty‐one client‐owned cats with aHCM.

Methods

Observational descriptive study. Variables (body weight [BW], body condition score [BCS], echocardiography, and serum concentrations of N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP], ultra‐sensitive troponin‐I [c‐TnI], serum amyloid A [SAA], insulin, glucose and IGF‐1) were evaluated for significant increases above echocardiography cutoff values and laboratory reference ranges, associations and effect of left atrial (LA) remodeling and generalized hypertrophy.

Results

Cats with aHCM had BCS ≥6/9 (P = .01) and insulin (P < .001), NT‐proBNP (P = .001) and cTn‐I (P < .001) above laboratory reference ranges. Associations were present between NT‐proBNP and maximum end‐diastolic interventricular septum thickness (IVSd; ρ = .32; P = .05), maximum end‐diastolic left ventricular free wall thickness;(ρ = .41; P = .01), LA/Aorta (ρ = .52; P = .001) and LA diameter (LA‐max; ρ = .32; P = .05); c‐TnI and LA/Aorta (ρ = .49; P = .003) and LA‐max (ρ = .28; P = .05); and SAA and number of IVSd regions ≥6 mm thickness (ρ = .28; P = .05). Body weight and BCS were associated with IGF‐1 (r = 0.44; P = .001), and insulin (ρ = .33; P = .02), glucose (ρ = .29; P = .04) and IGF‐1 (ρ = .32; P = .02), respectively. Concentrations of NT‐proBNP (P = .02) and c‐TnI (P = .01), and SAA (P = .02), were higher in cats with LA remodeling, and generalized hypertrophy, respectively.

Conclusions and clinical importance

Results suggest potential implications of insulin, IGF‐1, and inflammation in cats with aHCM, but it remains to be confirmed whether these findings represent a physiological process or a part of the pathogenesis and development of disease.

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<![CDATA[Oxidative status of erythrocytes, hyperglycemia, and hyperlipidemia in diabetic cats]]> https://www.researchpad.co/article/Ned806592-6fb4-4375-af55-4143fdb05ce2

Abstract

Background

Erythrocytes of diabetic cats have decreased superoxide dismutase activity, possibly indicative of oxidative stress.

Hypothesis

Erythrocytes of diabetic cats undergo oxidative stress, which is caused by hyperglycemia and hyperlipidemia, and improves with treatment.

Animals

Twenty‐seven client‐owned cats with diabetes mellitus, 11 matched healthy cats, and 21 purpose‐bred healthy cats.

Methods

Prospective study. Advanced oxidized protein products, carbonyls (protein oxidation by‐products), and thiols (antioxidants) were quantified in erythrocyte membrane, thiobarbituric acid reactive substances (TBAR, lipid peroxidation by‐products), and thiols in erythrocyte cytoplasm of all cats. Comparison were performed between diabetic and matched healthy cats, between diabetic cats achieving remission or not, and among purpose‐bred cats after 10 days of hyperglycemia (n = 5) or hyperlipidemia (n = 6) versus controls treated with saline (n = 5) or untreated (n = 5).

Results

Compared with controls, erythrocytes of diabetic cats initially had higher median membrane carbonyls (4.6 nmol/mg total protein [range: 0.1‐37.7] versus 0.7 [0.1‐4.7], P < .001) and lower cytoplasmic TBAR (1.9 nmol/mg [0.5‐2.4] versus 2.4 [1.4‐3.5] P < .001), and thiols (419 nmol/mg [165‐621] versus 633 [353‐824], P < 0.001). After 12‐16 weeks of treatment in diabetic cats, carbonyls decreased by 13% (P < .001), but remained higher (P < .001) and TBAR and thiols lower (P = .02, P < .001) than those in controls. No differences were observed between diabetic cats achieving remission or not, and among purpose‐bred cats.

Conclusions and Clinical Importance

Diabetes mellitus is associated with increased protein oxidation and reduced antioxidant defenses, which persist during treatment and remission, although mild improvement in protein oxidation occurs. Short‐term hyperglycemia or hyperlipidemia does not cause oxidative stress. The reason for decreased TBAR remains unknown.

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