The effect of neonatal dysphagia on subsequent racing performance in Standardbred horses.

BACKGROUND: Previously we described a clustering of dysphagic foal cases on a Pennsylvania (PA) Standardbred farm which was associated with exposure of pregnant mares to high concentrations of polycyclic aromatic hydrocarbons (PAHs) in the well water. The effect of dysphagia on future athleticism was uncertain. OBJECTIVES: To determine if, as adults, dysphagic foals were less likely to race and if athleticism (age of first race, Speed Index and Earnings Per Start Index) differed from that of healthy foals that raced as adults. STUDY DESIGN: Prospective cohort study. METHODS: All foals born during the study period (2014-2017) on the affected PA or an unaffected New York (NY) farm with the same proprietor were eligible for inclusion in the study. Foals with dysphagia attributed to causes other than PAH environmental exposure were excluded. The proportion of foals from both farms that raced, their age of first race, Earnings Per Start Index and Speed Index were compared between the dysphagic and normal foals using Chi-Square and Wilcoxon Rank Sum Tests. Significance level was P < .05. RESULTS: A total of 116 foals met the inclusion criteria. No significant difference was found in the percentages of foals that raced from each farm: On the PA farm, 54% of healthy and 72% of dysphagic foals raced; 70% of healthy NY farm foals raced. Median (interquartile range) age of first race, Earnings Per Start Index or Speed Index for dysphagic foals (2 years (2, 2); 57 (49, 60); 60 (45, 66) was not different from those of healthy foals from both farms (2 years (2, 3); 55 (39, 78)) or the PA farm (2 years (2, 2); 61(24, 73); 68 (57, 85)). All P > .05. MAIN LIMITATIONS: Small sample size and unique type of dysphagia. CONCLUSIONS: The athleticism of formerly dysphagic foals does not appear to be negatively impacted compared with normal foals as measured by age of first race, Earnings Per Start Index and Speed Index.

Environmental surveillance and adverse neonatal health outcomes in foals born near unconventional natural gas development activity.

Studies of neonatal health risks of unconventional natural gas development (UNGD) have not included comprehensive assessments of environmental chemical exposures. We investigated a clustering of dysphagic cases in neonatal foals born between 2014 and 2016 in an area of active UNGD in Pennsylvania (PA),USA. We evaluated equine biological data and environmental exposures on the affected PA farm and an unaffected New York (NY) farm owned by the same proprietor. Dams either spent their entire gestation on one farm or moved to the other farm in late gestation. Over the 21-month study period, physical examinations and blood/tissue samples were obtained from mares and foals on each farm. Grab samples of water, pasture soil and feed were collected; continuous passive sampling of air and water for polycyclic aromatic hydrocarbons was performed. Dysphagia was evaluated as a binary variable; logistic regression was used to identify risk factors. Sixty-five foals were born, 17 (all from PA farm) were dysphagic. Odds of dysphagia increased with the dam residing on the PA farm for each additional month of gestation (OR = 1.4, 95% CI 1.2, 1.7, p = 6.0E-04). Males were more likely to be born dysphagic (OR = 5.5, 95% CI 1.2, 24.5, p = 0.03) than females. Prior to installation of a water filtration/treatment system, PA water concentrations of 3,6-dimethylphenanthrene (p = 6.0E-03), fluoranthene (p = 0.03), pyrene (p = 0.02) and triphenylene (p = 0.01) exceeded those in NY water. Compared to NY farm water, no concentrations of PAHs were higher in PA following installation of the water filtration/treatment system. We provide evidence of an uncommon adverse health outcome (dysphagia) in foals born near UNGD that was eliminated in subsequent years (2017-2019) following environmental management changes. Notably, this study demonstrates that domestic large animals such as horses can serve as important sentinels for human health risks associated with UNGD activities.

Successful management of hydrallantois in a Standardbred mare at term resulting in the birth of a live foal.

A 6-year-old Standardbred mare was presented at 339 days of gestation for investigation of abnormal abdominal distension and ventral edema. Transrectal palpation and ultrasound examination revealed the uterus to be enlarged with an excessive volume of fetal fluid, characteristic of hydrops. Gradual transcervical drainage of 55 L of allantoic fluid over 45 minutes, with concurrent intravenous fluid therapy followed by assisted vaginal delivery, resulted in the birth of a live foal with long-term survival. The birth and long-term survival of a foal from a mare with hydrallantois at term has not been previously reported in horses. However, this report demonstrates that successful outcome for both mare and foal may be achieved in a mare at term with hydrallantois.

Gestion réussie de l'hydrallantois chez une jument Standardbred à terme donnant lieu à la naissance d'un poulain vivant. Une jument Standardbred âgée de 6 ans a été présentée à 339 jours de gestation pour investiguer une distension abdominale anormale et un oedème ventral. La palpation transrectale et l'échographie ont révélé que l'utérus était enflé en raison d'un volume excessif de liquide foetal, ce qui est caractéristique de l'hydrops fetalis. Un drainage transcervical graduel de 55 L de liquide allantoïdien pendant plus de 45 minutes et une fluidothérapie par intraveineuse suivis d'une mise bas vaginale assistée ont donné lieu à la naissance d'un poulain vivant avec survie à long terme. La naissance et la survie à long terme d'un poulain provenant d'une jument atteinte de l'hydrallantois à terme n'avaient pas été précédemment signalées chez les chevaux. Cependant, des résultats fructueux pour la jument et le poulain peuvent être obtenus chez une jument atteinte d'hydrallantois à terme.(Traduit par Isabelle Vallières).

Identification of loci affecting sexually dimorphic patterns for height and recurrent laryngeal neuropathy risk in American Belgian Draft Horses.

Equine recurrent laryngeal neuropathy (RLN) is a bilateral mononeuropathy with an unknown etiology. In Thoroughbreds (TB), we previously demonstrated that the haplotype association for height (LCORL/NCAPG locus on ECA3, which affects body size) and RLN was coincident. In the present study, we performed a genome-wide association scan (GWAS) for RLN in 458 American Belgian Draft Horses, a breed fixed for the LCORL/NCAPG risk alelle. In this breed, RLN risk is associated with sexually dimorphic differences in height, and we identified a novel locus contributing to height in a sex-specific manner: MYPN (ECA1). Yet this specific locus contributes little to RLN risk, suggesting that other growth traits correlated to height may underlie the correlation to this disease. Controlling for height, we identified a locus on ECA15 contributing to RLN risk specifically in males. These results suggest that loci with sex-specific gene expression play an important role in altering growth traits impacting RLN etiology, but not necessarily adult height. These newly identified genes are promising targets for novel preventative and treatment strategies.

Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO) Support an Interleukin-17 Immune Response.

Recurrent airway obstruction (RAO) is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest involvement of Interleukin-17 (IL-17). We examined global gene expression profiles in mediastinal (pulmonary-draining) lymph nodes isolated from RAO-affected and control horses. Differential expression of > 200 genes, coupled with network analysis, supports an IL-17 response centered about NF-κB. Immunohistochemical analysis of mediastinal lymph node sections demonstrated increased IL-17 staining intensity in diseased horses. This result, along with the finding of increased IL-17 concentrations in lymph node homogenates from RAO-affected horses (P = 0.1) and a down-regulation of IL-4 gene and protein expression, provides additional evidence of the involvement of IL-17 in the chronic stages of RAO. Additional investigations are needed to ascertain the cellular source of IL-17 in this equine model of occupational asthma. Understanding the immunopathogenesis of this disorder likely will enhance the development of therapeutic interventions beneficial to human and animal pulmonary health.

Genomic analysis establishes correlation between growth and laryngeal neuropathy in Thoroughbreds.

BACKGROUND: Equine recurrent laryngeal neuropathy (RLN) is a bilateral mononeuropathy with an unknown pathogenesis that significantly affects performance in Thoroughbreds. A genetic contribution to the pathogenesis of RLN is suggested by the higher prevalence of the condition in offspring of RLN-affected than unaffected stallions. To better understand RLN pathogenesis and its genetic basis, we performed a genome-wide association (GWAS) of 282 RLN-affected and 268 control Thoroughbreds. RESULTS: We found a significant association of RLN with the LCORL/NCAPG locus on ECA3 previously shown to affect body size in horses. Using height at the withers of 505 of these horses, we confirmed the strong association of this locus with body size, and demonstrated a significant phenotypic and genetic correlation between height and RLN grade in this cohort. Secondary genetic associations for RLN on ECA18 and X did not correlate with withers height in our cohort, but did contain candidate genes likely influencing muscle physiology and growth: myostatin (MSTN) and integral membrane protein 2A (ITM2A). CONCLUSIONS: This linkage between body size and RLN suggests that selective breeding to reduce RLN prevalence would likely reduce adult size in this population. However, our results do not preclude the possibility of modifier loci that attenuate RLN risk without reducing size or performance, or that the RLN risk allele is distinct but tightly linked to the body size locus on ECA3. This study is both the largest body size GWAS and the largest RLN GWAS within Thoroughbred horses to date, and suggests that improved understanding of the relationship between genetics, equine growth rate, and RLN prevalence may significantly advance our understanding and management of this disease.

B-cell multicentric lymphoma as a probable cause of abortion in a Quarter horse broodmare.

A 5-year-old Quarter horse broodmare was evaluated for inappetence, depression, and diarrhea 13 days after aborting a 9-month gestation fetus. Clinical and laboratory examination ruled out uterine rupture and peritonitis. Ultrasonography of the uterus combined with cytological analysis of peritoneal fluid suggested the existence of diffuse lymphoma. A multicentric B-cell lymphoma involving the uterus and ovary was confirmed at necropsy and histopathological examination.

Lymhome multicentrique à cellules B comme cause possible d'avortement chez une jument poulinière Quarter Horse. Une jument Quarter horse de 5 ans a été présentée pour anorexie, baisse d'état général et diarrhée, trente jours après un avortement à 9 mois de gestation. Lors de l'examen clinique initial, rupture utérine et péritonite ont pu être éliminées. L'analyse cytologique des liquides péritonéaux et pleuraux aspirés suggéra un lymphome diffus confirmé en nécropsie lors de l'examen histopathologique.(Traduit par les auteurs).

Expression of thymic stromal lymphopoietin in equine recurrent airway obstruction.

Thymic stromal lymphopoietin (TSLP) is a cytokine involved in lymphocyte development. In humans and mice, TSLP drives the differentiation of T helper 2 (Th2) cells and the development of allergic inflammation. The equine TSLP gene has been previously identified and characterized, but its role in the pathogenesis of equine allergic diseases is not known. Our objective was to assess the expression of TSLP in bronchoalveolar lavage (BAL) cells and in primary bronchial epithelial cells (BEC) isolated from horses with recurrent airway obstruction (RAO). RNA was isolated from BAL cells sampled from clinical cases of RAO (n=8) and from control horses (n=12). Furthermore, BAL samples were taken from an additional group of 8 RAO-susceptible and 8 control horses when on pasture (remission) and after 30 days of exposure to moldy hay (exacerbation). In order to study epithelial cells as a potential source of TSLP, cultures of primary bronchial epithelial cells (BEC) were established from 6 RAO-affected and 6 healthy horses and stimulated in vitro with hay dust solution (HDS). Expression of TSLP mRNA was assessed by quantitative real-time RT-PCR (qPCR). Clinical RAO-cases had higher TSLP expression in BAL than control horses (p<0.05). In an experimental group of horses there was no difference between healthy and susceptible horses in remission, whereas after 30-day experimental exposure to moldy hay, all susceptible horses upregulated TSLP expression in BAL (p=0.008, average 6.36-fold increase), whereas in healthy horses there was no significant increase in TSLP expression. BEC generated both from healthy and RAO-affected horses strongly upregulated TSLP expression after 6 h stimulation with HDS, which identifies epithelial cells as potential sources of TSLP in RAO. Finding of increased TSLP expression by BAL cells of RAO-affected horses is in agreement with the contribution of Th2-driven allergic inflammation in the pathogenesis of RAO.

Effects of in vitro exposure to autologous blood and serum on expression of interleukin-8, interleukin-1ß, and chemokine (C-X-C motif) ligand 2 in equine primary bronchial epithelial cell cultures.

OBJECTIVE: To examine the effects of in vitro exposure to solutions of autologous horse blood (AHB) and autologous horse serum (AHS) on expressions of selected cytokine genes in equine primary bronchial epithelial cell (BEC) cultures and to contrast these responses to those induced in BEC cultures by endotoxin and hay dust. SAMPLE: BEC cultures established from bronchi of 6 healthy horses. PROCEDURES: 5-day-old BEC cultures were treated with PBS solution, AHB (2 concentrations), AHS, hay dust solution, and lipopolysaccharide solution for 24 hours. Gene expressions of interleukin (IL)-8, IL-1ß, chemokine (C-X-C motif) ligand 2 (CXCL2), and glyceralde-hyde-3-phosphate dehydrogenase were subsequently measured with a kinetic PCR assay. RESULTS: With the exception of AHS, all treatments of the BECs resulted in upregulation of each target gene expression relative to its expression in cultures exposed to PBS solution. Treatment with AHB induced a dose-dependent increase of each target gene, with IL-1ß expression increasing the most (> 1,200-fold increase). Lipopolysaccharide and hay dust solution treatments each resulted in 20-fold increases in IL-8 and IL-1ß gene expressions. Lipopolysaccharide and hay dust solution treatments also resulted in a 7- and 8-fold increase in CXCL2 gene expression, respectively. The increases in IL-8 and CXCL2 gene expressions following treatment with the higher concentration of blood were equivalent to those associated with hay dust solution or lipopolysaccharide. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that chemokine expression by cultured equine BECs following exposure to pulmonary hemorrhage conditions may contribute to the development of inflammatory airway disease in horses.

Interferon-gamma, interleukin-4 and interleukin-10 production by T helper cells reveals intact Th1 and regulatory TR1 cell activation and a delay of the Th2 cell response in equine neonates and foals.

Cytokines produced by T helper (Th) cells are important in orchestrating the immune response during health and disease. Recent reports indicated that cytokine mRNA expression in foals is often quantitatively lower than that of adult horses suggesting that foal T cells are not fully mature. Here, peripheral blood mononuclear cells from foals and adult horses were stimulated with phorbol 12-myristate 13-acetate and analyzed for intracellular interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-10 production, representing the Th1, Th2 and regulatory TR1 cell phenotypes respectively, by flow cytometry. In agreement with previous reports, all three cytokines were quantitatively reduced in foals compared to adults. However, the balance between Th1 and Th2 cytokines (IFN-gamma/IL-4 ratio) showed a clear Th1-biased response in foals by 6 and 12 weeks of life, while similar IFN-gamma/IL-10 ratios were found in foals and adult horses. By day 5 after birth, intracellular IFN-gamma production by foal CD4+ and CD8+ T cells resembled that in adults. Overall, IL-4 production was low in foals. IL-4+ cells peaked at day 5 of age when IL-4 was mainly produced by IgE+ cells. Relative percentages of IL-4+ Th2 cells were significantly lower in foals at all time points. The data suggested that equine neonates and young foals have an impaired Th2 response, that the immune response of foals is Th1 biased, that IFN-gamma production by Th and cytotoxic T cells is qualitatively similar to adult horses, and regulatory IL-10 production by T cells is developmentally mature in foals during the first three months of life.

Induction of interleukin-4 production in neonatal IgE+ cells after crosslinking of maternal IgE.

Transfer of maternal IgE antibodies to the neonate with the colostrum has been described in different mammalian species. Previous work in horses has shown that IgE bound to the surface of neonatal basophils is solely of maternal origin. However, the functional role of the maternal IgE transfer remained unclear. We hypothesized that maternal IgE mediates the onset of innate IL-4 production in equine neonatal basophils. Intracellular IL-4 production was measured in PBMC of newborn and older foals by flow cytometric analysis. A small population of IL-4(+) cells was observed in the peripheral blood at days 3-5 after birth. Phenotyping of the IL-4(+) cells showed that they were IgE(+)/MHCII(low)/CD4(-) cells. Magnetic cells sorting of the IgE(+)/MHCII(low) cells identified them as basophils. Anti-IgE stimulation in vitro induced IL-4 in IgE(+)/MHCII(low) basophils, but not in MHCII(+) cells or cells collected before colostrum ingestion. In conclusion, stimulation via maternal IgE antibodies mediated innate IL-4 production in neonatal basophils which might provide a paragenetic mechanism to promote the development of adaptive T-cell responses in the neonate after birth.

Effects of in vitro exposure to hay dust on expression of interleukin-23, -17, -8, and -1beta and chemokine (C-X-C motif) ligand 2 by pulmonary mononuclear cells from horses susceptible to recurrent airway obstruction.

OBJECTIVE: To examine gene expression of selected cytokines in pulmonary mononuclear cells isolated from healthy horses and horses susceptible to recurrent airway obstruction (RAO), and to determine whether interleukin (IL)-17 and IL-23 were associated with pulmonary inflammation. ANIMALS: 6 RAO-susceptible and 5 healthy horses. PROCEDURES: Bronchoalveolar lavage cells were retrieved from horses that were stabled and fed dusty hay for 24 hours. Lavage cells devoid of neutrophils were incubated for 24 hours with solutions of PBS, hay dust, lipopolysaccharide, or B-glucan. Gene expression of IL-17, IL-23 (p19 and p40 subunits), IL-8, IL-1B, chemokine (C-X-C motif) ligand 2 (CXCL2), and B-actin was measured by use of real-time reverse transcription PCR assays. RESULTS: The degree of inherent expression of target genes in bronchoalveolar lavage cells treated with PBSS was not different between the 2 groups of horses. Relative to exposure to PBSS, exposure to the hay dust solution increased gene expression of all cytokines more than 2-fold in cells from both groups of horses, but the magnitudes of these increases were not different between the groups. Exposure to lipopolysaccharide solution increased gene expression of IL-8, CXCL2, and IL-1B in cells from RAO-susceptible horses, but this increase was not significantly different from that in cells from control horses. Exposure to B-glucan solution failed to increase gene expression in cells from either horse group, compared with gene expression when cells were exposed to PBSS. CONCLUSIONS AND CLINICAL RELEVANCE: The acute pulmonary neutrophilia characteristic of RAO was not associated with an increase in upregulation of gene expression of chemokines in pulmonary mononuclear cells from disease-susceptible horses.

Effects of in vitro exposure to hay dust on the gene expression of chemokines and cell-surface receptors in primary bronchial epithelial cell cultures established from horses with chronic recurrent airway obstruction.

OBJECTIVE: To examine effects of in vitro exposure to solutions of hay dust, lipopolysaccharide (LPS), or beta-glucan on chemokine and cell-surface receptor (CSR) gene expression in primary bronchial epithelial cell cultures (BECCs) established from healthy horses and horses with recurrent airway obstruction (RAO). SAMPLE POPULATION: BECCs established from bronchial biopsy specimens of 6 RAO-affected horses and 6 healthy horses. PROCEDURES: 5-day-old BECCs were treated with PBS solution, hay dust solutions, LPS, or beta-glucan for 6 or 24 hours. Gene expression of interleukin (IL)-8, chemokine (C-X-C motif) ligand 2 (CXCL2), IL-1beta, toll-like receptor 2, toll-like receptor 4, IL-1 receptor 1, and glyceraldehyde 3-phosphate dehydrogenase was measured with a kinetic PCR assay. RESULTS: Treatment with PBS solution for 6 or 24 hours was not associated with a significant difference in chemokine or CSR expression between BECCs from either group of horses. In all BECCs, treatment with hay dust or LPS for 6 hours increased IL-8, CXCL2, and IL-1beta gene expression > 3-fold; at 24 hours, only IL-1beta expression was upregulated by > 3-fold. In all BECCs, CSR gene expression was not increased following any treatment. With the exception of a 3.7-fold upregulation of CXCL2 in BECCs from RAO-affected horses (following 6-hour hay dust treatment), no differences in chemokine or CSR gene expression were detected between the 2 groups. At 24 hours, CXCL2 gene expression in all BECCs was downregulated. CONCLUSIONS AND CLINICAL RELEVANCE: Epithelial CXCL2 upregulation in response to hay dust particulates may incite early airway neutrophilia in horses with RAO.

What is your diagnosis? Pleural fluid from a neonatal Thoroughbred filly with pneumonia.

A 3-day-old filly was presented to the Cornell University Hospital for Animals with an umbilical hematoma and mild aspiration pneumonia. The foal underwent abdominal surgery for resection of the hematoma. Recovery was uneventful, but 3 days after surgery, the foal became progressively tachypneic. Imaging studies revealed bilateral pleural effusion and pleuropneumonia. Cytologic evaluation and bacterial culture of the pleural fluid from both sides of the chest revealed sterile exudates, consisting mostly of neutrophils, with fewer macrophages and lymphocytes. Pleural fluid macrophages contained variable amounts of purple-magenta globular material in their cytoplasm. A lighter colored granular precipitate was also seen throughout the background of the smears. Similar material was identified in a macrophage in a peripheral blood smear prepared 2 days after abdominal surgery. Large amounts of extracellular pink precipitate were also seen in the blood smear and persisted in the blood for 7 days after surgery. A protective lubricant, carboxymethylcellulose, had been instilled into the abdominal cavity during surgery to prevent intra-abdominal adhesions. The intracytoplasmic pigment within pleural fluid and blood macrophages and the extracellular precipitate in peripheral blood and pleural fluid smears was compatible with carboxymethylcellulose. The material was probably derived hematogenously and was considered an incidental finding. The pleuritis was attributed to exacerbation of the original aspiration pneumonia by the general anesthesia.

Effects of in vitro exposure to hay dust on expression of interleukin-17, -23, -8, and -1beta and chemokine (C-X-C motif) ligand 2 by pulmonary mononuclear cells isolated from horses chronically affected with recurrent airway disease.

OBJECTIVE: To examine effects of in vitro exposure to solutions of hay dust, lipopolysaccharide (LPS), or beta-glucan on cytokine expression in pulmonary mononuclear cells isolated from healthy horses and horses with recurrent airway obstruction (RAO). ANIMALS: 8 RAO-affected and 7 control horses (experiment 1) and 6 of the RAO-affected and 5 of the control horses (experiment 2). PROCEDURES: Bronchoalveolar lavage cells were isolated from horses that had been stabled and fed dusty hay for 14 days. Pulmonary mononuclear cells were incubated for 24 (experiment 1) or 6 (experiment 2) hours with PBS solution or solutions of hay dust, beta-glucan, or LPS. Gene expression of interleukin (IL)-17, IL-23(p19 and p40 subunits), IL-8, IL-1beta, and chemokine (C-X-C motif) ligand 2 (CXCL2) was measured with a kinetic PCR assay. RESULTS: Treatment with the highest concentration of hay dust solution for 6 or 24 hours increased expression of IL-23(p19 and p40), IL-8, and IL-1beta in cells from both groups of horses and increased early expression of IL-17 and CXCL2 in RAO-affected horses. Lipopolysaccharide upregulated early expression of IL-23(p40) and IL-8 in cells from both groups of horses but only late expression of these cytokines in cells from RAO-affected horses. Treatment with beta-glucan failed to increase cytokine expression at 6 or 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Cells from RAO-affected horses were not more responsive to the ligands tested than were cells from control horses, which suggests a minimal role of mononuclear cells in propagation of airway neutrophilia in horses with chronic RAO.

Cytokine profiles of peripheral blood mononuclear cells isolated from septic and healthy neonatal foals.

BACKGROUND: Septicemia initiates the production of pro-inflammatory (interleukin [IL] 1-beta [IL-1beta], interferon-gamma [IFN-gamma], IL-6), and anti-inflammatory (IL-4) cytokines. The transcription of some of these proteins (IL-8, IL-6) is linked to endotoxin-induced activation of the toll-like receptor 4 (TLR4) on peripheral blood mononuclear cells (PBMC). HYPOTHESES: Septic foals fail to increase gene expression of IFN-gamma. Nonsurviving septic foals exhibit distinctive cytokine profiles. ANIMALS: Twenty-one septic and 20 healthy neonatal foals. METHODS: Using real-time polymerase chain reaction, gene expression of IFN-gamma, IL-1beta, IL-6, IL-4, IL-8, TLR4, and beta-actin in PBMC were measured in samples obtained from septic foals at 0, 24, and 72 hours (T = 0, 24, and 72 hours) after admission to the Cornell University Hospital for Animals. Control foals were sampled at comparable times. RESULTS: At T=0 hours, septic foals exhibited a 6-fold decrease in gene expression of IL-4 and a 5-fold increase in gene expression of TLR4. Gene expression of IFN-gamma, IL-6, IL-8, or of IL-1beta did not differ between the 2 groups of foals at T = 0 hours. In septic foals that died (n = 3), there was a 15-fold increase in IL-6 at T = 0 hours compared to survivors. CONCLUSIONS AND CLINICAL IMPORTANCE: Septic foals, unlike septic human infants, up-regulate TLR4 gene expression, which may enhance pro-inflammatory cytokine production. Despite the presence of sepsis, IFN-gamma was not up-regulated. Additional studies are needed to verify that increased IL-6 expression is associated with a poor prognosis in septic foals.

A comparison of laryngoplasty and modified partial arytenoidectomy as treatments for laryngeal hemiplegia in exercising horses.

OBJECTIVE: To compare upper airway mechanics, arterial blood gases, and tracheal contamination in horses with induced left laryngeal hemiplegia (recurrent laryngeal neuropathy [RLN]) treated by laryngoplasty/vocal cordectomy (LPVC) or modified partial arytenoidectomy (MPA). STUDY DESIGN: Repeated measures under the following conditions: Control, RLN, LPVC, and MPA. ANIMALS: Six horses. METHODS: Two trials were conducted under all conditions at 80% and 100% of maximal heart rate (HR(max)). In Trial 1, arterial blood gases, tracheal and pharyngeal pressures, and laryngeal videoendoscopy were recorded. In Trial 2, upper airway pressure and airflow were determined. Tracheobronchial aspirates were performed after exercise to quantify airway contamination. RESULTS: Compared with control, RLN significantly increased inspiratory impedance and worsened exercise-induced hypoxemia. At 80% HR(max), LPVC restored most variables to control values. At 100% HR(max), LPVC improved all variables, but did not restore minute volume, arterial pH, and PaCO(2). At 80% HR(max), MPA restored all variables except bicarbonate to control values. At 100% HR(max), MPA improved all variables, but did not statistically restore minute ventilation or bicarbonate level. Only minor differences were noted between LPVC and MPA. Both resulted in equivalent tracheal contamination. CONCLUSIONS: Airway mechanics and arterial blood gas values were not restored to normal after either LPVC or MPA in horses exercising at HR(max). This does not affect ventilation at sub-maximal exercise, but has clinical implications at HR(max). Both procedures diminish normal laryngeal protective mechanisms. CLINICAL RELEVANCE: At sub-maximal exercise intensities both LPVC and MPA restore airway ventilation to normal. At maximal exercise the superiority of LPVC over MPA is slight.

Time-dependent alterations in gene expression of interleukin-8 in the bronchial epithelium of horses with recurrent airway obstruction.

OBJECTIVE: To evaluate time-dependent alterations in gene expression of chemokines in bronchial epithelium of recurrent airway obstruction (RAO)-affected horses and whether alterations resulted from increases in gene expression of interleukin (IL)-17 in cells isolated from bronchoalveolar lavage fluid (BALF). ANIMALS: 8 RAO-susceptible horses and 9 control horses. PROCEDURE: In 2 experiments, both groups of horses were evaluated after being maintained on pasture and after being stabled and fed dusty hay for 1, 14, 35, and 49 days (experiment 1) or 14 and 28 days (experiment 2). In experiment 1, gene expression of IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and Toll-like receptor 4 (TLR4) in epithelium and IL-8, IL-17, and TLR4 in BALF cells was measured. In experiment 2, bronchial biopsy specimens were evaluated for IL-8 immunoreactivity. RESULTS: In RAO-susceptible horses after 14 days of challenge exposure, there was a 3- and 10-fold increase in gene expression of IL-8 for epithelial and BALF cells and an increase in IL-8 immunoreactivity in epithelial cells. Challenge exposure failed to alter gene expression of CXCL1, GM-CSF, G-CSF, and TLR4 in epithelial cells of any horses at any time point. During challenge exposure, gene expression of BALF cell IL-17 was downregulated in control horses (day 1) and upregulated in RAO-affected horses (day 35). CONCLUSIONS AND CLINICAL RELEVANCE: Epithelial-derived IL-8 may promote airway neutrophilia, but the inciting stimulus is unlikely to be IL-17 because upregulation of this gene is subsequent to that of IL-8 in epithelial cells.

Thoracoscopic pericardiotomy as a palliative treatment in a cow with pericardial lymphoma.

A 5-year-old Holstein cow, pregnant with a valuable calf, was presented with signs of heart failure (tachycardia, peripheral edema, and distended jugular veins) related to pericardial lymphoma and associated cardiac tamponade. In addition, pleural effusion was present in both hemithoraces. Medical treatment, which consisted of repeated pericardiocenteses, placement of indwelling pleural catheters, administration of intravenous fluid therapy, antibiotics and anti-inflammatory drugs, was ineffective in controlling recurrence of clinical signs despite a temporary improvement. A standing thoracoscopic pericardiotomy was performed in an attempt to reduce clinical signs of heart failure and to prolong life. Clinical signs of heart failure abated and no recurrence was seen. Standing thoracoscopic pericardiotomy along with possible corticosteroids can be recommended as palliative treatment in an effort to extend life for reproductive performance in genetically valuable animals.

Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells.

In horses prone to developing recurrent airway obstruction (RAO), we tested the hypotheses that the cytokine profile in the bronchoalveolar lavage (BAL) cells of affected horses would reflect a polarized Th-2 response; that cytokine and chemokine alterations would occur within 24 h of allergen exposure; and that allergen exposure would induce alterations in the expression of the transcription factor t-bet (t-box-expressed in T-cells). The expression levels of interleukin-4 (IL-4), IL-13, Interferon-gamma (IFN-gamma), t-bet, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) were measured in BAL cells obtained from control and RAO-susceptible horses during an asymptomatic phase and at 24 h and 5 weeks post-stabling and hay exposure. At each sampling time, BAL neutrophil percentages in the RAO-group exceeded controls. In the RAO-group, only IL-13 expression was decreased 2-fold during the asymptomatic phase. No differences in cytokine or chemokine expression were detected during the acute exposure phase. During the chronic phase, IFN-gamma and IL-8 expression levels were 2.5- and 3-fold greater, respectively, in the RAO-group. No other differences in gene expression were detected. We conclude that the cytokine profile of the airway cells does not reflect a polarized Th-2 response; that increases in IFN-gamma result from a t-bet independent pathway and that chemokines from epithelial or interstitial cells may contribute to early neutrophil influx.