Dynein light chain regulates adaptive and innate B cell development by distinctive genetic mechanisms.

Mechanistic differences in the development and function of adaptive, high-affinity antibody-producing B-2 cells and innate-like, "natural" antibody-producing B-1a cells remain poorly understood. Here we show that the multi-functional dynein light chain (DYNLL1/LC8) plays important roles in the establishment of B-1a cells in the peritoneal cavity and in the ongoing development of B-2 lymphoid cells in the bone marrow of mice. Epistasis analyses indicate that Dynll1 regulates B-1a and early B-2 cell development in a single, linear pathway with its direct transcriptional activator ASCIZ (ATMIN/ZNF822), and that the two genes also have complementary functions during late B-2 cell development. The B-2 cell defects caused by loss of DYNLL1 were associated with lower levels of the anti-apoptotic protein BCL-2, and could be supressed by deletion of pro-apoptotic BIM which is negatively regulated by both DYNLL1 and BCL-2. Defects in B cell development caused by loss of DYNLL1 could also be partially suppressed by a pre-arranged SWHEL Igm-B cell receptor transgene. In contrast to the rescue of B-2 cell numbers, the B-1a cell deficiency in Dynll1-deleted mice could not be suppressed by the loss of Bim, and was further compounded by the SWHEL transgene. Conversely, oncogenic MYC expression, which is synthetic lethal with Dynll1 deletion in B-2 cells, did not further reduce B-1a cell numbers in Dynll1-defcient mice. Finally, we found that the ASCIZ-DYNLL1 axis was also required for the early-juvenile development of aggressive MYC-driven and p53-deficient B cell lymphomas. These results identify ASCIZ and DYNLL1 as the core of a transcriptional circuit that differentially regulates the development of the B-1a and B-2 B lymphoid cell lineages and plays a critical role in lymphomagenesis.

IL-10 mediates plasmacytosis-associated immunodeficiency by inhibiting complement-mediated neutrophil migration.

BACKGROUND: Plasmacytosis (ie, an expansion of plasma cell populations to much greater than the homeostatic level) occurs in the context of various immune disorders and plasma cell neoplasia. This condition is often associated with immunodeficiency that causes increased susceptibility to severe infections. Yet a causative link between plasmacytosis and immunodeficiency has not been established. OBJECTIVE: Because recent studies have identified plasma cells as a relevant source of the immunosuppressive cytokine IL-10, we sought to investigate the role of IL-10 during conditions of polyclonal and neoplastic plasmacytosis for the regulation of immunity and its effect on inflammation and immunodeficiency. METHODS: We used flow cytometry, IL-10 reporter (Vert-X) and B cell-specific IL-10 knockout mice, migration assays, and antibody-mediated IL-10 receptor blockade to study plasmacytosis-associated IL-10 expression and its effect on inflammation and Streptococcus pneumoniae infection in mice. ELISA was used to quantify IL-10 levels in patients with myeloma. RESULTS: IL-10 production was a common feature of normal and neoplastic plasma cells in mice, and IL-10 levels increased with myeloma progression in patients. IL-10 directly inhibited neutrophil migration toward the anaphylatoxin C5a and suppressed neutrophil-dependent inflammation in a murine model of autoimmune disease. MOPC.315.BM murine myeloma leads to an increased incidence of bacterial infection in the airways, which was reversed after IL-10 receptor blockade. CONCLUSION: We provide evidence that plasmacytosis-associated overexpression of IL-10 inhibits neutrophil migration and neutrophil-mediated inflammation but also promotes immunodeficiency.

Effects of administration of a synthetic low molecular weight/low molar substitution hydroxyethyl starch solution in healthy neonatal foals.

This study compared the effects of IV administration of isotonic fluid therapy and colloidal fluid therapy in healthy neonatal foals. Fifteen healthy neonatal foals were used in a randomized blinded prospective clinical study. Foals were randomly assigned to receive a bolus of 20 mL/kg of tetrastarch (TES) or balanced crystalloid solution. Vital parameters, colloid osmotic pressure (COP), and various clinicopathologic variables were assessed prior to infusion and at various time points up to 120 h after infusion. The treatment group (TES) had a significant increase in both COP and percentage increase in COP at 1 and 3 h. The COP was significantly lower than baseline at 3 h in the control group. No significant changes were observed in coagulation parameters in either group. Tetrastarch was effective in increasing COP for 3 h after infusion and had no notable adverse clinical effects in this group of healthy foals. Further studies are warranted regarding optimal dosing and effects in clinically ill foals.

Effets de l'administration d'une solution de substitution synthétique d'amidon hydroxyéthylé de faible poids moléculaire/faible molarité chez des poulains néonataux en santé. Cette étude a comparé les effets de l'administration IV d'une fluidothérapie isotonique et d'une fluidothérapie colloïdale chez des poulains néonataux en santé. Quinze poulains néonataux ont été utilisés dans une étude clinique prospective randomisée. Les poulains ont été assignés au hasard pour recevoir un bolus de 20 mL/kg de tétra-amidon (TEA) ou d'une solution cristalloïde équilibrée. Les paramètres vitaux, la pression osmotique colloïdale (POC) et diverses variables clinicopathologiques ont été évalués avant l'infusion et à divers moments jusqu'à 120 heures après l'infusion. Le groupe de traitement (TEA) a subi une hausse importante de la POC et une augmentation du pourcentage de POC à 1 et 3 heures dans le groupe témoin. Aucun changement significatif n'a été observé dans les paramètres de coagulation des deux groupes. Le tétra-amidon a été efficace pour l'augmentation de la POC pendant 3 heures après l'infusion et il n'a pas eu d'effets cliniques négatifs notables dans ce groupe de poulains en santé. De nouvelles études sont justifiées concernant le dosage optimal et les effets chez les poulains cliniquement malades.(Traduit par Isabelle Vallières).

Defining the Systemic Inflammatory Response Syndrome in Equine Neonates.

Defining and describing the systemic inflammatory response syndrome (SIRS) and sepsis facilitated recognition and investigation of the complex disease processes involving the host response to infection and trauma. Over the years a variety of definitions of SIRS have been examined and applied to numerous research studies to improve critical care in both human and veterinary clinical practice. This article summarizes the history of the development of the SIRS definition, outlines the pathophysiologic processes that are involved in SIRS, and provides a specific definition for use in foal medicine.

Episodic blindness and ataxia in a horse with cholesterinic granulomas.

An 11-year-old Oldenburg mare presented following three episodes of acute, transient blindness, ataxia, and disorientation within the preceding 7 months. Clinical improvement, including return of vision, occurred within 1 week of initiating corticosteroid therapy for each of the three episodes. However, mild right-sided miosis was a consistent finding on ophthalmic examinations. Routine clinicopathologic testing revealed no significant abnormalities, and testing of cerebral spinal fluid for selected infectious diseases was unrewarding. Computed tomography of the brain demonstrated a hyperattenuating mass with peripheral mineralization in the rostroventral aspect of each lateral ventricle. The mare was euthanized due to a guarded to poor prognosis. On histopathology, the masses consisted of clusters of cholesterol clefts admixed with leukocytes, mineral deposits, and connective tissue. Cholesterinic granulomas of the lateral ventricles and hydrocephaly were diagnosed. Cholesterinic granulomas should be considered a differential diagnosis in horses presenting for intermittent blindness.

Pharmacokinetics of multiple oral doses of acetaminophen in equine neonates.

OBJECTIVE: To determine the pharmacokinetics and clinical safety of acetaminophen after oral administration of 40 mg/kg q 12 hours or 60 mg/kg q 24 hours for 14 days. ANIMALS: 12 healthy light-breed neonatal foals. PROCEDURES: 6 foals received acetaminophen at 40 mg/kg q 12 hours and 6 foals received 60 mg/kg q 24 hours for 14 days. The study dates were January 31 to April 15, 2023. Physical examinations were performed daily. Plasma disposition of acetaminophen was determined after the first, mid-point drug administration. Hematology and biochemistry analysis was performed before the study, day 7, and the last day of drug administration. Plasma acetaminophen concentrations were determined by high-performance liquid chromatography. Plasma pharmacokinetic parameters were estimated using noncompartmental analysis. RESULTS: No statistically significant changes occurred on hematology or biochemistry profiles. Elevations in γ-glutamyl transferase (GGT) and sorbitol dehydrogenase (SDH) were noted in 4 foals at various time points. The maximum plasma concentration (Cmax) occurred within 2 hours for both doses. The 60 mg/kg dose resulted in a larger median Cmax (range) at 28 µg/mL (22-32) than the 40 mg/kg dose at 23 µg/mL (19-27). The median area under the concentration-vs-time curve from 0 to 8 hours (AUC0-8 hour [range]) was 100 h•µg/mL (82-100) at 40 mg/kg and 128 h•µg/mL (120-168) for 60 mg/kg. Trough concentrations decreased over time for both regimens. CLINICAL RELEVANCE: Foals tolerate oral acetaminophen at 40 mg/kg q 12 hours or 60 mg/kg q 24 hours. Further analgesic and antipyretic studies will help to delineate optimal dosage regimens of acetaminophen to treat foals.

Risk factors associated with development of colitis in horses post-exploratory laparotomy.

BACKGROUND: Diagnosis of colitis has been shown to impact morbidity and mortality in hospitalised horses. There are no studies to date that describe the incidence of infectious colitis after exploratory laparotomy. OBJECTIVES: To investigate risk factors associated with the development of colitis and infectious colitis post-exploratory laparotomy. STUDY DESIGN: Retrospective case-control. METHODS: Medical records of equids admitted from 2011 to 2020 were reviewed. The primary outcome was a diagnosis of colitis following exploratory laparotomy. Bivariable associations between colitis and risk factors were assessed using the 2-sample t-test and Fisher's exact test. All risk factors were subjected to a backward elimination variable reduction algorithm within a logistic regression framework (p-value set to 0.05). Odds ratios and 95% confidence intervals were computed for the final model. RESULTS: A total of 504 equids were included in the study. Forty-two patients (8.3%) were diagnosed with postoperative colitis. Five patients were diagnosed with Salmonella spp. and two with Clostridioides difficile. The odds of postoperative colitis were higher among patients that had pelvic flexure enterotomy (OR = 3.7, 95% CI = 1.7-7.9, p = 0.001), postoperative leukopenia or leukocytosis (OR = 21.2, 95% CI = 9.7-46.7, p < 0.001), or plasma lactate 2.0-4.0 mmol/L (OR = 3.0, 95% CI = 1.3-6.7, p < 0.008). Patients diagnosed with colitis had a longer median length of hospitalisation (9 days; range 2-21) compared with patients without colitis (7 days; range 2-25). Patients with colitis had a survival to discharge rate similar to patients without colitis (95% compared to 93%). MAIN LIMITATIONS: Risk factors for infectious colitis could not be determined due to variation in testing protocols in this retrospective study and the low number of positive cases. CONCLUSIONS: Colitis as a postoperative complication does not negatively impact survival to discharge but is associated with longer hospitalisation. Pelvic flexure enterotomy, postoperative leukopenia or leukocytosis, and increased plasma lactate were identified as significant risk factors associated with colitis.

INTRODUCTION/CONTEXTE: Il a été démontré qu'un diagnostic de colite a un impact sur la morbidité et la mortalité des chevaux hospitalisés. Il n'y a aucune étude décrivant l'incidence de colites infectieuses suivant une laparotomie exploratrice. OBJECTIFS: Investiguer les facteurs de risque associés au développement de colites et de colites infectieuses en période post-opératoire suivant une laparotomie exploratrice. TYPE D'ÉTUDE: Étude de type rétrospective avec cas témoins. MÉTHODES: Les dossiers médicaux de chevaux admis entre 2011 et 2020 ont été utilisés. La résultante primaire était un diagnostic de colite suivant une laparotomie exploratrice. Les analyses bivariées entre colites et facteurs de risque ont été évalués par le biais d'un test de Fisher exact et un test de T à deux échantillons. Tous les facteurs de risque ont été sujet à un algorithme de réduction par élimination régressive des variables dans le cadre d'une régression logistique (valeur de p à 0.05). Les probabilités (odds ratio) et les intervalles de confiance à 95% ont été inclus dans le modèle final. RÉSULTATS: Au total, 504 chevaux ont été inclus dans l'étude. Quarante-deux patients (8.3%) ont reçu un diagnostic de colite post-opératoire. Cinq patients ont reçu un diagnostic de Salmonella spp. et deux, de Clostridioides difficile. Les chances de colites post-opératoires étaient plus élevées chez les patients ayant subi une entérotomie de la courbure pelvienne (OR = 3.7, 95% CI = 1.7-7.9, p = 0.0008), ayant souffert d'une leucopénie ou leucocytose (OR = 21.2, 95% CI = 9.7-46.7, p < 0.0001), ou ayant eu une valeur de lactate plasmatique de 2.0-4.0 mmol/L (OR = 3.0, 95% CI = 1.3-6.7, p < 0.0084). Les patients diagnostiqués avec une colite ont eu une durée d'hospitalisation médiane supérieure (9 jours; étendu 2-21) comparativement aux patients sans colite (7 jours; étendu 2-25). Il n'y avait pas de différence entre les patients avec et ceux sans colite, en ce qui a trait au taux de survie de congé hospitalier (95% comparé à 93%). LIMITES PRINCIPALES: Les facteurs de risque pour les colites infectieuses n'ont pas pu être identifié en raison de variations des protocoles de tests employés dans cette étude rétrospective et du faible nombre de cas positifs. CONCLUSIONS: Les colites en tant que complication post-opératoire n'ont pas d'impact négatif sur le taux de survie hospitaliser mais sont associées à une période d'hospitalisation de plus longue durée. Une entérotomie de la courbure pelvienne, une leucopénie ou leucocytose post-opératoire et une valeur élevée de plasma sanguin ont été identifiés comme facteurs de risque associés au développement de colite.

Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow.

Long-lived plasma cells in the bone marrow produce memory antibodies that provide immune protection persisting for decades after infection or vaccination but can also contribute to autoimmune and allergic diseases. However, the composition of the microenvironmental niches that are important for the generation and maintenance of these cells is only poorly understood. Here, we demonstrate that, within the bone marrow, plasma cells interact with the platelet precursors (megakaryocytes), which produce the prominent plasma cell survival factors APRIL (a proliferation-inducing ligand) and IL-6 (interleukin-6). Accordingly, reduced numbers of immature and mature plasma cells are found in the bone marrow of mice deficient for the thrombopoietin receptor (c-mpl) that show impaired megakaryopoiesis. After immunization, accumulation of antigen-specific plasma cells in the bone marrow is disturbed in these mice. Vice versa, injection of thrombopoietin allows the accumulation and persistence of a larger number of plasma cells generated in the course of a specific immune response in wild-type mice. These results demonstrate that megakaryocytes constitute an important component of the niche for long-lived plasma cells in the bone marrow.

Long-term bortezomib treatment reduces allergen-specific IgE but fails to ameliorate chronic asthma in mice.

BACKGROUND: Allergen-specific immunoglobulin (Ig) E initiates the effector cascade of allergic asthma and has been identified as a valuable target for therapeutic treatment of this disease. The proteasome inhibitor bortezomib was previously shown to deplete Ig-secreting plasma cells and to efficiently suppress Ig serum titers. The present study aimed at evaluating the therapeutic potential of the proteasome inhibitor bortezomib in allergic bronchial asthma. METHODS: To address this question, a chronic experimental asthma mouse model was used in a therapeutic setting. Mice were sensitized to ovalbumin (OVA) and challenged with OVA aerosol for 12 weeks. After 6 weeks of challenge, bortezomib treatment was started and continued for 1 week (short-term) or 6 weeks (long-term) with a dosage of 0.75 mg/kg body weight twice a week. Lung function, lung histology, Ig serum titers and plasma cell numbers were assessed. RESULTS: Whereas short-term treatment lowered bronchoalveolar lavage eosinophils, long-term treatment considerably reduced serum titers of anti-OVA IgE in mice with chronic experimental asthma. However, neither short-term nor long-term treatment significantly reduced plasma cell numbers, anti-OVA IgG1 serum titers or allergic airway inflammation or ablated airway hyperresponsiveness. CONCLUSION: Our results suggest that bortezomib treatment has only limited value as plasma cell-depleting therapy against allergic bronchial asthma.

Systemic calcinosis in a Quarter Horse gelding homozygous for a myosin heavy chain 1 mutation.

CASE DESCRIPTION: A 9-year-old Quarter Horse gelding was presented for lethargy, decreased appetite, polyuria and polydipsia (PU/PD), and severe muscle wasting suggestive of immune-mediated myositis. CLINICAL FINDINGS: The horse displayed lethargy, fever, tachyarrhythmia, inappetence, PU/PD, and severe epaxial and gluteal muscle wasting. Clinicopathologic findings were consistent with previously reported cases of systemic calcinosis in horses, including increased muscle enzyme activity, hyperphosphatemia, increased calcium-phosphorus product, hypoproteinemia, and an inflammatory leukogram. A diagnosis of systemic calcinosis was established by histopathologic evaluation of biopsy specimens from skeletal muscle, lung, and kidney. TREATMENT AND OUTCOME: Symptomatic treatment was complemented by IV treatment with sodium thiosulfate to reverse calcium-phosphate precipitation in soft tissue and PO aluminum hydroxide to decrease intestinal phosphorus absorption and serum phosphorus concentration. CLINICAL RELEVANCE: This is the first report in the veterinary literature of an antemortem diagnosis of systemic calcinosis in the horse that was successfully treated and had favorable long-term outcome.

Comparison of two glucose-monitoring systems for use in horses.

OBJECTIVE: To determine the accuracy of 2 interstitial glucose-monitoring systems (GMSs) for use in horses compared with a point-of-care (POC) glucometer and standard laboratory enzymatic chemistry method (CHEM). ANIMALS: 8 clinically normal adult horses. PROCEDURES: One of each GMS device (Dexcom G6 and Freestyle Libre 14-day) was placed on each horse, and blood glucose concentration was measured via POC and CHEM at 33 time points and compared with simultaneous GMS readings. An oral glucose absorption test (OGAT) was performed on day 2, and glucose concentrations were measured and compared. RESULTS: Glucose concentrations were significantly correlated with one another between all devices on days 1 to 5. Acceptable agreement was observed between Dexcom G6 and Freestyle Libre 14-day when compared with CHEM on days 1, 3, 4, and 5 with a combined mean bias of 10.45 mg/dL and 1.53 mg/dL, respectively. During dextrose-induced hyperglycemia on day 2, mean bias values for Dexcom G6 (10.49 mg/dL) and FreeStyle Libre 14-day (0.34 mg/dL) showed good agreement with CHEM. CLINICAL RELEVANCE: Serial blood glucose measurements are used to diagnose or monitor a variety of conditions in equine medicine; advances in near-continuous interstitial glucose monitoring allow for minimally invasive glucose assessment, thereby reducing stress and discomfort to patients. Data from this study support the use of the Dexcom G6 and Freestyle Libre 14-day interstitial glucose-monitoring systems to estimate blood glucose concentrations in horses.

Blood thiamine (vitamin B1 ), ascorbic acid (vitamin C), and cortisol concentrations in healthy and ill neonatal foals.

BACKGROUND: Sepsis is common in foals and several treatments are used to facilitate recovery. Evidence in people suggests an association between low blood concentrations of thiamine, ascorbic acid, and cortisol and sepsis, with further evidence suggesting that administration of hydrocortisone, thiamine, and ascorbic acid may improve outcome. No information is available with regard to these treatments in foals. HYPOTHESIS/OBJECTIVES: To compare blood concentrations of thiamine, ascorbic acid, and cortisol in healthy and ill foals. ANIMALS: Fifteen healthy and 27 ill (septic and sick-nonseptic [SNS]) foals were evaluated at admission. Fewer healthy and ill foals were available for sampling at 72 and 120 hours. METHODS: Prospective study. Blood was collected from healthy foals at 12 (n = 15), 72 (n = 11), and 120 (n = 9) hours of age and from ill foals <48 hours old at admission (n = 27), 72 (n = 8), and 120 (n = 8) hours after presentation. Thiamine, ascorbic acid, and cortisol concentrations were measured in blood samples and compared between groups of foals. RESULTS: Blood concentrations of thiamine were significantly lower in septic compared to healthy foals at 72 (median, 1.72 ng/mL; P = .02) and 120 (median, 2.0 ng/mL; P = .04) hours after admission; blood concentrations of ascorbic acid also were significantly lower in septic compared to healthy foals at 72 (median, 4.4 µg/mL; P = .02) and 120 hours (median, 4.8 µg/mL; P = .03). Blood concentrations of ascorbic acid were lower in SNS compared to healthy foals at 72 (median, 6.9 µg/mL; P = .03) and 120 (median, 6.4 µg/mL; P = .04) hours after admission. Serum cortisol concentrations were significantly higher at admission in septic (median, 4.23 µg/dL) compared to SNS (median, 1.8 µg/dL; P = .01) and healthy (median, 2.2 µg/dL; P = .002) foals. CONCLUSIONS AND CLINICAL IMPORTANCE: A potential association exists between illness in foals and lower blood concentrations of thiamine and ascorbic acid during hospitalization. Additional studies are needed to examine a larger population of foals and determine the clinical impact of low vitamin concentrations, if any, on morbidity and mortality.

Protease-activated receptor 2 has pivotal roles in cellular mechanisms involved in experimental periodontitis.

The tissue destruction seen in chronic periodontitis is commonly accepted to involve extensive upregulation of the host inflammatory response. Protease-activated receptor 2 (PAR-2)-null mice infected with Porphyromonas gingivalis did not display periodontal bone resorption in contrast to wild-type-infected and PAR-1-null-infected mice. Histological examination of tissues confirmed the lowered bone resorption in PAR-2-null mice and identified a substantial decrease in mast cells infiltrating the periodontal tissues of these mice. T cells from P. gingivalis-infected or immunized PAR-2-null mice proliferated less in response to antigen than those from wild-type animals. CD90 (Thy1.2) expression on CD4(+) and CD8(+) T-cell-receptor beta (TCRbeta) T cells was significantly (P < 0.001) decreased in antigen-immunized PAR-2-null mice compared to sham-immunized PAR-2-null mice; this was not observed in wild-type controls. T cells from infected or antigen-immunized PAR-2-null mice had a significantly different Th1/inflammatory cytokine profile from wild-type cells: in particular, gamma interferon, interleukins (interleukin-2, -3, and -17), granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha demonstrated lower expression than wild-type controls. The absence of PAR-2 therefore appears to substantially decrease T-cell activation and the Th1/inflammatory response. Regulation of such proinflammatory mechanisms in T cells and mast cells by PAR-2 suggests a pivotal role in the pathogenesis of the disease.

Proteinase-activated receptor-2 (PAR2) and mouse osteoblasts: regulation of cell function and lack of specificity of PAR2-activating peptides.

1. Using synthetic proteinase-activated receptor-2 (PAR(2))-activating peptides (PAR(2)APs) corresponding to the tethered ligand domain of the extracellular N-terminus of PAR(2) to mimic the actions of activating proteinases and using primary cultures of calvarial osteoblasts derived from both wild-type (WT) and PAR(2)-null (KO) mice, we investigated the potential role of PAR(2) in regulating osteoblast function. 2. Primary calvarial osteoblasts from WT and KO mice were evaluated for their growth kinetics and mineralization in the absence of PAR(2) agonists and for their responses in a variety of functional assays to the PAR(2)APs Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-NH(2)) and 2-furoyl-Leu-Ile-Gly-Arg-Leu-Orn-amide (2-fLIGRLO-NH(2)), as well as to trypsin. 3. In contrast with WT cells, PAR(2)-KO osteoblasts did not exhibit increased collagen Type I mRNA expression in response to SLIGRL-NH(2). When grown in serum-containing medium, KO cells increased in number more rapidly than WT cells, an effect that could be attributed to decreased apoptosis rather than increased proliferation. Surprisingly, in both WT and KO osteoblasts, the two PAR(2)APs induced mobilization of intracellular calcium stores. Similarly, the PAR(2)APs inhibited serum deprivation-induced apoptosis and parathyroid hormone-, 1,25-dihydroxyvitamin D(3)- or interleukin-11-induced mineralization in WT and KO cells. 4. We conclude that PAR(2) plays a role in osteoblast survival and collagen Type I mRNA induction and that osteoblasts can respond to the PAR(2)APs via both PAR(2)-dependent and -independent mechanisms.

Physiologic effects of nasopharyngeal administration of supplemental oxygen at various flow rates in healthy neonatal foals.

OBJECTIVE: To evaluate the effects of various flow rates of oxygen administered via 1 or 2 nasal cannulae on the fraction of inspired oxygen concentration (FIO2) and other arterial blood gas variables in healthy neonatal foals. ANIMALS: 9 healthy neonatal (3- to 4-day-old) foals. PROCEDURES: In each foal, a nasal cannula was introduced into each naris and passed into the nasopharynx to the level of the medial canthus of each eye; oxygen was administered at 4 flow rates through either 1 or both cannulae (8 treatments/foal). Intratracheal FIO2, intratracheal end-tidal partial pressure of carbon dioxide, and arterial blood gas variables were measured before (baseline) and during unilateral and bilateral nasopharyngeal delivery of 50, 100, 150, and 200 mL of oxygen/kg/min. RESULTS: No adverse reactions were associated with administration of supplemental oxygen except at the highest flow rate, at which the foals became agitated. At individual flow rates, significant and dose-dependent increases in FIO2, PaO2, and oxygen saturation of hemoglobin (SaO2) were detected, compared with baseline values. Comparison of unilateral and bilateral delivery of oxygen at similar cumulative flow rates revealed no differences in evaluated variables. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that administration of supplemental oxygen via nasal cannulae appeared to be a highly effective means of increasing FIO2, PaO2, and SaO2 in neonatal foals. These findings may provide guidance for implementation of oxygen treatment in hypoxemic neonatal foals.

Baseline plasma cortisol and ACTH concentrations and response to low-dose ACTH stimulation testing in ill foals.

OBJECTIVE: To evaluate baseline plasma cortisol and ACTH concentrations and responses to low-dose ACTH stimulation testing in ill foals. DESIGN: Cross-sectional study. ANIMALS: 58 ill foals. PROCEDURES: Baseline cortisol and ACTH concentrations and cortisol concentrations after administration of a low dose of cosyntropin were determined within 6 hours after admission. Foals were assigned to 4 groups on the basis of age (

Multinodular pulmonary fibrosis in five horses.

CASE DESCRIPTION: 5 horses were evaluated because of decreased appetite, weight loss, fever, cough, tachypnea, and respiratory distress. CLINICAL FINDINGS: Tachycardia, tachypnea, increased respiratory effort, lethargy, fever, poor body condition, and nasal discharge were detected in various combinations on initial physical examination. Evaluation of the lower portion of the respiratory tract via radiography and ultrasonography revealed a severe nodular interstitial pattern. Histologic examination of lung tissue revealed interstitial expansion of alveolar parenchyma with collagen, intraluminal accumulation of neutrophils and macrophages within the alveoli, and occasional intranuclear inclusion bodies within alveolar macrophages. Equine herpesvirus type 5 was detected in samples of lung tissue, bronchoalveolar lavage fluid, or both via polymerase chain reaction assay in all cases. A diagnosis of equine multinodular pulmonary fibrosis (EMPF) was established. TREATMENT AND OUTCOME: Horses were provided supportive treatment and were administered a variety of medications including corticosteroids and acyclovir. Two horses survived and returned to their previous level of activity. Three horses were euthanized because of either deterioration of clinical condition (n=2) or failure to improve within 4 weeks of initiation of treatment (1). CLINICAL RELEVANCE: EMPF should be considered as a differential diagnosis for adult horses with interstitial pneumonia and should be suspected on the basis of characteristic radiographic, ultrasonographic, and histopathologic findings. Equine herpesvirus type 5 is found in association with EMPF; although the exact pathogenic role this virus plays in EMPF is unknown, equine herpesvirus type 5 may be an etiologic agent or cofactor in the development of EMPF.

Measured and calculated variables of global oxygenation in healthy neonatal foals.

OBJECTIVE To assess multiple central venous and arterial blood variables that alone or in conjunction with one another reflect global oxygenation status in healthy neonatal foals. ANIMALS 11 healthy neonatal foals. PROCEDURES Central venous and arterial blood samples were collected from healthy neonatal foals at 12, 24, 36, 48, 72, and 96 hours after birth. Variables measured from central venous and arterial blood samples included oxygen saturation of hemoglobin, partial pressure of oxygen, lactate concentration, partial pressure of carbon dioxide, and pH. Calculated variables included venous-to-arterial carbon dioxide gap, estimated oxygen extraction ratio, ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen, bicarbonate concentration, base excess, and blood oxygen content. RESULTS Significant differences between arterial and central venous blood obtained from neonatal foals were detected for several variables, particularly partial pressure of oxygen, oxygen saturation of hemoglobin, and oxygen content. In addition, the partial pressure of carbon dioxide in central venous blood samples was significantly higher than the value for corresponding arterial blood samples. Several temporal differences were detected for other variables. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study provided information about several variables that reflect global oxygenation in healthy neonatal foals. Values for these variables in healthy foals can allow for comparison with values for critically ill foals in future studies. Comparison of these variables between healthy and ill foals may aid in treatment decisions and prognosis of clinical outcome for critically ill foals.