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1.
Postgrad Med J ; 93(1096): 61-66, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27307473

ABSTRACT

BACKGROUND: Many acute hospital specialties are experiencing low recruitment and high attrition of trainees. Understanding what is important to current trainees is critical in terms of identifying and addressing factors which adversely affect recruitment and retention. OBJECTIVES: To identify and explore factors involved in anaesthetic trainees' career decision making. METHODS: This was a mixed methods study using a questionnaire survey (assessing how influential 18 different factors were when choosing anaesthetics, using a five-point Likert scale), supplemented by semi-structured interviews, carried out in August-December 2014, in Scotland, UK. RESULTS: 42/68 (62%) completed responses were received, representing over half of all core (58%) and Acute Care Common Stem (65%) trainees across Scotland. Overall, questionnaire data indicated that the following were most important in career decision making: perceived job satisfaction among those already in the specialty, structured training, the nature of the work (practical, varied, immediate outcomes). Thirteen interviews were carried out. These highlighted that prior positive exposure and experience with anaesthetists encouraged trainees into the specialty. Enthusiastic, supportive colleagues and structured training (including clear milestones, regular teaching and feedback) were considered to enhance the quality of training. Sustainable working conditions, flexibility within programme and out-of-programme opportunities were valued. Respondents reported concerns about the impact of increasing service delivery demands on training quality. CONCLUSIONS: Many of the elements important to today's anaesthetics trainees are related to positive learning and working environments. This fits with research findings from other professional groups. These findings can inform the development of programmes which cultivate trainee commitment to, and enthusiasm for, anaesthetics.


Subject(s)
Anesthesiology/education , Career Choice , Education, Medical, Graduate , Specialization/statistics & numerical data , Students, Medical/statistics & numerical data , Adult , Attitude of Health Personnel , Choice Behavior , Female , Humans , Job Satisfaction , Male , Scotland/epidemiology , Students, Medical/psychology , Surveys and Questionnaires
2.
CPT Pharmacometrics Syst Pharmacol ; 5(9): 495-502, 2016 09.
Article in English | MEDLINE | ID: mdl-27639260

ABSTRACT

The literature on the pharmacokinetics of vancomycin in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy is sparse. A population pharmacokinetic (PK) model for vancomycin in ECMO patients was developed using a nonlinear mixed effects modeling on the concentration-time profiles of 14 ECMO patients who received intravenous vancomycin. Model selection was based on log-likelihood criterion, goodness of fit plots, and scientific plausibility. Identification of covariates was done using a full covariate model approach. The pharmacokinetics of vancomycin was adequately described with a two-compartment model. Parameters included clearance of 2.83 L/hr, limited central volume of distribution 24.2 L, and low residual variability 0.67%. Findings from the analysis suggest that standard dosing recommendations for vancomycin in non-ECMO patients are adequate to achieve therapeutic trough concentrations in ECMO patients. This further shows that ECMO minimally affects the PK of vancomycin in adults including in higher-weight patients.


Subject(s)
Anti-Bacterial Agents/blood , Extracorporeal Membrane Oxygenation/statistics & numerical data , Models, Biological , Nonlinear Dynamics , Vancomycin/blood , Adult , Aged , Anti-Bacterial Agents/pharmacokinetics , Female , Humans , Male , Middle Aged , Monte Carlo Method , Prospective Studies , Vancomycin/pharmacokinetics
3.
Vet Immunol Immunopathol ; 155(1-2): 1-8, 2013 Sep 01.
Article in English | MEDLINE | ID: mdl-23820116

ABSTRACT

Although clinical evidence of endotoxemia has been associated with the development of acute laminitis in hospitalized horses with gastrointestinal diseases and endotoxins have been detected in the circulation of horses with experimentally-induced laminitis, it is unclear what role, if any, endotoxins have play the pathogenesis of the disease. Therefore, in the present study we compared the effects of endotoxin infusion to that of intra-gastric administration of mixed carbohydrate (CHO) on clinical signs of laminitis, plasma concentrations of TNF-α and IL-10, and laminar tissue expression of 20 genes associated with inflammation. Horses were divided into 4 groups: Control (water placebo, n=7), endotoxin infusion (LPS, n=6), CHO/Developmental (30% decrease in central venous pressure, n=6) and CHO/Lame (Obel grade I laminitis, n=7). Horses in the LPS group developed clinical signs consistent with systemic inflammation, had rapid increases in plasma concentrations of both TNF-α and IL-10, and leukopenia, but did not have any changes in laminar tissue expression of the genes associated with inflammation. In contrast, horses administered CHO developed clinical signs consistent with systemic inflammation, had more delayed increases in TNF-α, IL-10 and total leukocyte counts, and had marked increases in laminar tissue expression of the genes associated with inflammation. Only the horses administered CHO developed clinical signs of laminitis, providing additional credence to the concept that factors other than endotoxin are responsible for the changes in laminar tissue gene expression that occur during the development of acute equine laminitis.


Subject(s)
Foot Diseases/veterinary , Hoof and Claw , Horse Diseases/etiology , Horses/genetics , Horses/immunology , Inflammation/veterinary , Animals , Dietary Carbohydrates/administration & dosage , Endotoxemia/genetics , Endotoxemia/immunology , Endotoxemia/veterinary , Female , Foot Diseases/genetics , Foot Diseases/immunology , Gene Expression/drug effects , Horse Diseases/genetics , Horse Diseases/immunology , Inflammation/genetics , Inflammation/immunology , Interleukin-10/blood , Lameness, Animal/etiology , Lameness, Animal/genetics , Lameness, Animal/immunology , Lipopolysaccharides/administration & dosage , Male , Tumor Necrosis Factor-alpha/blood
4.
J Vet Pharmacol Ther ; 35(5): 472-7, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22091605

ABSTRACT

The purpose of this study was to determine the pharmacokinetics (PK) of the 5-HT(2A) receptor antagonist ketanserin in healthy adult horses, and to develop a computational model that could be used to optimize dosing. Plasma concentrations of ketanserin were determined using liquid chromatography with mass spectrometry after single and multiple intravenous administration in the horse. A two-compartment linear pharmacokinetic model described the plasma concentration-time profile of ketanserin after single and multiple doses in healthy horses; the terminal half-life was 11.5 h; steady-state volume of distribution was 10.5 L/kg; AUC was 115 ng · h/mL; and clearance was 0.87 L/h/kg. Model simulations followed by the examination in three healthy horses suggest 0.3 mg/kg q.8 h exhibited linear PK and produced consistent systemic blood concentrations of ketanserin above 3 ng/mL.


Subject(s)
Horses/blood , Ketanserin/pharmacokinetics , Platelet Aggregation Inhibitors/pharmacokinetics , Animals , Area Under Curve , Female , Half-Life , Horses/metabolism , Ketanserin/blood , Ketanserin/chemistry , Molecular Structure , Platelet Aggregation Inhibitors/blood , Platelet Aggregation Inhibitors/chemistry
5.
J Vet Intern Med ; 25(2): 307-14, 2011.
Article in English | MEDLINE | ID: mdl-21314719

ABSTRACT

BACKGROUND: Coagulopathies in horses with gastrointestinal disease are frequently identified and associated with morbidity and fatality. OBJECTIVE: Determine if thrombelastography (TEG) identifies abnormalities associated with lesion type, presence of systemic inflammatory response syndrome (SIRS), morbidity, and fatality more consistently than traditional coagulation testing. ANIMALS: One-hundred and one horses examined for gastrointestinal disease and 20 healthy horses. METHODS: TEG, tissue factor (TF)-TEG, and traditional coagulation panels parameters and percentages of horses with coagulopathies were compared for lesion type, presence of SIRS, complications, and survival. RESULTS: Changes in individual parameters and increased incidence of coagulopathies were associated with fatality (R, P= .007; k-value [K], P= .004; clot lysis [CL]30, P= .037; CL60, P= .050; angle [Ang], P= .0003; maximum amplitude [MA], P= .006; lysis [Ly]30, P= .042; Ly60, P= .027; CI, P= .0004; ≥ 2 TEG coagulopathies, P= .013; ≥ 3 TEG coagulopathies, P= .038; TF-R, P= .037; TF-K, P= .004; TF-CL30, P < .0001; TF-CL60, P < .0001; TF-Ang, P= .005; TF-Ly30, P= .0002; TF-Ly60, P < .0001; TF-CI, P= .043; ≥ 1 TF-TEG coagulopathies, P= .003; ≥ 2 TF-TEG coagulopathies, P= .0004; prothrombin tme [PT], P < .0001; activated partial throboplastin time [aPTT], P= .021), inflammatory lesions (MA, P= .013; TF-CL30, P= .033; TF-CL60, P= .010; TF-Ly60, P= .011; ≥ 1 TF-TEG coagulopathy, P= .036; ≥ 2 TF-TEG coagulopathy, P= .0007; PT, P= .0005; fibrinogen, P= .019), SIRS (MA, P= .004; TF-CL30, P= .019; TF-CL60, P= .013; TF-Ly30, P= .020; TF-Ly60, P= .010; PT, P < .0001; aPTT, P= .032; disseminated intravascular coagulation, P= .005), and complications (ileus: aPTT, P= .020; diarrhea: TF-CL30, P= .040; TF-Ly30, P= .041; thrombophlebitis: ≥ 1 TF-TEG coagulopathy, P= .018; laminitis: MA, P= .004; CL60, P= .045; CI, P= .036; TF-MA, P= .019; TF-TEG CI, P= .019). Abnormalities in TEG and TF-TEG parameters were indicative of hypocoagulation and hypofibrinolysis. CONCLUSIONS AND CLINICAL IMPORTANCE: TEG identifies changes in coagulation and fibrinolysis associated with lesion type, SIRS, morbidity, and fatality in horses with gastrointestinal disease.


Subject(s)
Blood Coagulation/physiology , Gastrointestinal Diseases/veterinary , Horse Diseases/blood , Thrombelastography/veterinary , Animals , Blood Coagulation Factors/metabolism , Blood Coagulation Tests/methods , Blood Coagulation Tests/veterinary , Case-Control Studies , Female , Gastrointestinal Diseases/blood , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/mortality , Hemostasis , Horse Diseases/diagnosis , Horse Diseases/mortality , Horses , Male , Prospective Studies , Survival Analysis , Thromboplastin/chemistry
6.
J Vet Intern Med ; 25(1): 116-22, 2011.
Article in English | MEDLINE | ID: mdl-21143302

ABSTRACT

BACKGROUND: Critically ill horses are susceptible to thrombotic disease, which might be related to increased platelet reactivity and activation. OBJECTIVES: To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function. ANIMALS: Six healthy adult horses. METHODS: Horses received clopidogrel (2 mg/kg p.o. q24h) or ASA (5 mg/kg p.o. q24h) for 5 days in a prospective randomized cross-over design. Platelet aggregation responses to adenosine diphosphate (ADP) and collagen via optical aggregometry, and platelet secretion of serotonin (5HT) and production of thromboxane B(2) (TXB(2) ) by ELISA were evaluated. In horses receiving clopidogrel, high-performance liquid chromatography analysis for clopidogrel and its carboxylic-acid metabolite SR 26334 was performed. RESULTS: SR 26334 was identified in all clopidogrel-treated horses, although the parent compound was not detected. Clopidogrel resulted in decreases in ADP-induced platelet aggregation persisting for 120 hours after the final dose. ADP-induced platelet aggregation decreased from a baseline of 70.2 ± 14.7% to a minimum of 15.9 ± 7.7% 24 hours after the final dose (P < .001). Collagen-induced aggregation decreased from a baseline of 93 ± 9.5% to a minimum of 70.8 ± 16.9% 48 hours after the final dose (P < .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB(2) from a baseline value of 1310 ± 1045 to 128 ± 64 pg/mL within 24 hours (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Clopidogrel effectively decreases ADP-induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.


Subject(s)
Aspirin/pharmacology , Blood Platelets/drug effects , Horses/physiology , Serotonin/blood , Thromboxane B2/biosynthesis , Ticlopidine/analogs & derivatives , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Area Under Curve , Aspirin/pharmacokinetics , Blood Platelets/physiology , Clopidogrel , Cross-Over Studies , Female , Horses/blood , Male , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Platelet Count/veterinary , Prospective Studies , Random Allocation , Thrombosis/prevention & control , Thrombosis/veterinary , Thromboxane B2/blood , Ticlopidine/pharmacokinetics , Ticlopidine/pharmacology
7.
Vet Immunol Immunopathol ; 131(1-2): 65-72, 2009 Sep 15.
Article in English | MEDLINE | ID: mdl-19376596

ABSTRACT

Quantification of gene expression using real-time reverse transcription quantitative PCR (RT-qPCR) is a reliable method to monitor cellular responses to pro-inflammatory stimuli. The main objective of this study was to validate a set of equine primer pairs that can be routinely used to monitor expression of genes that are central to inflammatory and immune responses. This paper describes the steps used to optimize and validate 29 equine primer pairs for RT-qPCR assays using SYBR Green detection. To validate these assays, monocytes were isolated from three horses and stimulated with Escherichia coli LPS. Because four of the 29 genes demonstrated poor amplification efficiency due to weak induction of gene expression by LPS, monocytes were stimulated with alternative agents (PMA and Poly I:C) known to induce gene expression in monocytes. These agents, acting through different pathways than LPS, improved the level of gene expression and yielded good amplification efficiency for these genes. PCR efficiency was based on a standard curve for each gene and the calculated efficiency was approximately 100% for all 29 genes. The PCR efficiencies for the majority of the target genes were equivalent to that of the housekeeping gene (18S rRNA) used in all experiments. Dissociation curve analysis and gel electrophoresis revealed a single product for each gene analyzed. To exemplify utilization of the validated primer pairs in studies of inflammatory cell activation, temporal changes in mRNA expression of a subset of genes were monitored in equine monocytes incubated with LPS. The availability of the 29 validated primer pairs reported herein will allow investigators to elucidate the response of horses to a variety of inflammatory stimuli and will further our understanding of disease pathogenesis in horses.


Subject(s)
DNA Primers , Horses/immunology , Leukocytes/metabolism , Reverse Transcriptase Polymerase Chain Reaction/methods , Animals , RNA, Messenger/analysis
8.
Vet Immunol Immunopathol ; 129(3-4): 155-7, 2009 Jun 15.
Article in English | MEDLINE | ID: mdl-19131119

ABSTRACT

The horse with gram negative sepsis is known to be at particular risk of succumbing to laminitis. This review summarizes recent evidence indicating that similar pathologic events relating to inflammatory injury occur in laminar failure in laminitis as occur in organ injury/failure in human sepsis. The discussion also points out some important differences between the laminae and target organs in human sepsis that impact the clinical nature of the disease.


Subject(s)
Foot Diseases/veterinary , Gram-Negative Bacterial Infections/veterinary , Hoof and Claw , Horse Diseases/etiology , Sepsis/veterinary , Animals , Foot Diseases/etiology , Foot Diseases/immunology , Gram-Negative Bacterial Infections/complications , Gram-Negative Bacterial Infections/immunology , Horse Diseases/immunology , Horse Diseases/pathology , Horses , Humans , Inflammation/etiology , Inflammation/immunology , Inflammation/veterinary , Sepsis/complications , Sepsis/immunology
9.
J Neurol Neurosurg Psychiatry ; 79(11): 1202-7, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18469029

ABSTRACT

BACKGROUND: Accurate diagnosis of the cause of parkinsonism during life can be difficult, particularly at presentation, but few studies have described changes in clinical diagnosis over time and the effect of applying strict research criteria. METHODS: Incident patients with a possible/probable diagnosis of degenerative or vascular parkinsonism had a standardised assessment at diagnosis and at yearly intervals thereafter at which the most likely clinical diagnosis was recorded without strict application of research criteria. Four years after the beginning of the incident period, formal research criteria were applied retrospectively using patient records at baseline and the latest yearly follow-up. RESULTS: Of 82 incident patients, 66 underwent at least 1 year of follow-up. After a median follow-up of 29 months, clinical diagnosis had changed in 22 (33%). Most (82%) changes occurred in the first year and were due to the development of atypical clinical features, particularly early cognitive impairment; the results of brain imaging; responsiveness to levodopa; and the rate of disease progression. Diagnosis on research criteria differed from latest clinical diagnosis in eight participants (12%). Research criteria gave a "probable" diagnosis in 71% of parkinsonian patients at follow-up but in only 15% at the initial assessment. DISCUSSION: The clinical diagnosis of the cause of parkinsonism at presentation was often incorrect, even when made by those with a special interest. In particular, Parkinson's disease was overdiagnosed. Research criteria were often unhelpful in clarifying the diagnosis, even after a median of 29 months of follow-up. Further research is required to identify factors that may be used to improve the accuracy of diagnosis at initial assessment.


Subject(s)
Parkinsonian Disorders/diagnosis , Aged , Antiparkinson Agents/therapeutic use , Brain/diagnostic imaging , Brain/pathology , Brain/physiopathology , Diagnosis, Differential , Disease Progression , Female , Follow-Up Studies , Humans , Levodopa/therapeutic use , Magnetic Resonance Imaging , Male , Parkinsonian Disorders/drug therapy , Parkinsonian Disorders/physiopathology , Pilot Projects , Predictive Value of Tests , Severity of Illness Index , Surveys and Questionnaires , Tomography, X-Ray Computed
10.
Equine Vet J ; 39(3): 243-8, 2007 May.
Article in English | MEDLINE | ID: mdl-17520976

ABSTRACT

REASONS FOR PERFORMING STUDY: Endotoxaemia currently is associated with a poor prognosis in horses. The results of recent trials in other species indicate that phospholipid emulsions reduce the deleterious effects of endotoxin (LPS). However, in a previous study in horses, a 2 h infusion of emulsion caused an unacceptable degree of haemolysis. HYPOTHESIS: Rapid administration of a lower total dose of emulsion would reduce the effects of LPS and induce less haemolysis; the emulsion would reduce inflammatory effects of LPS in vitro. METHODS: Twelve healthy horses received an i.v. infusion either of saline or a phospholipid emulsion (100 mg/kg), followed immediately by E. coli 055:B5 LPS (30 ng/kg). Clinical parameters, haematological profiles, serum tumour necrosis factor (TNF) activity, serum lipid profiles, urine analyses and severity of haemolysis were monitored before and at selected times after LPS. Monocytes were also incubated in vitro with LPS in the presence or absence of emulsion, after which TNF and tissue factor activities were determined. RESULTS: Clinical signs of endotoxaemia were reduced in horses receiving the emulsion, including clinical score, heart rate, rectal temperature, serum TNF activity, and the characteristic leucopenic response to LPS, when compared to horses not receiving the emulsion. Three horses receiving the emulsion had none, 2 had mild and one had moderate haemolysis. There were no differences in urinalysis results and creatinine concentrations, either within the groups over time or between the groups. Serum concentrations of phosphatidylcholine, bile acids and triglycerides peaked immediately after the infusion; there were no significant changes in concentrations of nonesterified fatty acids or cholesterol. Incubation of equine monocytes with emulsion prevented LPS-induced TNF and tissue factor activities. CONCLUSIONS: Rapid administration of emulsion significantly reduced inflammatory effects of LPS in vivo and caused a clinically insignificant degree of haemolysis. The results of the in vitro studies indicate that emulsion prevents not only LPS-induced synthesis of cytokines, but also expression of membrane-associated mediators (i.e. tissue factor). POTENTIAL RELEVANCE: Rapid i.v. administration of emulsions containing phospholipids that bind endotoxin may provide a clinically useful method of treating endotoxaemia in horses.


Subject(s)
Endotoxemia/veterinary , Fat Emulsions, Intravenous/therapeutic use , Hemolysis/drug effects , Horse Diseases/therapy , Phospholipids/therapeutic use , Animals , Area Under Curve , Body Temperature/drug effects , Dose-Response Relationship, Drug , Endotoxemia/therapy , Fat Emulsions, Intravenous/adverse effects , Female , Heart Rate/drug effects , Horse Diseases/chemically induced , Horses , Infusions, Intravenous/veterinary , Kinetics , Male , Phospholipids/adverse effects , Severity of Illness Index , Time Factors , Treatment Outcome
11.
Vet Immunol Immunopathol ; 116(3-4): 182-9, 2007 Apr 15.
Article in English | MEDLINE | ID: mdl-17320193

ABSTRACT

Sepsis and endotoxaemia are important causes of morbidity and mortality in humans. Research on sepsis focuses on rodent models most of which are poorly responsive to lipopolysaccharide (LPS), and thus do not mimic very well the high sensitivity of humans. Therefore, there is a need to develop more clinically relevant models. Horses suffer from a similar endotoxaemic syndrome to humans with high morbidity and mortality. LPS analogues that act as antagonists at Toll-like receptor 4 (TLR4) are being developed as novel treatments for endotoxaemia. Due to differences in recognition of ligands by TLR4 from different mammalian species, individual LPS molecules may act as agonists in some species and antagonists in others. The synthetic lipid A analogue E5531 is an antagonist at TLR4 in humans and mice, but its effects at TLR4 from other species are unknown. In the studies reported here, Escherichia coli LPS is a full agonist on equine bone marrow macrophage-like cells and its effects are antagonised by E5531. Similarly, E. coli LPS is an agonist and E5531 an antagonist on monocytes isolated from peripheral blood of healthy horses and human embryonic kidney (HEK) cells, transiently transfected to express horse TLR4 and its associated cell surface proteins MD2 and CD14. In contrast, both E. coli LPS and E5531 behave as agonists in horse whole blood by inducing production of equivalent amounts of the inflammatory mediator prostaglandin. This finding suggests that modification of E5531 may occur in whole blood, for example, deacylation, which alters its activity. This comparative study has revealed a novel pharmacological action of E5531 and emphasises the importance of extending studies of this nature beyond the normal rodent models.


Subject(s)
Lipid A/analogs & derivatives , Toll-Like Receptor 4/agonists , Toll-Like Receptor 4/antagonists & inhibitors , Animals , Cell Line , Dinoprostone/blood , Disease Models, Animal , Endotoxemia/etiology , Epoprostenol/blood , Female , Humans , In Vitro Techniques , Interferon-gamma/pharmacology , Lipid A/pharmacology , Lipopolysaccharides/pharmacology , Male , Mice , Monocytes/drug effects , Monocytes/metabolism , Recombinant Proteins/agonists , Recombinant Proteins/antagonists & inhibitors , Recombinant Proteins/genetics , Sepsis/etiology , Species Specificity , Toll-Like Receptor 4/blood , Toll-Like Receptor 4/genetics , Transfection
12.
Equine Vet J ; 37(6): 546-51, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16295933

ABSTRACT

REASONS FOR PERFORMING STUDY: Equine laminitis purportedly involves haemodynamic dysfunction at the level of the laminar vasculature. However, to date, no studies have been performed characterising the function of laminar arteries and veins during the prodromal stages of equine laminitis. HYPOTHESIS: That the prodromal stages of laminitis are associated with contractile dysfunction of the equine laminar vasculature. OBJECTIVE: To assess contractile function of laminar arteries and veins to phenylephrine (PE) and 5-hydroxytryptamine (5-HT). METHODS: Horses were administered black walnut heartwood extract (BWHE) or water (control horses) via nasogastric intubation. After euthanasia, laminar vessels (100-800 microm internal diameter) were isolated and mounted on small vessel myographs to assess contractile function. RESULTS: Contractile responses to PE or 5-HT were identical in laminar arteries isolated from either control horses or those administered BWHE. In contrast, responses to PE or 5-HT were significantly reduced in laminar veins isolated from BWHE-administered horses when compared with laminar veins isolated from control horses. CONCLUSIONS AND POTENTIAL RELEVANCE: These results are consistent with the prodromal stages of laminitis being associated with selective dysfunction of laminar veins. Further studies are required to discern the precise nature of this dysfunction and its potential relevance to the pathogenesis of acute laminitis in the horse and possible therapeutic targets for treatment.


Subject(s)
Foot Diseases/veterinary , Hoof and Claw/blood supply , Horse Diseases/physiopathology , Lameness, Animal/physiopathology , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Animals , Foot Diseases/pathology , Foot Diseases/physiopathology , Forelimb/blood supply , Horse Diseases/pathology , Horses , Juglans , Lameness, Animal/pathology , Phenylephrine/pharmacology , Plant Extracts/pharmacology , Random Allocation , Serotonin/pharmacology
14.
Equine Vet J ; 37(3): 212-6, 2005 May.
Article in English | MEDLINE | ID: mdl-15892228

ABSTRACT

REASONS FOR PERFORMING STUDY: Prognosis of Rhodococcus equi pneumonia can be challenging because the course of the disease is often insidious and overt clinical signs are subtle. Early diagnosis is considered desirable because it may offer the chance of more successful implementation of treatment and, thereby, improved outcome. Serological tests have previously failed to be accurate for early detection or diagnosis. Measurement of serum amyloid A (SAA) prior to and at the time of clinical signs was therefore chosen in order to assess its potential clinical use. OBJECTIVE: To determine whether SAA concentrations differentiate foals affected with R. equi pneumonia from unaffected foals, either prior to the onset of disease or at the time of onset of clinical signs. HYPOTHESIS: SAA concentrations are significantly higher among foals that develop R. equi pneumonia than in foals from the same environment that remain clinically unaffected. METHODS: Serum samples were obtained from 212 foals 7-14 days and 196 foals 21-28 days post partum, and from affected foals and age-matched controls at the time of onset of signs of pneumonia. SAA concentration was determined for each sample. RESULTS: There were no significant differences between SAA concentrations of foals with R. equi and clinically unaffected foals during the 2 periods of examination or at the time of onset of clinical signs of R. equi pneumonia. CONCLUSIONS: Concentrations of SAA are variable among foals with R. equi pneumonia and cannot be used reliably either as an ancillary diagnostic tool or to screen for early detection of disease during the first month post partum. POTENTIAL RELEVANCE: Bimonthly monitoring concentration of SAA is not useful as a screening test for early detection of R. equi pneumonia and does not facilitate diagnosis of this disease when used according to the protocol of this study.


Subject(s)
Actinomycetales Infections/veterinary , Horse Diseases/blood , Pneumonia, Bacterial/veterinary , Rhodococcus equi , Serum Amyloid A Protein/analysis , Actinomycetales Infections/blood , Actinomycetales Infections/diagnosis , Aging/blood , Animals , Animals, Newborn/blood , Diagnosis, Differential , Horse Diseases/diagnosis , Horses , Pneumonia, Bacterial/blood , Pneumonia, Bacterial/diagnosis , Predictive Value of Tests , Prognosis , Sensitivity and Specificity
15.
Phys Rev Lett ; 92(25 Pt 1): 251601, 2004 Jun 25.
Article in English | MEDLINE | ID: mdl-15244994

ABSTRACT

We describe and numerically test the velocity-dependent one-scale string evolution model, a simple analytic approach describing a string network with the averaged correlation length and velocity. We show that it accurately reproduces the large-scale behavior (in particular the scaling laws) of numerical simulations of both Goto-Nambu and field theory string networks. We explicitly demonstrate the relation between the high-energy physics approach and the damped and nonrelativistic limits which are relevant for condensed matter physics. We also reproduce experimental results in this context and show that the vortex-string density is significantly reduced by loop production, an effect not included in the usual "coarse-grained" approach.

16.
Vet Immunol Immunopathol ; 97(3-4): 187-94, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14741137

ABSTRACT

Three overlapping fragments of the equine interleukin-4 receptor alpha chain gene (IL4R) were cloned and sequenced. The resulting 3553 bp cDNA sequence exhibited homology to human, murine and bovine IL4R. The equine IL4R exhibits many conserved features when compared to other species, including intron-exon boundary positions and amino acid sequence motifs characteristic of type I cytokine receptors. The IL4R gene was localized to horse chromosome ECA13 by synteny mapping on a somatic cell hybrid panel. Evidence for an alternative splice variant of IL4R was found in the genomic sequence and subsequently verified using RT-PCR on equine monocyte RNA. A polymorphism screen of the largest exon, homologous to exon 12 of the human IL4R gene, was performed using DNA from 60 horses of various breeds which yielded 11 coding-region single nucleotide polymorphisms (SNPs), 7 synonymous and 4 non-synonymous. Three of the four non-synonymous SNPs occur at high frequencies and are found very near a conserved tyrosine residue.


Subject(s)
Horse Diseases/genetics , Horse Diseases/immunology , Horses/genetics , Receptors, Interleukin-4/genetics , Alternative Splicing , Amino Acid Sequence , Animals , Base Sequence , Chromosome Mapping/veterinary , Cloning, Molecular , DNA, Complementary/genetics , Humans , Molecular Sequence Data , Polymorphism, Single Nucleotide , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Receptors, Interleukin-4/immunology , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Sequence Alignment , Sequence Analysis, DNA
18.
Am J Vet Res ; 62(5): 714-20, 2001 May.
Article in English | MEDLINE | ID: mdl-11341391

ABSTRACT

OBJECTIVE: To study expression of interleukin-1beta (IL-1beta) in the digital laminae of horses in the prodromal stage of experimentally induced laminitis. ANIMALS: 8 healthy adult horses with no signs of laminitis. PROCEDURES: Black walnut extract was administered via nasogastric tube to 4 horses, and water was administered to the remaining 4 (controls). Complete blood counts and physical examinations were performed every 30 minutes after administration of black walnut extract or water. General anesthesia was induced when total WBC count decreased by 30% in horses given the black walnut extract and 3 hours after water administration in control horses. The left forefoot was perfusion fixed with neutral-buffered 10% formalin, and paraffin-embedded sections of the digit were used for in situ hybridization with an equine-specific IL-1beta probe. RESULTS: IL-1beta mRNA expression was observed in perivascular cells of the small laminar venules and capillaries in all 4 horses given black walnut extract and in interstitial cells remote from the microvasculature in 1 of the 4. Other cellular components of the laminar tissue and cellular components of the digital arterioles and veins did not exhibit IL-1beta mRNA expression. Expression of IL-1beta mRNA was not detected in laminae from control horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that IL-1beta mRNA is expressed by perivascular cells in the laminar tissues of horses in the prodromal stage of experimentally induced laminitis. This provides evidence of an inflammatory process during the prodromal stage of laminitis, indicating that local digital proinflammatory cytokine expression may be an initiating factor in laminitis.


Subject(s)
Foot Diseases/veterinary , Horse Diseases/metabolism , Interleukin-1/biosynthesis , Lameness, Animal/metabolism , Animals , Foot Diseases/metabolism , Foot Diseases/pathology , Forelimb/metabolism , Forelimb/pathology , Hoof and Claw/metabolism , Hoof and Claw/pathology , Horse Diseases/pathology , Horses , In Situ Hybridization , Interleukin-1/analysis , Interleukin-1/genetics , Lameness, Animal/pathology , Leukocyte Count/veterinary , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction
19.
Am J Vet Res ; 62(12): 1957-63, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11763188

ABSTRACT

OBJECTIVE: To determine messenger RNA expression of cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-alpha, and interleukin- (IL)-1beta from cultured equine smooth muscle cells (SMC). SAMPLE POPULATION: Segments of palmar digital artery harvested from 6 clinically normal adult horses. PROCEDURE: Explants were collected from the tunica media of arteries for primary culture of SMC. Equine mononuclear cells were used as control cells. Subcultured vascular SMC and control cells were exposed to lipopolysaccharide (20 microg/ml and 100 ng/ml, respectively). Northern blot analysis with equine-specific probes for COX-2, TNF-alpha, and IL-1beta was performed, using isolated total cellular RNA. RESULTS: Although no message was detected for IL-1beta or TNF-alpha in control or endotoxin-exposed equine vascular SMC from all horses, COX-2 underwent a distinct substantial up-regulation after endotoxin exposure. Endotoxin-exposed equine mononuclear cells had up-regulation of IL-1beta and TNF-alpha mRNA. CONCLUSIONS AND CLINICAL RELEVANCE: Increased expression of COX-2 mRNA by equine vascular SMC may be an important early pathophysiologic event in the onset of endotoxemia in horses. Potentiated local vascular production of various prostanoids after increased expression of mRNA for COX-2 may result in vasoactive events observed with laminitis.


Subject(s)
Interleukin-1/biosynthesis , Isoenzymes/biosynthesis , Lipopolysaccharides/pharmacology , Muscle, Smooth, Vascular/metabolism , Prostaglandin-Endoperoxide Synthases/biosynthesis , RNA, Messenger/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Blotting, Northern/veterinary , Cells, Cultured , Cyclooxygenase 2 , Horses , Interleukin-1/genetics , Isoenzymes/genetics , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/immunology , Muscle, Smooth, Vascular/physiology , Prostaglandin-Endoperoxide Synthases/genetics , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Tumor Necrosis Factor-alpha/genetics , Up-Regulation/genetics
20.
Shock ; 14(2): 222-8, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10947170

ABSTRACT

The effect of intravenous administration of lipid emulsions enriched with omega-3 (n3) and omega-6 (n6) fatty acids on equine monocyte phospholipid fatty acid composition and the synthesis of inflammatory mediators in vitro was evaluated. In a randomized crossover design, horses were infused intravenously with 20% lipid emulsions containing n3 or n6 fatty acids. Monocytes were isolated from the horses before and 0 h, 8 h, 24 h, and 7 days after lipid infusion. Monocyte fatty acid analysis demonstrated incorporation of the parenteral n3 and n6 fatty acids in monocyte phospholipids immediately after infusion, with changes in the fatty acid composition persisting for up to 7 days after infusion. In vitro production of the inflammatory mediators thromboxane B2/thromboxane B3 (TXB(2/3)) and tumor necrosis factor-alpha (TNFalpha) by peripheral blood monocytes was diminished by n3 lipid infusion and was unchanged or increased by n6 lipid infusion. The results of this study demonstrate that short-term infusions of n3 and n6 fatty acid-enriched lipid emulsions alter the fatty acid composition of equine monocyte phospholipids and modify the inflammatory response of these cells in vitro. These results also support further investigation into the use of parenteral n3 fatty acids as part of the supportive therapy of patients with multiple organ dysfunction (MODS) or systemic inflammatory response syndrome (SIRS).


Subject(s)
Fatty Acids, Omega-3/pharmacology , Fatty Acids, Unsaturated/pharmacology , Fatty Acids/blood , Monocytes/drug effects , Thromboxane B2/analogs & derivatives , Thromboxane B2/biosynthesis , Thromboxanes/analogs & derivatives , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Calcimycin/pharmacology , Cells, Cultured , Cross-Over Studies , Emulsions , Endotoxemia/metabolism , Endotoxemia/veterinary , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-6 , Fatty Acids, Unsaturated/administration & dosage , Female , Gene Expression Regulation/drug effects , Horse Diseases/metabolism , Horses , Infusions, Intravenous , Ionophores/pharmacology , Lipopolysaccharides/pharmacology , Male , Membrane Lipids/blood , Monocytes/metabolism , Phospholipids/blood , Thromboxane B2/genetics , Tumor Necrosis Factor-alpha/genetics
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