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Background: Donkeys with clinical signs of pituitary pars intermedia dysfunction are treated with oral pergolide mesylate despite the lack of species-specific pharmacokinetic data., Objective: To evaluate the pharmacokinetics of intragastric and oral pergolide mesylate in healthy donkeys (Equus asinus)., Study Design: Pharmacokinetic study., Methods: Six healthy donkeys were administered pergolide mesylate (Prascend®) at 2 μg/kg bodyweight (bwt) intragastrically once, then once daily per os (PO) for 5 days. Blood samples were collected at 0, 10, 20, 30 and 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h after the single intragastric dose, once daily immediately before the PO dose, and then again at the above times after Day 5 of once daily oral dosing. Plasma pergolide concentration was quantified via ultra-performance liquid chromatography-tandem mass spectrometry. Pergolide concentration versus time data after the first and last doses were analysed based on noncompartmental pharmacokinetics using commercial software. Paired t-tests were used to compare single and multiple doses (p < 0.05). In a follow-up study, a single oral dose was then administered to two donkeys followed by concurrent blood sampling from the jugular and cephalic veins to evaluate the effect of route of administration on pergolide pharmacokinetics., Results: C max , T max AUC, and t ½λz differed significantly (p ≤ 0.03) after single and multiple doses, with significantly lower C max (0.16 ± 0.16 ng/ml) and t ½λz (9.74 ± 1.35 h) after intragastric dosing on Day 1 than after 5 days of oral dosing (3.74 ± 2.26 ng/ml and 16.35 ± 5.21 h, respectively). Pergolide plasma concentrations were higher in jugular vein samples compared to cephalic vein samples after a single oral dose., Main Limitations: Small sample size; varied administration routes., Conclusions: Pergolide mesylate (dosed at 2 μg/kg bwt) is bioavailable in donkeys after intragastric and PO administration. Differences in pharmacokinetics were noted after multiple doses, related to different routes of administration and sublingual absorption of pergolide., (© 2022 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Blood culture is considered the gold standard test for documenting bacteraemia in patients with suspected bacterial sepsis in veterinary and human medicine. However, blood culture often fails to yield bacterial growth even though the clinical picture is strongly suggestive of bacterial sepsis, or contaminating organisms can overgrow the true pathogen, making accurate diagnosis and appropriate management of this life-threatening condition very challenging. Methodology for collecting blood cultures in equine medicine, and even in human hospitals, is not standardised, and many variables can affect the yield and type of microorganisms cultured. Microbiological culture techniques used in the laboratory and specific sample collection techniques, including volume of blood collected, aseptic technique utilised, and the site, timing and frequency of sample collection, all have substantial impact on the accuracy of blood culture results. In addition, patient-specific factors such as husbandry factors, the anatomical site of the primary infection, and changing microflora in different geographic locations, also can impact blood cultures. Thus, blood cultures obtained in practice may not always accurately define the presence or absence of, or specific organisms causing, bacteraemia in horses and foals with suspected sepsis. Erroneous blood culture results can lead to inappropriate antimicrobial use, which can result in poor outcomes for individual patients and contribute to the development of antimicrobial resistance in the patient's microflora and the environmental microcosm. This review summarises current indications and methodology, and specific factors that may be optimised, for equine blood culture, with particular focus on available literature from neonatal foals with suspected bacterial sepsis. To standardise and optimise blood culture techniques in horses and foals, future research in this area should be aimed at determining the optimal volume of blood that should be collected for culture, and the ideal site, timing, and frequency of sample collection., (© 2022 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background: Seizures are a common manifestation of neurological disease in the neonatal foal and are an important cause of morbidity and mortality in this population. Current antiepileptic options are effective, but often have undesirable adverse effects, short duration of action and high cost. Levetiracetam has an ideal safety and pharmacokinetic profile in multiple species, including the adult horse, and may be a safe and cost-effective alternative anticonvulsant in neonatal foals. Due to differences in drug disposition and clearance dosages in neonates, dosing recommendations in other species or adult horses cannot be extrapolated to foals., Objective: To establish the pharmacokinetic profile of single-dose i.v. and intragastric administration of levetiracetam in healthy neonatal foals., Study Design: Randomised crossover experimental study., Methods: Levetiracetam was administered as a single dose to six healthy foals (ages 1-10 days) at a dose of 32 mg/kg bwt i.v. or intragastrically. Plasma levetiracetam concentrations were measured using a validated HPLC protocol., Results: After i.v. administration to healthy foals, levetiracetam had a mean (±s.d.) elimination half-life of 7.76 ± 0.51 h, a mean systemic clearance of 61.67 ± 10.96 (mL/h/kg) and a mean apparent volume of distribution at steady state of 0.670 ± 0.124 (L/kg). Following intragastric administration, levetiracetam had a peak concentration of 38.34 ± 7.42 mg/L and time to achieve peak concentration was 0.875 (0.5-1.5) h. Mean bioavailability for IG administration was excellent (103.04 ± 14.51%). No significant differences in pharmacokinetic variables between routes and order of administration were observed., Main Limitations: Small sample size and single-dose administration., Conclusions: Levetiracetam has excellent intragastric bioavailability in foals and is predicted to maintain plasma concentrations at or above the proposed target concentration with twice daily i.v. or oral administration. Once-daily administration may be possible in some foals based on the therapeutic range recommended in other species., (© 2017 EVJ Ltd.)

Background: Nebulisation of the injectable dexamethasone sodium phosphate (DSP) would offer an inexpensive way of delivering a potent corticosteroid directly to the lungs of horses with asthma. However, this approach would be advantageous only if systemic absorption is minimal and if the preservatives present in the formulation do not induce airway inflammation., Objective: To investigate the bioavailability of nebulised DSP and determine whether it induces airway inflammation or hypothalamic-pituitary-adrenal (HPA) axis suppression in healthy adult horses., Study Design: Randomised crossover experiment., Methods: Dexamethasone sodium phosphate was administered to six healthy adult horses at a dose of 5 mg q. 24 h for 5 days via nebulised, or intravenous (i.v.) routes. Plasma dexamethasone concentrations were measured by UPLC/MS-MS to calculate bioavailability. Cytological examination of bronchoalveolar fluid was performed at baseline and after the last dose of DSP. A validated chemiluminescent immunoassay was used to measure basal serum cortisol concentrations., Results: After nebulisation to adult horses, dexamethasone had a mean (±s.d.) maximum plasma concentration of 0.774 ± 0.215 ng/mL and systemic bioavailability of 4.3 ± 1.2%. Regardless of route of administration, there was a significant decrease in the percentage of neutrophils in bronchoalveolar lavage fluid over time. During i.v. administration, basal serum cortisol concentration decreased significantly from baseline to Day 3 and remained low on Day 5. In contrast, basal serum cortisol concentration did not change significantly during administration via nebulisation., Main Limitations: Small sample size and short period of drug administration., Conclusions: Dexamethasone sodium phosphate administered via nebulisation had minimal systemic bioavailability and did not induce lower airway inflammation or HPA axis suppression in healthy horses., (© 2017 EVJ Ltd.)

Reasons for Performing Study: N-butylscopolammonium bromide (NBB) is an anticholinergic agent used to treat spasmodic colic in horses. Intestinal smooth muscle spasm also occurs in horses with intraluminal intestinal obstructions, such as ileal impactions. The antispasmodic effects of NBB may be useful in managing ileal impactions, but the effects of NBB on equine ileal smooth muscle are unknown., Objectives: To investigate the effects of NBB on spontaneous and induced contraction of the equine ileum in an ex vivo model., Study Design: Ex vivo biomechanical study assessing contractile properties in isolate equine ileal smooth muscle with and without exposure to NBB., Methods: Ileal tissue was collected from 6 healthy horses after euthanasia, and isolated circular and longitudinal smooth muscle strips were connected to isometric force transducers in organ baths. After equilibration, the effect of NBB (1 nmol/l to 100 μmol/l) on spontaneous and carbachol-induced contraction was determined and compared with responses in control tissue., Results: At ≥30 μmol/l, NBB inhibited spontaneous contractions in all muscle strips that exhibited spontaneous activity. N-butylscopolammonium bromide pre-treatment inhibited carbachol-induced contraction in circular (NBB-treated half maximal effective concentration [EC₅₀] 0.530 × 10(-8) mol/l vs. control EC₅₀ 41.57 × 10(-8) mol/l) and longitudinal muscle strips (NBB-treated EC50 0.243 × 10(-8) mol/l vs. control EC₅₀ 90.84 × 10(-8) mol/l). Abolition of carbachol-induced contraction with NBB was observed at lower concentrations in circular than longitudinal muscle strips. Pretreatment with NBB significantly inhibited carbachol-induced contractions; NBB-treated tissue required greater carbachol concentrations to produce sustained contractions than control muscle strips. Histamine-evoked contraction was not affected by NBB., Conclusions: N-butylscopolammonium bromide inhibits spontaneous and cholinergically mediated contraction in equine ileal smooth muscle strips ex vivo. Thus, NBB might reduce intestinal spasm in equine ileal impactions and could be useful for medical management of these cases, although further study is needed to confirm these effects in vivo., (© 2014 EVJ Ltd.)

Reasons for Performing Study: Medical management of sand enteropathy is common in equine practice, but the clinical features and outcomes associated with medically managed sand enteropathy are not well described., Objectives: To review clinical features, therapeutic approaches and outcomes associated with primary medical management of sand enteropathy in the mature horse., Methods: Medical record databases at 3 equine referral hospitals from January 2000 to April 2010 were reviewed for cases of sand enteropathy diagnosed via abdominal radiographs in mature horses that were initially managed medically. Data were collected and descriptive analyses compiled. Uni- and multivariate logistic regression was used to evaluate factors potentially associated with treatment failure., Results: The medical records of 62 horses were analysed; 90% of horses survived to discharge and 50% of horses that had repeat abdominal radiographs taken demonstrated improvement in the degree of sand accumulation after treatment. Nine horses underwent exploratory laparotomy during hospitalisation, and colonic sand impaction was found in all 9, with a concurrent gastrointestinal lesion identified in 7. Four horses were subjected to euthanasia during or after surgery because of disease severity or complications. Need for exploratory laparotomy was the factor most strongly associated with nonsurvival., Conclusions: These data suggest that medical management can result in clinical and radiographic resolution of uncomplicated sand enteropathy in mature horses, and is associated with a good prognosis. Horses with sand enteropathy that exhibit persistent colic signs despite medical management are likely to have a concurrent gastrointestinal lesion, so prompt exploratory laparotomy should be considered in such cases., Potential Relevance: Uncomplicated sand enteropathy can be managed medically in mature horses, and serial abdominal radiography can be used to monitor sand clearance. Surgery to evaluate for and correct concurrent gastrointestinal lesions should be recommended without delay in horses showing persistent colic signs., (© 2012 EVJ Ltd.)

The objective of this document is to provide health care professionals with recommendations for genetic counseling and testing of individuals with a suspected or confirmed diagnosis of Fabry disease, with a family history of Fabry disease, and those identified as female carriers of Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as an individual with Fabry disease who is a founder of a Fabry disease patient advocacy group in the United States. The recommendations are U.S. Preventive Task Force Class III, and they are based on clinical experience, a review of pertinent English-language articles, and reports of expert committees. This document reviews the genetics of Fabry disease, the indications for genetic testing and interpretation of results, psychosocial considerations, and references for professional and patient resources. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a healthcare provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.