Clinical findings and outcomes of ulcerative keratomycosis in 30 horses in the mid‐Atlantic United States (2006–2007)

The purpose of this study was to determine the clinical course and outcome associated with keratomycosis in horses in the mid‐Atlantic USA. Records of horses diagnosed with keratomycosis at New Bolton Center from November 2006 to November 2007 with positive fungal culture were retrospectively studied. Neither horses with ulcerative keratitis and a negative fungal culture nor those with stromal abscesses were included. Subject details, history, clinical findings, therapy and outcome were recorded. Thirty horses fitted both inclusion criteria (diagnosis of keratomycosis and positive corneal fungal culture). Fourteen of 30 cases occurred during summer. Aspergillus was the most commonly cultured fungal genus (17/30, or 57%) followed by Alternaria (4/30). Seventeen horses had positive bacterial and fungal cultures. Fifteen of 30 horses were treated surgically by a keratectomy and amnion (8) or conjunctival (7) graft. Itraconazole was the most common topical anti‐fungal therapy and was utilised in 25/30 horses. Globe survival was 97% (29/30). All surviving globes had a positive menace response and were visual at the last examination. It was concluded that in the mid‐Atlantic USA, fungal keratitis is common, has the highest incidence in summer, and is usually associated with a positive outcome. Aspergillus may be a relatively more common corneal pathogen in this region than elsewhere in the USA. Surgical cases were more likely to have fungal hyphae identified on cytology and tended to be hospitalised longer than medical cases. There was no apparent association between surgical disease and all other patient, organism and treatment variables.     

Consumption of Low Larkspur (Delphinium nuttallianum) by Grazing Sheep

Low larkspur (Delphinium nuttallianum Pritz.) poisoning causes serious economic loss to livestock producers that graze cattle on foothill and mountain ranges in western North America. In general, all Delphinium spp. are five times less toxic to sheep than to cattle. Because low larkspurs are less toxic to sheep than cattle, grazing sheep before cattle on rangelands with dense populations of low larkspur can reduce larkspur density and risk of poisoning to grazing cattle. All previous published work on sheep and larkspur interactions has involved tall larkspurs. This series of studies was conducted to determine if sheep would consume sufficient low larkspur to reduce subsequent risk to cattle. Four summer trials were conducted in Collbran, Colorado, and Soda Springs, Idaho on pastures with dense (> 9 plants · m^?2) low larkspur populations. In all trials, sheep ate very little low larkspur (< 0.5% of bites). During one final trial using high sheep density (two sheep · 0.015 ha^?1 for 9 d), sheep consumed little low larkspur, but animals appeared to trample much of the low larkspur. Toxic alkaloid concentrations in low larkspur ranged from 1.1 mg · g^?1 to 1.6 mg · g^?1 in all trials. The use of sheep to graze low larkspurs to reduce subsequent consumption by grazing cattle does not appear to be a viable option.     

Four multistate outbreaks of human Salmonella infections associated with live poultry contact, United States, 2009

Outbreaks of human salmonellosis associated with live poultry contact have been reported since 1955. Multiple Salmonella serotypes have been associated with these outbreaks, and specific outbreak strains have been repeatedly linked to single hatcheries over multiple years. During 2009, four multistate outbreaks of human Salmonella infections associated with direct and indirect exposure to live poultry purchased from mail-order hatcheries and agricultural feed stores were identified, resulting in 165 culture-confirmed cases in 30 states. This report describes the epidemiologic, environmental and laboratory investigations conducted by state and local health departments, state departments of agriculture, the U.S. Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), National Poultry Improvement Plan (NPIP) and National Veterinary Services Laboratories (NVSL), and the Centers for Disease Control and Prevention (CDC). Case-patients were identified through PulseNet, the national molecular subtyping network for foodborne disease surveillance, and interviewed using the CDC standard live poultry contact questionnaire that asks about poultry-related exposures during the 7 days before illness onset. These outbreaks highlight the need to focus efforts on strategies to decrease and prevent human illness associated with live poultry contact through comprehensive interventions at the mail-order hatchery, agricultural feed store and consumer levels. Additional consumer education and interventions at mail-order hatcheries and venues where live poultry are sold, including agricultural feed stores, are necessary to prevent transmission of Salmonella from poultry to humans.     

Evaluation of cognitive learning, memory, psychomotor, immunologic, and retinal functions in healthy puppies fed foods fortified with docosahexaenoic acid-rich fish oil from 8 to 52 weeks of age

Objective-To assess effects of foods fortified with docosahexaenoic acid (DHA)-rich fish oil on cognitive, memory, psychomotor, immunologic, and retinal function and other measures of development in healthy puppies. Design-Evaluation study. Animals-48 Beagle puppies. Procedures-Puppies were assigned to 3 groups after weaning (n = 16/group) and received 1 of 3 foods (low-DHA, moderate-DHA, or high-DHA food) as their sole source of nutrition until 1 year of age. Visual discrimination learning and memory tasks, psychomotor performance tasks, and physiologic tests including blood and serum analysis, electroretinography, and dual-energy x-ray absorptiometry were performed at various time points. Anti-rabies virus antibody titers were evaluated 1, 2, 4, and 8 weeks after vaccination at 16 weeks of age. Results-Foods had similar proximate analysis results but varied in concentration of DHA from fish oil; the high-DHA food also contained higher concentrations of vitamin E, taurine, choline, and l-carnitine than did other foods. The high-DHA group had significantly better results for reversal task learning, visual contrast discrimination, and early psychomotor performance in side-to-side navigation through an obstacle-containing maze than did the moderate-DHA and low-DHA groups. The high-DHA group had significantly higher anti-rabies antibody titers 1 and 2 weeks after vaccination than did other groups. Peak b-wave amplitudes during scotopic electroretinography were positively correlated with serum DHA concentrations at all evaluated time points. Conclusions and Clinical Relevance-Dietary fortification with fish oils rich in DHA and possibly other nutrients implicated in neurocognitive development following weaning improved cognitive, memory, psychomotor, immunologic, and retinal functions in growing dogs.     

Successful drug development despite adverse preclinical findings part 1: processes to address issues and most important findings

Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to characterize them, to evaluate their risk for man, and in proposing measures to mitigate the risk particularly in early clinical trials. A careful scientific evaluation is crucial while termination of the development of a potentially useful drug must be avoided. This first part of the review discusses processes to address unexpected APFs and provides an overview over typical APFs in particular classes of drugs. If the mode of action (MoA) by which a drug candidate produces an APF is known, this supports evaluation of its relevance for humans. Tailor-made mechanistic studies, when needed, must be planned carefully to test one or several hypotheses regarding the potential MoA and to provide further data for risk evaluation. Safety considerations are based on exposure at no-observed-adverse-effect levels (NOAEL) of the most sensitive and relevant animal species and guide dose escalation in clinical trials. The availability of early markers of toxicity for monitoring of humans adds further safety to clinical studies. Risk evaluation is concluded by a weight of evidence analysis (WoE) with an array of parameters including drug use, medical need and alternatives on the market. In the second part of this review relevant examples of APFs will be discussed in more detail.     

A novel treatment for dynamic laryngeal collapse associated with poll flexion: the modified checkrein

Reasons for performing the study: Dynamic laryngeal collapse (DLC) associated with poll flexion is a performance limiting dynamic upper airway disorder commonly diagnosed in Coldblooded trotters. An inspiratory obstruction occurs when affected horses are driven with tension on the reins, inducing poll flexion. To date, surgical treatment and conservative management have failed to improve racing performance in affected horses. Objectives: To test the efficacy of an external device, the modified checkrein, in limiting poll flexion, diminishing laryngeal collapse and improving airway mechanics when horses are driven on a treadmill with tension on the reins and test the hypothesis that the modified checkrein will limit poll flexion thereby improving endoscopic appearance of the larynx and reduce airway obstruction in harness racehorses affected with DLC. Methods: Fourteen Norwegian Coldblooded trotter (NCT) racehorses previously diagnosed with DLC associated with poll flexion exercised on a high‐speed treadmill at speeds that resulted in heart rate >200 beats/min. Upper airway videoendoscopy recordings, tracheal pressures and video recordings of the head and neck position were collected while horses exercised with the conventional checkrein on Day 1 and the modified checkrein on Day 2. Results: The modified checkrein successfully limited poll flexion as measured by no change in head position parameters between phases of no rein tension and phases of rein tension. Endoscopic scores were significantly improved (arytenoids cartilage collapse P<0.0001; vocal fold collapse P<0.0001) and tracheal peak inspiratory pressures were significantly less negative (P = 0.0162) when horses were fitted with the modified checkrein compared to the conventional checkrein. Conclusions and potential relevance: The modified checkrein successfully limited poll flexion and also prevented upper airway obstruction in NCT horses affected with DLC associated with poll flexion. The modified checkrein seems promising in offering a method of conservative management in harness racehorses affected with this disorder.     

Exogenous eFSH, follicle coasting, and hCG as a novel superovulation regimen in mares

The objective of this study was to evaluate various equine follicle-stimulating hormone (eFSH) treatment protocols and the effect of “follicle coasting” on ovulation and embryo recovery rates in mares. Cycling mares (n = 40) were randomly assigned to one of four groups 7 days after ovulation: (1) 12.5 mg eFSH twice daily until follicles were 35 mm or larger; (2) 12.5 mg eFSH twice daily until follicles were 32 mm or larger; (3) 12.5 mg eFSH twice daily for 3.5 days followed by 12.5 mg eFSH enriched with luteinizing hormone (LH) twice daily until follicles were 35 mm or larger; and (4) 25 mg eFSH once daily until follicles were 32 mm or larger. Mares in groups 1 and 3 were injected with human chorionic gonadotropin (hCG) (2500 IU intravenously) at the end of eFSH treatment, whereas mares in groups 2 and 4 were given hCG approximately 42 and 54 hours, respectively, after the last eFSH treatment (“follicle coasting”). Nonsurgical embryo collection was performed 6.5 to 7.5 days after ovulation. Each mare experienced a nontreated estrous cycle before being reassigned to a second treatment. Ovulation rates for mares in treatment groups 1 to 4 were 3.3 ± 0.4, 4.1 ± 0.4, 3.5 ± 0.4, and 2.8 ± 0.4 (mean ± SEM; P < .05), respectively. One or more embryos were recovered from more than 80% of mares in each treatment group, and embryo recovery rate per flush was similar among treatment groups (1.9 ± 0.3, 2.6 ± 0.3, 1.9 ± 0.3 and 1.9 ± 0.3, respectively; P > .05). The overall embryo recovery rate was 2.1 ± 1.5 embryos per flush. In summary, ovulation rate was higher for mares treated with eFSH (3.4 ± 0.4) compared with non-treated controls (1.1 ± 0.2). Ovulation rate in mares in which hCG was delayed (follicle coasting) was higher (P < .05) when treatments were given twice per day versus once per day. Administration of equine luteinizing hormone (eLH) in conjunction with eFSH did not have an advantage over mares treated only with eFSH.