Longitudinal assessment of the impact of aging on wastage, productivity and welfare of ewes.

Retention of aging ewes is a strategy producers may use to maintain or increase flock size. Older ewes can have a higher risk of mortality and health issues, but these may be minimised with early intervention and culling. This retrospective study examined the incidence and causes of mortality and culling in a flock of Merino ewes as they aged from 4.5 to 5.5 until 9.5 to 10.5 years. The annual rate of ewe mortality ranged from 6.2% to 9.9%, with lambing complications being the major source of reported loss. Annual culling rates ranged from 1.6% to 42.8%, the larger rates reflecting opportunistic replacement with younger ewes rather than essential culling to maintain welfare and productivity. The major reasons for culling were low condition score, worn or missing teeth or faulty udders. The incidence of other faults was low. Only 18.3% of ewes remained when aged 9.5-10.5 years and these were fertile (89% pregnant) with a high proportion of multiple fetuses (52%) in their final year, although fleece weight had declined. Younger ewes born in 2004/2005 tended to have lower annual mortality rates than the aged ewes, but 8%-12% were still culled annually. It is concluded that an annual inspection pre-joining of all ewes and preventative culling for health issues is necessary to minimise any increase in mortality and risk to ewe welfare from retaining aging ewes. More frequent inspection will be required as potential health issues develop during the year, as these may not be evident pre-joining.

A survey of producer practices and reproductive performance of containment and supplementary fed ewes.

Containment feeding, where ewes are fed complete rations, is used to maintain flock numbers in periods of inadequate pasture supply. Producer practices influence both the reproductive performance of ewes and the risk of health challenges. The aim of this study was to evaluate the reproductive, feeding and health management practices of producers using containment or supplementary feeding, and quantify any associations between practice and reproductive performance. An online survey of Australian producers was conducted in 2020. The number of responses (n = 43) allowed benchmarking but was insufficient to determine correlations between practice and performance. The reported pregnancy rate of adult Merino ewes was variable between respondents (78%-95%; n = 11), and lambs marked per ewe joined ranged from 60% to 110% (n = 9). In non-Merino flocks, lambs marked ranged from 82% to 161% (n = 4). Most respondents (9/11) fed cereal grain with hay or straw, either daily or two or three times a week. However, some respondents fed grain only or roughage only, such that the percentage of roughage in diets ranged from 0% to 100%. Ewes were most frequently separated into age groups for feeding, and shy feeders were only removed by 25% of respondents. Although generally the reported reproductive rate was high, wide variation indicates potential for improvement. Best practice management for containment remains unclear and requires further research given the diverse practices used. Veterinary practitioners should be aware that some of the practices used may contribute to reduced productivity or health issues in ewes.

Maternal caffeine administration to ewes does not affect perinatal lamb survival.

Perinatal mortality of lambs is the major source of reproductive loss in extensive sheep production systems. Treatment with caffeine has reduced intra-partum mortality and/or improved metabolic indicators in other species following hypoxia. This study was conducted to evaluate the efficacy of caffeine for improving perinatal lamb survival. Experiment 1 comprised group-fed Merino ewes grazing pasture and offered 1.8 g/day (estimated 20 mg/kg live weight) caffeine throughout a 4-week lambing period, and a control without caffeine. The survival of lambs to marking (vaccinated, tail docked, males castrated) age in the caffeine treatment group (0.81) did not differ (P = 0.199) from that of control lambs (0.73; total born n = 877). Experiment 2 comprised Merino ewes lambing from three successive weekly joining groups. Treated ewes were drenched with an aqueous caffeine solution at a dose rate of 10 mg/kg live weight from the day before anticipated lambing, until the individual lambed. Control ewes were drenched with water. The proportion of lambs born dead (0.07) and the survival of lambs to marking age (caffeine 0.61; control 0.62) were similar between treatment groups (total born n = 1158). In both experiments, ewe mortality and the weight of lambs at marking were not altered by caffeine treatments. The results from this large-scale field study indicate caffeine is not an effective therapeutic agent to increase either intra-partum or perinatal survival, or lamb growth rates.

Usefulness of pathological examinations of the central nervous system for monitoring and controlling perinatal lamb mortality.

Correct diagnosis of cause of death is necessary to suggest the most effective management interventions to reduce perinatal lamb mortality. Haemorrhage on the surface of the brain has been used as a field diagnostic tool to allocate lambs to a cause of death category, but the usefulness of this method was unclear. This study aimed to evaluate whether gross pathology was related to neuronal death and whether haemorrhage of the central nervous system (CNS) was distinct between differing causes of death, enabling indicators to be used in field diagnoses. Lambs dying from natural causes (n = 64) and from euthanasia (n = 7) underwent postmortem examination, then the brain and spinal cord were extracted and examined histologically. Histological changes consistent with neuronal death were not detected in any lamb. Haemorrhage of the meninges and/or parenchyma of the CNS occurred in all lambs. The age of the haemorrhage indicated that it occurred near the time of death in most lambs. Dilation of blood vessels varied in severity but appeared to be unrelated to causal diagnosis, severity of subcutaneous oedema, breathing or milk status. Moderate or severe dilation of blood vessels and haemorrhage of the CNS did not occur in all lambs with alternative clear indicators of dystocia and occurred in all death classifications, so it could not be used as diagnostic indicators for classification of cause of death. Dilation and haemorrhage were unrelated to neuronal damage and may have been artefactual. In conclusion, haemorrhage of the CNS was not indicative of neuronal damage and could not be used to distinguish between lambs with clear indicators of differing causes of death, so it is not recommended as a field diagnostic tool.

Caffeine supplementation of ewes during lambing may increase lamb survival.

Perinatal mortality of lambs is on average 20% of lambs born in extensive Australian grazing systems, constituting a substantial production loss and welfare concern. Hypoxia resulting from prolonged or difficult births contributes to lower rates of lamb survival, and caffeine may reduce the effects of hypoxia. This study evaluated whether oral supplementation of grazing ewes with caffeine could improve lamb survival. Pregnant Merino ewes (n=492) which had been naturally mated to Merino rams in February/March were allocated to three replicates of control (no caffeine) or caffeine treatments. Caffeine was fed daily in troughs in each paddock at a rate of 1.6 g/ewe per day (estimated at 20 mg/kg live weight) from the day before the first lamb was born, for 14 days, with lambing continuing for 6 weeks. Intake was facilitated using 320 g/day per ewe of barley grain with molasses, which was fed to both treatments. The proportion of lambs born alive during the period of supplementation did not differ (P>0.05) between treatments. The proportion mortality of lambs to 1 day of age was lower (P=0.029) in the caffeine (0.01) compared with the control (0.16) treatment for lambs born during the 1st week of supplementation, but not in later weeks. This difference in mortality for lambs born in the 1st week of supplementation was maintained to marking age (caffeine 0.09; control 0.30; P=0.027). Extreme weather during the 2nd week of supplementation may have prevented any reduction in mortality due to caffeine in that week. Feeding caffeine to a naturally lambing flock of grazing ewes may be a highly effective and commercially practical method of increasing lamb survival, but further research is needed to confirm these results, and caffeine be regulated for use.

Shelter type and birth number influence the birth and death sites of lambs and ewe movement around lambing time.

A significant number of lambs born each yr in Australia die within 72 h of birth. Periods of high wind, combined with rain and low temperatures, can lead to marked increases in the level of mortality. Under these weather conditions mortality levels may be reduced with the provision of shelter, provided it is utilized by lambs. This study used GPS collars to determine the use of shelter by ewes and lambs, to compare the movement of ewes with twin lambs across 2 types of shelter (hedgerows and shrubs), while also comparing ewes with single and twin lambs in a single shelter type (hedgerows). Additionally, the birth sites of 364 lambs and death sites of 252 lambs were recorded across the 3 shelter type and litter size combinations (Twins in shrubs, Twins in hedgerows, Singles in hedgerows) plus an unsheltered group (Singles in unsheltered). A higher (P < 0.001) than randomly expected percentage of ewes lambed in the areas closest to both shelter types; in the shrub shelter 42% of ewes lambed within 2.5 m of shrub rows compared to an expected 11% based on the proportion of the paddock this area constituted. Despite the higher than expected percentage of ewes lambing close to the shelter rows, ewes in both twin lamb shelter types avoided the areas close to the shelter before and after lambing (Hedgerows-2.5 m; Shrubs- 6.25 m) and single bearing ewes showed no preference for or against these areas. With a high proportion of twin bearing ewes lambing close to the shelter, a design that reduces the potential for ewe and offspring separation while providing good shelter will offer the greatest potential reduction in newborn twin lamb mortality arising from exposure.

Reproductive performance of ewes grazing lucerne during different periods around mating.

High intake of lucerne pastures or feeding of other high quality diets during early pregnancy may increase embryo mortality, negating any benefit of improved nutrition on ovulation rate in ewes. This study was conducted to determine whether grazing ewes on lucerne (Medicago sativa) pastures for 7 days prior to and throughout joining would result in greater foetal numbers than if ewes were removed 7 days after the commencement of joining, or if ewes grazed senescent pasture throughout the joining period. Merino ewes (300) were allocated to two replicates of three treatments, grazing pastures between Days -7 and 36 of an unsynchronised, natural autumn joining. Grazing lucerne to Day 7 of joining resulted in 30% more (P<0.05) foetuses per ewe than grazing senescent pasture (1.60±0.07 and 1.31±0.07, respectively), and 19% more lambs marked per ewe joined. Extending grazing of lucerne past Day 7 of joining did not result in additional foetuses per ewe (1.61±0.06) in comparison with only grazing lucerne to Day 7 of joining. Greater than 80% of ewes mated during the first 14 days of joining, and the proportions of ewes returning to oestrus and re-mating (0.18±0.022) and of non-pregnant (0.09±0.017) ewes were similar (P>0.05) among all treatment groups, suggesting no differences between treatments in embryo mortality. Grazing naturally cycling ewes on lucerne prior to and during joinings in autumn is recommended as a means to increase the number of lambs born, although additional gains may not be obtained by grazing past day seven of joining.

Reproductive performance in ewes fed varying levels of cut lucerne pasture around conception.

Elevated intakes of protein and energy may increase embryo mortality, but it is not clear whether fresh lucerne (Medicago sativa) pasture poses a risk. A two-year pen study using oestrous synchronised and artificially inseminated Merino ewes (n=175 in 2013 and 215 in 2014) evaluated whether feeding freshly cut lucerne pasture (mean crude protein 19.7%, metabolisable energy 9.4MJ/kg DM) at maintenance or ad libitum during different periods around insemination altered reproductive performance in comparison with ewes fed a Control diet (mean crude protein 7.8%, metabolisable energy 9.0MJ/kg DM) of pelleted faba bean hulls and oat grain hulls at maintenance. The proportion of pregnant ewes carrying multiple fetuses was reduced (P=0.026) when ewes were fed lucerne ad libitum between days 0 and 17 after insemination compared with the Control diet (0.18 and 0.34, respectively), but not when ewes were fed lucerne ad libitum between days 0 and 7 after insemination (0.22). Reproductive performance, including the proportion of ewes pregnant and the proportion with multiple fetuses, was not different (P>0.05) when ewes were fed lucerne at maintenance between days 0 and 7 compared with the Control diet. While reproductive performance was similar when ewes were fed lucerne at maintenance between 0 and 17 days after artificial insemination compared with pellets at maintenance, fetal numbers per pregnant ewe were reduced by feeding lucerne ad libitum after insemination.

Affective symptoms and change in diabetes self-efficacy and glycaemic control.

AIMS: To examine the role of baseline depression, anxiety and stress symptoms on post-intervention diabetes self-efficacy and glycaemic control (HbA(1c)). METHODS: The current study analysed data from patients (n = 85) with treated but uncontrolled Type 2 diabetes who participated in a comparative effectiveness study of two diabetes self-management interventions. Hierarchical linear regression was used to examine the relationships between baseline affective symptoms and post-intervention diabetes self-efficacy and the moderating effects of baseline affective symptoms on the relationship between changes in diabetes self-efficacy and post-intervention HbA(1c). RESULTS: Baseline depression was inversely associated with post-intervention diabetes self-efficacy (P = 0.0001) after adjusting for baseline characteristics including diabetes self-efficacy. In contrast, normal-mild levels of stress were associated with higher post-intervention diabetes self-efficacy (P = 0.04). Anxiety and stress symptoms significantly and independently moderated the relationship between changes in diabetes self-efficacy and post-intervention HbA(1c) (P = 0.02 and P = 0.03, respectively). Further evaluation of these interactions demonstrated that changes in diabetes self-efficacy were associated with lower post-intervention HbA(1c), but only among those with higher baseline affective symptoms. CONCLUSIONS: We found a moderating effect across affective symptoms on the relationship between diabetes self-efficacy changes and post-intervention HbA1c in the context of a self-management intervention. Results suggest that patients with poorly controlled diabetes who have higher levels of depression, anxiety and stress symptoms may derive greater benefits from self-management interventions known to improve diabetes self-efficacy.

Do wind and brass players snore less? A cross-sectional study of snoring and daytime fatigue in professional orchestral musicians.

OBJECTIVES: To determine whether playing a wind or brass musical instrument is associated with reduced snoring or daytime fatigue. DESIGN: Cross-sectional, controlled, anonymous, questionnaire-based observational study. SETTING: Rehearsal and performance halls. PARTICIPANTS: Three hundred and forty musicians from Scotland's five professional orchestras. MAIN OUTCOME MEASURES: Snore Outcomes Survey questionnaire and the Epworth Sleepiness Score. STATISTICAL METHOD: Hierarchical linear regression analysis. RESULTS: No significant difference was found between the snoring severity (Snore Outcomes Survey score) or daytime sleepiness (Epworth score) of wind/brass and other professional musicians. A regression model with snoring severity (Snore Outcomes Survey score) as the dependent variable and the three covariates of gender, age and body mass index as independent variables was significant [F(3, 206) = 28.77, P < 0.01, adjusted r(2) = 0.285]. Increasing age, body mass index and male gender were all significantly associated with lower Snore Outcomes Survey scores (i.e. worse snoring).The addition of instrument type did not significantly increase the fit of the model, and the regression coefficient for instrument type was not significant. There were similar results when the Epworth Sleepiness Score was used as the dependent variable. CONCLUSIONS: This study demonstrated no significant difference between the snoring severity or daytime sleepiness of brass/wind players and other professional orchestral musicians. This result may have been attributed to comparatively low levels of snoring/daytime sleepiness in the population studied. The findings contrast with previous studies examining the effects of singing and didgeridoo playing but concur with a recent similar study of orchestral musicians. A prospective interventional study would be required to determine whether playing a wind or brass instrument improves these variables in patients complaining of disruptive snoring.

The role of clinical pharmacology in supporting the emergency use authorization of an unapproved anti-influenza drug, peramivir.

On 23 October 2009, the commissioner of the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for peramivir for intravenous injection, an unapproved neuraminidase inhibitor used for treating certain hospitalized adult and pediatric patients infected with 2009 H1N1 influenza. This was the first EUA of an unapproved drug product. This report summarizes the critical contributions of the clinical pharmacology review team in support of the peramivir EUA.

Short-term grazing of lucerne and chicory increases ovulation rate in synchronised Merino ewes.

This study evaluated the ability of short-term grazing of live=green pasture to increase ovulation rate during late summer when annual pasture is generally dead and of low quality. Ovulation rates, measured by the number of corpora lutea, were compared between 4 nutritional treatments: senesced phalaris (Phalaris aquatica), phalaris plus 500g lupin grain per day, lucerne (Medicago sativa) or chicory (Chicorum intybus) pastures. The study used 100 Merino ewes per treatment, divided between 2 replicates. The experiment was repeated in 3 years; February 2006, and January 2007 and 2008. Oestrus was synchronised and the ewes grazed the pastures for 9 days prior to ovulation at times corresponding to days 8-17 of the cycle in 2006, and days 6-14 in 2007 and 2008. The proportion of ewes producing multiple ovulations was higher (P<0.05) in the lucerne and chicory (0.36, 0.38) than the phalaris (0.27), and intermediate in the lupin (0.33) treatment. Regression analysis showed that the proportion of ewes with multiple ovulations increased with the quantity of live herbage (P<0.04). Responses were achieved even at low levels of live herbage with 90% of the maximum proportion of multiples occurring at 350kg DM/ha. It is concluded that providing short-term grazing of live chicory or lucerne to ewes can increase ovulation rates relative to ewes grazing senesced phalaris and to levels similar to those achieved by lupin grain supplementation.

Social and emotional impacts of farmwork injuries: an exploratory study.

CONTEXT: The physical hazards of farming have been extensively studied and reported upon. Far less studied are the social and emotional impacts of farmwork injuries and deaths. PURPOSE: To investigate and document broad but targeted issues regarding the impact on individuals, families, and communities of farmwork injuries and fatalities of farmer leaders. METHODS: Ten incidents of farmwork injuries with disabilities or fatalities in Pennsylvania were used for a collective case study. Data were collected through a total of 47 interview sessions with 66 individuals including next of kin, other family members, injured persons, and community members. Thematic analysis was used to identify themes and issues in this descriptive study. FINDINGS: Community members missed the rich, broad, and comprehensive skills, abilities, and perspectives that farmers brought to community service. Participants expressed that the community assistance and support provided to injured persons and families benefited not only the injured persons and their families and farms but also the community members. Participants reported emotional anguish and loss as well as positive transformations and consequences. As expressed by participants, God and religion play an important role in their beliefs regarding the occurrence and outcome of farmwork injury incidents. CONCLUSIONS: Social and emotional impacts on individuals, families, and communities are varied and multileveled. The role that religion and storytelling play in the process of dealing with serious injury incidents raises questions regarding agricultural injury prevention.

Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: This study evaluated the safety and intraocular pressure-lowering efficacy of two concentrations of travoprost (0.0015% and 0.004%) compared with latanoprost 0.005% and timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. METHODS: Eight hundred one patients with open-angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.0015%, travoprost 0.004%, latanoprost 0.005%, or timolol 0.5%. The efficacy and safety of travoprost (0.0015% and 0.004%) daily was compared with latanoprost daily and timolol twice daily for a period of 12 months. RESULTS: Travoprost was equal or superior to latanoprost and superior to timolol with mean intraocular pressure over visits and time of day ranging from 17.9 to 19.1 mm Hg (travoprost 0.0015%), 17.7 to 19.1 mm Hg (travoprost 0.004%), 18.5 to 19.2 mm Hg (latanoprost), and 19.4 to 20.3 mm Hg (timolol). For all visits pooled, the mean intraocular pressure at 4 PM for travoprost was 0.7 mm Hg (0.0015%, P =.0502) and 0.8 mm Hg (0.004%, P =.0191) lower than for latanoprost. Travoprost 0.004% was more effective than latanoprost and timolol in reducing intraocular pressure in black patients by up to 2.4 mm Hg (versus latanoprost) and 4.6 mm Hg (versus timolol). Based on a criterion of 30% or greater intraocular pressure reduction from diurnal baseline or intraocular pressure 17 mm Hg or less, travoprost 0.0015% and 0.004% had an overall response to treatment of 49.3% and 54.7%, respectively, compared with 49.6% for latanoprost and 39.0% for timolol. Iris pigmentation change was observed in 10 of 201 of patients (5.0%) receiving travoprost 0.0015%, six of 196 of patients (3.1%) receiving travoprost 0.004%, 10 of 194 of patients (5.2%) receiving latanoprost, and none of the patients receiving timolol (0 of 196). The average ocular hyperemia score was less than 1 on a scale of 0 to 3, indicating that on average patients experienced between none/trace and mild for all treatment groups. There were no serious, unexpected, related adverse events reported for any therapy. CONCLUSIONS: Travoprost (0.0015% and 0.004%), a highly selective, potent prostaglandin F (FP) receptor agonist, is equal or superior to latanoprost and superior to timolol in lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. In addition, travoprost 0.004% is significantly better than either latanoprost or timolol in lowering intraocular pressure in black patients. Travoprost is safe and generally well tolerated in the studied patient population.

A transitional stage in the commitment of mesoderm to hematopoiesis requiring the transcription factor SCL/tal-1.

In this report, we describe the identification and characterization of an early embryoid body-derived colony, termed the transitional colony, which contains cell populations undergoing the commitment of mesoderm to the hematopoietic and endothelial lineages. Analysis of individual transitional colonies indicated that they express Brachyury as well as flk-1, SCL/tal-1, GATA-1, (beta)H1 and (beta)major reflecting the combination of mesodermal, hematopoietic and endothelial populations. This pattern differs from that found in the previously described hemangioblast-derived blast cell colonies in that they typically lacked Brachyury expression, consistent with their post-mesodermal stage of development (Kennedy, M., Firpo, M., Choi, K., Wall, C., Robertson, S., Kabrun, N. and Keller, G. (1997) Nature 386, 488-493). Replating studies demonstrated that transitional colonies contain low numbers of primitive erythroid precursors as well as a subset of precursors associated with early stage definitive hematopoiesis. Blast cell colonies contain higher numbers and a broader spectrum of definitive precursors than found in the transitional colonies. ES cells homozygous null for the SCL/tal-1 gene, a transcription factor known to be essential for development of the primitive and definitive hematopoietic systems, were not able to form blast colonies but did form transitional colonies. Together these findings suggest that the transitional colony represents a stage of development earlier than the blast cell colony and one that uniquely defines the requirement for a functional SCL/tal-1 gene for the progression to hematopoietic commitment.

Factors related to adiposity among children aged 3 to 7 years.

OBJECTIVE: To compare diet and physical activity between a group of children aged 4 to 7 years who had increased their sum of 7 skinfolds by 1.5 standard deviations or more since the previous year and those who had not. SUBJECTS/DESIGN: A longitudinal design was used wherein children had their body composition assessed at 4 annual intervals. Fifteen study subjects were identified from a larger study on the development of cardiovascular risk factors in children. Three matched control subjects were identified for all but 4 study subjects. Children were included if they were 3 or 4 years old at the time of the first of 4 annual clinics to collect data. Children were volunteers from a mid-sized city. MEASURES: Seven skinfold sites were assessed, each 3 times. An average was taken of the mean at each site. Diet and physical activity were assessed using observational methods for up to 4 days for each of 3 years between the 4 annual clinics (held in the summers of 1986, 1987, 1988, and 1989). RESULTS: Children consumed significantly (P = .02) more fat grams and suggestively higher percentages of energy from fat (P = .06), total energy (P = .08), and percentage energy from protein (P = .10). No differences were detected for percent energy from carbohydrate, physical activity, or height. CONCLUSIONS: Programs to prevent childhood obesity might have success by targeting dietary fat consumption among children as young as 4 years old, but further research is needed.

Cholecystectomy in sickle cell anemia patients: perioperative outcome of 364 cases from the National Preoperative Transfusion Study. Preoperative Transfusion in Sickle Cell Disease Study Group.

Cholecystectomy is the most common surgical procedure performed in sickle cell anemia (SCA) patients. We investigated the effects of transfusion and surgical method on perioperative outcome. A total of 364 patients underwent cholecystectomy: group 1 (randomized to aggressive transfusion) 110 patients; group 2 (randomized to conservative transfusion) 120 patients; group 3 (nonrandomized nontransfusion) 37 patients; and group 4 (nonrandomized transfusion) 97 patients. Patients were similar except group 3 patients were more likely to be female, over 20 years old, smokers, and more healthy by American Society of Anesthesiologists (ASA) physical status score. Total complication rate was 39%: sickle cell events 19%; intraoperative or recovery room events 11%; transfusion complications 10%; postoperative surgical events 4%; and death 1%. Group 3 patients had the highest incidence of sickle cell events (32%). Open cholecystectomies were performed in 58% and laparoscopic in 42%. Laparoscopic patients were younger and more healthy by ASA score. Laparoscopic patients had longer anesthesia time (3.2 v 2.9 hours), but shorter hospitalization time (6.4 days v 9.8). Complications were similar between these two groups. We conclude that SCA patients undergoing cholecystectomy have a high perioperative morbidity, and the incidence of sickle cell events may be higher in patients not preoperatively transfused. We recommend a conservative preoperative transfusion regimen, and we encourage the use of the laparoscopic technique for SCA patients undergoing elective cholecystectomy.

Leflunomide: inhibition of S-antigen induced autoimmune uveitis in Lewis rats.

Leflunomide (LEF) is a novel immunomodulator which has been reported to be efficacious in experimental models of systemic autoimmune diseases and in treating rheumatoid arthritis in man. Leflunomide's ability to ameliorate ocular disease processes was investigated in a model of autoimmune eye disease, experimental autoimmune uveitis (EAU). EAU was induced by the injection of retinal S-antigen (S-Ag) into the foot-pad of Lewis rats. Leflunomide, or the reference compound cyclosporin A (CSA), was administered orally or topically (to one eye) each day beginning on the day of S-Ag injection. Drug efficacy was measured by the suppression in clinical signs of ocular inflammation and confirmed by histology. Both oral and topical ocular treatment with LEF suppressed the ocular disease signs and symptoms and retinal necrosis and reduced the S-Ag antibody levels associated with EAU in a dose-dependent manner. Both LEF and CSA were able to inhibit totally the disease manifestations of EAU; however, a comparison of the IC50 and IC90 values indicate that LEF is more potent than CSA in inhibiting EAU. These results suggest that leflunomide may be useful for treating autoimmune diseases of the eye.