Retrospective comparison of caffeine and doxapram for the treatment of hypercapnia in foals with hypoxic-ischemic encephalopathy

BACKGROUND: Despite a lack of data regarding their efficacy, both caffeine and doxapram have been recommended for treatment of hypercapnia in equine neonates with central nervous system damage. HYPOTHESIS: Caffeine and doxapram alleviate hypercapnia in foals with hypoxic-ischemic encephalopathy. ANIMALS: Sixteen foals treated with either caffeine (n = 8) or doxapram (n = 8). METHODS: Information on age, body temperature, heart rate, respiratory rate, arterial blood gas parameters, duration of therapy, and outcome was abstracted from each medical record. RESULTS: Therapy with doxapram resulted in a significant decrease in partial pressure of carbon dioxide (PaCO2 [P= .004]), bicarbonate concentration (P= .002), and base excess (P= .005) compared with baseline values but failed to correct acidemia. In contrast, administration of caffeine did not result in significant changes from baseline values. The percentage decrease in PaCO2 and bicarbonate concentration was significantly greater in foals treated with doxapram than in foals treated with caffeine (P= .004). The proportions of foals that achieved the targeted PaCO2 (< or = 50 mmHg) were significantly higher in foals treated with doxapram than in foals treated with caffeine (P= .029). The proportion of survivors in the 2 treatment groups was not significantly different. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxapram is more effective than caffeine for rapid correction of hypercapnia in foals with hypoxic-ischemic encephalopathy.     

Assessment of synovial fluid biomarkers in healthy foals and in foals with tarsocrural osteochondrosis

Although alterations in biomarkers of cartilage turnover in synovial fluid (SF) have been demonstrated in horses with osteochondrosis (OC), there have been few investigations of such alterations in animals <1 year old. In this study tarsocrural SF samples from foals aged 18, 22 and 52 weeks of age were assessed for: (1) ‘turnover’ biomarkers of type II collagen (CPII and C2C) and proteoglycan (CS846 and glycosaminoglycans [GAG]); (2) matrix metalloproteinase (MMP) activity; (3) insulin-like growth factor (IGF)-1; (4) transforming growth factor (TGF)-β1; (5) prostaglandin (PG) E₂; and (6) leukotriene B₄.Using a linear mixed model, the concentration of biomarkers was compared between animals that developed or did not develop radiographic evidence of OC at 24 or 48 weeks of age. The CPII:C2C ratio tended to be higher in OC-affected joints compared to controls at all ages, and this difference was statistically significant at 22 weeks of age. The concentrations of CS846 and IGF-1, and the CS846:GAG ratio were reduced in OC-affected joints relative to controls at 18 weeks of age only. At 52 weeks of age, the PGE₂ concentration was lower in joints with OC. Overall, there appears to be a consistent anabolic shift in type II collagen turnover in juvenile joints affected by OC. Aberrant proteoglycan turnover is not a hallmark of the late repair of this lesion but reduced concentrations of IGF-1 in SF may be associated with early-stage lesions.     

Association of growth, feeding practices and exercise conditions with the prevalence of Developmental Orthopaedic Disease in limbs of French foals at weaning

Developmental Orthopaedic Disease (DOD) in limb joints of horses is frequent and is a common cause of pain and lameness. DOD is a multifactorial disease involving genetics, growth, feeding practices and exercise conditions leading to joint injuries. However, there is no clear understanding of the contribution of each factor. The aim of this cohort study was to assess the adjusted effects of breed and gender, growth, feeding practices and exercise conditions on the prevalence of DOD in the limbs of foals at weaning and on the prevalence restricted to osteochondrosis (OC).Twenty-one farms in Normandy, France, were convenience sampled and enrolled in a cohort study. The study sample consisted of 401 foals from 3 breeds, followed from the 8th month of pregnancy of the mares until weaning period at approximately 6 months of age of the foals. Stud farms were regularly visited to collect growth, feeding practices and exercise conditions data. The carpus, the front and hind digits, the hock and the stifle of the foals were X-rayed at the end of follow-up. Foals were categorised as affected or unaffected by DOD or by OC. Two mixed-effects logistic regression models were used to determine risk factors for DOD or OC, adjusting for clustering by farm.Of the 378 foals with complete data, 47% (95% CI: 42–52) were affected by DOD and 36% (95% CI: 31–41) by OC. Risk was significantly increased for DOD and for OC in Warmblood foals compared to Thoroughbreds (OR 2.8; 95% CI: 1.2–6.5 for DOD, OR 2.9; 95% CI: 1.1–7.5 for OC), in foals with a high wither height at 30 days of age, and in foals with a rapid increase of wither height (for DOD only). Exercise conditions such as large area of pasture, some irregular exercise, or some batch changes were also significant risk factors for DOD or OC. No association was found with quantitative feeding practices; it was likely due to the limited variability of horse regimens and to the partial inclusion of nutritional effects in other factors such as breed and growth. In order to reduce the prevalence of DOD or OC in foals, following the growth and reducing nutritional supply in subjects growing fast, limiting the pasture areas offered and providing a regular exercise to foals seems appropriate. To our knowledge, to date the assessment of adjusted effects of potential risk factors for DOD has never been proposed.     

No evidence of horizontal infection in horses kept in close contact with dogs experimentally infected with canine influenza A virus (H3N8)

Background

Since equine influenza A virus (H3N8) was transmitted to dogs in the United States in 2004, the causative virus, which is called canine influenza A virus (CIV), has become widespread in dogs. To date, it has remained unclear whether or not CIV-infected dogs could transmit CIV to horses. To address this, we tested whether or not close contact between horses and dogs experimentally infected with CIV would result in its interspecies transmission.

Methods

Three pairs of animals consisting of a dog inoculated with CIV (10^8.3 egg infectious dose₅₀/dog) and a healthy horse were kept together in individual stalls for 15 consecutive days. During the study, all the dogs and horses were clinically observed. Virus titres in nasal swab extracts and serological responses were also evaluated. In addition, all the animals were subjected to a gross pathological examination after euthanasia.

Results

All three dogs inoculated with CIV exhibited clinical signs including, pyrexia, cough, nasal discharge, virus shedding and seroconversion. Gross pathology revealed lung consolidations in all the dogs, and Streptococcus equi subsp. zooepidemicus was isolated from the lesions. Meanwhile, none of the paired horses showed any clinical signs, virus shedding or seroconversion. Moreover, gross pathology revealed no lesions in the respiratory tracts including the lungs of the horses.

Conclusions

These findings may indicate that a single dog infected with CIV is not sufficient to constitute a source of CIV infection in horses.     

The interrelations of good welfare indicators assessed in working horses and their relationships with the type of work

This paper presents a different approach to the welfare of working horses through the indicators of good welfare, their interrelations and their relationships with the type of work performed by the horses. 697 working horses were assessed by using observation, behavioural tests, clinical exams and questionnaires. The correlated results highlight the complex and multiple interrelations between the good welfare indicators, showing once again that animal welfare is under the influence of all its three dimensions (physical and emotional wellbeing and naturalness). In working horses, the heavier the work they perform is, the more important it is for horse owners/breeders/farmers to fulfil their inherent needs so as to help them cope with the multiple specific risks imposed by their work.     

Acute kidney injury due to Leptospira interrogans in 4 foals and use of renal replacement therapy with intermittent hemodiafiltration in 1 foal

Four 2-month-old foals were presented to an equine hospital with acute kidney injury caused by Leptospira interrogans infection. Clinical signs were nonspecific and included lethargy, fever, and unwillingness to nurse. The most important hematologic and clinicopathologic findings were azotemia, anemia, thrombocytopenia, hyponatremia, and hypochloremia. The diagnosis was based on urinary real-time PCR, serology using a microscopic agglutination test, or both. The most important serovars involved were L. interrogans serogroup australis serovar Bratislava and Australis. Treatment consisted of IV fluid therapy and antimicrobial treatment. Renal replacement therapy with hemodiafiltration was performed in 1 of the foals. All foals survived to discharge. This report highlights the importance of early diagnosis and treatment in foals with acute kidney injury caused by L. interrogans infection.     

The pharmacokinetics of cytarabine administered at three distinct subcutaneous dosing protocols in dogs with meningoencephalomyelitis of unknown origin

The objective of this study was to evaluate the pharmacokinetics of the standard cytarabine (Ara‐C) protocol (50 mg/m² subcutaneously every 12 hr for 2 days) used for dogs with neuroinflammatory disease and compare it to two more practical protocols (a single 200 mg/m² subcutaneous dose and two 100 mg/m² subcutaneous doses every 12 hr). Four client‐owned dogs previously diagnosed with meningoencephalomyelitis of unknown origin were administered three distinct Ara‐C protocols with a 21‐day washout between each protocol. A complete blood count was performed seven days after each dosing protocol to assess for clinically relevant myelosuppression. No adverse events were observed. Plasma Ara‐C concentrations were measured using a validated liquid chromatography coupled to tandem mass spectrometry assay. The mean maximal concentrations in this study were 4,230, 9,293, and 16,675 ng/ml for a single dose of 50, 100, and 200 mg/m², respectively. There was a linear relationship between dose and drug exposure. Drug exposure was similar regardless of the dosing protocol when the total dose was analyzed, with an area under the concentration versus time curve of 37,026, 38,465, and 32,510 ng × hr/ml for 50, 100, and 200 mg/m², respectively.     

Evaluation of biomarkers of kidney injury following 4% succinylated gelatin and 6% hydroxyethyl starch 130/0.4 administration in a canine hemorrhagic shock model

Objective : To investigate the association between synthetic colloids and biomarkers of acute kidney injury (AKI) in dogs with hemorrhagic shock. Design : Experimental interventional study. Setting : University. Animals : Twenty‐four healthy ex‐racing Greyhounds. Interventions : Anesthetized Greyhounds subjected to hemorrhage for 60 min were resuscitated with 20 mL/kg of fresh whole blood (FWB), 6% hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL/kg of isotonic crystalloid (CRYST) over 20 min (n = 6 per treatment). Concentrations of biomarkers of AKI were measured at baseline, end of hemorrhage, and at 40 (T60), 100 (T120), and 160 (T180) min after fluid bolus. Biomarkers included neutrophil gelatinase‐associated lipocalin in urine and serum (uNGAL; sNGAL), and urine cystatin C (uCYSC), kidney injury molecule‐1 (uKIM), clusterin (uCLUST), osteopontin, gamma‐glutamyl transferase, monocyte chemoattractant protein‐1 (uMCP), interleukin‐6, interleukin‐8, protein (uPROT), hyaluronan, and F₂‐isoprostanes. Renal histology was scored for tubular injury and microvesiculation. Biomarker fold‐change from baseline was compared between groups using mixed effects models (Bonferroni–Holm corrected P<0.05). Frequencies of histology scores were compared by Fisher's exact test. Measurements and main results : In dogs treated with GELO, uNGAL fold‐change was markedly greater compared with all other groups at T60, T120, and T180 (all P<0.001), and uCYSC was greater at T60 compared with CRYST (P<0.001), and at T120 and T180 compared with all other groups (all P<0.001). Smaller, albeit significant, between‐group differences in uKIM, uCLUST, uMCP, and urine protein concentration were observed across the FWB, GELO, and HES groups, compared with CRYST. The GELO group more frequently had marked tubular microvesiculation than the other groups (P = 0.015) although tubular injury scores were comparable. Conclusion : In dogs with hemorrhagic shock, GELO was associated with greater magnitude increases in urine biomarkers of AKI and more frequent marked tubular microvesiculation, compared with FWB, CRYST, and HES.     

Tolerability and pharmacokinetic profile of a novel benzene‐poly‐carboxylic acids complex with cis‐diammineplatinum (II) dichloride in dogs with malignant mammary tumours

The pharmacokinetic profile, tolerability and efficacy of benzene‐poly‐carboxylic acids complex with cis‐diammineplatinum (II) dichloride (BP‐C1) were studied in dogs with mammary cancer. A three‐level response surface pathway designed trial was performed on seven dogs. At each level BP‐C1 was administered subcutaneously daily for 7 days followed by a 7‐day rest period in a dose escalating manner. Adverse events according to VCOG‐CTCAE, performance status and tumour progression were recorded. The pharmacokinetic profile followed a two‐compartment model with rapid absorption, short distribution, and a slow elimination phase. The overall elimination half‐life was 125 h. The maximum tolerated dose of BP‐C1 was estimated to be above 0.46 mg kg^?1. A significant reduction in VCOG‐CTCAE toxicity which correlated negatively with increasing dose was found. The dogs' general performance status remained unchanged. No decrease in total tumour burden was found, although temporary tumour reduction was seen in some target tumours.     

生长猪回肠末端瘘管中食糜养分流量及指示剂回收率的变异

食糜样品的代表性是研究养分在猪体内消化过程的关键。通过T型瘘管获得的代表性食糜采样方案必须基于瘘管中食糜养分的流量及指示剂的回收率。本试验以4头在回肠末端安装瘘管的生长猪[(21.3±1.0)kg]为试验对象,饲喂玉米-豆粕型饲粮。采用3×16双因素完全随机设计,其中采样日设3个水平,即试验期第8、9、10天。日内采样时间设16个水平,即08:00~24:00,每小时通过瘘管采集1次回肠食糜样品,记录鲜食糜的重量并分析食糜样品中总能,干物质、粗蛋白质及三氧化二铬的含量。研究结果如下:1)双因素方差分析表明,日内采样时间显著地影响了瘘管中食糜的鲜食糜、干物质、总能、粗蛋白质和三氧化二铬的流量(P<0.05);在采样日间,瘘管中食糜的鲜食糜、干物质、粗蛋白质和三氧化二铬的日内平均流量均无显著性差异(P>0.05),但回肠末端食糜的总能流量有显著性差异(P<0.05)。2)日内16 h累计流经回肠瘘管的食糜及全天流经回肠末端的食糜在干物质、总能、粗蛋白质总流量的日间变异上有显著性差异(P<0.05),其中试验期第8天的流量均显著地高于第9、10天的相应值(P<0.05),而第9、10天间流量无显著性差异(P>0.05)。通过瘘管连续收集16 h回肠末端食糜的各养分流量占全天流经回肠末端食糜相应养分总流量的比例都在68%以上,且不同采样日间无显著性差异(P>0.05)。3)通过回肠末端瘘管收集日内16 h食糜的三氧化二铬总流量及回收率在日间无显著性差异(P>0.05),平均回收率为72.9%,变异系数为6.87%。上述结果表明,在3 d的收集中,后面2 d回肠末端食糜养分的平均流量相对稳定。这2 d采食后8 h连续收集食糜有较好的代表性。建议3 d采样中,第1天作为采样预试期,后面2 d作为采样正试期。     

H9亚型禽流感病毒感染鸡生理指标的分析

通过测定H9亚型禽流感发病鸡群及健康鸡群的某些生化指标,发现H9亚型禽流感疾病状态下皮质醇激素、甲状腺激素和血清钙的水平均与健康鸡群差异显著,而生长激素和血清磷无明显差异.这些变化是由于机体对疾病的抵抗或代谢紊乱产生的,可以作为疾病诊断的依据.     

Efficacy assessment of an intramammary treatment with a new recrystallized enrofloxacin vs ceftiofur and parenteral enrofloxacin in dairy cows with nonsevere clinical mastitis

A recrystallized form of enrofloxacin as dehydrate‐HCl (enro‐C) was assessed for bacteriological and clinical cure efficacies in Holstein‐Friesian cows affected of nonsevere clinical mastitis. Treatments were enro‐C_susp (n = 81), treated with a pharmaceutical suspension of enro‐C/quarter; group enro‐C_pd (n = 80) treated as above, but using enro‐C powder suspended in water; group CF (n = 65), treated with ceftiofur HCl/quarter; and group enro_R (n = 66), treated with standard enrofloxacin solution (5 mg/kg, intramuscular). Cows had a mean milk production of 31 L/day and were 2‐3 lactational periods old. Treatments were administered every 24 hr for 3 days. Groups treated with enro‐C exhibited statistically significant (p > .05) better clinical cure as compared to groups treated with CF or enro_R (95.06%, 96.25%, 67.79%, and 57.55%, for enro‐C_susp, enro‐C_pd, CF, and enro_R, respectively). In contrast, probability of bacteriological cure was not statistically different among treatments. Yet, the outstanding clinical and bacteriological cure rates obtained for enro‐C for nonsevere cases of mastitis is superior to previously reported data for parenteral enrofloxacin and other antibacterial‐intramammary treatments. Impact of using enro‐C on the rate and pattern of bacterial resistance, somatic cell counts and milk electric conductivity, must be studied. Also, the use of enro‐C for complicated cases of mastitis should be studied and milk withdrawal times must be accurately established.     

Administration of RRR‐α‐tocopherol to pregnant mares stimulates maternal IgG and IgM production in colostrum and enhances vitamin E and IgM status in foals

This study assessed the effect of a vitamin E supplement given to pregnant mares on immunoglobulins (Ig) levels in foals. In addition, the fatty acid (FA) content and composition of the mares’ milk was assessed. Milk α‐tocopherol concentrations were compared between pregnant Danish Warmblood mares (n = 17) given a daily oral supplement of 2500 international units (IU) RRR‐α‐tocopherol in the last 4 weeks of pregnancy and a group of unsupplemented mares (n = 17) receiving 170–320 IU vitamin E daily originating from the feed. Milk α‐tocopherol was higher in supplemented mares (36.7, 12.4 and 9.8 μmol/l respectively) in relation to control mares (13.1, 6.4 and 5.8 μmol/l on days 1, 2 and 3 respectively; p < 0.001). Milk IgG was higher on days 2 and 3 post‐partum (PP) in supplemented mares (1.03 and 0.73 mg/ml respectively) in relation to control mares (0.79 and 0.56 mg/ml respectively; p < 0.05). Milk IgM was higher on days 2 and 3 post‐partum (PP) in supplemented mares (0.19 and 0.17 mg/ml) in relation to control mares (0.13 and 0.11 mg/ml respectively; p < 0.05). Plasma α‐tocopherol in foals was higher from supplemented mares on days 1, 2 and 3 (5.7, 14.8 and 19.2 μmol/l respectively) in relation to foals from control mares (3.6, 6.1 and 7.6 respectively; p < 0.001). Foal plasma IgM was higher from supplemented mares on day 3 (0.50 mg/ml) in relation to foals from control mares (0.32 mg/ml; p < 0.001). The total FA content in milk was highest on day 1 (21.6 g FA/kg milk) in relation to days 2 and 3 (13.6 and 13.5 g FA/kg milk respectively; p < 0.001). In conclusion, a daily oral supplement of 2500 IU RRR‐α‐tocopherol increased α‐tocopherol content in mare milk and foal plasma, IgG and IgM in mare milk and IgM in foal plasma.