Molecular and serologic characterization, pathogenicity, and protection studies with infectious bronchitis virus field isolates from California

In this study, we characterized three variant infectious bronchitis virus (IBV) strains isolated in 2003 and 2004 from broiler chickens in California and compared them to previously isolated California variant viruses and to common vaccine serotypes used in the United States. We conducted genetic, serologic, and pathogenicity studies on all three isolates, then tested different vaccines against one of the viruses. Genetically the three variant IBV strains, designated CA557/03, CA706/03, and CA1737/04, were not related to each other. GenBank BLAST database search and phylogenetic analysis of the hypervariable region of the S1 subunit of the spike gene to determine the most closely related viruses to the three variants showed the CA557/03 variant to be 81.8% similar to the CAV/CA56b/91 whereas the CA706/03 and CA1737/04 variant viruses were only distantly related to Dutch/D1466/81 (72.2%), a vaccine strain used in Europe, and Korea/K142/02 (72.7%), a Korean field isolate, respectively. Cross virus-neutralization testing showed that none of the 2003-04 California IBV variant viruses were serologically related to each other or to Ark, Conn, or Mass vaccine strains. In addition the CA1737/04 isolate was also tested against DE072 and found not to be serologically related. All three variant viruses were pathogenic in 1-wk-old broilers and vaccination with Mass/Conn followed by Holland/Conn provided 80% protection against the CA1737/04 virus. The 2003-04 California variant viruses were not compared with variants isolated in California during 1970s and 1980s because, to our knowledge, no genetic information is available and those viruses are no longer obtainable. This study shows that the CA557/03 virus was distantly related to the CAV-type viruses isolated in California in the early 1990s, but that none of the 2003-04 viruses were similar genetically or serologically to the CAL99-type viruses, indicating that new IBV variants continue to emerge and cause disease in commercial chickens in California.     

Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma

Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T‐lymphocyte (CD3), FOXP3+ cell, B‐lymphocyte (Pax‐5), and CD204+ macrophage infiltration. We found that T‐lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T‐ and B‐lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti‐tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.     

An exploratory investigation of echocardiographic parameters and the effects of posture on cardiac structure and function in the Livingstone's fruit bat (Pteropus livingstonii)

There is growing evidence that dilated cardiomyopathy may be a major cause of death in captive Livingstone's fruit bats (Pteropus livingstonii). Therefore, the primary aim of this prospective, exploratory study was to examine whether a systematic cardiac ultrasound protocol is feasible in this critically endangered species and to report basic measures of cardiac structure and function from a cohort of apparently healthy bats. A secondary aim was to test the effect posture (dorsal recumbency vs. roosting) has upon cardiac function in this species. Transthoracic echocardiograms, including 2D, Doppler, and tissue Doppler measures of cardiac structure and function were completed as part of routine health examinations for bats at a single center (n = 19). Bats were then grouped by age and disease status and the mean and range data reported for each group. In healthy adult bats, with the exception of a reduction in heart rate (P ≤ 0.05), right atrial systolic area (P ≤ 0.05), and right ventricular velocity during atrial contraction, there were no significant changes in cardiac structure or function in response to the roosting position. However, in the bats presenting with dilated cardiomyopathy the current data suggest that left ventricular ejection fraction is improved while roosting. Further work is required to confirm our initial findings, generate diagnostic reference intervals, and explore the causes of dilated cardiomyopathy in this species.     

Fractionated oral dosing and its effect on cyclophosphamide pharmacokinetics in dogs with high-grade multicentric lymphoma

Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200–250 mg/m² over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h⁻¹; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200–250 mg/m².     

Direct measurement of intracranial pressure in adult horses

OBJECTIVE: To develop a method for surgical placement of a commercial microsensor intracranial pressure (ICP) transducer and to characterize normal ICP and cerebral perfusion pressures (CPP) in conscious adult horses. ANIMALS: 6 healthy castrated male adult horses (1 Holsteiner, 1 Quarter Horse, and 4 Thoroughbreds). PROCEDURE: Anesthesia was induced and maintained by use of isoflurane as the sole agent. Catheters were inserted percutaneously into the jugular vein and carotid artery. A microsensor ICP transducer was inserted in the subarachnoid space by means of right parietal craniotomy. The burr hole was then sealed with bone wax, the surgical incision was sutured, and the transducer was secured in place. Measurements were collected 1 hour after horses were able to stand during recovery from anesthesia. RESULTS: Mean +/- SD values for ICP and CPP were 2 +/- 4 and 102 +/- 26 mm Hg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: This report describes a relatively facile technique for obtaining direct and accurate ICP measurements for adult horses. The ICP values obtained in this study are within reference ranges established for other species and provide a point of reference for the diagnosis of abnormal ICP in adult horses.     

Effects of administration of antimicrobials in feed on growth rate and feed efficiency of pigs in multisite production systems

OBJECTIVE: To evaluate effect of various regimens for administration of antimicrobials in feed on growth rate and feed efficiency (feed/gain) of pigs in multisite production systems. DESIGN: Controlled trial. ANIMALS: 24,099 growing pigs in 3 multisite production systems. PROCEDURE: 10 trials involving various regimens for administration of antimicrobials in feed were evaluated. Trial 1 compared effects of 2 antimicrobial regimens on finishing pig performance. Trials 2 through 10 compared growth rate and feed efficiency of nursery and finishing pigs given antimicrobials in feed with values for control pigs not given antimicrobials. RESULTS: In trial 1, no significant differences were observed between the 2 antimicrobial regimens. In the remaining trials, growth rate of nursery pigs fed antimicrobials was significantly improved, compared with growth rate of control pigs. However, growth rate of finishing pigs and feed efficiency of nursery and finishing pigs were not significantly improved by adding antimicrobials to the feed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of antimicrobials in the feed to promote growth should be limited to the nursery phase in multisite pig production systems. Use of antimicrobials in the feed of finishing pigs should be limited to therapeutic applications in which a diagnosis of bacterial infection susceptible to the antimicrobial to be used has been confirmed.     

Varying dietary levels of wheat pollard and wheat bran in growing pigs: effect on growth and carcass traits

To study the effect of increasing levels of wheat pollard as a replacement for wheat bran on growth and carcass characteristics of growing pigs, 64 crossbred (Landrace?×?Large white Yorkshire) pigs were fed with diets in which wheat pollard was added back to wheat bran in ratios of 15, 30, 45 and 60 %. The pigs were divided into groups of four, balanced for sex, ancestry and body weight. They were then allotted to the dietary treatments in a completely randomised design with four replications. The trial lasted 4 months and data were collected on feed intake and weight gain. A digestibility trial was carried out on eight male pigs per treatment during the growth period. At the end of the growth period, two pigs per replicate in each treatment (n?=?32) were slaughtered for determination of carcass characteristics. There were significant differences in the rate of gain and efficiency of feed utilisation among treatments. Diet significantly affected weights of the liver, lungs and small intestine (P?<?0.05). The availability of nutrients was not a limiting factor for the growing pigs and that substituting wheat bran by wheat pollard at 60 % improved the pig’s average daily gain and feed efficiency.     

Pre- and postoperative force plate analysis of dogs with experimentally transected cranial cruciate ligaments treated using tibial plateau leveling osteotomy

Objective— Quantitative and objective assessment of hindlimb kinetics after cranial cruciate ligament (CrCL) transection and subsequent stifle stabilization using the tibial plateau leveling osteotomy (TPLO) in normal dogs.
Study Design— In vivo experimental biomechanical evaluation.
Animals— Six healthy adult foxhounds.
Methods— Dogs were screened by orthopedic and radiographic examination before study entry. Force plate analysis of gait was measured before extirpation of the right CrCL and TPLO and again at 8 and 18 weeks after surgery.
Results— There was a significant decrease in peak vertical forces (PVFs) and vertical impulse (VI) of the treated hindlimb at 8 weeks when compared with preoperative and 18-week measurements. When compared with preoperative values, there was no significant difference in 18 week PVF and VI in dogs that had TPLO.
Conclusion— TPLO can restore kinetic measures of limb function at 18-weeks after surgery when compared with preoperative values after experimental transection of the CrCL in dogs.
Clinical Relevance— TPLO induces lameness that returns to near normal at 18 weeks. The severity and duration of lameness was similar to that reported for other experimental models of stifle instability repaired by different techniques.