Veterinary pharmacovigilance. Part 2. Veterinary pharmacovigilance in practice -- the operation of a spontaneous reporting scheme in a European Union country -- the UK, and schemes in other countries

Veterinary pharmacovigilance, as it operates in the European Union (EU), covers a very broad remit, including adverse effects in treated animals, exposed humans and the environment, and in addition, it extends to cover the violation of maximum residue limits. The mainstay of veterinary pharmacovigilance is the spontaneous reporting scheme working along side other systems such as those reporting on residues surveillance. One of the most well established schemes in the EU is that operating in the UK and this paper examines the evolution of that scheme and some of its findings, data from other countries, and information available from the literature. It also tentatively examines the ways that pharmacovigilance can be used for regulatory purposes, and the contribution from pharmacoepidemiology.     

Dietary zinc concentration and lipopolysaccharide injection affect circulating trace minerals,acute phase protein response,and behavior as evaluated by an ear-tag–based accelerometer in beef steers

To assess plasma trace mineral (TM) concentrations, the acute phase protein response, and behavior in response to a lipopolysaccharide (LPS) challenge, 96 Angus cross steers (average initial body weight [BW]: 285 ± 14.4 kg) were sorted into two groups by BW (heavy and light; n = 48/group), fitted with an ear-tag–based accelerometer (CowManager SensOor; Agis, Harmelen, Netherlands), and stagger started 14 d apart. Consecutive day BW was recorded to start the 24-d trial (days −1 and 0). Dietary treatments began on day 0: common diet with either 30 (Zn30) or 100 (Zn100) mg supplemental Zn/kg DM (ZnSO₄). On day 17, steers received one of the following injection treatments intravenously to complete the 2 × 3 factorial: 1) SALINE (~2–3 mL of physiological saline), 2) LOWLPS: 0.25 µg LPS/kg BW, or 3) HIGHLPS: 0.375 µg LPS/kg BW. Blood, rectal temperature (RT), and BW were recorded on day 16 (−24 h relative to injection), and BW was used to assign injection treatment. Approximately 6, 24 (day 18), and 48 (day 19) h after treatment, BW, RT, and blood were collected, and final BW recorded on day 24. Data were analyzed in Proc Mixed of SAS with fixed effects of diet, injection, diet × injection; for BW, RT, dry matter intake (DMI), plasma TM, and haptoglobin-repeated measures analysis were used to evaluate effects over time. Area under the curve analysis determined by GraphPad Prism was used for analysis of accelerometer data. Body weight was unaffected by diet or injection (P ≥ 0.16), but there was an injection × time effect for DMI and RT (P < 0.05), where DMI decreased in both LPS treatments on day 16, but recovered by day 17, and RT was increased in LPS treatments 6 h post-injection. Steers receiving LPS spent less time highly active and eating than SALINE (P < 0.01). Steers in HIGHLPS spent lesser time ruminating, followed by LOWLPS and then SALINE (P < 0.001). An injection × time effect (P < 0.001) for plasma Zn showed decreased concentrations within 6 h of injection and remained decreased through 24 h before recovering by 48 h. A tendency for a diet × time effect (P = 0.06) on plasma Zn suggests plasma Zn repletion occurred at a greater rate in Zn100 compared to Zn30. These results suggest that increased supplemental Zn may alter the rate of recovery of Zn status from an acute inflammatory event. Additionally, ear-tag–based accelerometers used in this study were effective at detecting sickness behavior in feedlot steers, and rumination may be more sensitive than other variables.     

Pregnancy rates of mares inseminated with semen cooled for 18 hours and then frozen

The ability to ship cooled stallion sperm for subsequent freezing at a facility specializing in cryopreservation would be beneficial to the equine industry. Stallion sperm has been centrifuged, cooled to 5 degrees C for 12 h, and frozen without a detrimental effect on motility in a previous study; however, no fertility data were available. Experiment 1 compared the post-thaw motility of sperm cooled for 18 h at 15 or 5 degrees C at either 400 or 200 x 10(6) sperm/mL and then frozen. Storage temperature, sperm concentration, or the interaction of temperature and concentration had no effect on total (TM) and progressive motility (PM) after cooling. Post-thaw TM and PM were higher for control than (P < 0.05) for treated samples. There was no difference in post-thaw TM and PM due to temperature or concentration. Experiment 2 further evaluated procedures for cooling before freezing. Ejaculates were either cooled to 5 degrees C for 18 h and centrifuged, centrifuged at room temperature and then cooled to 5 degrees C for 18 h before freezing, or centrifuged and frozen immediately (control). There was no difference among treatments on post-thaw TM or PM. In Exp. 3, mares were inseminated with semen that had been extended in skim milk-egg yolk without glycerol, centrifuged, resuspended at 200 x 10(6) sperm/mL, cooled to 5 degrees C for 18 h, and then frozen or not cooled for 18 h before freezing (control). Pregnancy rates did not differ for mares receiving semen cooled and then frozen (21 of 30, 70%) or semen frozen directly without prior cooling (16 of 30, 53%). In summary, a procedure was developed for cooling stallion sperm for 18 h before freezing without a resultant decrease in fertility.     

Congenital ocular anomalies and ventricular septal defect in a dromedary camel (Camelus dromedarius).

A 5-wk-old female dromedary camel (Camelus dromedarius) was clinically diagnosed with bilateral corneal dermoids, incomplete congenital cataracts, a left persistent hyaloid artery (PHA), and a ventricular septal defect (VSD). The corneal dermoids were removed by lamellar keratectomy, and vision improved in the left eye. Thirteen months after dermoid surgery, the calf was presented for enlargement of the right eye. Glaucoma was confirmed in the right eye, and corneal fibrosis and cataract were noted in the left eye. Persistence of the VSD was confirmed by cardiac ultrasonography. The calf was euthanized, and necropsy findings confirmed VSD. Histopathologic examination revealed bilateral corneal thinning and fibrosis, cataracts with retrolental fibroplasia, and retinal dysplasia. Additional changes in the right globe were anterior segment dysgenesis, ruptured lens capsule, chronic phacoclastic uveitis, and retinal separation. The PHA was confirmed in the left eye.     

A modified laryngoplasty approach promoting ankylosis of the cricoarytenoid joint

Objective: To perform a modification to the standard laryngoplasty procedure in vivo that would result in ankylosis of the cricoarytenoid (CA) joint, and determine the stability provided to the abducted arytenoid in vitro. Study Design: Experimental study. Animals: Horses (n=8). Methods: Horses were assigned to either control laryngoplasty (n=3) or modified laryngoplasty (5) procedure. Endoscopic upper airway evaluations were used to measure right:left quotients 1 day and 3 months postoperatively to assess maintenance of abduction. Horses were euthanatized 3 months after surgery and larynges collected for measurement of translaryngeal impedance and histologic evaluation of CA joint ankylosis. Each specimen was exposed to increasing negative pressure with the sutures intact or cut while translaryngeal impedance was recorded. Data were analyzed using ANOVA with significance set at P<.05. Results: Loss of left arytenoid cartilage abduction at 3 months was greater in the control laryngoplasty group. Overall, impedance was significantly lower for the modified laryngoplasty group compared with the control laryngoplasty group and lower with the sutures intact than cut. Histologic evaluation of the joints confirmed fibrous bridging of the left CA joints of the modified laryngoplasty group. Conclusions: A modified laryngoplasty approach promotes ankylosis of the CA joint and decreases the loss of abduction of the arytenoid.