Active vaccination against interleukin-5 as long-term treatment for insect-bite hypersensitivity in horses.

BACKGROUND: Insect-bite hypersensitivity (IBH) in horses is a chronic allergic dermatitis caused by insect bites. Horses suffer from pruritic skin lesions, caused by type-I/type-IV allergic reactions accompanied by prominent eosinophil infiltration into the skin. Interleukin-5 (IL-5) is the key cytokine for eosinophils and we have previously shown that targeting IL-5 by vaccination reduces disease symptoms in horses. OBJECTIVE: Here, we analyzed the potential for long-term therapy by assessing a second follow-up year of the previously published study. METHODS: The vaccine consisted of equine IL-5 (eIL-5) covalently linked to a cucumber mosaic virus-like particle (VLP) containing a universal T cell epitope (CuMVTT ) using a semi-crossover design to follow vaccinated horses during a second treatment season. Thirty Icelandic horses were immunized with 300 µg of eIL-5-CuMVTT without adjuvant. RESULTS: The vaccine was well tolerated and did not reveal any safety concerns throughout the study. Upon vaccination, all horses developed reversible anti-eIL-5 auto-antibody titers. The mean course of eosinophil levels was reduced compared to placebo treatment leading to significant reduction of clinical lesion scores. Horses in their second vaccination year showed a more pronounced improvement of disease symptoms when compared to first treatment year, most likely due to more stable antibody titers induced by a single booster injection. Hence, responses could be maintained over two seasons and the horses remained protected against disease symptoms. CONCLUSION: Yearly vaccination against IL-5 may be a long-term solution for the treatment of IBH and other eosinophil-mediated diseases in horses and other species including humans.

Treating insect-bite hypersensitivity in horses with active vaccination against IL-5.

BACKGROUND: Insect-bite hypersensitivity is the most common allergic dermatitis in horses. Excoriated skin lesions are typical symptoms of this seasonal and refractory chronic disease. On a cellular level, the skin lesions are characterized by massive eosinophil infiltration caused by an underlying allergic response. OBJECTIVE: To target these cells and treat disease, we developed a therapeutic vaccine against equine IL-5 (eIL-5), the master regulator of eosinophils. METHODS: The vaccine consisted of eIL-5 covalently linked to a virus-like particle derived from cucumber mosaic virus containing the tetanus toxoid universal T-cell epitope tt830-843 (CMVTT). Thirty-four Icelandic horses were recruited and immunized with 400 µg of eIL-5-CMVTT formulated in PBS without adjuvant (19 horses) or PBS alone (15 horses). RESULTS: The vaccine was well tolerated and did not reveal any safety concerns but was able to induce anti-eIL-5 autoantibody titers in 17 of 19 horses. This resulted in a statistically significant reduction in clinical lesion scores when compared with previous season levels, as well as levels in placebo-treated horses. Protection required a minimal threshold of anti-eIL-5 antibodies. Clinical improvement by disease scoring showed that 47% and 21% of vaccinated horses reached 50% and 75% improvement, respectively. In the placebo group no horse reached 75% improvement, and only 13% reached 50% improvement. CONCLUSION: Our therapeutic vaccine inducing autoantibodies against self IL-5 brings biologics to horses, is the first successful immunotherapeutic approach targeting a chronic disease in horses, and might facilitate development of a similar vaccine against IL-5 in human subjects.

Salter-Harris type II metacarpal and metatarsal fracture in three foals. Treatment by minimally-invasive lag screw osteosynthesis combined with external coaptation.

OBJECTIVES: To describe minimally-invasive lag screw osteosynthesis combined with external coaptation for the treatment of Salter-Harris type II third metacarpal and third metatarsal bone fractures. METHODS: Three foals aged two weeks to four months with a Salter-Harris type II third metacarpal or third metatarsal fracture. Surgery was carried out under general anaesthesia in lateral recumbency. After fracture reduction, the metaphyseal fragment was stabilized with two cortical screws placed in lag fashion under fluoroscopic control. A cast was applied for at least two weeks. RESULTS: All foals had a good outcome with complete fracture healing and return to complete soundness without any angular limb deformity. All foals had moderate transient digital hyperextension after cast removal. CLINICAL SIGNIFICANCE: Internal fixation of Salter-Harris type II third metacarpal or third metatarsal fractures with two cortical screws in lag fashion, combined with external coaptation provided good stabilization and preserved the longitudinal growth potential of the injured physis.

Arthroscopically accessible anatomy of the tarsal collateral ligaments in the horse.

OBJECTIVE: To describe the arthroscopically accessible anatomy of the tarsal collateral ligaments in the horse. STUDY DESIGN: Descriptive study. ANIMALS: Cadaveric equine hind limbs (n = 24) obtained from horses without tarsal disease. METHODS: Two pairs of tarsal joints were used to obtain silicone models of the tarsocrural joint and dissect the tarsal collateral ligaments (CLs). Ten pairs of tarsocrural joints had arthroscopic exploration and the accessible parts of the tarsal CLs were marked with an arthroscopic hook knife. Subsequently, the limbs were dissected and the marked positions were allocated to the specific parts of the CLs. RESULTS: Ipsilateral arthroscope and instrument portals were used in each pouch of the tarsocrural joint. Via the plantaromedial pouch, the superficial (2/20 limbs), middle (7), deep (6) or both middle and deep (3) short medial CL and the long medial CL (14) were reached. Access via the plantarolateral pouch allowed manipulation of the deep short lateral CL (20/20 limbs) and the long lateral CL (20). Dorsally, arthroscopy via the dorsomedial pouch gave access to the deep short medial CL (20/20 limbs), while the superficial (9) or middle (10) or both superficial and middle (1) short lateral CL could be reached via the dorsolateral joint recess. CONCLUSIONS: Limited parts of the tarsal CLs can be observed or manipulated arthroscopically in normal equine tarsocrural joints.

Endoscopic-assisted electrohydraulic shockwave lithotripsy in standing sedated horses.

OBJECTIVE: To report use of transendoscopic electrohydraulic shockwave lithotripsy for fragmentation of urinary calculi in horses. STUDY DESIGN: Case series. ANIMALS: Male horses (n = 21). METHODS: Fragmentation of cystic calculi (median, 6 cm diameter; range, 4-11 cm diameter) was achieved by transurethral endoscopy in standing sedated horses using an electrohydraulic shockwave fiber introduced through the biopsy channel of an endoscope. The fiber was advanced until it contacted the calculus. Repeated activation of the fiber was used to disrupt the calculus into fragments <1 cm diameter. Visibility within the bladder was maintained by repeated lavage with saline solution. RESULTS: Complete calculus removal was achieved in 20 horses (95%) with mean total surgical time of 168.6 minutes (range, 45-450). In the 20 horses with single calculi, 1-6 sessions were required to completely fragment the calculus. Except for 1 horse, in which perineal urethrotomy was eventually performed for complete fragment removal, fragments calculi were excreted via the urethra. Postoperative complications included hematuria because of severe mucosal erosion (n = 2), dysuria because of a trapped urethral fragment (2), small amount of urinary debris (1). One horse was euthanatized because of bladder rupture. Complete clearance of calculi and urinary debris was confirmed endoscopically 20 (3-45) days after the last session. Telephone follow-up (mean, 18.8 months; range, 7-24 months) revealed that horses had returned to previous activity levels without recurrence of clinical signs. CONCLUSIONS: Transendoscopic electrohydraulic lithotripsy appears to be an effective method for fragmentation of low-density calcium carbonate cystic calculi in male horses.

Locking compression plate osteosynthesis of sacral fractures in three heifers.

OBJECTIVE: To describe a technique used for reduction and internal fixation of sacral fractures in cattle. STUDY DESIGN: Case series. ANIMALS: Three heifers aged 19-32 months with deformation of the tail head and tail paralysis attributable to a closed fracture of S5 or S4 and S5. METHODS: Fractures were reduced and repaired under general anesthesia. A narrow, 6-10-hole, locking compression plate (LCP) was placed on the spinous processes of S5 and the first coccygeal (Co1) using 5.0 mm locking head screws. Follow-up inquiries were made by telephone (3/3), and cows were examined clinically and radiographically 2 (1 cow) to 9 (1 cow) months postoperatively. RESULTS: No complications were encountered. The range of movement of the tail improved so that soiling of the tail during defecation was no longer a problem. In all heifers, the normal top line was restored and there was no narrowing of the pelvic canal. Unassisted calving occurred in all heifers, and follow-up radiographs for 2 cows showed complete fracture healing. CONCLUSION: LCP-osteosynthesis of the spinous processes provided sufficient stability for internal fixation of sacral fractures. Marked improvement in tail function occurred postoperatively without decompression by laminectomy.

Evaluation of a motorized morcellator for laparoscopic removal of granulosa-theca cell tumors in standing mares.

OBJECTIVE: To describe a motorized morcellator technique for laparoscopic removal of granulosa-theca cell tumors (GCT) in standing mares and to evaluate long-term outcome. STUDY DESIGN: Case series. ANIMALS: Mares (n=7) aged 4-15 years, with unilateral GCT. METHODS: Tumor size was determined by transrectal palpation and ultrasonography. Standing sedated mares had 3 laparoscopic portal sites in the paralumbar fossa. After laparoscopic observation of the GCT, the mesovarium was desensitized, the ovarian pedicle transected with a LigaSure device, and the ovary grasped with forceps and cut in cylindrical tissue blocks using a motorized morcellator. Tissue blocks were removed through the laparoscopic sleeve. Outcome was determined by telephone interview of owners 6-40 months after surgery. RESULTS: Estimated ultrasonographic median GCT diameter was 17 cm (range, 10-22 cm). Surgical time was 2-4.5 hours. There were no surgical complications. Two mares had mild subcutaneous emphysema at the portals after surgery. Convalescence was short, owners were satisfied with cosmetic outcome, and clinical signs associated with GCT did not recur. CONCLUSION: The motorized morcellator allows piecemeal removal of large GCT through a relatively small laparoscopic portal. Surgical complications were rare and the cosmetic outcome is favorable. CLINICAL RELEVANCE: A motorized morcellator is a safe and minimally invasive technique for laparoscopic removal of GCT in mares.

Evaluation of anesthesia recovery quality after low-dose racemic or S-ketamine infusions during anesthesia with isoflurane in horses.

OBJECTIVE: To compare anesthesia recovery quality after racemic (R-/S-) or S-ketamine infusions during isoflurane anesthesia in horses. ANIMALS: 10 horses undergoing arthroscopy. PROCEDURES: After administration of xylazine for sedation, horses (n = 5/group) received R-/S-ketamine (2.2 mg/kg) or S-ketamine (1.1 mg/kg), IV, for anesthesia induction. Anesthesia was maintained with isoflurane in oxygen and R-/S-ketamine (1 mg/kg/h) or S-ketamine (0.5 mg/kg/h). Heart rate, invasive mean arterial pressure, and end-tidal isoflurane concentration were recorded before and during surgical stimulation. Arterial blood gases were evaluated every 30 minutes. Arterial ketamine and norketamine enantiomer plasma concentrations were quantified at 60 and 120 minutes. After surgery, horses were kept in a padded recovery box, sedated with xylazine, and video-recorded for evaluation of recovery quality by use of a visual analogue scale (VAS) and a numeric rating scale. RESULTS: Horses in the S-ketamine group had better numeric rating scale and VAS values than those in the R-/S-ketamine group. In the R-/S-ketamine group, duration of infusion was positively correlated with VAS value. Both groups had significant increases in heart rate and mean arterial pressure during surgical stimulation; values in the R-/S-ketamine group were significantly higher than those of the S-ketamine group. Horses in the R-/S-ketamine group required slightly higher end-tidal isoflurane concentration to maintain a surgical plane of anesthesia. Moderate respiratory acidosis and reduced oxygenation were evident. The R-norketamine concentrations were significantly lower than S-norketamine concentrations in the R-/S-ketamine group. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with R-/S-ketamine, anesthesia recovery was better with S-ketamine infusions in horses.

Ventral locking compression plate for treatment of cervical stenotic myelopathy in a 3-month-old warmblood foal.

OBJECTIVE: To report a novel technique for cervical vertebral fusion in a foal with cervical vertebral malformation (CVM). STUDY DESIGN: Case report. METHODS: A 3-month-old Warmblood filly with ataxia, weakness, and stenotic myelopathy at the level of the articulation of the 6th (C6) and 7th (C7) cervical vertebrae had a 7-hole broad locking compression plate (LCP) applied to the ventral aspect of C6 and C7 using seven 5.0-mm locking screws. Revision surgery was required to replace the self-drilling screws, which had migrated, with longer non self-drilling screws. Fusion and growth of the vertebrae were monitored radiographically at 4, 10, and 16 months using radiography and the filly was followed for 32 months. RESULTS: The filly recovered well from the surgical procedures and by 30 months had improved by 2.5 neurologic grades. Ventral inter-central joint fusion was evident by 10 months. Continued vertebral growth occurred in all but the cranial physis of the C7 vertebral body. CONCLUSIONS: A ventrally placed LCP provided adequate support for fusion and stability of cervical vertebrae. CLINICAL RELEVANCE: Use of an LCP applied ventrally offers an alternative to basket use in small or immature horses for fusion of cervical vertebrae.

Comparison of the trimming procedure of six different farriers by quantitative evaluation of hoof radiographs.

Hoof preparation and shoe fit are integral to the long term soundness and athletic ability of horses. The farrier influences the balance of the hoof by both the trimming and the shoeing procedure. The goal of this study was to investigate and quantify the influence of the farrier on hoof parameters by trimming. Forty Warmblood horses ranging in age from 6-12 years and withers height 162-172cm were included. They were divided into six groups consisting of six or seven horses each, shod by one of six different farriers. The hoofs of the horses were radiographed twice using a standardised method before and after trimming. Measurements were taken from digitalised radiographs using a software program. Significant differences were identified between farriers for almost all parameters on the lateromedial radiographic views after two consecutive trimming procedures. Comparing the results of both trimming procedures, significant differences for several farriers were found in the lateromedial and dorsopalmar views. There were significant differences for most of the measured hoof parameters between the six farriers and between consecutive trimmings of the same farrier. The results underline the individual influence of the farrier on hoof shape and balance.

The effect of hoof trimming on radiographic measurements of the front feet of normal Warmblood horses.

The understanding of the normal position of the third phalanx (P3) and the distal sesamoid bone in relation to the size and shape of the hoof capsule in sound horses is helpful in the diagnosis of equine foot lameness. Some measurements on radiographs used to define the position of the pedal bone within the hoof capsule are significantly influenced by hoof trimming and the height of the withers. In this study, the front hooves of 40 Warmblood horses were radiographed twice, eight weeks apart, both before and after their hooves were trimmed by an experienced farrier. Using the software programme Metron PX, 22 parameters on the lateromedial view and 16 parameters on the dorsopalmar view were measured and the effect of hoof trimming and height of the withers were calculated, respectively. Some of the hoof parameters showed mild positive correlation with the height of the withers. In 70% of the horses the left hoof capsule and P3 were significantly larger than the right. Hoof trimming had a remarkable influence on hoof conformation, especially for parameters in the toe region. Of all the measurements that describe the position of the third phalanx (P3) in relation to the hoof capsule, the distances between the distal tip of P3 to the solar surface of the foot, P3 to the tip of the toe and P3 to the point of break-over showed the greatest differences before and after trimming. The database of the present study can be used by farriers and veterinarians as a guideline for routine and corrective shoeing of Warmblood horses.