Effective Penetration of a Liposomal Formulation of Bleomycin through Ex-Vivo Skin Explants from Two Different Species.

Bleomycin is a chemotherapy agent that, when administered systemically, can cause severe pulmonary toxicity. Bleosome is a novel formulation of bleomycin encapsulated in ultra-deformable (UD) liposomes that may be applicable as a topical chemotherapy for diseases such as non-melanoma skin cancer. To date, the ability of Bleosome to effectively penetrate through the skin has not been evaluated. In this study, we investigated the ability of Bleosome to penetrate through ex vivo skin explants from dogs and horses. We visualized the penetration of UD liposomes through the skin by transmission electron microscopy. However, to effectively image the drug itself we fluorescently labeled bleomycin prior to encapsulation within liposomes and utilized multiphoton microscopy. We showed that UD liposomes do not penetrate beyond the stratum corneum, whereas bleomycin is released from UD liposomes and can penetrate to the deeper layers of the epidermis. This is the first study to show that Bleosome can effectively penetrate through the skin. We speculate that UD liposomes are penetration enhancers in that UD liposomes carry bleomycin through the outer skin to the stratum corneum and then release the drug, allowing diffusion into the deeper layers. Our results are comparative in dogs and horses and warrant further studies on the efficacy of Bleosome as topical treatment.

Equine "Idiopathic" and Infundibular Caries-Related Cheek Teeth Fractures: A Long-Term Study of 486 Fractured Teeth in 300 Horses.

Background: Limited objective information is available on the prevalence of non-traumatic equine cheek teeth fractures, the signalment of affected horses, and the clinical features and treatment of these fractures. Objectives: This study aims to document patterns of idiopathic and infundibular caries-related cheek teeth fractures in a referral population and evaluate associations between fracture patterns and horse age, Triadan position of affected teeth, clinical signs, and deemed necessity for treatment. Study Design: A retrospective case review. Methods: The clinical records at Edinburgh University Veterinary School (2010-2018) were examined for the presence of non-traumatic equine cheek teeth fractures. Variations in the frequencies of different fracture patterns were compared between horse ages, Triadan tooth positions, clinical signs, and deemed necessity for treatment. Results: Records of 300 horses with 486 non-traumatic cheek teeth fractures including 77% maxillary and 23% mandibular teeth with a mean of 1.6 (range 1-10) fractured teeth/horse were available. Fracture patterns included maxillary first and second pulp horn ("slab") cheek teeth fractures (n = 171), caries-related infundibular fractures (n = 88), other maxillary teeth fracture patterns (n = 92), mandibular first and second pulp horn ("slab") fractures (n = 44), other mandibular fracture patterns (n = 62), and complete clinical crown loss (n = 29; including 23 maxillary and 6 mandibular teeth). The median age of affected horses ranged from 11 years with maxillary "slab" fractures to 15 years with infundibular caries-related fractures. Triadan 08-10s were the most commonly (86%) fractured maxillary teeth. The Triadan 08 and 09 positions were the most commonly (64%) fractured mandibular teeth. No clinical signs were noted in horses with 48% of the fractured teeth; oral pain/quidding was recorded with 26%, clinical apical infection with 23%, and bitting/headshaking problems with 6%. Treatments included extraction of 40% fractured teeth, extraction of small/loose fragments (10%), and odontoplasty. Stable remnants of 60% of fractured teeth were left in horses without clinical signs. Main Limitations: Long-term follow-up information was not available for all cases. Conclusions: There is increasing recognition of equine non-traumatic cheek teeth fractures, with about half not causing clinical signs. Teeth with apical infection, multiple fractures, or advanced caries require extraction. Other fractured teeth with subclinical endodontic disease may not need exodontia unless they later cause clinical signs.

Multidetector CT and cone-beam CT have substantial agreement in detecting dental and sinus abnormalities in equine cadaver heads.

The performance of cone-beam CT (CBCT) systems compared to conventional helical multidetector CT (MDCT) imaging of the equine head is unknown. The aim of this prospective, method-comparison study was to compare the ability of CBCT and MDCT to detect abnormalities in equine cadaver heads. Eleven equine cadaver heads were scanned using a CBCT scanner and a 64-slice MDCT scanner. Consensus evaluations for CBCT and MDCT scans were performed by three observers. Identified abnormalities were grouped into subcategories with a focus on dental abnormalities. Kappa agreement values between detected abnormalities for CBCT and MDCT methods were calculated. Of 468 teeth evaluated, 122 (26.1%) were found to have abnormalities (including in 58 infundibula and 7 pulps) using MDCT and 105 (22.4%) were found to have abnormalities (including in 52 infundibula and 2 pulps) using CBCT. The agreement between CBCT and MDCT was almost perfect for overall detection of dental abnormalities (k = 0.90) with k = 1 for diastema k = 0.95 for clinical crown abnormalities, and k = 0.93 for infundibular abnormalities. However, the detection of pulp changes by CBCT was only moderate k = 0.44. Increased scatter radiation, non-calibrated Hounsfield Unit and artefacts in CBCT images made accurate identification of the pulp density difficult. In conclusion, CBCT results were similar to conventional MDCT for the majority of dental abnormalities, however, pulp abnormalities were not reliably identified using CBCT, potentially limiting its clinical use for detecting endodontic disease in its current form. Further comparison with more cases with confirmed dental disease and studies in clinical cases are warranted.

Studies on Age-Related Changes in Equine Cheek Teeth Angulation and Dental Drift.

BACKGROUND: Cheek teeth (second through fourth premolars and first through third molars) diastema is a common and painful equine disorder caused by the absence of effective tight interdental contact between these teeth. Limited objective information is available on the angulation of equine cheek teeth that control dental drift or on mesial or distal equine cheek teeth drift that should normally prevent this disorder. OBJECTIVES: To measure the angulation of the mesial and distal cheek teeth in horses of different ages, quantify age-related cheek teeth mesial and distal dental drift, and measure the cheek teeth row length in horses of different ages. STUDY DESIGN: Retrospective review of computed tomographic images of equine heads. METHODS: Case details and CT images from clinical equine cases that had undergone standing CT head examination were collated.Three sets of measurements were acquired from each head. "Head size" calculated as the distance between the caudal aspect of the orbit and the caudal aspect of the naso-incisive notch was used to standardize measurements in different sized heads. The length of the cheek teeth rows measured from the mesial aspect of the Triadan 06 occlusal surface to the distal aspect of the Triadan 11 occlusal surface. The rostro-caudal (antero-posterior) position and angulation of the mandibular and maxillary Triadan 06 and 11 teeth were measured in relation to reference lines drawn on CT images. RESULTS: Significant mesial drift occurred in the maxillary and mandibular Triadan 11s. Despite their distal angulation, the upper and lower Triadan 06s also drifted mesially. The mean angulation of Triadan 06 and 11 mandibular teeth (17.8 and 26.2°, respectively) was almost double that of maxillary teeth (9.2 and 13.3°, respectively) with both Triadan 11s having greater angulation than the 06s. Cheek teeth angulation only significantly decreased in the mandibular 06s. Cheek teeth arcade lengths decreased with age, but these decreases were not significant. MAIN LIMITATIONS: Limitations include the relatively small sample size. CONCLUSIONS: In the population of horses used for this study, age related mesial drift occurred in both Triadan 06 and 11s, and the angulation of these teeth did not decrease with age in most arcades.

A long-term study of sinoscopic treatment of equine paranasal sinus disease: 155 cases (2012-2019).

BACKGROUND: There is little objective information concerning the intra- and post-operative complications or the long-term outcome of sinoscopic treatment of equine sinus disorders. OBJECTIVES: To document the long-term outcome, including intra-operative complications, reasons for treatment failure and other complications, in horses undergoing standing sinoscopic treatment of sinus disorders. STUDY DESIGN: Retrospective clinical study. METHODS: Records of sinus disease cases presented to The University of Edinburgh Veterinary School between January 2012 and July 2019 were reviewed. Follow-up information was obtained from clinical records and a telephone questionnaire. RESULTS: Long-term follow up for 155 cases treated sinoscopically showed that 108/155 (69.7%) fully responded to their initial treatment. Concurrent intranasal lesions were identified in 37.4% of cases. Sinusotomy was later required in 10 cases to improve surgical access or sinonasal drainage. Reasons for failure to fully respond to the initial treatment (n = 47) included: intra-sinus bone sequestra (n = 9), inspissated exudate (n = 6) or insects (n = 2); similar material and/or infected conchal bullae in the middle meatus (n = 7); persistent oro-maxillary fistulae (n = 4), misdiagnosed dental apical infections (n = 4); impaired sinonasal drainage (n = 4), progressive ethmoid haematoma regrowth (n = 3) and undiagnosed causes (n = 5). Further treatment of 43 of these cases (67% as outpatients) showed 34/43 cases fully responding to their second treatment. Only 4/155 cases (2.6%) required sinonasal fenestration. In the long term, 149/155 cases (96.1%) showed full and 2/155 cases (1.3%) showed partial improvement. Sinoscopy portal wound infection occurred in nine cases. MAIN LIMITATIONS: The length of time between treatment and obtaining follow-up information in some cases. Advances in knowledge and techniques over the duration of the study. CONCLUSIONS: Sinoscopic treatment is a minimally-invasive technique causing minimal morbidity and was successful in 96.1% of cases. Meticulous care should be taken to ensure that bony sequestrae and inspissated exudate are fully removed from the sinuses and nasal cavity during sinoscopic treatments.

Computed Tomographic Assessment of Individual Paranasal Sinus Compartment and Nasal Conchal Bulla Involvement in 300 Cases of Equine Sinonasal Disease.

Background: Computed tomographic (CT) imaging has allowed new anatomical studies and detailed clinical imaging of the complex, overlapping equine sinonasal structures. Despite the widespread use of CT, no study has specifically identified which compartments are most commonly affected with sinus disorders. CT has also shown the presence of intercurrent, ipsilateral nasal disorders, especially infection of the nasal conchal bullae (NCB) in many cases of sinus disease, but the frequency of intercurrent NCB infections has not been reported. Objectives: To identify which sinus compartments are most commonly affected in horses with clinical sinus disorders and to record the prevalence of NCB involvement in such cases. Study Design: Retrospective examination of CT images of horses with confirmed unilateral sinus disease. Methods: The CT images of 300 horses, from three different equine hospitals with clinically confirmed sinus disease [mainly dental (53%) and primary sinusitis (25.7%)] were retrospectively examined to determine which sinus compartments and NCBs were affected. Results: The rostral, more dependent sinus compartments were most commonly involved, i.e., the rostral maxillary sinus in 284/300 (94.7% affected) and the ventral conchal sinus (87% affected). The caudal maxillary sinus (65.3%), dorsal conchal sinus (52.7%), frontal sinus (26%), ethmoidal sinus (32%) and sphenopalatine sinus (28.7%) were less commonly affected. There was infection or destruction of the ipsilateral NCBs in 56% of horses with sinus disorders, including the ventral NCBs in 42.3%, dorsal NCBs in 29% and both NCBs in 18% of cases. Main Limitations: The horses with sinonasal disease that underwent head CT imaging include more problematic cases and horses of high value, rather than the general horse population. Conclusions: The more dependant (i.e., the RMS and VCS) sinus compartments are most commonly involved in sinus disorders, with the RMS involved in nearly every case. The more dorsally located sinuses (i.e., caudal group) are less commonly involved. Many horses with sinus disease also have disorders of their nasal conchal bullae and so the term sinonasal disease seems appropriate for these disorders.

A Computed Tomographic Assessment of Osteitis of Sinus Bony Structures in Horses With Sinonasal Disorders.

Background: Computed tomographic (CT) imaging has shown some horses with sinonasal diseases to have changes in their sinus bony structures. Scintigraphic and clinical evidence of sinus osteitis have also been reported. However, no study has objectively examined for the presence and degree of osteitis in equine sinonasal disease. Objectives: To assess for the presence and extent of osteitis of sinus-related bony structures by examination of CT images of horses with clinically and sinoscopically confirmed unilateral sinonasal disease. Study Design: Retrospective examination of CT images of horses with confirmed, mainly chronic (>2 month duration) unilateral sinus disease of different etiologies. Methods: Bone thickness at designated sites of the maxillary bone (n = 3), frontal bone (n = 1), infraorbital canal (n = 2), and bony nasolacrimal duct (n = 1) were measured, as were the maximal diameters of the infraorbital canal and the bony nasolacrimal duct on both affected and control sides. Maxillary bone density (in Hounsfield Units) was also assessed bilaterally. Bone thickness was compared between affected and controlled sides using paired statistical tests. Results: Bone was significantly thicker in the affected sinuses compared to the control sides at the three maxillary bone sites (all, P < 0.001) and at both infraorbital bone sites (both, P < 0.001), but not at the two most dorsal sites examined, i.e. frontal bone (P = 0.188) and bony nasolacrimal duct (P = -0.260) sites. Infraorbital canal and bony nasolacrimal duct diameters were significantly wider in the affected as compared to the control sides (P < 0.001 and P = 0.002, respectively). Maxillary bone density did not differ significantly between the affected (mean = 1,075 HU, SD = 230.01) and control (mean = 1,100, SD = 200.71) sides (t (58) = -1.03, P = 0.306). Main Limitations: Possible variation in selecting measurement sites. Variation in the severity and chronicity of sinonasal disease between horses. Conclusions: Osteitis and enlargement of paranasal bony structures commonly occurs in horses with sinonasal disease and can explain the clinical presence of ipsilateral diffuse soft tissue facial swelling, epiphora, and scintigraphic evidence of bone inflammation in sinonasal disease.

A long-term study of equine cheek teeth post-extraction complications: 428 cheek teeth (2004-2018).

BACKGROUND: Complications, especially delayed alveolar healing, are common following equine cheek teeth extraction, however, limited objective information is available on the prevalence and nature of these problems. OBJECTIVES: To document the type and prevalence of complications that occur following equine cheek tooth extraction and to identify possible risk factors for these complications that could be used to predict their occurrence and hopefully reduce their prevalence. STUDY DESIGN: Retrospective cohort study. METHODS: Clinical records of all cheek teeth extractions performed between February 2004 and September 2018 were examined and written questionnaires sent to owners. Details of post-extraction complications were analysed and logistic regression was used to evaluate potential associations between the likelihood of post-extraction nonhealing alveolus managed by the authors and the variables: age, breed, reason for extraction, Triadan position and extraction technique. RESULTS: Post-extraction complications were recorded following 58/428 extractions giving an overall complication rate of 13.6%, that caused a longer term clinical problem in 34/428 (7.9%) cases, with complications being asymptomatic or quickly self-resolving in the other 24 cases (5.6%). The most frequent complication was alveolar bone sequestration, including alveolar infection. Risk of developing a post-extraction alveolar disorder managed by the authors (n = 53) increased following extraction of the mandibular 06s, 07s or 08s compared with all other cheek teeth combined (P = .001); for cheek teeth with apical infections (P = .002) compared with those without; and following repulsion or minimally invasive transbuccal extraction (MTE) than following oral extraction (P = .01 and P = .02 respectively). MAIN LIMITATIONS: Length of time between exodontia and survey data collection for some cases, use of clinical records and survey data and biases associated with decision to treat. CONCLUSIONS: In agreement with previous studies, oral extraction had the lowest risk of complications. This study provides new information regarding the prevalence, types and risk of development of post extraction complications. Knowledge of these risk factors may help reduce these complications.

Ex Vivo Comparison of the Accuracy of a Clamped with a Hand-Held Drill Guide for Drilling Distal Third Metacarpals and Metatarsals in Equids.

OBJECTIVES: The aim of this study was to determine whether a clamped drill guide can be used effectively to drill across equine distal third metacarpals and metatarsals and to compare accuracy and speed of a drilling with a hand-held drill guide. STUDY DESIGN: Eighty equine cadaver limbs were divided between four surgeons with varying experience. The limbs were randomly allocated to clamped or hand-held drill guides and placed in a stand in an upright/standing position on a metal table. Drilling times from cis- to trans cortices were measured. Post-drilling computed tomography images were used to assess drilling deviations in the dorsopalmar and proximodistal directions. RESULTS: Mean proximodistal deviation of the drill hole was distad for both guides and significantly (p = 0.01) less for the clamped drill guide +0.35° (range: -5.42°, +6.61°, standard deviation [SD] ± 3.18°) than the hand-held drill guide +2.05° (range: -5.24°, +9.81°, SD ± 3.69°). Mean dorsopalmar/plantar deviation was non-significantly (p = 0.17) less for the clamped drill guide -0.27° (range: -9.72°, +6.58°, SD ± 3.57°) than the hand-held drill guide +0.60° (range: -9.74°, + 12.33°, SD ± 4.51°). Mean time taken to drill from cis to trans cortex was significantly (p < 0.001) shorter with the clamped drill guide (41.2s) than the hand-held guide (56.6s). CONCLUSION: The clamped drill guide could be used successfully on the equine distal third metacarpals and metatarsals and resulted in some improved accuracy and reduced drilling time compared with the hand-held guide. The use of the clamped drill guide in vivo could be supported. This may be of benefit for certain fracture repairs in equids.

Frequency of Undetected Glove Perforation and Associated Risk Factors in Equine Surgery.

OBJECTIVE: To estimate the frequency of undetected perforations in surgical gloves during equine surgery and to identify risk factors associated with occurrence. STUDY DESIGN: Observational cohort study. SAMPLE POPULATION: Surgical gloves-292 pairs. METHODS: Water leak tests were performed on gloves after equine surgery to detect perforations. Fifty pairs of unused gloves were also tested. Potential risk factors were recorded. Logistic regression was used to explore associations between putative risk factors and perforation. RESULTS: No perforations were detected in the unused gloves. Of 292 pairs of used gloves tested, 80 (27%) had at least one glove perforation per pair. The frequency of perforations was not different between surgery diplomates and residents (P=.69). The length and type of surgery were significantly associated with the likelihood of undetected glove perforation with surgeries longer than 60 minutes approximately 2.5 times more likely to result in glove perforation (P=.005). Surgery classified as soft tissue, orthopedic or exploratory celiotomy was 3 times more likely to result in glove perforation than minimally invasive surgery. The perforations occurred significantly more frequently in the nondominant hand (19%) than the dominant hand (11%) (P=.009). CONCLUSION: There is a high occurrence of undetected glove perforation in equine surgery. Precautions can be suggested based on this study although further investigation is required to assess whether glove perforations are associated with surgical site infections.

Frequency of Penetration of the Digital Flexor Tendon Sheath and Distal Interphalangeal Joint Using a Direct Endoscopic Approach to the Navicular Bursa in Horses.

OBJECTIVE: To evaluate the frequency of inadvertent penetration of the digital flexor tendon sheath (DFTS) and/or distal interphalangeal joint (DIPJ) when using a direct endoscopic approach to the navicular bursa, and to evaluate an alternate direct approach to the navicular bursa. STUDY DESIGN: Cadaveric study. SAMPLE POPULATION: Equine cadaver limbs (n = 40 for direct; n = 12 for alternate approach). METHODS: Four surgeons performed the direct endoscopic approach to the navicular bursa on 10 limbs each. Frequencies of inadvertent synovial penetration and iatrogenic damage were compared between surgeons. Use of an alternate direct approach, adopting a straight parasagittal trajectory, was evaluated by 2 surgeons. RESULTS: Inadvertent synovial penetration occurred in 45% of limbs (DFTS 37.5%; DIPJ 17.5%; and both structures 10%). Successful bursa entry was achieved on the first attempt in 45% of limbs. Significant variation in frequency of inadvertent synovial penetration was observed between surgeons (range 10-80%). Inadvertent synovial penetration did not occur when using the alternate direct technique. Iatrogenic damage to navicular bone fibrocartilage and/or deep digital flexor tendon occurred in 55% of limbs using the direct endoscopic approach and in 0% of limbs using the alternate direct approach. CONCLUSION: Because of the considerable risk of inadvertent penetration of the DFTS and/or the DIPJ when making a direct endoscopic approach to the navicular bursa, it is advisable to investigate for inadvertent penetration when treating navicular bursa sepsis using a direct approach. The alternate direct technique may reduce the risk of inadvertent penetration; however, the view within the bursa may be restricted.

Risk factors for epistaxis in jump racing in Great Britain (2001-2009).

The aim of this study was to evaluate risk factors associated with developing epistaxis in jump racing in Great Britain (GB). A retrospective analysis of records from horses running in all hurdle and steeplechase races in GB between 2001 and 2009 identified diagnoses of epistaxis whilst still at the racecourse. Data were used from 603 starts resulting in epistaxis (event) and 169,065 starts resulting in no epistaxis (non-event) in hurdle racing, and from 550 event starts and 102,344 non-event starts in steeplechase racing. Two multivariable logistic regression models to evaluate risk factors associated with epistaxis were produced. The potential effect of clustering of data (within horse, horse dam, horse sire, trainer, jockey, course, race and race meet) on the associations between risk factors and epistaxis was examined using mixed-effects models. Multiple factors associated with increased risk of epistaxis were identified. Those identified in both types of jump racing included running on firmer ground; horses with >75% of career starts in flat racing and a previous episode of epistaxis recorded during racing. Risk factors identified only in hurdle racing included racing in the spring and increased age at first race; and those identified only in steeplechase racing included running in a claiming race and more starts in the previous 3-6 months. The risk factors identified provide important information about the risk of developing epistaxis. Multiple avenues for further investigation are highlighted, including unmeasured variables at the level of the racecourse. The results of this study can be used to guide the development of interventions to minimise the risk of epistaxis in jump racing.

The application of exhaled breath analysis in racing Thoroughbreds and the influence of high intensity exercise and ambient temperature on the concentration of carbon monoxide and pH in exhaled breath.

Analyses of exhaled breath (EB) and exhaled breath condensate (EBC) are non-invasive modalities for assessing the lower airways but these methods have not been applied to Thoroughbred racehorses in training. The aims of this study were to determine whether EB and EBC could be obtained from Thoroughbred racehorses in the field and to investigate the effects of exercise per se and during different ambient temperatures and humidity on exhaled concentrations of nitric oxide (eNO), carbon monoxide (eCO) and EBC pH. EB and EBC samples were obtained from 28 Thoroughbred racehorses pre- and post-exercise during warm (n=23) and/or cold (n=19) ambient temperatures. eNO was detected in 19/84 EB samples. eCO was measured in 39/42 EB samples pre-exercise (median 1.3 ppm) and concentrations decreased significantly post-exercise (median 0.8 ppm, P<0.005) and were associated with ambient temperature. EBC pH was 4.51 ± 0.23 pre-exercise and increased significantly post-exercise (4.79 ± 0.59, P=0.003). The study documented the collection of EB and EBC from Thoroughbred racehorses in a field setting. Alterations in concentrations of volatile gases and EBC pH occurred in response to exercise, and were likely to have been influenced by environmental factors.

An in vitro biomechanical comparison of a locking compression plate fixation and kerf cut cylinder fixation for ventral arthrodesis of the fourth and the fifth equine cervical vertebrae.

OBJECTIVES: To (1) define mechanical properties in flexion, extension, and left lateral bending of cadaveric equine 4th and 5th cervical (C4-C5) articulations, (2) compare biomechanical properties of C4-C5 when stabilized with a kerf cut cylinder (KCC) compared with a ventrally placed 4.5 mm locking compression plate (LCP). STUDY DESIGN: In vitro biomechanical investigation. SAMPLE POPULATION: Cadaveric adult equine cervical vertebral columns (n=54). METHODS: Cervical vertebrae aged by horse dentition and size measured from radiographs were divided into 3 age groups then randomly allocated to 3 groups. The C4-C5 articulation was treated differently in each of the groups: KCC group; KCC-implanted LCP group; 8-hole 4.5 mm LCP implanted and intact group; no implant. Specimens were randomly subdivided into 1 of 3 loading conditions, before testing to failure under 4-point bending. Stiffness, yield bending moment, failure bending moment, and failure mode were recorded. General linear models were performed to analyze associations between biomechanical properties and test variables. RESULTS: All specimens failed at the C4-C5 intervertebral articulation. The cervical vertebrae with the LCP construct had significantly higher stiffness, yield bending moment, and failure bending moment than the KCC-implanted cervical vertebrae. Failure modes differed between groups and varied with loading direction: KCC group, fractures of C5 associated with the KCC were common; LCP group, screw pull out or fractures (of C4 and C5 bodies, during extension and the caudal aspect of C4 during left lateral bending) were common; and intact group, subluxations were most common. CONCLUSIONS: In this model, LCP constructs had superior biomechanical properties compared with KCC constructs. Further research investigating the effect of repetitive loading is indicated.