Evaluation of a procaspase-3 activator with hydroxyurea or temozolomide against high-grade meningioma in cell culture and canine cancer patients.

BACKGROUND: High-grade meningioma is an aggressive type of brain cancer that is often recalcitrant to surgery and radiotherapy, leading to poor overall survival. Currently, there are no FDA-approved drugs for meningioma, highlighting the need for new therapeutic options, but development is challenging due to the lack of predictive preclinical models. METHODS: To leverage the known overexpression of procaspase-3 in meningioma, PAC-1, a blood-brain barrier penetrant procaspase-3 activator, was evaluated for its ability to induce apoptosis in meningioma cells. To enhance the effects of PAC-1, combinations with either hydroxyurea or temozolomide were explored in cell culture. Both combinations were further investigated in small groups of canine meningioma patients and assessed by MRI, and the novel apoptosis tracer, [18F]C-SNAT4, was evaluated in patients treated with PAC-1 + HU. RESULTS: In meningioma cell lines in culture, PAC-1 + HU are synergistic while PAC-1 + TMZ show additive-to-synergistic effects. In canine meningioma patients, PAC-1 + HU led to stabilization of disease and no change in apoptosis within the tumor, whereas PAC-1 + TMZ reduced tumor burden in all three canine patients treated. CONCLUSIONS: Our results suggest PAC-1 + TMZ as a potentially efficacious combination for the treatment of human meningioma, and also demonstrate the utility of including pet dogs with meningioma as a means to assess anticancer strategies for this common brain tumor.

Evaluation of bronchial narrowing in coughing dogs with heart murmurs using computed tomography.

BACKGROUND: The origin of cough in dogs with heart murmurs is controversial, because the cough could be primary cardiac (eg, pulmonary edema, bronchi compression by left-sided cardiomegaly) or respiratory (eg, bronchomalacia, other bronchial or bronchiolar disease, interstitial lung disease) in origin. HYPOTHESIS/OBJECTIVES: To study the association between left atrium (LA) dilatation and cardiomegaly and bronchial narrowing in coughing dogs with heart murmurs using computed tomography (CT). ANIMALS: Twenty-one client-owned coughing dogs with heart murmurs and 14 historical control dogs. METHODS: Dogs with cough and murmur were prospectively recruited over 4 months. Cervical and thoracic radiography, echocardiography, and thoracic CT were performed in enrolled dogs. Control dogs, with no disease on thoracic CT and no records of heart murmur and coughing, were gathered from the institution's computerized database. Degree of bronchial narrowing was assessed using the bronchial-to-aorta (Ao) ratio, measured by 3 radiologists blinded to the clinical findings. After identifying bronchi that were significantly narrowed in dogs with murmur compared to controls, the relationship between degree of narrowing and LA/Ao ratio (measured echocardiographically) and vertebral heart scale (VHS) measured radiographically was studied in dogs with murmur using mixed-effects regression. RESULT: Significant narrowing was identified for all left-sided bronchi and the right principal, middle, and caudal bronchi in the coughing dogs, compared with controls. Increasing LA size and VHS were significantly inversely associated with diameter for all left-sided and right-sided bronchi indicated above. CONCLUSION AND CLINICAL IMPORTANCE: Results indicate an association between LA enlargement and cardiomegaly and bronchial narrowing and support heart size-associated exacerbation of cough in dogs with murmurs.

BODY CONDITION OF EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) EVALUATED BY COMPUTED TOMOGRAPHY.

Conservation efforts determining the health status of individuals can aid in assessing population health and sustainability. Body condition was determined in 65 free-ranging Eastern box turtles (Terrapene carolina carolina) from four locations in Vermilion County, Illinois, in the months of May, July, and September 2014, 2015, and 2016 using computed tomography (CT). Physical examinations were performed to determine morphometric measurements, and CT scans measured body fat. Twenty-three linear models were constructed to determine which morphometric measurements best correlated to fat content. The top two models of body fat included a relationship between mass and carapace width. Fat increases as both mass and carapace width increase. CT, while impractical for daily use, improved on previous methods of measuring body condition and created a calculation that can be applied broadly to Eastern box turtles. By understanding how measurements of mass and carapace width correlate to body condition, practitioners, researchers, and conservationists can evaluate chelonians with increased confidence in the accuracy of their assessment.

Modified lateral orbitotomy with combined partial zygomatic arch and vertical ramus ostectomies for excision of a frontal and parietal bone osteoma in a dog.

OBJECTIVE: To describe modifications to the lateral orbitotomy for surgical excision of tumors affecting the frontal, parietal, palatine, or temporal bones. STUDY DESIGN: Case report. ANIMAL: A 5-year-old female spayed American pit bull terrier. METHODS: The dog presented for excision of a bone tumor affecting the right frontal and parietal bones. A modified lateral orbitotomy was performed with combined partial zygomatic arch and vertical ramus ostectomies to increase working space and allow drilling of the calvarium ventral to the mass. RESULTS: The dog tolerated the procedure well, and there were no complications from either the ostectomies or the craniectomy. Histopathological examination was consistent with complete excision of an osteoma. The dog survived 2 years with no recurrence and was euthanized due to an intestinal mass. CONCLUSION: The lateral orbitotomy approach can be modified with combined partial zygomatic arch and vertical ramus ostectomies to increase exposure and working space for resection of tumors affecting the frontal, parietal, palatine, or temporal bones.

Detection of intra-cardiac thrombi and congestive heart failure in cats using computed tomographic angiography.

Arterial thromboembolism is a life-threatening condition in cats most commonly secondary to cardiac disease. Echocardiography is the reference standard to evaluate for presence of a thrombus. In humans, computed tomographic (CT) angiography is becoming widely used to detect left atrial thrombi precluding the use of sedation. The purpose of this prospective, controlled, methods comparison pilot study was threefold: (1) describe new CT angiography protocol used in awake cats with cardiac disease and congestive heart failure; (2) determine accuracy of continuous and dynamic acquisition CT angiography to identify and characterize cardiac thrombi from spontaneous echocardiographic contrast using transthoracic echocardiography as our reference standard; (3) identify known negative prognostic factors and comorbidities of the thorax that CT angiography may provide that complement or supersede echocardiographic examination. Fourteen cats with heart disease were recruited; 7 with thrombi and 7 with spontaneous echocardiographic contrast. Echocardiography and awake CT angiography were performed using a microdose of contrast. Six of 7 thrombi were identified on CT angiography as filling defects by at least one reviewer within the left auricle (n = 6) and right heart (n = 1). Highest sensitivity (71.4%) was in continuous phase and highest specificity (85.7%) was in dynamic studies with fair to moderate interobserver agreement (0.38 and 0.44). CT angiography identified prognostic cardiac information (left atrial enlargement, congestive heart failure, arterial thromboembolism) and comorbidities (suspected idiopathic pulmonary fibrosis, asthma). This study indicates CT angiography can readily identify cardiac thrombi, important prognostic information and comorbidities, and can be safely performed in cats with cardiac disease and congestive heart failure.

Acute surgical intervention for a depressed skull fracture causing a laceration to the brain parenchyma from a bite wound in a dog.

A 5-month-old spayed female mixed breed dog was attacked by another dog causing multiple fractures of the left calvarium with a fragment penetrating through the gray matter of the parietal lobe. Surgery was performed to remove the bone fragment. A 6-month follow-up showed dramatic improvement in neurologic status.

Intervention chirurgicale d'urgence pour une fracture du crâne pénétrante causant une lacération au parenchyme du cerveau suite à une morsure chez une chienne. Une chienne stérilisée de race croisée âgée de 5 mois a été attaquée par un autre chien causant des fractures multiples de la voûte crânienne gauche avec un fragment pénétrant dans la matière grise du lobe pariétal. La chirurgie a été réalisée pour enlever le fragment d'os. Un suivi de 6 mois a démontré une amélioration spectaculaire de l'état neurologique.(Traduit par Isabelle Vallières).

Computed tomographic study of safe implantation corridors in rabbit lumbar vertebrae.

OBJECTIVES: A study was performed to evaluate the lumbar vertebrae of domestic rabbits using computed tomography (CT) in order to identify safe corridors for implant insertion. METHODS: Computed tomography imaging of 20 adult New Zealand white rabbits was evaluated using three-dimensional multiplanar reconstruction, and safe corridors were determined. Following corridor determination, implant placement was performed, and imaging was repeated. RESULTS: The cranial and caudal endplates contained the majority of the vertebral bone stock, and were an average of 3.14 and 3.30 mm in length, respectively. The mean safe corridor angle was 62.9 degrees (range: 58.8-66.7), and the mean width of the corridor was 2.03 mm (range: 1.60- 2.07). Post-placement imaging revealed that 35% of the pins demonstrated errors of placement, most commonly canal impingement. CONCLUSIONS: The results of the corridor evaluation indicate that an insertion angle of approximately 60 degrees relative to the sagittal midline is appropriate for implant insertion in the lumbar vertebrae of New Zealand white rabbits. Additionally, due to the hourglass shape of rabbit vertebrae, the endplates provide maximal bone stock for implant purchase, so insertion should be attempted in these regions. However, the high percentage of errors in placement indicate the need to more clearly define entry points to access the canal, and highlight the challenges of appropriate placement in the small bones of rabbits.

Three-dimensional printing of orbital and peri-orbital masses in three dogs and its potential applications in veterinary ophthalmology.

OBJECTIVE: To describe the technique and utility of three-dimensional (3D) printing for orbital and peri-orbital masses and discuss other potential applications for 3D printing. ANIMALS STUDIED: Three dogs with a chronic history of nonpainful exophthalmos. PROCEDURES: Computed tomography (CT) and subsequent 3D printing of the head was performed on each case. CT confirmed a confined mass, and an ultrasound-guided biopsy was obtained in each circumstance. An orbitotomy was tentatively planned for each case, and a 3D print of each head with the associated globe and mass was created to assist in surgical planning. RESULTS: In case 1, the mass was located in the cranioventral aspect of the right orbit, and the histopathologic diagnosis was adenoma. In case 2, the mass was located within the lateral masseter muscle, ventral to the right orbit between the zygomatic arch and the ramus of the mandible. The histopathologic diagnosis in case 2 was consistent with a lipoma. In case 3, the mass was located in the ventral orbit, and the histopathologic diagnosis was histiocytic cellular infiltrate. CONCLUSIONS: Three-dimensional printing in cases with orbital and peri-orbital masses has exceptional potential for improved surgical planning and provides another modality for visualization to help veterinarians, students, and owners understand distribution of disease. Additionally, as the techniques of 3D printing continue to evolve, the potential exists to revolutionize ocular surgery and drug delivery.

Use of manual alveolar recruitment maneuvers to eliminate atelectasis artifacts identified during thoracic computed tomography of healthy neonatal foals.

OBJECTIVE To evaluate use of single manual alveolar recruitment maneuvers (ARMs) to eliminate atelectasis during CT of anesthetized foals. ANIMALS 6 neonatal Standardbred foals. PROCEDURES Thoracic CT was performed on spontaneously breathing anesthetized foals positioned in sternal (n = 3) or dorsal (3) recumbency when foals were 24 to 36 hours old (time 1), 4 days old (time 2), 7 days old (time 3), and 10 days old (time 4). The CT images were collected without ARMs (all times) and during ARMs with an internal airway pressure of 10, 20, and 30 cm H2O (times 2 and 3). Quantitative analysis of CT images measured whole lung and regional changes in attenuation or volume with ARMs. RESULTS Increased attenuation and an alveolar pattern were most prominent in the dependent portion of the lungs. Subjectively, ARMs did not eliminate atelectasis; however, they did incrementally reduce attenuation, particularly in the nondependent portion of the lungs. Quantitative differences in lung attenuation attributable to position of foal were not identified. Lung attenuation decreased significantly (times 2 and 3) and lung volume increased significantly (times 2 and 3) after ARMs. Changes in attenuation and volume were most pronounced in the nondependent portion of the lungs and at ARMs of 20 and 30 cm H2O. CONCLUSIONS AND CLINICAL RELEVANCE Manual ARMs did not eliminate atelectasis but reduced attenuation in nondependent portions of the lungs. Positioning of foals in dorsal recumbency for CT may be appropriate when pathological changes in the ventral portion of the lungs are suspected.

Effect of Cortical Screw Diameter on Reduction and Stabilization of Type III Distal Phalanx Fractures: An Equine Cadaveric Study.

OBJECTIVE: To compare reduction of type III distal phalangeal fractures using 4.5 and 5.5 mm cortical screws placed in lag fashion and an intact hoof capsule model. STUDY DESIGN: Cadaveric experimental study. SAMPLE POPULATION: Hooves from 12 adult horses (n=24). METHODS: Sagittal fractures were created in pairs of distal phalanges after distal interphalangeal joint disarticulation and were reduced with either 4.5 or 5.5 mm cortical screws placed in lag fashion. Contralateral phalanges served as non-reduced controls. Fracture reduction following screw placement was assessed by comparing pre-reduction and post-reduction fracture gap measurements from radiographs using paired t-tests. Effects of incremental loading (0, 135, 270, 540, 800, 1070, and 1335 kg) on fracture gaps in 6 phalanges reduced with 4.5 mm screws and 5 phalanges reduced with 5.5 mm screws were measured from fluoroscopic images and assessed by 2-way ANOVA. Significance was set at P<.05. RESULTS: Type III distal phalanx fractures were reliably created. Only 5.5 mm cortical screws, not 4.5 mm screws, significantly reduced fracture gaps and constrained fracture gap expansion 3 cm distal to the articular surface. Compressive loading closed the fracture gaps at the articular surface in both non-reduced control groups and those reduced with either 5.5 or 4.5 mm screws. CONCLUSION: The 5.5 mm cortical screws were more effective than 4.5 mm screws in reducing type III distal phalanx fractures and restricting distal fracture gap expansion under load.

Diagnostic Imaging of the Lower Respiratory Tract in Neonatal Foals: Radiography and Computed Tomography.

Diagnostic imaging plays an essential role in the diagnosis and monitoring of lower respiratory disease in neonatal foals. Radiography is most widely available to equine practitioners and is the primary modality that has been used for the characterization of respiratory disease in foals. Computed tomography imaging, although still limited in availability to the general practitioner, offers advantages over radiography and has been used diagnostically in neonatal foals with respiratory disease. Recognition of appropriate imaging protocols and patient-associated artifacts is critical for accurate image interpretation regardless of the modality used.

SALINE ARTHROGRAPHY OF THE DISTAL INTERPHALANGEAL JOINT FOR LOW-FIELD MAGNETIC RESONANCE IMAGING OF THE EQUINE PODOTROCHLEAR BURSA: FEASIBILITY STUDY.

Abnormalities of the deep digital flexor tendon, navicular bone, and collateral sesamoidean ligament can be difficult to visualize using magnetic resonance imaging (MRI) if bursal fluid is absent. The use of saline podotrochlear bursography improves podotrochlear apparatus evaluation, however, the technique has disadvantages. The objective of this prospective feasibility study was to describe saline arthrography of the distal interphalangeal joint as an alternative technique for improving MRI visualization of the deep digital flexor tendon, navicular bone, collateral sesamoidean ligament, and podotrochlear bursa, and to compare this technique with saline podotrochlear bursography. Eight paired cadaver forelimbs were sampled. Saline podotrochlear bursography or saline arthrography techniques were randomly assigned to one limb, with the alternate technique performed on the contralateral limb. For precontrast and postcontrast studies using each technique, independent observers scored visualization of the dorsal aspect of the deep digital flexor tendon, palmar aspect of the navicular bone, collateral sesamoidean ligament, and podotrochlear bursa. Both contrast techniques improved visualization of structures over precontrast MR images and visualization scores for both techniques were similar. Findings from this study demonstrated that saline arthrography is feasible and comparable to saline podotrochlear bursography for producing podotrochlear bursa distension and separation of the structures of the podotrochlear apparatus on nonweight bearing limbs evaluated with low-field MRI. Clinical evaluation of saline arthrography on live animals is needed to determine if this technique is safe and effective as an alternative to saline podotrochlear bursography in horses with suspected pathology of the podotrochlear apparatus.

Comparison of Dorsal and Buccal Approaches for Surgical Extraction of the Mandibular Canine Tooth in Cat Specimens Using Radiographic and Computed Tomographic Analysis.

The purpose of this study was to compare the buccal and dorsal approaches for surgical extraction of mandibular canine teeth in the cat. Parameters evaluated included extraction time, surgical wound closure time, volume of bone loss, and incidence of complications. Both mandibular canine teeth were extracted from each of 12 feline cadaver specimens, using a different surgical approach for each side, and recording the time for extraction and closure. Computed tomography was used to measure the volume of each rostral mandible before and after extraction, and the bone lossfor each approach was computed. The mean extraction time and volume of bone loss was less for the buccal approach, but the results were not statistically significant (P = 0.22 and P = 0.32, respectively). The closure time for the dorsal approach was significantly less than for the buccal approach (P = 0.023). Total time (extraction plus closure time) was not significantly different between the approaches (P = 0.40). There were no complications associated with either approach.

Evaluating the clinical and physiological effects of long term ultraviolet B radiation on guinea pigs (Cavia porcellus).

Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B received only ambient fluorescent light for 12 hours daily. Animals in both groups were offered the same diet and housed under the same conditions. Blood samples were collected every three weeks to measure blood chemistry values, parathyroid hormone, ionized calcium, and serum 25-hydroxyvitamin D3 (25-OHD3) levels. Serial ophthalmologic examinations, computed tomography scans, and dual energy x-ray absorptiometry scans were performed during the course of the study. At the end of the study the animals were euthanized and necropsied. Mean ± SD serum 25-OHD3 concentrations differed significantly in the guinea pigs (p<0.0001) between the UVB supplementation group (101.49±21.81 nmol/L) and the control group (36.33±24.42 nmol/L). An increased corneal thickness in both eyes was also found in the UVB supplementation compared to the control group (right eye [OD]: p<0.0001; left eye [OS]: p<0.0001). There were no apparent negative clinical or pathologic side effects noted between the groups. This study found that exposing guinea pigs to UVB radiation long term significantly increased their circulating serum 25-OHD3 levels, and that this increase was sustainable over time. Providing guinea pigs exposure to UVB may be an important husbandry consideration that is not currently recommended.

Magnetic resonance imaging contrast enhancement of extra-ocular muscles in dogs with no clinical evidence of orbital disease.

Enhancement of extra-ocular muscles has been reported in cases of orbital pathology in both veterinary and medical magnetic resonance imaging. We have also observed this finding in the absence of orbital disease. The purpose of this retrospective study was to describe extra-ocular muscle contrast enhancement characteristics in a group of dogs with no known orbital disease. Magnetic resonance images (MRI) from dogs with no clinical evidence of orbital disease and a reportedly normal MRI study were retrieved and reviewed. Contrast enhancement percentages of the medial, lateral, ventral, and dorsal rectus muscles were calculated based on signal-to-noise ratios that were in turn determined from hand-traced regions of interest in precontrast, immediate postcontrast and 10-min postcontrast scans. Comparison measurements were made in the pterygoid muscle. Contrast enhancement of the extra-ocular muscles was observed in all patients (median contrast enhancement percentage 45.0%) and was greater than that of pterygoid muscle (median contrast enhancement percentage 22.7%). Enhancement of the extra-ocular muscles persisted 10 min after contrast administration (median contrast enhancement percentage 43.4%). Findings indicated that MRI contrast enhancement of extra-ocular muscles is likely normal in dogs.