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.

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.

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.