Rebecca A. Packer

Pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy

OBJECTIVE To assess tolerability and short-term efficacy of oral administration of pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with poorly controlled suspected idiopathic epilepsy. DESIGN Open-label, noncomparative clinical trial. ANIMALS 11 client-owned dogs suspected of having idiopathic epilepsy that was inadequately controlled with phenobarbital, potassium bromide, or a combination of these 2 drugs. PROCEDURES Dogs were treated with pregabalin (3 to 4 mg/kg [1.4 to 1.8 mg/lb], PO, q 8 h) for 3 months. Number of generalized seizures in the 3 months before and after initiation of pregabalin treatment was recorded. Number of responders (>or= 50% reduction in seizure frequency) was recorded, and seizure frequency before and after initiation of pregabalin treatment was compared by use of a nonparametric Wilcoxon signed rank test. RESULTS Seizures were significantly reduced (mean, 57%; median, 50%) after pregabalin administration in the 9 dogs that completed the study; 7 were considered responders with mean and median seizure reductions of 64% and 58%, respectively. Adverse effects for pregabalin were reported in 10 dogs. Mean and median plasma pregabalin concentrations for all dogs were 6.4 and 7.3 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Pregabalin may hold promise as a safe and effective adjunct anticonvulsant drug for epileptic dogs poorly controlled with the standard drugs phenobarbital or potassium bromide. Adverse effects of pregabalin appeared to be mild. Additional studies with larger numbers of dogs and longer follow-up intervals are warranted.

Hand-gesture-based sterile interface for the operating room using contextual cues for the navigation of radiological images

This paper presents a method to improve the navigation and manipulation of radiological images through a sterile hand gesture recognition interface based on attentional contextual cues. Computer vision algorithms were developed to extract intention and attention cues from the surgeons behavior and combine them with sensory data from a commodity depth camera. The developed interface was tested in a usability experiment to assess the effectiveness of the new interface. An image navigation and manipulation task was performed, and the gesture recognition accuracy, false positives and task completion times were computed to evaluate system performance. Experimental results show that gesture interaction and surgeon behavior analysis can be used to accurately navigate, manipulate and access MRI images, and therefore this modality could replace the use of keyboard and mice-based interfaces.

Vaccination for Invasive Canine Meningioma Induces in Situ Production of Antibodies Capable of Antibody-Dependent Cell-Mediated Cytotoxicity

Malignant and atypical meningiomas are resistant to standard therapies and associated with poor prognosis. Despite progress in the treatment of other tumors with therapeutic vaccines, this approach has not been tested preclinically or clinically in these tumors. Spontaneous canine meningioma is a clinically meaningful but underutilized model for preclinical testing of novel strategies for aggressive human meningioma. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with toll-like receptor ligands. Therapy was well tolerated, and only one dog had tumor growth that required intervention, with a mean follow up of 585 days. IFN-γ-elaborating T cells were detected in the peripheral blood of 2 cases, but vaccine-induced tumor-reactive antibody responses developed in all dogs. Antibody responses were polyclonal, recognizing both intracellular and cell surface antigens, and HSP60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, showing common antigens across breed and species. Histologic analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in posttreatment compared with pretreatment samples. Tumor-reactive antibodies were capable of inducing antibody-dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. These data show the feasibility and immunologic efficacy of vaccine immunotherapy for a large animal model of human meningioma and warrant further development toward human trials.

An ADAMTSL2 Founder Mutation Causes Musladin-Lueke Syndrome, a Heritable Disorder of Beagle Dogs, Featuring Stiff Skin and Joint Contractures

Background Musladin-Lueke Syndrome (MLS) is a hereditary disorder affecting Beagle dogs that manifests with extensive fibrosis of the skin and joints. In this respect, it resembles human stiff skin syndrome and the Tight skin mouse, each of which is caused by gene defects affecting fibrillin-1, a major component of tissue microfibrils. The objective of this work was to determine the genetic basis of MLS and the molecular consequence of the identified mutation. Methodology and Principal Findings We mapped the locus for MLS by genome-wide association to a 3.05 Mb haplotype on canine chromosome 9 (CFA9 (50.11–54.26; praw <10−7)), which was homozygous and identical-by-descent among all affected dogs, consistent with recessive inheritance of a founder mutation. Sequence analysis of a candidate gene at this locus, ADAMTSL2, which is responsible for the human TGFβ dysregulation syndrome, Geleophysic Dysplasia (GD), uncovered a mutation in exon 7 (c.660C>T; p.R221C) perfectly associated with MLS (p-value = 10−12). Murine ADAMTSL2 containing the p.R221C mutation formed anomalous disulfide-bonded dimers when transiently expressed in COS-1, HEK293F and CHO cells, and was present in the medium of these cells at lower levels than wild-type ADAMTSL2 expressed in parallel. Conclusions/Significance The genetic basis of MLS is a founder mutation in ADAMTSL2, previously shown to interact with latent TGF-β binding protein, which binds fibrillin-1. The molecular effect of the founder mutation on ADAMTSL2 is formation of disulfide-bonded dimers. Although caused by a distinct mutation, and having a milder phenotype than human GD, MLS nevertheless offers a new animal model for study of GD, and for prospective insights on mechanisms and pathways of skin fibrosis and joint contractures.

Evaluation of minimally invasive excisional brain biopsy and intracranial brachytherapy catheter placement in dogs

OBJECTIVE To evaluate a technique for minimally invasive excisional brain biopsy and intracranial brachytherapy catheter placement in dogs. ANIMALS 5 healthy adult female dogs. PROCEDURES Computed tomographic guidance was used to plan a biopsy trajectory to a selected area of brain with reference to a localizer grid. The procedure was performed through a 1-cm skin incision and 6-mm burr hole by use of a 9-gauge biopsy device. Five cylindrical samples (3 to 4 mm in diameter and 7 to 12 mm in length) were removed over 5 cycles of the vacuum-assisted tissue excision system, leaving approximately a 2-cm³ resection cavity. A balloon-tipped intracranial brachytherapy catheter was placed through the burr hole into the resection cavity, expanded with saline (0.9% NaCl) solution, and explanted 7 days later. RESULTS 4 of 5 dogs survived the procedure. The fifth died because of iatrogenic brain damage. Neurologic deficits were unilateral and focal. Twenty-four hours after surgery, all surviving dogs were ambulatory, 2 dogs exhibited ipsiversive circling, 4 had contralateral proprioceptive deficits, 3 had contralateral menace response deficits, 2 had a reduced contralateral response to noxious nasal stimulation, and 1 had dull mentation with intermittent horizontal nystagmus and ventrolateral strabismus. Neurologic status improved throughout the study period. Histologic quality of biopsy specimens was excellent. CONCLUSIONS AND CLINICAL RELEVANCE This technique enabled histologic diagnosis from high-quality biopsy specimens obtained through a minimally invasive technique and has potential applications for multimodal treatment of deep brain tumors in dogs.

Sarcocystis sp. encephalomyelitis in a cat.

Abstract: A 5‐month‐old male neutered domestic shorthair cat was evaluated for spinal pain, ataxia, and anisocoria. Neuroanatomic localization indicated diffuse or multifocal central nervous system disease. On cerebrospinal fluid analysis, neutrophilic pleocytosis and intracellular protozoal merozoites were observed. The merozoites were oval, 2–4 μm in width and 4–6 μm in length, and had linear arrays of nuclear material concentrated at one pole. Serum was positive for Sarcocystis sp. antibodies and negative for Toxoplasma gondii antibodies. The organism was determined to be either Sarcocystis neurona or Sarcocystis dasypi based on sequence analysis of the internal transcribed spacer 1 ribosomal RNA genomic region. Clinical disease resolved following treatment with 3 different protocols for protozoal infection. This case is the first to demonstrate the antemortem diagnosis and survival of a domestic cat with Sarcocystis sp.‐associated encephalomyelitis. Clinicians and cytopathologists should include Sarcocystis sp. as a differential for feline inflammatory central nervous system disease characterized by neutrophilic pleocytosis.

Increase in oxidative stress biomarkers in dogs with ascending–descending myelomalacia following spinal cord injury

Multiple biochemical and immunohistochemical tests were performed to elucidate the role of oxidative stress during ascending-descending (A-D) myelomalacia by comparing dogs with this progressive terminal condition to dogs with chronic, focal spinal cord injuries (SCIs) and controls without SCI. Dogs with A-D myelomalacia exhibited increased biochemical markers for oxidative stress, including 8-isoprostane F2α and acrolein, as well as decreased endogenous glutathione with greatest changes occurring at the lesion center. Inflammation, as evident by the concentration of CD18+ phagocytes and hemorrhagic necrosis, was also exacerbated in the lesion of A-D myelomalacic spinal cord compared to focal SCI. The greatest differences in oxidative stress occurred at the lesion center and diminished distally in both spinal cords with A-D myelomalacia and focal SCIs. The spatial progression and time course of A-D myelomalacia are consistent with the development of secondary injury post-SCI. Ascending-descending myelomalacia is proposed as a clinical model that may further the understanding of the role of oxidative stress during secondary injury. Our results indicate that the pathology of A-D myelomalacia is also similar to subacute progressive ascending myelopathy in humans, which is characterized by recurrent neurodegeneration of spinal cord post-injury.

Intention, Context and Gesture Recognition for Sterile MRI Navigation in the Operating Room

Human-Computer Interaction (HCI) devices such as the keyboard and the mouse are among the most contaminated regions in an operating room (OR). This paper proposes a sterile, intuitive HCI to navigate MRI images using freehand gestures. The system incorporates contextual cues and intent of the user to strengthen the gesture recognition process. Experimental results showed that while performing an image navigation task, mean intent recognition accuracy was 98.7% and that the false positive rate of gesture recognition dropped from 20.76% to 2.33% with context integration at similar recognition rates.

Evaluation of an acute focal epidural mass model to characterize the intracranial pressure-volume relationship in healthy Beagles

OBJECTIVE To characterize the intracranial pressure-volume relationship (ICPVR) in dogs by use of an acute frontal-parietal mass lesion model. ANIMALS 7 healthy adult female Beagles. PROCEDURES Dogs were anesthetized with isoflurane to achieve a surgical plane of anesthesia. A fiberoptic intracranial pressure (ICP) monitor was inserted to a depth of 1 cm in the parenchyma of the right frontal-parietal region of the brain. A Foley balloon-tipped catheter was placed in the epidural space of the left frontal-parietal area through a separate 1-cm burr hole. Baseline measurements were obtained with the balloon deflated. The balloon was then inflated incrementally with 0.5 mL of 0.9% NaCl solution every 10 minutes until ICP exceeded mean arterial blood pressure. Nonlinear regression analysis with 2-factor and 3-factor exponential equations was used to characterize the ICPVR. RESULTS The mean baseline ICP was 11 mm Hg, with a 95% confidence interval of 2 to 20 mm Hg. The ICPVR was well characterized by 2-factor or 3-factor exponential equations for all dogs (R² > 0.93). Balloon volumes of > 1. 2 mL were associated with ICP > 20 mm Hg. CONCLUSIONS AND CLINICAL RELEVANCE Characterization of the ICPVR may provide clinically useful information regarding the safety of obtaining CSF from the atlanto-occipital space or implantation of brachytherapy catheters and for determining the need for decompressive craniectomy in dogs with acute intracranial disease. High ICP should be suspected in dogs that have an acute frontal-parietal mass lesion estimated to exceed 2% of the brain volume.

Canine Intervertebral Disc Fenestration Using a Vacuum‐Assisted Tissue Resection Device

OBJECTIVE Describe the use and feasibility of a novel vacuum-assisted tissue resection device (VRD) for canine intervertebral disc fenestration, and compare the effectiveness of manual fenestration to the VRD. STUDY DESIGN Randomized prospective study. ANIMALS Canine cadavers (n = 15). METHODS A cadaveric lumbar spine study was performed to compare the use of manual fenestration to a novel VRD for intervertebral disc fenestration. Both fenestration groups were compared to a control group. Effectiveness of fenestration was assessed by calculating a ratio of remaining nuclear weight postfenestration to total nuclear volume. Fenestrated discs with lower ratios were indicative of greater removal of nucleus pulposus. RESULTS There was a statistically significant reduction in mean ratio (±SD) of remaining nuclear weight to volume with both fenestration groups compared to controls (0.39 ± 0.07; P < .001). There was an improved ratio using the VRD (0.23 ± 0.09) compared to manual fenestration (0.30 ± 0.10); this was not statistically significant (P = .069). It was technically difficult to fenestrate the disc spaces at L5-L6 and L6-L7 because of location and anatomy, resulting in a statistically significant increase in the median ratio of nuclear weight-to-volume ratios in both manual and VRD fenestration groups when compared to the more cranial L4-L5 disc spaces, 0.32 ± 0.08, and 0.35 ± 0.08 versus 0.25 ± 0.13 at L4-L5 (P = .026 and P = .004, respectively). CONCLUSIONS The VRD is a feasible instrument for canine intervertebral disc fenestration. It is at least as effective as manual fenestration, and provides additional safety features.