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Canine immunoglobulins of the IgG group were shown to be intimately associated with the cuticle of circulating non-infection Dirofilaria immitis microfilaria. The significance of these immunoglobulins in blocking a complete immune response in the definitive host is discussed. Immunodiffusion, immunoelectrophoresis and fluorescent inhibition techniques are described and their applicability to the study of host-parasite relationships are evaluated. A rapid reproducible method for the production of specifically labeled anti-D. immitis microfilaria globulins is presented.

This study monitored the storage lesion of 15 units of canine platelet concentrates harvested by differential centrifugation. Canine platelet concentrates were stored at 20-24°C in a platelet rotator for a total of 9 days; the storage lesion of three second generation platelet storage containers was compared. The battery of in vitro tests used to monitor the storage lesion were selected from previous studies performed with human platelet concentrates separated by differential centrifugation. Based on these tests, canine platelet concentrates exhibited a storage lesion similar to human platelet concentrates. Metabolic analytes demonstrated decreasing pH, carbon dioxide, bicarbonate and glucose concentrations concurrent with increasing oxygen and lactate dehydrogenase activity over the 9-day period. Platelet structural changes were monitored by mean platelet volume, which began to increase on Day-5. Platelet function appeared to be compromised, as indicated by aggregation studies using collagen and adenosine diphosphate as agonists. Product sterility was maintained. There was no consensus of data supporting superior performance of one platelet storage container. This study indicates that canine platelet concentrates may be harvested by differential centrifugation of whole blood. In vitro studies utilizing three second-generation platelet storage bags support a previous study and concurs that canine platelet concentrates stored at 20-24°C using continuous agitation are viable for at least 5 days. / Master of Science

This study tested the hypothesis that administration of immunosuppressive doses of prednisone in conjunction with ultralow-dose aspirin (0.5 mg/kg/day) would result in gastroduodenal lesion scores similar to those found in dogs administered only immunosuppressive doses of prednisone, but that the gastroduodenal scores from both of these treatment groups would be significantly higher than placebo when administered to healthy dogs for 27 days. Eighteen healthy adult purpose-bred dogs were divided randomly into three groups. Group I received placebo capsules and placebo suspension, Group II received prednisone capsules (mean 2.3 mg/kg, range 2.0-2.4) and placebo suspension, and Group III received prednisone capsules (mean 2.3 mg/kg, range 2.3-2.5) and aspirin suspension (0.5 mg/kg) by mouth once daily for 27 days. Gastroduodenoscopy was performed on days -7 (baseline), 5, 14, and 27 of treatment. Four regions of the stomach (angularis incisura, body, pylorus, and cardia) and the proximal descending duodenum were systematically scored on a scale of 1 (normal) to 11 (perforating ulcer) by an experienced observer who was blinded to the treatment groups and clinical signs of each subject. Dogs were observed every 8 hours for vomiting, diarrhea, and inappetence. Feces were scored on a scale of 1-5 with diarrhea defined as a fecal score <4. Lesion scores for each group, at each location, and total scores, at each time period were evaluated for the effects of time and treatment using a Kruskal-Wallis test. Total dog days of vomiting and dog days of diarrhea in each group were compared using a Wilcoxon rank sums test. Significance was determined at p<0.05. There were no significant differences in median total gastric lesion scores between any of the groups at any time during the study. There was no location effect on regional gastroduodenal lesion scores and there was no significant change in gastroduodenal lesion scores over time in any of the groups during treatment. Significantly more dog-days of diarrhea occurred within the prednisone and aspirin group during the experimental period (Period 2) in comparison to Period 1. However, no significant differences were found between any of the groups for dog-days of vomiting, diarrhea or inappetence at any time in the study. / Master of Science

Tricyclic antidepressants have been shown to alter thyroid function in man and laboratory animals, but have not been evaluated in the dog. The effect of administration of clomipramine on canine thyroid function was studied in a prospective protocol in which 14 mature, healthy dogs were administered clomipramine (3 mg/kg PO q12h) for 112 days. Thyroid-stimulating hormone (TSH), total thyroxine (T4), total 3,5,3' triiodothyronine (T3), free thyroxine (fT4), and 3,3',5' triiodothyronine (reverse T3; rT3) concentrations were measured on selected days. Thyrotropin-releasing hormone (TRH) response tests were performed concurrently. Repeated measures analysis of variance was applied to test for effects of day of treatment; when significance (p < 0.05) was noted, it was further investigated using orthogonal polynomial trends. Significant decreases were found in serum T4 (26 ± 1.2 to 17 ± 0.5 nmol/L, p < 0.001), fT4, (29 ± 2.4 to 19 ± 1.3 pmol/L, p < 0.0002), and rT3 (1.2 ± 0.1 to 0.83 ± 0.08 nmol/L, p < 0.0001) concentrations. The effect of time on serum T3 concentration was also significant (p < 0.0001), but no consistent trend could be identified. No significant effect of time was noted in either pre- or post-TRH TSH concentrations. The results of this study indicate that significant and substantial decreases in T4 (35%), fT4 (38%), and rT3 can occur during clomipramine administration. Long-term administration of clomipramine may result in a misdiagnosis of hypothyroidism if a dog is tested while taking this medication and, since decreased serum fT4 occurs, hypothyroidism may result. / Master of Science

Meningioma is one of the most commonly diagnosed intracranial tumors in dogs and humans. Treatment failures resulting in local recurrence and death remain common in tumors of high grade, prompting a need for additional therapeutic options that are both effective and affordable. Genetic modification of the LaSota strain of Newcastle Disease Virus (rLAS) has allowed the virus' fusion protein cleavage site to be replaced with that belonging to urokinase plasminogen activator (rLAS-uPA). This site is cleavable exclusively by the uPA receptor (uPAR), which is overexpressed in canine meningioma. The rLAS-uPA represents a targeted therapy that has the potential to be efficacious against meningioma when administered systemically. A Phase I clinical trial was designed to evaluate the safety and preliminary efficacy of rLAS-uPA administered to dogs with presumptive intracranial meningioma. The primary endpoint was to define the safety of rLAS-uPA, as determined by serial clinical and laboratory assessments during and after viral administration, using standard toxicity metrics defined by the Veterinary Cooperative Oncology Group (VCOG). Secondary end-points included anti-tumor activity quantified by magnetic resonance imaging (MRI) assessment of tumor size, and characterization of immune responses to the rLAS-uPA. Four dogs completed the trial without significant toxicity. No objective tumor responses were noted on MRI from any dog. All dogs produced antiviral antibodies and increased circulating cytokines during the course of treatment. No virus was recovered from plasma, urine, or cerebrospinal fluid. These results indicate that further investigation into the rLAS-uPA dose intensity and interval are required to further develop this therapy. / Master of Science / The use of a modified Newcastle Disease Virus intravenous infusion to treat brain tumors in dogs has been shown to have no overt significant adverse effects. However, further investigation is required to determine the efficacy and optimal dosing protocol for this potential treatment.

Background: Glaucoma is a chronic ocular disease of both dogs and humans that results in blindness and ocular discomfort. Most commonly, end-stage glaucomatous eyes in dogs are enucleated to provide comfort. This intervention requires significant financial investment, general anesthesia, and has a psychological impact on some owners. Retrobulbar neurolytic injections are used in humans to provide immediate and long-acting pain relief, while simultaneously preserving the globe. Objectives: To determine the safety and efficacy of retrobulbar neurolytic ethanol injection in canine eyes with end-stage glaucoma. Animals: 16 client-owned dogs (19 eyes) diagnosed with end-stage glaucoma. Methods: All eyes underwent an ophthalmic examination, including Schirmer Tear Testing (STT), intraocular pressure (IOP) measurement, corneal touch threshold (CTT), anterior and posterior segment examination, and fluorescein staining. Subjects were sedated and administered a retrobulbar block with bupivacaine, followed by retrobulbar injection of ethanol or saline solution. At specified time points after the procedure, clients assessed their pet's comfort and side effects of the injections via survey. Subjects returned for enucleation. Owner perceived comfort after the enucleation was assessed at identical post-procedure time points and compared to that achieved with retrobulbar ethanol injection or control solution. Overall client satisfaction with each procedure, as well as the effects of retrobulbar ethanol injection on STT, IOP, CTT, and histological changes in retrobulbar tissues were investigated. Results: Retrobulbar neurolytic ethanol injections did not signficiantly improve owner perceived comfort compared to control group treatment or provide more comfort than enucleation. Retrobulbar ethanol injections did not signficantly lower IOP, but did significantly elevate CTT. There was a trend towards lower STT in eyes receiving retrobulbar ethanol injections. Retrobulbar ethanol injections were safe, well tolerated, and no differences in client satisfaction with particpation in the study were noted in either injection group. Histologically, globes in the treatment group displayed significantly greater inflammation and fibrosis; retrobublar tissue samples were not significantly different between control and treatment groups with regard to inflammation or fibrosis. Conclusions and Clinical Importance: Retrobulbar neurolytic ethanol injections were not determined to be an effective globe-sparing alternative treatment to provide analgesia for end-stage canine glaucoma. Enucleation remains an effective way to provide comfort to dogs with elevated IOP. / Master of Science / The glaucomas represent a diverse group of blinding and painful diseases associated with elevated intraocular pressure (IOP). Despite advances in the medical and surgical treatment of glaucoma, the long-term prognosis in dogs remains dismal for IOP control, comfort, and globe retention. Blindness and pain are common long-term outcomes, necessitating surgical salvage procedures aimed at restoring patient comfort, including enucleation (eye removal), intrascleral prosthesis, or intravitreal chemical cyclodestruction. The most commonly performed, effective, and predictable of these options is enucleation, but this requires general anesthesia, a considerable financial investment, risks post-surgical complications, and has a negative psychological impact on some owners. Retrobulbar neurolytic injections with absolute ethanol have been performed in humans with blind, painful eyes since the early 1900s. Immediate and long lasting pain relief can be achieved from 2 weeks to 2 years after a single injection. The purpose of this study is to determine the safety and efficacy of retrobulbar ethanol injections as a globe-sparing therapeutic option for end-stage glaucoma in dogs. Nineteen dogs presenting to the VTH ophthalmology service with end-stage glaucoma were enrolled in a prospective, randomized, double-masked clinical trial. Subjects were sedated and administered a retrobulbar injection of ethanol (n=9) or control saline solution (n=10). At specified time points after the procedure, clients assessed their pet’s comfort and side effects of the injections via survey. Three weeks later, subjects returned for enucleation and the level of comfort after the enucleation was assessed at identical post-procedure time points and compared to that achieved with retrobulbar ethanol injection or control solution. Retrobulbar neurolytic ethanol injections did not significantly improve comfort compared to control group sham treatment or provide more comfort than enucleation. Retrobulbar ethanol injections did not significantly lower IOP, but did significantly elevate corneal touch threshold in treated patients. There was a trend towards lower tear production in eyes receiving retrobulbar ethanol injections. Retrobulbar ethanol injections were safe, well tolerated, and no differences in client satisfaction with participation in the study were noted in either injection group. Further investigation is warranted to determine the optimal volume of retrobulbar ethanol to provide analgesia for patients with end-stage glaucoma as well as to determine the duration of clinical effect of these injections.

Objectives: Phase 1) Establish echocardiographic reference intervals for measurements of the normal canine right heart. Phase 2) Describe the repeatability of normal right heart echocardiographic measurements. Phase 3) Describe the repeatability of right heart echocardiographic measurements which predict pulmonary artery pressure. Materials and Methods: Phase 1) 45 healthy adult dogs. Dogs underwent one echocardiographic examination by the same operator. Phase 2) 6 randomly selected dogs from the pool of Phase 1 dogs. Dogs underwent repeated echocardiograms by two operators. Phase 3) 4 client-owned dogs. Dogs underwent repeated echocardiographic examination by two operators. Results: Phase 1) The linear relationship between dimension and transformed body weight was highly variable. For linear dimensions, most of the scaling exponents were close to the theoretical value of 1/3. For area measurements, most of the scaling exponents were close to 2/3. Phase 2) Of the 168 within-day, between-day and between-operator coefficients of variation (CV) generated, 154 (91.7%) were below 15% and 135 (80.4%) were less than 10%. Phase 3) Of the 100 within-day, between-day and between-operator CVs generated, 72 (72%) were below 20% and 46 (46%) were below 10%. Conclusions: The right heart can be measured with relatively low repeatability. Measurement of the tricuspid regurgitation velocity should be the first priority when attempting to predict pulmonary artery pressure. If tricuspid regurgitation is not present, the use of transpulmonic acceleration time (AT) and the ratio of transpulmonic acceleration-to-ejection time (AT:ET) to indirectly assess pulmonary artery pressure is recommended. / Master of Science

Vascular endothelial growth factor A (VEGF) is a potent mediator of blood vessel formation throughout the body. Intraocular diseases characterized by inflammation, hypoxia or neoplasia induce new blood vessel formation within the eye. The end result of such blood vessel formation may be blinding sequellae such as glaucoma from outflow obstruction or hyphema from intraocular hemorrhage. Elevated VEGF concentrations in the aqueous humor and vitreous are documented in a number of human intraocular disease processes, including tumors, retinal detachment and uveitic glaucoma. Pharmacotherapy inhibiting VEGF expression demonstrates promise for control of some of these ophthalmic conditions. We quantified and compared VEGF concentrations in canine aqueous humor samples from 13 dogs with normal eyes and 226 eyes from 178 dogs with a variety of ophthalmic diseases by ELISA. Dogs with primary cataract, diabetic cataract, primary glaucoma, uveitic glaucoma, aphakic/pseudophakic glaucoma, retinal detachment, lens luxation and neoplasia were evaluated. Elevated VEGF concentrations were found in all disease conditions tested as compared to normal dogs excepting cataracts and diabetic cataracts. Elevated aqueous humor VEGF concentrations were found in dogs with pre-iridal fibrovascular membranes (PIFM) as compared to dogs without PIFM. These results are consistent with the hypothesis that VEGF has a role in the causation or progression of a variety of canine ocular disorders. / Master of Science

Microfilarial enhancement of viral transmission is well documented, however only one previously studied model used components that occur together in nature and therefore has realistic implications. La Crosse (LAC) virus encephalitis is the most common mosquito-borne illness affecting children in the United States. LAC virus is prevalent in the Great Lake and Mid-Atlantic states and coincidently this area overlaps the region of highest infection for Dirofilaria immitis, the nematode that cause canine heartworm disease. Ae. albopictus and Oc. triseriatus are important vectors of La Crosse virus and among the numerous species able to transmit D. immitis. In this study, Aedes albopictus and Ochlerotatus triseriatus were infected with La Crosse virus and Dirofilaria immitis to determine the effects of dual infection on the dissemination and transmission of the virus. The effects of dual infection varied between the species tested. Ae. albopictus had significantly higher tolerance to D. immitis infection than Oc. triseriatus. Dissemination for dually infected Ae. albopictus were higher than the control group for all days tested, except one. Transmission rates for D. immitis infected Ae. albopictus were significantly higher than the control group on day 14 post infection. No microfilarial enhancement of viral dissemination or transmission was observed for Oc. triseriatus. The infection, dissemination, and tranmission rates were low for both species compared to rates of previous studies. Low rates could be a result of low susceptibility for the strains tested. In a second study, mosquitoes were collected from two counties in Southwestern Virginia to determine the abundance of potential La Crosse virus and D. immitis vector species. The abundance and distribution of mosquito species were examined in 2003 and 2004 using gravid traps. An unexpected finding was the significant increase in the abundance of Ochlerotatus japonicus. In 2003, collections were made over 192 trap nights from June to August yielding 5,879 mosquitoes of which only 24 were Oc. japonicus. In 2004, 12,151 mosquitoes were trapped from June to September over 160 trap nights. Oc. japonicus was the second most abundant mosquito species and the dominant Ochlerotatus species collected in gravid traps. Oc. japonicus was collected in low numbers in June, but the abundance increased significantly in July and remained consistent throughout the rest of the season. Of the other major mosquito species collected in this study, only Aedes albopictus exhibited a similar seasonal pattern as Oc. japonicus. Other biological similarities of Oc. japonicus and Ae. albopictus are discussed. / Master of Science in Life Sciences