Scintigraphic Assessment of Deposition of Radiolabeled Fluticasone Delivered from a Nebulizer and Metered Dose Inhaler in 10 Healthy Dogs.

BACKGROUND: Aerosolized medications are increasingly being used to treat respiratory diseases in dogs. No previous studies assessing respiratory tract deposition of radiolabeled aerosols have been performed in conscious dogs. HYPOTHESIS/OBJECTIVES: Assess respiratory tract deposition of radiolabeled, inhalant corticosteroid (fluticasone propionate labeled with 99m Tc) delivered from a nebulizer and metered dose inhaler (MDI) to healthy dogs. ANIMALS: Ten healthy Foxhounds. METHODS: Prospective, randomized, cross-over pilot study. Initial inhalation method (nebulizer or MDI) was randomly assigned. Treatments were crossed over after a 7-day washout period. Treatments initially were performed using sedation. Dogs were imaged using 2-dimensional planar scintigraphy, with respiratory tract deposition quantified by manual region-of-interest analysis. Deposition calculated as percentage of delivered dose. Six of 10 dogs were randomly selected and reassessed without sedation. RESULTS: Inhalation method had significant effect on respiratory tract deposition (P = 0.027). Higher deposition was achieved by nebulization with mean deposition of 4.2% (standard deviation [SD], 1.4%; range, 1.9-6.1%); whereas MDI treatment achieved a mean of 2.3% (SD, 1.4%; range, 0.2-4.2%). Nebulization achieved higher respiratory tract deposition than MDI in 7 of 10 dogs. No statistical difference (P = 0.68) was found between mean respiratory tract deposition achieved in dogs when unsedated (3.8%; SD, 1.5%) or sedated (3.6%; SD, 1.7%). CONCLUSIONS AND CLINICAL IMPORTANCE: Study confirms respiratory tract deposition of inhalant medications delivered from a nebulizer and MDI in healthy dogs, breathing tidally with and without sedation. Respiratory tract deposition in these dogs was low compared to reported deposition in adult humans, but similar to reported deposition in children.

Disseminated peripheral neuroblastoma in a Rhodesian Ridgeback dog.

CASE REPORT: A 4-year-old neutered male Rhodesian Ridgeback dog with right-sided Horner's syndrome, bilateral laryngeal paralysis, neck pain and bilateral hindlimb ataxia was euthanased following deterioration of its neurological status. Necropsy examination revealed an off-white retropharyngeal neoplastic mass (100 × 30 × 30 mm) attached to the base of the skull on the right side and macroscopic nodular metastases in the spleen and three vertebral bodies (C6, C7 and T6), including a nodule attached to the dura at C7. Histological evidence of neuroblastic tumour was detected in these macroscopic lesions, a regional lymph node, bone marrow of a femur and all 15 vertebral bodies (C1-T8) examined, including the three with macroscopic metastases, and in the lumens of small blood vessels in the lungs and liver. Ganglion cell differentiation was detected only in the primary retropharyngeal mass, one splenic nodule and the C7 dural nodule. Neoplastic cells were immunoreactive to neurofilament protein (ganglion cells only), vimentin and synaptophysin, and were negative for S100 protein, GFAP, CD3 and Pax5. CONCLUSION: The diagnosis was disseminated peripheral neuroblastoma, differentiating subtype (International Neuroblastoma Pathology Classification), with likely primary involvement of the right cranial cervical ganglion. This appears to be the first report of neuroblastoma in a dog with widespread occult haematogenous metastasis to bone marrow.

Computed tomographic features of feline sino-nasal and sino-orbital aspergillosis.

Feline upper respiratory tract aspergillosis (URTA) occurs as two distinct anatomical forms, namely, sino-nasal aspergillosis (SNA) and sino-orbital aspergillosis (SOA). An emerging pathogen, Aspergillus felis, is frequently involved. The pathogenesis of URTA, in particular the relationship between the infecting isolate and outcome, is poorly understood. In this study, computed tomography was used to investigate the route of fungal infection and extension in 16 cases (SNA n = 7, SOA n = 9) where the infecting isolate had been identified by molecular testing. All cases had nasal cavity involvement except for one cat with SNA that had unilateral frontal sinus changes. There was a strong association between the infecting species and anatomic form (P = 0.005). A. fumigatus infections remained within the sino-nasal cavity, while cryptic species infections were associated with orbital and paranasal soft-tissue involvement and with orbital lysis. Cryptic species were further associated with a mass in the nasal cavity, paranasal sinuses or nasopharynx. Orbital masses showed heterogeneous contrast enhancement, with central coalescing hypoattenuating foci and peripheral rim enhancement. Severe, cavitated turbinate lysis, typical of canine SNA, was present only in cats with SNA. These findings support the hypothesis that the nasal cavity is the portal of entry for fungal spores in feline URTA and that the route of extension to involve the orbit is via direct naso-orbital communication from bone lysis. Additionally, a pathogenic role for A. wyomingensis and a sinolith in a cat with A. udagawae infection are reported for the first time.

Methicillin-resistant Staphylococcus aureus: an issue for veterinary hospitals.

OBJECTIVE: To investigate the spread of methicillin-resistant Staphylococcus aureus (MRSA) isolated from a cluster of clinical cases at a veterinary hospital by molecular epidemiological techniques. METHODS: Antimicrobial susceptibility testing, spa typing, multilocus sequence typing and pulsed-field gel electrophoresis were used to compare 16 isolates of MRSA. Four isolates were cultured from clinical cases thought to be involved in the cluster. A single isolate that was unrelated to the cluster and the remaining 10 isolates were obtained from nasal swabs submitted by staff and students during a subsequent survey of MRSA carriage. RESULTS: Isolates from four clinical cases and an isolate obtained from a staff member were the same strain of MRSA. Some key risk factors associated with transmission of MRSA within veterinary hospitals were identified. CONCLUSION: The information provided by these techniques was invaluable in developing procedures and identifying risk factors to help reduce the effect of future outbreaks within veterinary hospitals.

Sedation of hyperthyroid cats with subcutaneous administration of a combination of alfaxalone and butorphanol.

OBJECTIVE: To evaluate the sedative, respiratory and cardiovascular effects of subcutaneously administered alfaxalone and butorphanol in a group of hyperthyroid cats. DESIGN: A prospective, single-centre observational study. METHODS: Client-owned hyperthyroid cats (n=20) were examined and sedated with alfaxalone (3 mg/kg) and butorphanol (0.2 mg/kg) administered subcutaneously. Sedation scores, heart rate, respiratory rate and blood pressure were measured at 15-min intervals during the 45-min observation period and compared with pre-sedation values. At the end of 45 min, cats were assessed to be adequately sedated for oral administration of iodine-131 if there was minimal resistance and an intact gag reflex. RESULTS: The maximum median sedation score was reached 45 min after injection. The lowest mean heart and respiratory rates and blood pressure values occurred 30 min after injection. Significant decreases were noted in respiratory rates at all three time points (P<0.001). Systolic, diastolic and mean blood pressure measurements were also significantly decreased at 15 and 30 min after injection (P<0.05). CONCLUSION: Subcutaneously administered alfaxalone and butorphanol can be used for sedation in cats undergoing procedures of short duration. Blood pressure should be monitored because of transient decreases observed in some cats. Further studies are required to determine whether the sedative, respiratory and cardiovascular effects are similar in euthyroid cats.

Disseminated Scedosporium prolificans infection in a German Shepherd dog.

Disseminated Scedosporium prolificans infection in a 1-year-old female spayed German Shepherd dog is described. Clinical signs were predominantly associated with fungal pyelonephritis and the organism was cultured from the urine. The dog was treated with itraconazole and later, terbinafine was added. Subsequent antifungal susceptibility testing of the isolate showed it to be resistant to all available antifungal drugs. The dog was euthanased because of acute abdominal haemorrhage and associated clinical deterioration. Postmortem examination revealed extensive pyogranulomas containing fungal organisms in the renal parenchyma, myocardium, bone marrow, skeletal muscle, liver, lung, spleen, multiple lymph nodes and pancreas.

Use of transcolonic portal scintigraphy to evaluate efficacy of cellophane banding of congenital extrahepatic portosystemic shunts in 16 dogs.

OBJECTIVE: To evaluate the efficacy of cellophane banding of single congenital extrahepatic portosystemic shunts in dogs using transcolonic portal scintigraphy. To investigate the portal circulation of those dogs with elevated postoperative shunt fractions to determine the cause of the persistent shunting. Further, to evaluate whether presenting signs, clinical pathology findings and liver histopathology are predictive of outcome. DESIGN: Prospective study of 16 dogs presenting with single congenital extrahepatic portosystemic shunts. PROCEDURE: Dogs with single extrahepatic portosystemic shunts attenuated by cellophane banding underwent portal scintigraphy and bile acids tolerance testing pre- and post-operatively. Dogs identified with elevated shunt fractions at 10 weeks post-operatively underwent mesenteric portovenography. Qualitative hepatic histopathology from all dogs was reviewed by a veterinary pathologist and assigned a semi-quantitative score to identify any abnormalities that may predict surgical outcome. RESULTS: At 10 weeks post cellophane banding, 10 of 16 cases (63%) had normal shunt fractions, whilst six dogs (37%) had increased shunt fractions and seven dogs (44%) had increased serum bile acids. Of these dogs, mesenteric portovenography revealed incomplete closure of the shunt in three dogs (18.6%) and multiple acquired shunts in three dogs (18.6%). Liver histopathology findings were similar for all dogs, regardless of outcome. CONCLUSIONS: Cellophane banding is an efficacious method for complete gradual occlusion of single extrahepatic shunts when the shunt vessel is attenuated to < or = 3 mm. Transcolonic portal scintigraphy is a reliable method for assessment of shunt attenuation and, unlike serum bile acids, is not influenced by other causes of liver dysfunction.

Recurrent rectal prolapse caused by colonic duplication in a dog.

A 9-month-old female Shar Pei cross-bred dog was presented with a history of recurrent rectal prolapse over 7 months. Repeated reduction and anal purse string sutures and subsequent incisional colopexy failed to prevent recurrent rectal prolapse. Digital rectal examination following reduction of the prolapse identified a faeces-filled sac within the ventral wall of the rectum and an orifice in the ventral colonic wall, cranial to the pubic brim. A ventral, communicating tubular colonic duplication was diagnosed by means of a barium enema. Surgical excision of the duplicated colonic tube was performed via a caudal ventral midline laparotomy. At 20 weeks post-operation, there has been no recurrence of rectal prolapse.

Reference limits for urinary fractional excretion of electrolytes in adult non-racing Greyhound dogs.

OBJECTIVE: To determine reference limits for urinary fractional excretion of electrolytes in Greyhound dogs. METHODS: Urinary fractional excretion was calculated using a spot clearance method preceded by a 16 to 20 hour fast in 48 Greyhound dogs. Raw data analysed using the bootstrap estimate was used to calculate the reference limits. RESULTS: The observed range for urinary fractional excretion in Greyhound dogs was 0.0 to 0.77% for sodium, 0.9 to 14.7% for potassium, 0 to 0.66% for chloride, 0.03 to 0.22% for calcium and 0.4 to 20.1% for phosphate. Expressed as percentages, the suggested reference limits for fractional excretion in Greyhound dogs are as follows: sodium < or = 0.72, potassium < or = 12.2, chloride < or = 0.55, calcium < or = 0.13 and phosphate < or = 16.5. CLINICAL SIGNIFICANCE: Veterinary practitioners may use these reference limits for urinary electrolyte fractional excretion when investigating renal tubular disease in Greyhound dogs.

Transient renal tubulopathy in a racing Greyhound.

A 2-year-old female Greyhound was presented for inappetence and lethargy. On referral, results of diagnostic tests indicated renal glucosuria, increased excretion of selected amino acids and abnormal fractional excretion of electrolytes consistent with renal tubular dysfunction. Systemic blood pressure was elevated. Renal biopsy revealed mild proximal renal tubular damage consistent with a subacute toxic or hypoxic insult. Systemic hypertension, renal glucosuria and altered fractional excretion of electrolytes resolved during the 7 day period of hospital treatment. The Greyhound resumed training without recurrence of renal dysfunction.

Acute renal failure following Bull ant mass envenomation in two dogs.

Acute renal failure was diagnosed in a German Short Haired Pointer bitch and a Kelpie cross-bred dog following envenomation by Bull ants. Both dogs had been tethered over a Bull ant nest and had experienced mass envenomation. There was local reaction at the envenomation sites and each dog had experienced vomiting that was poorly controlled by symptomatic therapy. Intensive treatment of renal failure was successful in the German Short Haired Pointer and the bitch remains well 19 months after envenomation. The Kelpie cross-bred deteriorated despite intensive treatment and was euthanased 36 hours after presentation. Necropsy examination revealed haemorrhage and necrosis of the small intestine and myocardium, bilateral nephrosis with tubular necrosis, and patchy haemorrhage of the lung alveoli, pancreas and adrenal cortices. Electron microscopy revealed necrosis of the small intestine and hydropic swelling of proximal renal tubules with necrosis of medullary tubules.

Effect of oral ursodeoxycholic acid on bile acids tolerance tests in healthy dogs.

OBJECTIVE: To determine whether oral administration of ursodeoxycholic acid (UDCA) to healthy dogs alters the results of the bile acids tolerance test. METHODS: UDCA (15 mg/kg once daily) was administered to 16 healthy dogs for 7 days. Health of the dogs was assessed by clinical examination, haematology, serum biochemistry and a bile acids tolerance test. Normal liver structure was confirmed by histopathology at the end of the study. Bile acids tolerance tests were performed before and at the end of the treatment period, with each dog serving as its own control. For the posttreatment bile acids tolerance test, UDCA was administered at the time of feeding. RESULTS: Pretreatment, the fasted serum total bile acid concentrations ranged between 0 and 9 micromol/L. In the majority of dogs, the postprandial total bile acid concentration was greater than the preprandial value, with a range of 0 to 16 micromol/L. The fasted total bile acid concentration was 0 micromol/L in most dogs (93.75%) after treatment with UDCA. Postprandial serum bile acids also remained within the reference range for the majority of dogs (93.75%) after UDCA treatment. A single dog had a postprandial bile acid concentration above the reference range, but the concentration was within the reference range when the assay was repeated the following day without concurrent administration of UDCA. The pre- and postprandial total serum bile acid concentrations were not significantly affected by UDCA treatment. CONCLUSION: The administration of UDCA does not alter the bile acids tolerance test of normal healthy dogs.

Renal dysplasia and urinary tract infection in a Bull Mastiff puppy.

Renal dysplasia and concurrent pyelonephritis were diagnosed in a 15-week-old female Bull Mastiff which presented with clinical signs compatible with chronic renal failure. Ultrasound examination was consistent with renal dysplasia and clinical pathology supported a diagnosis of chronic renal failure and urinary tract infection. Renal histological examination demonstrated inflammation and scarring with concurrent tubular dysplasia and persisting primitive glomeruli, although the presence of chronic inflammation complicated interpretation. It is uncertain whether renal dysplasia was inherited or due to a urinary tract infection acquired in the neonatal period. Renal dysplasia has not previously been reported in the Bull Mastiff breed.

Diagnosis of sciatic nerve tumour in two dogs by electromyography and magnetic resonance imaging.

Sciatic nerve tumour was diagnosed in a Staffordshire Bull Terrier cross-bred and a Bichon Frise, both presenting with chronic left hind limb lameness. Neurological examination in each case was consistent with left sciatic nerve deficits and this was confirmed by EMG studies. Rectal examination of both dogs revealed a palpable intrapelvic mass that was not apparent on survey radiographs. A sciatic nerve tumour was identified using MRI in each case. Histological examination of tissue taken from the Staffordshire Bull Terrier cross-bred was consistent with a malignant peripheral nerve sheath tumour.

Asymptomatic anomalous pulmonary veins in a Siberian Husky.

A 2-year-old, neutered male Siberian Husky presented with depression, weight loss and an inability to prehend food and water. Cerebrospinal fluid was collected under general anaesthesia prior to euthanasia. The elevated white cell count comprised mostly mononuclear cells. Histological changes within the brain were variable and multifocal. Non-suppurative meningitis secondary to lymphoma was diagnosed. At necropsy, abnormal venous drainage of the right cranial and middle lung lobes was found. A dilated major pulmonary vein from these lobes passed across the lateral aspect of the right caudal lung lobe prior to entering the heart, and subpleural veins from the affected lobes were enlarged and tortuous. These vascular abnormalities were considered incidental. There were no apparent congenital abnormalities of the heart and the animal's clinical signs were related to lymphoma of the brain.

Treatment of an acromegalic cat with the dopamine agonist L-deprenyl.

Acromegaly was diagnosed in a 14-year-old domestic short hair cat presented for investigation and management of apparently insulin-resistant diabetes mellitus. Treatment with L-deprenyl and high doses of insulin was commenced. The L-deprenyl did not reduce the requirement for high doses of insulin and did not appear to reduce the clinical signs associated with the disease. The cat was euthanased one year after initial presentation.

Altered mRNA expression for brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase in the hippocampus of patients with intractable temporal lobe epilepsy.

The expression of brain-derived neurotrophic factor and the alpha subunit of calcium/calmodulin-dependent protein kinase II mRNA in hippocampi obtained during surgical resections for intractable temporal lobe epilepsy were examined. Both calcium/calmodulin-dependent protein kinase II and brain-derived neurotrophic factor are localized heavily within the hippocampus and have been implicated in regulating hippocampal activity (Kang and Schuman [1995] Science 267:1658-1662; Suzuki [1994] Intl J Biochem 26:735-744). Also, the autocrine and paracrine actions of brain-derived neurotrophic factor within the central nervous system make it a likely candidate for mediating morphologic changes typically seen in the epileptic hippocampus. Quantitative assessments of mRNA levels in epileptic hippocampi relative to autopsy controls were made by using normalized densitometric analysis of in situ hybridization. In addition, correlations between clinical data and mRNA levels were studied. Relative to autopsy control tissue, decreased hybridization to mRNA of the alpha subunit of calcium/calmodulin-dependent protein kinase II and increased hybridization to brain-derived neurotrophic factor mRNA were found throughout the granule cells of the epileptic hippocampus. There also was a significant negative correlation between the duration of epilepsy and the expression of mRNA for brain-derived neurotrophic factor. These results are similar qualitatively to those found in animal models of epilepsy and suggest that chronic seizure activity in humans leads to persistent alterations in gene expression. Furthermore, these alterations in gene expression may play a role in the etiology of the epileptic condition.

Expression of protease-activated receptor-2 by osteoblasts.

Osteoblasts express protease-activated receptor-1 (PAR-1), which is activated by thrombin or by synthetic peptides corresponding to the new "tethered ligand" N-terminus of PAR-1 created by receptor cleavage. Both thrombin and human PAR-1-activating peptide stimulate an elevation of [Ca2+]i in the human SaOS-2 osteoblast-like cell line, but the peptide stimulates receptor-mediated Ca+ entry, whereas thrombin does not. Stimulation of proliferation in rat primary osteoblast-like cells is greater in response to rat PAR-1-activating peptide than to thrombin. Because the PAR-1-activating peptides are now known to activate PAR-2, the current study was undertaken to investigate whether osteoblasts express this receptor and, if so, whether this could account for the observed discrepancies between responses of osteoblasts to thrombin and to PAR-1-activating peptides. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemical studies demonstrated expression of PAR-2 by primary cultures of rat calvarial osteoblast-like cells. In immunohistochemical studies of embryonic mouse bones, osteoblasts showed positive staining for the presence of PAR-2. Activators of PAR-2 include trypsin, mast cell tryptase, gingipain-R, and synthetic peptides corresponding to the PAR-2 tethered ligand sequence. Treatment of primary rat osteoblast-like cells with rat PAR-2-activating peptide (SLIGRL), or SaOS-2 cells with human PAR-2-activating peptide (SLIGKV), caused a dose-dependent increase in [Ca2+]i. Trypsin or gingipain-R also induced an increase in intracellular calcium concentration, and caused reciprocal cross desensitization. Activators of PAR-2 caused a sharp peak in [Ca2+]i followed by a sustained plateau; [Ca2+]i returned to baseline levels upon treatment with ethylene-glycol tetraacetic acid (EGTA). Treatment of rat osteoblast-like cells in vitro with SLIGRL did not affect thymidine incorporation or endogenous alkaline phosphatase activity. The results presented here demonstrate that osteoblasts express PAR-2, and that such expression is able to account for the observed discrepancies between thrombin and PAR-1-activating peptides in their ability to evoke calcium entry, but not proliferative responses.

In vitro stimulation of equine articular cartilage proteoglycan synthesis by hyaluronan and carprofen.

The effects of hyaluronan and carprofen (both racemic mixture and separate R and S enantiomers) on proteoglycan (PG) synthesis by equine cultured chondrocytes and cartilage explants were examined. Hyaluronan stimulated PG synthesis in both cell and explant cultures. The concentration-response curve of the latter was bell-shaped. Racemic carprofen and R and S enantiomers also stimulated PG synthesis, although concentration-response relationships varied for each preparation and high concentrations inhibited synthesis. It was concluded that (a) hyaluronan exerts a stimulatory effect on PG synthesis at low concentrations and (b) stimulatory effects of carprofen on PG synthesis are, to some degree, enantioselective with the carprofen S-enantiomer exerting the greatest effect. Hyaluronan and carprofen are used clinically despite incompletely understood mechanisms of action. These results suggest (a) hyaluronan and carprofen might exert an anti-arthritic action through stimulation of PG synthesis and (b) there is possible justification for therapeutic administration of enantiomeric rather than racemic carprofen.