PHARMACOKINETICS OF TRAMADOL AND O-DESMETHYLTRAMADOL IN GIANT TORTOISES (CHELONOIDIS VANDENBURGHI, CHELONOIDIS VICINA).

The objective of this study was to determine the pharmacokinetics of two orally administered doses of tramadol (1 mg/kg and 5 mg/kg) and its metabolite, O-desmethyltramadol (M1) in giant tortoises (Chelonoidis vandenburghi, Chelonoidis vicina). Eleven giant tortoises (C. vandenburghi, C. vicina) received two randomly assigned, oral doses of tramadol (either 1 mg/kg or 5 mg/kg), with a washout period of 3 wk between each dose. The half-life (t½) of orally administered tramadol at 1 mg/kg and 5 mg/kg was 11.9 ± 4.6 h and 13.2 ± 6.1 h, respectively. After oral administration of tramadol at 1 mg/kg and 5 mg/kg, the maximum concentration (Cmax) was 125 ± 69 ng/ml and 518 ± 411 ng/ml, respectively. There were not enough data points to determine pharmacokinetic (PK) parameters for the M1 metabolite from either dose. Tramadol administered orally to giant tortoises at both doses provided measurable plasma concentrations of tramadol for approximately 48 h with occasional transient sedation. Oral tramadol at 5 mg/kg, on average, achieves concentrations of >100 ng/ml, the reported human therapeutic threshold, for 24 h. Based on the low levels of M1 seen in this study, M1 may not be a major metabolite in this taxon.

MYCOTIC PNEUMONIA AND ENCEPHALITIS IN SOUTHERN PUDU (PUDU PUDA).

This case series describes six confirmed cases of mycotic encephalitis and/or mycotic pneumonia in southern pudu (Pudu puda). One case involved a 10.5-yr-old intact female that presented with an inability to stand, eventually progressing to grand mal seizures. Magnetic resonance imaging showed a lesion within the cerebellar vermis with edema causing cerebellar herniation. The animal was euthanized based on a grave prognosis. Gross and histologic examination revealed primary central nervous system phaeohyphomycosis. Curvularia spicifera was sequenced from the cerebellar tissue. This is the first time this fungus has been reported as a primary central nervous system infection in an artiodactyl species. The remaining five cases occurred in neonates between 17 and 67 days old. Clinical signs varied widely, including facial swelling, weakness, posterior paresis, and sudden death. Antifungal therapy was initiated in three neonatal animals but was unsuccessful in each case. All neonates had active mycotic pneumonia caused by Aspergillus fumigatus or Mucor spp. at time of death; four of these animals also had disseminated disease that caused mycotic encephalitis. This case series indicates that fungal disease should be included in the differential diagnosis list of any pudu presenting for neurologic or respiratory clinical signs.

RETROSPECTIVE ANALYSIS AND VALIDATION OF SERUM SYMMETRIC DIMETHYLARGININE (SDMA) CONCENTRATIONS IN CHEETAHS ( ACINONYX JUBATUS).

Kidney disease is common among captive cheetahs ( Acinonyx jubatus). Serum creatinine is the most common measurement to estimate glomerular filtration rate (GFR) because of the ease of its clinical use, but it is a crude estimate that only increases after significant disease is already present and is affected by extrarenal factors. Symmetric dimethylarginine (SDMA) is a renal biomarker in humans, dogs, and cats that correlates with serum creatinine and GFR and appears to be an earlier and more specific biomarker for kidney disease. Ninety-two banked serum samples from 11 cheetahs housed at the Oklahoma City Zoo from 1992 to 2012 were retrospectively analyzed. Histopathology results were available for 10/11 cheetahs, and all 10 had histologic renal lesions. General categories of renal lesions included glomerulosclerosis (7/10; 70%), amyloidosis (7/10; 70%), inflammatory (9/10; 90%), and oxalate nephrosis (2/10; 20%). SDMA immunoassay and mass spectrometry were measured for validation and compared with creatinine to assess for correlation. Serum creatinine concentrations were determined by enzymatic colorimetric methods. SDMA immunoassay was validated in cheetahs and correlated well with serum creatinine ( R2=0.687; P < 0.0001). SDMA and serum creatinine measured from freeze-thawed stored samples show high correlation in individual cheetahs ( R2 = 0.972; P < 0.0001). These data support that SDMA could be a promising renal biomarker in cheetahs. Further research is warranted to investigate whether SDMA might be an earlier indicator of kidney disease in cheetahs and whether this assay can be extended to other nondomestic carnivores.

MANAGEMENT OF PODODERMATITIS WITH AN ORTHOTIC BOOT IN A SOUTHERN ISABELA GIANT TORTOISE (CHELONOIDIS VICINA).

A 62-yr-old male Southern Isabela giant tortoise (Chelonoidis vicina) had a 1-yr history of chronic, reoccurring pododermatitis on the palmar surface of the left forelimb. Aggressive wound management was instituted and included surgical debridement, vacuum-assisted closure, and orthotic boot support during healing. A custom fabricated, carbon fiber clamshell Charcot Restraint Orthotic Walker walking boot was utilized to reduce focal pressure over the wound during weight bearing and promote a more normal gait. Distal padding was used to distribute pressure on the palmar surface of the left forelimb, with a focal depression in the padding preventing pressure directly over the wound. The design and trim lines were adjusted to allow shoulder and elbow motion without impingement. The clamshell design allowed relatively easy removal for wound inspection and dressing changes. The wound ultimately resolved after 9 wk of management with the orthotic boot, with no reoccurrence over the next 3 yr.

ATTEMPTED SURGICAL CORRECTION OF A PERSISTENT RIGHT FOURTH AORTIC ARCH IN A JUVENILE ROTHSCHILD'S GIRAFFE (GIRAFFA CAMELOPARDALIS ROTHSCHILDI).

A 5-mo-old female Rothschild's giraffe ( Giraffa camelopardalis rothschildi) presented for regurgitation. Esophagoscopy at 24 wk of age revealed a markedly dilated cranial esophagus with a tight stricture at the level of the heart base consistent with a vascular ring anomaly. Surgical exploration confirmed persistent right fourth aortic arch with ductus originating from left subclavian artery at its junction with the aorta and left subclavian artery. The patent ductus arteriosus was surgically ligated. The procedure was complicated by limited surgical access and vascular friability resulting in uncontrollable hemorrhage, and the animal was euthanatized. The animal's large size and unique shape precluded preoperative examination by computed tomography. Surgical accessibility was poor because cranial retraction of the thoracic limb was limited. Histology revealed focal degeneration of the aorta and subclavian artery and muscular degeneration of the esophagus. Degeneration was attributed to local hypoxia from compression by the vascular structure as the animal grew.

Management of a Nonhealing, Superficial Corneal Ulcer in a Hyacinth Macaw (Anodorhynchus hyacinthinus).

A 26-year-old, female hyacinth macaw (Anodorhynchus hyacinthinus) was presented for ophthalmology consultation for a history of a chronic, nonhealing corneal ulcer of the right eye. On examination, a 5 × 4-mm axial, superficial corneal ulcer with loose epithelial edges was found. During multiple recheck examinations over 4 months, the ulcer was treated by debridement with a sterile cotton-tipped applicator, diamond burr debridement, diamond burr debridement with cyanoacrylate tissue adhesive, and grid keratotomy with cyanoacrylate tissue adhesive, all performed under anesthesia with eventual resolution of the corneal ulcer.

PHARMACOKINETIC EVALUATION OF A LONG-ACTING FENTANYL SOLUTION AFTER TRANSDERMAL ADMINISTRATION IN HELMETED GUINEAFOWL (NUMIDA MELEAGRIS).

The objective of this study was to investigate the pharmacokinetics of a long-acting fentanyl solution in helmeted guineafowl ( Numida meleagris ) after transdermal administration. Twenty-one guineafowl received a single administration of 5 mg/kg of fentanyl transdermal solution. No adverse effects on behavior were appreciated. Plasma fentanyl concentrations were determined by liquid chromatography-mass spectrometry analysis of protein-precipitated samples. Mean maximum plasma concentration was 228.8 ng/ml at 4 hr. The mean plasma terminal half-life was 33.2 hr. At 168 hr the mean plasma concentration was 1.3 ng/ml. A single topical dose of 5 mg/kg appears to be safe for use in this species and maintained plasma concentrations above those reported to be analgesic in dogs for at least 7 days.

Pharmacokinetics of selamectin in helmeted guineafowl (Numida meleagris) after topical administration.

Twenty-one healthy helmeted guineafowl (Numida meleagris) housed at the Oklahoma City Zoo were used to evaluate the pharmacokinetic parameters of topical selamectin. Birds were divided randomly into three groups of seven birds each. On day 1, all birds received one dose of 20 mg/kg selamectin topically. Based on the group number, blood was collected from each bird on three separate occasions over a 28-day period. Plasma using liquid chromatography with mass spectrometry was used to determine selamectin concentrations. Mean plasma terminal half-life and maximum plasma concentrations of selamectin were 5.8 days and 16.1 ng/ml, respectively, with maximum plasma levels reached at 3 days. No adverse effects were detected. Birds in this study did reach and maintain plasma levels reported as therapeutic in other species for 19 days. Based on these results, selamectin may be a valuable antiparasiticide in some avian species.

Retroperitoneal abscesses in two western lowland gorillas (Gorilla gorilla gorilla).

This report describes two cases of retroperitoneal abscesses in female western lowland gorillas (Gorilla gorilla gorilla). Clinical symptoms included perivulvar discharge, lameness, hindlimb paresis, and general malaise. Retroperitoneal abscesses should be considered as part of a complete differential list in female gorillas with similar clinical signs.

Intraocular pressure in free-ranging anuran species in Oklahoma.

Ocular disease appears to be a common issue in anurans. Intraocular pressures were measured for six species of free-ranging anurans in central Oklahoma. No significant differences were identified between left or right eyes. There was a significant negative relationship between the weight of the anuran and intraocular pressure. The intraocular pressure range for the six species was 3-10 mm Hg. Tonometry values in anurans are, to the authors' knowledge, previously unreported and this study provides initial information on intraocular pressure measurement in anurans.

Persimmon phytobezoars in meerkats (Suricata suricatta).

Two meerkats (Suricata suricatta) died acutely and gastric bezoars were found at necropsy. Four of the eight remaining meerkats had bezoars identified radiographically. Surgical gastrotomies were performed and bezoars containing orange fibrous material were removed. Histologic examination of the bezoars and persimmon fruit from a tree in the exhibit revealed that the materials were identical. Tannins found in ripe persimmons are known to coagulate in the presence of gastric acid, and the resultant phytobezoars can lead to gastrointestinal obstructions. All four meerkats recovered uneventfully. The combination of interspecies aggression and a diet change may have led to consumption of persimmons produced by a tree in the exhibit. Persimmon phytobezoars are also seen in humans and horses.

Physiologic and serum biochemistry values in free-ranging Hoffmann's two-toed (Choloepus hoffmanni) and brown-throated three-toed (Bradypus variegatus) sloths immobilized using dexmedetomidine and ketamine.

Dexmedetomidine, a highly selective alpha-2 adrenergic agonist and dextrorotary enantiomer of medetomidine, was combined with ketamine and used to immobilize 14 free-ranging Choloepus hoffmanni (Hoffmann's two-toed sloths) and 11 Bradypus variegatus (brown-throated three-toed sloths) in Upala, Costa Rica. Following intramuscular injection of ketamine (2.1 mg/kg) and dexmedetomidine (11 microg/kg), heart rate, respiratory rate, and indirect systolic blood pressure were measured every 5 min for a total of 25 min. An iStat (CG8+) was used to evaluate serum biochemical and hematologic values during anesthesia. After 30 min of anesthesia, atipamezole (0.13 mg/kg) was administered intramuscularly, which resulted in rapid and smooth recoveries. Mean heart rate and respiratory rate remained unchanged in both C. hoffmanni and B. variegatus over time. Progressive decreases in mean indirect systolic blood pressure were documented in both species. Results of this study suggest a combination of dexmedetomidne and ketamine is a safe and effective anesthetic protocol for use in free-ranging C. hoffmanni and B. variegatus. Similar to other alpha-2 adrenergic agonist-based immobilization protocols, close monitoring of cardiovascular and respiratory parameters are recommended. This study also provides serum biochemical and hematologic data in free-ranging C. hoffmanni and B. variegatus.

Oral squamous cell carcinoma in a Vietnamese pot-bellied pig (Sus scrofa).

An 18-year-old, neutered, male Vietnamese pot-bellied pig (Sus scrofa) was treated for chronic, intermittent nasal discharge and sneezing. The animal was diagnosed with severe periodontal disease (grade IV), an oronasal fistula, and multiple tooth root abscesses via dental examination and computed tomography of the skull. Dentistry was performed, including multiple tooth extractions, and antibiotic therapy was initiated. Eighteen months later, the animal was evaluated for lethargy, anorexia, and a firm, 12 cm x 12 cm mass between the 2 rami of the mandible. Laboratory testing revealed moderate anemia, severe leukocytosis, and hyperglobulinemia. Skull radiographs indicated osteomyelitis of the mandible and soft-tissue swelling. A fine-needle aspirate and biopsy were taken, and results were consistent with squamous cell carcinoma. Treatment with piroxicam and antibiotics was initiated as needed to control signs of pain and secondary infection, respectively. Three months after diagnosis, the pig was euthanized due to cachexia and severe depression secondary to squamous cell carcinoma. On postmortem examination, the right mandibular area contained multiple, coalescing, irregular masses extending from the ramus rostrally to the mandibular canine teeth and ventrally within the intermandibular space, completely obliterating the normal anatomy. An open midshaft fracture was present on the right mandible. On histopathology, the masses were confirmed as locally invasive and destructive squamous cell carcinoma. No evidence of metastasis was noted in regional lymph nodes or in any of the distant sites evaluated.

Analgesic effects of intramuscular administration of meloxicam in Hispaniolan parrots (Amazona ventralis) with experimentally induced arthritis.

OBJECTIVE-To evaluate the analgesic efficacy of meloxicam in parrots with experimentally induced arthritis, with extent of weight bearing and rotational perch walking used as outcome measures. ANIMALS-15 adult Hispaniolan parrots (Amazona ventralis). PROCEDURES-Arthritis was experimentally induced via intra-articular injection of microcrystalline sodium urate suspension (MSU) into 1 intertarsal joint. Parrots were treated in a crossover design. Five treatments were compared as follows: meloxicam (4 dosages) at 0.05, 0.1, 0.5, and 1.0 mg/kg (IM, q 12 h, 3 times) and 0.03 mL of saline (0.9% NaCl) solution (IM, q 12 h, 3 times). The first treatment was given 6 hours following MSU administration. Lameness was assessed by use of a biomechanical perch to record weight-bearing load and a rotational perch to determine dexterity. Feces were collected to assay for occult blood. RESULTS-Parrots treated with meloxicam at 1.0 mg/kg had significantly better return to normal (baseline) weight bearing on the arthritic pelvic limb, compared with control parrots or parrots treated with meloxicam at 0.05, 0.1, and 0.5 mg/kg. All fecal samples collected from parrots following induction of arthritis and treatment with meloxicam had negative results for occult blood. CONCLUSIONS AND CLINICAL RELEVANCE-Meloxicam administered at 1.0 mg/kg, IM, every 12 hours effectively relieved arthritic pain in parrots.

Postmortem evaluation of reintroduced migratory whooping cranes in eastern North America.

Reintroduction of endangered Whooping Cranes (Grus americana) in eastern North America has successfully established a migratory population between Wisconsin and Florida. Eighty birds (47 males, 33 females) were released between 2001 and 2006, and all birds were tracked following release with satellite and/or VHF monitoring devices. By the end of 2006, 17 deaths (12 males, five females) were recorded from this population. Postmortem findings and field data were evaluated for each bird to determine the cause of death. Causes included predation (n=8, 47%), trauma (n=2, 12%), and degenerative disease (n=1, 6%); the cause of death was undetermined for 35% (n=6) of the birds. Based on physical evidence, the primary predator of the birds was the bobcat (Lynx rufus). Limited roosting habitat availability or bird behavior were likely prime factors in the occurrence of predation. Traumatic injuries and mortality were caused by gunshot, electrical utility lines, and an unknown source. The lone case of degenerative disease was due to chronic exertional myopathy associated with translocation. Available postmortem testing did not indicate the presence of infectious disease in this limited sample.

Clinical use of recombinant human bone morphogenic protein-2 in a whooping crane (Grus americana).

OBJECTIVE: To report use of recombinant human bone morphogenetic protein-2 (rhBMP-2) as adjunctive therapy for treatment of a comminuted, open, proximal humeral fracture in an avian species. STUDY DESIGN: Clinical report. ANIMALS: A 3.5-month-old male whooping crane (Grus americana). METHODS: An open, severely comminuted humeral facture was stabilized with an intramuscular (IM) pin/type IA external skeletal fixator with tie-in configuration. rhBMP-2 was applied in a calcium phosphate matrix (CPM) paste directly to the fracture site as a bone graft substitute. Radiographic evidence of bone healing was monitored for 14 weeks. RESULTS: Substantial bony callus was evident at 4 weeks and at 8 weeks there was bridging callus with obvious bony remodeling. The fixation was destabilized at 9 weeks by IM pin removal, bone healing progressed and the fixator was removed at 11 weeks. By 14 weeks both cortices had been re-established with continued callus remodeling evident. CONCLUSION: rhBMP-2, applied in a CPM paste, was used as a bone graft substitute in the treatment of a comminuted, open humeral fracture in a whooping crane. CLINICAL RELEVANCE: Use of rhBMP-2/CPM should be considered in treatment of avian fractures.

Pheochromocytoma in an African warthog (Phacochoerus aethiopicus).

A 14-yr-old male African warthog (Phacochoerus aethiopicus) with a chronic history of intermittent unilateral epistaxis, degenerative osteoarthritis, and intermittent weakness in the distal lumbar trunk was evaluated to determine the source of epistaxis. No obvious cause was determined, and in light of severe osteoarthritis and a holosystolic cardiac murmur, the animal was euthanized. A tumor of the right adrenal gland involving the medulla was found at gross necropsy. Immunohistochemical staining of the tumor was positive for chromogranin and negative for neurofilament protein, which was diagnostic for pheochromocytoma. No lesions were observed in either nasal cavity. Systolic, diastolic, and mean arterial pressures measured at the time of immobilization were elevated when compared with another African warthog immobilized with a similar anesthetic regimen. Additionally, the warthog had pronounced serum norepinephrine dominance with a norepinephrine:epinephrine ratio of 10.0, compared with 0.36 from clinically normal warthogs. Practitioners should consider pheochromocytoma when evaluating warthogs or swine for epistaxis.

Three cases of systemic atypical granulomatous disease in moluccan cockatoos (Cacatua moluccensis): a new syndrome.

A 1.5-year-old male Moluccan cockatoo (Cacatua moluccensis) presented to Kansas State University Veterinary Medical Teaching Hospital with a 4-month history of lethargy and weakness. Hematologic and radiographic diagnostic testing revealed profound leukocytosis and coelomic and pulmonary granulomatous masses of unknown origin. The bird died during laparoscopic evaluation under general anesthesia. Necropsy revealed multiple pulmonary and hepatic soft-tissue nodules and an intracoelomic mass over the left kidney communicating with external subcutaneous masses and a pericloacal mass of similar gross appearance. Histopathologic findings identified a severe, disseminated, inflammatory infiltration of multiple tissues and multiple granulomas containing bizarre multinucleated cells. No causative agent of this granulomatous disease was identified. To our knowledge, this is the first report of systemic atypical granulomatous disease in Moluccan cockatoo. Traditional causes of granulomatous disease include mycotic disease, bacterial (ie, Mycobacterium) disease, and neoplasia. Attempts to identify an causative agent or neoplasia were unsuccessful. A retrospective review of pathology records revealed 2 additional cases with identical pathologic lesions. All 3 cases occurred in young Moluccan cockatoos and are assumed to be a disease of unknown origin that could be unique to this species.

Pharmacokinetics of meloxicam after intravenous, intramuscular, and oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

OBJECTIVE: To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). ANIMALS: 11 healthy parrots. PROCEDURES: Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. RESULTS: Initial mean ± SD plasma concentration of 17.3 ± 9.0 µg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 µg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 µg/mL) and IM (3.5 ± 2.2 µg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 µg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 µg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.