BIOLOGICAL VARIATION OF HEMATOLOGY PARAMETERS AND CLINICAL APPLICATION IN AFRICAN ELEPHANTS (LOXODONTA AFRICANA).

Detailed knowledge of biological variation can facilitate accurate interpretation of clinical pathology parameters. A recent biological variation study in Asian elephants (Elephas maximus) found that hematology parameters had high individuality, which suggests that population-derived reference intervals may be an insensitive diagnostic tool. In elephant medicine, sensitive hematology-related diagnostics are crucial for clinical decision-making, particularly in elephants at risk for elephant endotheliotropic herpesvirus hemorrhagic disease (EEHV-HD). The objective of this study was to assess biological variation of hematology parameters in African elephants to determine whether population-derived reference intervals are a sensitive diagnostic tool for interpreting results and to provide a useful alternative. Eight healthy African elephants had blood collected under behavioral training every other week for 8 wk. Complete blood cell count (CBC) analysis was performed in duplicate to assess analytical variation. Previous methods were used to determine between-individual variation, within-individual variation, index of individuality, and reference change values (RCV). This study found that most hematology parameters displayed intermediate-to-high individuality, which suggests that alternatives to population-derived reference intervals are necessary to detect pathologic changes. To test the results of our biological variation data, a case of EEHV-HD was retrospectively evaluated. Individual normal values and calculated RCV detected a clinically significant monocytopenia, leukopenia, and thrombocytopenia associated with EEHV2 viremia. However, none of these parameters fell outside a population-derived reference interval. This study highlights the utility of biological variation in clinical decision-making and demonstrates that individual normal values and RCV may be important diagnostic tools for CBC interpretation in African elephants.

HYPERLIPIDEMIA AND XANTHOMATOSIS IN YELLOW-FOOTED ROCK WALLABIES (PETROGALE XANTHOPUS) UNDER MANAGED CARE.

Xanthomas are localized lipid deposits in organs with associated granulomatous inflammation. Xanthomatosis is a rare condition in both human and veterinary medicine and is often linked to inherited or acquired dyslipidemias. Three female yellow-footed rock wallabies (Petrogale xanthopus) at a single institution were diagnosed via biopsy with cutaneous xanthomas secondary to hypertriglyceridemia and hypercholesterolemia, and an additional two female yellow-footed rock wallabies were diagnosed with xanthomas at a second institution. All cases presented with cutaneous masses at the haired skin and paw pad junctions of the extremities, and/or mucocutaneous junctions of the face or urogenital tract. The clinically affected individuals were overconditioned or obese, had lipemic serum, and had elevations in blood cholesterol and triglyceride levels. When full lipid panels were performed, inverse high- and low-density lipoprotein fractions were observed. Six other individuals at the first institution had identical husbandry but were of more appropriate body condition, were normolipidemic, and had no xanthomas. One of the affected animals was also concurrently diagnosed with hepatic lipidosis via liver biopsy. Pedigree review and evaluation for underlying endocrine diseases such as hypothyroidism were performed. Because all affected animals were found to be related, a genetic predisposition is possible but requires further investigation. Consideration for the predisposition of some individuals for obesity, hyperlipidemia, and subsequent xanthoma formation should be factored in the husbandry and medical management of this species.

OUTCOMES OF TRANSPLACENTAL TRANSMISSION OF TOXOPLASMA GONDII FROM CHRONICALLY INFECTED FEMALE RED RUFFED LEMURS (VARECIA RUBRA).

Ten red ruffed lemurs (Varecia rubra)-two adult females and their eight offspring-were evaluated in this case series. Two adult females were diagnosed with chronic, latent toxoplasmosis based on serologic testing. The first female lemur had two successive pregnancies. The first pregnancy resulted in transplacental transmission of Toxoplasma gondii. The only surviving offspring was diagnosed with congenital toxoplasmosis based on serologic testing and compatible ophthalmic lesions. The two deceased offspring had disseminated nonsuppurative inflammation and intralesional protozoal organisms consistent with T. gondii, which was confirmed by polymerase chain reaction. The second pregnancy did not result in transplacental transmission. The second chronically infected adult female lemur had one pregnancy that resulted in a single stillborn fetus without evidence of transplacental transmission of T. gondii. Treatment with trimethoprim-sulfamethoxazole and folinic acid was administered to the first adult female and one offspring, but no treatment was given to the second adult female. All surviving lemurs had no further complications associated with toxoplasmosis. This case series demonstrates that chronic, latent infection of reproductive female red ruffed lemurs with T. gondii may result in variable outcomes: (1) transplacental transmission with disseminated fetal infection and stillbirth, (2) transplacental transmission with congenital infection and survival, or (3) lack of transplacental transmission and healthy offspring. Information gained from these cases may help guide recommendations for breeding of this critically endangered species.

Comparison of the effects of a dexmedetomidine-ketamine-midazolam anesthetic protocol versus isoflurane inhalation anesthesia on echocardiography variables and plasma cardiac troponin I concentration in black-tailed prairie dogs (Cynomys ludovicianus).

OBJECTIVE: To compare the effects of a dexmedetomidine-ketamine-midazolam (DKM) anesthetic protocol versus isoflurane inhalation anesthesia on echocardiographic variables and plasma cardiac troponin 1 (cTnI) concentration in black-tailed prairie dogs (BTPDs; Cynomys ludovicianus). ANIMALS: Nine 6-month-old sexually intact male captive BTPDs. PROCEDURES: Each BTPD was randomly assigned to be anesthetized by IM administration of dexmedetomidine (0.25 mg/kg), ketamine (40 mg/kg), and midazolam (1.5 mg/kg) or via inhalation of isoflurane and oxygen. Three days later, each BTPD underwent the alternative anesthetic protocol. Echocardiographic data and a blood sample were collected within 5 minutes after initiation and just prior to cessation of each 45-minute-long anesthetic episode. RESULTS: Time or anesthetic protocol had no significant effect on echocardiographic variables. For either protocol, plasma cTnI concentration did not differ with time. When administered as the first treatment, neither anesthetic protocol significantly affected plasma cTnI concentration. However, with regard to findings for the second treatments, plasma cTnI concentrations in isoflurane-treated BTPDs (n = 4; data for 1 animal were not analyzed because of procedural problems) were higher than values in DKM-treated BTPDs (4), which was suspected to be a carryover effect from prior DKM treatment. CONCLUSIONS AND CLINICAL RELEVANCE: The DKM and isoflurane anesthetic protocols did not have any significant effect on echocardiographic measurements in the BTPDs. Increases in plasma cTnI concentration during the second anesthetic episode were evident when BTPDs underwent the DKM anesthetic protocol as the first of the 2 treatments, suggestive of potential myocardial injury associated with that anesthetic protocol. Clinicians should consider these findings, especially when evaluating BTPDs with known or suspected cardiac disease.

Effects of injectable dexmedetomidine-ketamine-midazolam and isoflurane inhalation anesthetic protocols on ocular variables in captive black-tailed prairie dogs (Cynomys ludovicianus).

OBJECTIVE: To evaluate the effects of injectable dexmedetomidine-ketamine-midazolam (DKM) and isoflurane inhalation (ISO) anesthetic protocols on selected ocular variables in captive black-tailed prairie dogs (Cynomys ludovicianus; BTPDs). ANIMALS: 9 zoo-kept BTPDs. PROCEDURES: The BTPDs received dexmedetomidine hydrochloride (0.25 mg/kg, IM), ketamine hydrochloride (40 mg/kg, IM), and midazolam hydrochloride (1.5 mg/kg, IM) or inhalation of isoflurane and oxygen in a randomized complete crossover design (2-day interval between anesthetic episodes). Pupil size, globe position, tear production, and intraocular pressure measurements were recorded at 5, 30, and 45 minutes after induction of anesthesia. For each BTPD, a phenol red thread test was performed in one randomly selected eye and a modified Schirmer tear test I was performed in the other eye. Intraocular pressure was measured by rebound tonometry. RESULTS: Compared with findings for the DKM protocol, pupil size was smaller at all time points when the BTPDs underwent the ISO protocol. Globe position remained central during anesthesia with the DKM protocol, whereas it varied among central, ventromedial, and ventrolateral positions during anesthesia with the ISO protocol. Tear production and intraocular pressure decreased significantly over time when the BTPDs underwent either protocol. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that ophthalmic examination findings for anesthetized BTPDs can be influenced by the anesthetic protocol used. The DKM protocol may result in more consistent pupil size and globe position, compared with that achieved by use of the ISO protocol. Tear production and intraocular pressure measurements should be conducted promptly after induction of anesthesia to avoid the effect of anesthetic episode duration on these variables.

An Investigation of a Novel Tendon Transfer Surgery for High Median-Ulnar Nerve Palsy in a Chicken Model.

PURPOSE: The state-of-the-art tendon transfer surgery for high median-ulnar nerve palsy involves directly suturing four finger flexor tendons to one wrist extensor muscle. This couples finger flexion limiting the patient's ability to grasp objects. Therefore, we propose a new approach to attach a novel passive implant to the extensor digitorum longus tendon in order to create a differential mechanism in situ. The implant is expected to enable the fingers to adapt to an object's shape during grasping. Chickens have been used as a model in tendon research, but studies have primarily focused on the digital flexor tendon mechanism. Thus, the aim of this study was to explore the feasibility of the chicken model for extensor tendon research and to validate the surgical technique for a new approach to tendon transfer surgery. MATERIALS AND METHODS: Twenty-nine chickens were randomly divided into three groups: implant (n = 12), sham (n = 10), and control (n = 7). Postoperative healing and complications were documented. RESULTS: Surgery was successful in all chickens. All animals healed appropriately by Day 16 postoperatively. Chickens in the implant group experienced significantly more intermittent toe-knuckling gait than the sham group (p = 0.001). CONCLUSIONS: The described surgical technique allowed for successful application of a novel implantable passive mechanism in a live chicken model. In combination with previous work, findings from the present study further validated a novel tendon-transfer surgery for high median-ulnar nerve palsy. Based on the degree of intermittent abnormal gait experienced by the implant group, refinement to the implant design is warranted in future studies.

Comparison of Dexmedetomidine-Ketamine-Midazolam and Isoflurane for Anesthesia of Black-tailed Prairie Dogs (Cynomys ludovicianus).

Few studies evaluate anesthesia in black-tailed prairie dogs (Cynomys ludovicianus). Isoflurane inhalant anesthesia is used in this species most commonly, but injectable protocols are poorly described. Here we compared the physiologic effects, including anesthetic depth, vital signs, and hematologic changes, of anesthetic protocols using isoflurane or a combination of dexmedetomidine, ketamine, and midazolam in black-tailed prairie dogs. In a randomized, complete crossover study design, intact male black-tailed prairie dogs (n = 9; age, 6 mo) were anesthetized by using a combination of dexmedetomidine (0.25 mg/kg IM), ketamine (40 mg/kg IM), and midazolam (1.5 mg/kg IM). For reversal, atipamezole (0.15 mg/kg) and flumazenil (0.05 mg/kg) were administered 45 min after induction. For comparison, isoflurane was administered at 5% in 100% oxygen at 5 L/min in an anesthetic induction chamber, followed by maintenance isoflurane 2% in 2 L/min oxygen through a tight-fitting facemask for 45 min. Induction and recovery time, respiratory rate, heart rate, body temperature, SpO2, indirect blood pressure, and reflexes were monitored every 5 min during the anesthetic period. Blood samples for venous blood gases, PCV, and refractometric total protein were obtained from the cranial vena cava at 5 min and 45 min. Both protocols appeared to achieve safe and effective anesthesia. Except for blood pressure, all vital signs differed between the 2 treatments. Isoflurane anesthesia resulted in a slightly longer induction and lower respiratory rate and body temperature but increased likelihood of absent reflexes. DKM anesthesia resulted in a faster induction and less hypothermia but also prolonged recovery and lower heart rate and SpO2 readings. These findings suggest that isoflurane provides a more stable and consistent anesthetic plane, whereas dexmedetomidine-ketamine-midazolam anesthesia may be an effective alternative for short procedures that require fast induction and limited analgesia.

PHARMACOKINETICS OF ORAL GABAPENTIN IN CARIBBEAN FLAMINGOS ( PHOENICOPTERUS RUBER RUBER).

Gabapentin is a first-line treatment for neuropathic pain and adjunct anticonvulsant medication in humans and other species. Gabapentin may have advantages over other analgesics because of its broad therapeutic range with limited adverse effects and wide availability as an oral formulation. This study determined the pharmacokinetics of gabapentin in Caribbean flamingos ( Phoenicopterus ruber ruber) after a single-dose oral administration of either 15 mg/kg ( n = 6) or 25 mg/kg ( n = 6). Plasma gabapentin concentrations were determined using liquid chromatography with mass spectrometry, and pharmacokinetic analysis was performed using noncompartmental methods. Respectively for the 15 mg/kg and 25 mg/kg dose, mean peak plasma concentration ( Cmax) was (mean ± pseudo SD) 13.23 ± 1.47 and 24.48 ± 5.81 µg/ml; mean time to peak plasma concentration ( Tmax) was 0.50 ± 0.24 and 0.56 ± 0.28 hr; mean area under the curve (AUC) was 76.0 ± 26.3 and 114.7 ± 27.5 hr·µg/ml; and mean terminal half-life ( T1/2) was 3.39 ± 0.90 and 4.46 ± 1.12 hr. Based on the results of this study, gabapentin dosed at 25 mg/kg orally in most Caribbean flamingos is likely to maintain plasma concentrations above the therapeutic range established for humans for approximately 12 hr.

CLINICAL INFECTION OF CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS) WITH ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 4.

Elephant endotheliotropic herpesvirus (EEHV) can cause lethal hemorrhagic disease in juvenile Asian elephants. A number of EEHV types and subtypes exist, where most deaths have been caused by EEHV1A and EEHV1B. EEHV4 has been attributed to two deaths, but as both diagnoses were made postmortem, EEHV4 disease has not yet been observed and recorded clinically. In this brief communication, two cases of EEHV4 infection in juvenile elephants at the Houston Zoo are described, where both cases were resolved following intensive treatment and administration of famciclovir. A quantitative real-time polymerase chain reaction detected EEHV4 viremia that correlated with clinical signs. High levels of EEHV4 shedding from trunk wash secretions of the first viremic elephant correlated with subsequent infection of the second elephant with EEHV4. It is hoped that the observations made in these cases--and the successful treatment regimen used--will help other institutions identify and treat EEHV4 infection in the future.