Pharmacokinetics of diphenhydramine following single-dose intravenous and oral administration in non-fasted adult horses.

Diphenhydramine is an H1 receptor antagonist used to control urticaria and other allergic signs caused by type I hypersensitivity reactions in horses (Equus caballus). Limited studies have been conducted on pharmacokinetics of this drug in horses, with no studies involving oral formulations. Our study investigated pharmacokinetics of an oral diphenhydramine formulation compared to intravenous administration in non-fasted adult horses. Six healthy horses underwent a single administration of three different doses of diphenhydramine (1 mg/kg intravenously, 1 mg/kg intragastrically, and 5 mg/kg intragastrically) with a two-week washout period between doses. Bioavailability of intragastric diphenhydramine was less than one percent and six percent for 1 mg/kg and 5 mg/kg intragastric doses, respectively. This poor bioavailability is similar to what is reported in dogs. Two of six horses experienced transient side effects after intravenous diphenhydramine administration, emphasizing the need for determining therapeutic plasma levels in efforts to determine the lowest effective dose minimizing risk of adverse effects. The main conclusion of our study was that oral diphenhydramine at doses up to 5 mg/kg are unlikely to achieve therapeutic plasma levels in adult horses.

Esthesiometric evaluation of corneal analgesia after topical application of 1% morphine sulfate in normal horses.

OBJECTIVE: To evaluate whether topical ocular application of 1% morphine sulfate would change corneal sensitivity and to identify the duration of action. ANIMAL STUDIED: Eight healthy adult horses. PROCEDURE: Corneal touch threshold (CTT) was measured in the center of one randomly selected eye of each horse by Cochet-Bonnet esthesiometer (Luneau Cochet-Bonnet Esthesiometer; Western Ophthalmics, Lynnwood, WA, USA). Immediately following baseline CTT measurement, 0.3 ml of 1.0% preservative-free morphine sulfate (Morphine Sulfate 25 mg/ml Preservative-free; Hospira, Lake Forest, IL, USA) (3 mg) was applied to the tested eye. The same volume of artificial tear (LiquiTears; Major Pharmacauticals, Livonia, MI, USA) solution was then applied to the control eye following acquisition of baseline CTT. Corneal touch threshold was then subsequently measured at 1 min after medication application, followed by every 5 min until 60 min post administration. If the corneal touch threshold had not returned to baseline by 60 min, measurements were continued at 15-min intervals until corneal sensitivity returned to baseline CTT measurement up to 180 min post administration if needed. The control eye was treated identically and measurements on the control eye stopped when the corresponding treated eye returned to baseline. RESULTS: Mean baseline CTT of both eyes was 21.8 mm with an identical range of 15-30 mm. Mean corneal touch threshold was not statistically different between morphine-treated and control eyes (P = 0.22). There was a large degree of inter- and intrasubject variation in the CTT measurements obtained. All but three horses were considered to be at baseline values by 60 min. CONCLUSIONS: Topical ophthalmic 1% morphine sulfate did not have a clinically significant analgesic effect on the corneal touch threshold of intact healthy equine corneas.

Pharmacokinetic evaluation and safety of topical 1% morphine sulfate application on the healthy equine eye.

OBJECTIVE: To determine if corneal epithelial cell integrity is detrimentally affected by short-term administration of 1.0% morphine sulfate. Additionally, we sought to determine if topical 1.0% morphine applied to the equine cornea would result in ocular or systemic absorption. ANIMAL STUDIED: Six healthy horses. PROCEDURE: Morphine sulfate (1.0%) was applied topically to one eye every four hours for 72 h before horses were euthanized. Serum samples were collected at varying time points during the study and aqueous and vitreous humor were collected immediately after euthanasia. Morphine quantification in serum, aqueous, and vitreous humor was performed by ELISA. Treated and control corneas were submitted for histopathology. Horses were monitored for adverse ocular and systemic effects throughout the study period. RESULTS: All horses developed mild mucoid ocular discharge in the treated eye. One horse developed a fever during treatment. Morphine was detected in the aqueous humor of the treated eye for all horses with mean ± standard deviation of 165.18 ng/mL ± 87.69 ng/mL. Morphine was detected in vitreous humor of the treated eye of 5 of 6 horses with mean ± standard deviation of 4.87 ± 4.46 ng/mL. Morphine was detected in the serum of 5 of 6 horses at varying time points. Maximum systemic concentration reached in a single horse was 6.98 ng/mL. Corneal histopathology revealed no difference in microscopic appearance between morphine-treated and control corneas. CONCLUSIONS: Topical administration of 1.0% morphine sulfate did not appear to cause any significant ocular or systemic adverse effects. Topical ophthalmic morphine application resulted in both ocular and systemic absorption.

Neurotropic T-cell-rich B-cell lymphoma in a 14-year-old Morgan gelding.

A 14-year-old Morgan gelding was presented for progressive weakness and muscle atrophy. The horse was initially diagnosed with equine protozoal myelitis based on history, physical examination, and laboratory diagnostics. Despite therapy, the horse declined clinically and was euthanized. Necropsy revealed a rare form of neurotropic lymphoma, described in this report.

Lymphome de cellules-B riches en cellules-T neurotropes chez un hongre Morgan âgé de 14 ans. Un hongre Morgan âgé de 14 ans a été présenté pour une faiblesse progressive et une atrophie musculaire. On a d'abord diagnostiqué la myélite protozoaire équine chez le cheval en se basant sur l'anamnèse, l'examen physique et le diagnostic en laboratoire. Malgré la thérapie, l'état clinique du cheval s'est détérioré et il a été euthanasié. La nécropsie a révélé une forme rare de lymphome neutropique, qui est décrite dans ce rapport.(Traduit par Isabelle Vallières).

Pyogranulomatous enteritis and mesenteric lymphadenitis in an adult llama caused by Rhodococcus equi carrying virulence-associated protein A gene.

We report herein Rhodococcus equi infection in an 11-y-old, male llama with a history of diarrhea and endoparasitism. Postmortem examination revealed granulomatous and ulcerative enteritis, pyogranulomatous mesenteric lymphadenitis, fibrinosuppurative peritonitis, and granulomatous hepatitis. Intralesional macrophages were laden with gram-positive cocci. Bacteriology identified R. equi, and cultures tested positive for R. equi choE and vapA genes by PCR. This case expands the reported spectrum of lesions associated with R. equi infections in llamas from pyogranulomatous bronchopneumonia and peripheral lymphadenitis to pyogranulomatous mesenteric lymphadenitis and enteritis. We also link a R. equi that is carrying the virulent-associated protein gene VapA to clinical disease in New World camelids.

Cryptosporidiosis in 20 alpaca crias.

CASE DESCRIPTION: 20 alpaca crias (13 females and 7 males) were examined for diarrhea (n=20), weight loss (15), and poor appetite (5). Fourteen crias were between 8 and 18 days of age at time of admission. CLINICAL FINDINGS: Cryptosporidiosis was diagnosed in all crias. Common biochemical abnormalities included acidemia, hyperlactemia, azotemia, and hyperglycemia and increases in aspartate transaminase and gamma-glutamyltransferase activities. Serum sodium and chloride concentrations were high or low. Other potential gastrointestinal tract pathogens were identified in only 7 crias. TREATMENT AND OUTCOME: Supportive care was instituted, including i.v. administration of fluids with partial parenteral administration of nutrients (n=19 crias), antimicrobials (19), supplemental orally administered nutrients (11), administration of plasma (10), and insulin treatment (9). Other palliative treatments used by attending clinicians were sucralfate, flunixin meglumine, vitamin A/D/E/B complex, antiparasitic agents, antidiarrheal agents, and azithromycin. Three crias with inadequate urine production and severe azotemia were treated with furosemide administered i.v. as a bolus or as a constant-rate infusion. Treatment resulted in a successful outcome in 16 of 20 crias. Weight loss and refractory azotemia were common in nonsurvivors but not in surviving crias. CLINICAL RELEVANCE: Findings suggested that Cryptosporidium spp may be a diarrheal pathogen of unweaned alpaca crias that may be more widespread than has been recognized and can become endemic on some farms. Metabolic derangements were unpredictable and should be determined by biochemical analysis before fluid and electrolyte replacement is initiated. Cryptosporidiosis has zoonotic potential, and the infection can be self-limiting in alpacas receiving supportive treatment.

Klossiella equi infection in a Cheval Canadien Mare.

A 6-year-old Cheval Canadien mare was presented for clinical signs related to acute kidney injury after receiving a course of nonsteroidal anti-inflammatory therapy. Cytologic examination of concentrated urine revealed small protozoal organisms that were later identified as Klossiella equi. Both sporocysts and free-floating sporozoites were identified in the urine, which has not been previously documented. The mare responded well to intravenous fluid therapy, and as she regained tubular function, the presence of the protozoa in the urine also abated. The mare was discharged from the hospital after approximately 1 week of therapy. Repeat serum chemistries for up to 1 year following discharge demonstrated that all renal parameters had returned to normal, and the protozoa were not visualized on cytologic examination of the collected urine samples.

Eimeria macusaniensis infection in 15 llamas and 34 alpacas.

CASE DESCRIPTION: 15 llamas and 34 alpacas between 3 weeks and 18 years old with fecal oocysts or intestinal coccidial stages morphologically consistent with Eimeria macusaniensis were examined. Nineteen of the camelids were admitted dead, and 30 were admitted alive. Camelids admitted alive accounted for 5.5% of all camelid admissions during this period. CLINICAL FINDINGS: Many severely affected camelids had signs of lethargy, weight loss, decreased appetite, and diarrhea. Camelids with clinical infection also commonly had evidence of circulatory shock, fat mobilization, and protein loss. Nonsurviving camelids also had evidence of shock, edema, bile stasis, renal insufficiency, hepatic lipidosis, muscle damage, relative hemoconcentration, and sepsis. Postmortem examination frequently revealed complete, segmental replacement of the mucosa of the distal portion of the jejunum with coccidial meronts and gamonts. For 17 of 42 camelids, results of initial fecal examinations for E macusaniensis were negative. TREATMENT AND OUTCOME: Most camelids admitted alive were treated with amprolium hydrochloride, plasma, and various supportive treatments. Fifteen of the 30 treated camelids died or were euthanized. CLINICAL RELEVANCE: Findings suggest that E macusaniensis may be an important gastrointestinal tract pathogen in camelids of all ages. Clinical signs were frequently nonspecific and were often evident before results of fecal examinations for the parasite were positive. As with other coccidia, severity of disease was probably related to ingested dose, host immunity, and other factors. The clinical and herd relevance of positive fecal examination results must be determined.

Rapid, multiwell colorimetric assay for measuring neutrophil chemoattractant activity in bronchoalveolar lavage fluid of horses with recurrent airway obstruction.

The criteria used to diagnose recurrent airway obstruction (RAO) in affected horses include demonstration of reversible lower airway obstruction and greater than 25% neutrophils in bronchoalveolar lavage fluid (BALF). Additional objective laboratory tests are needed to improve diagnostic accuracy and to monitor response to treatment. The goal of this study was to determine if neutrophil chemoattractant activity of BALF could be measured by using a previously described, rapid, multiwell colorimetric assay for chemotaxis. In this assay, neutrophils that have migrated through a membrane filter are collected into the bottom well of a disposable chemotaxis-cell migration chamber. The number of viable cells collected in the bottom well is quantified by measurement of the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol tetrazolium bromide (MTT), which is reduced by dehydrogenase in mitochondria of live cells. The number of migrating cells corresponds to the amount of MTT reduced, which is measured with an enzyme-linked immunosorbent assay plate reader. Fourteen adult horses were enrolled in this study, 7 of which had owner histories consistent with RAO. Each horse was sedated, a bronchoalveolar lavage tube was passed, and saline was infused and immediately aspirated. An aliquot of BALF was used for differential cell count, and BALF supernatant was harvested to assess neutrophil chemoattractant activity. Normal control horses and RAO-affected horses were distinguished according to clinical signs and percent neutrophils in BALF. Neutrophil chemoattractant activity of BALF was significantly greater in RAO-affected horses (P = 0.001) compared with control horses. This assay may be useful in future studies for monitoring response to therapy in RAOaffected horses.

Assessment of serum concentrations and sedative effects of fentanyl after transdermal administration at three dosages in healthy llamas.

OBJECTIVE: To determine the serum concentrations and sedative effects of fentanyl after transdermal administration at 3 dosages in llamas. ANIMALS: 9 healthy adult female llamas (mean age, 8 +/- 3 years; mean weight, 150 +/- 18 kg). PROCEDURE: Llamas were allocated to 1 of 3 groups (3 llamas/group). Fentanyl patches (each providing transdermal delivery of 75 microg of fentanyl/h) were placed on shaved areas of the antebrachium of all llamas. In group 1, llamas were treated with 1 patch (anticipated fentanyl dosage, 75 microg/h). In group 2, llamas were treated with 2 patches (anticipated fentanyl dosage, 150 microg/h). In group 3, llamas were treated with 4 patches (anticipated fentanyl dosage, 300 microg/h). For each llama, the degree of sedation was assessed by use of a subjective scoring system and a blood sample was collected for determination of serum fentanyl concentration at 12, 24, 36, 48, 60, and 72 hours after patch placement. RESULTS: Following the placement of 4 patches, mean +/- SD serum fentanyl concentration in group 3 llamas reached 0.3 +/- 0.08 ng/mL within 12 hours. This concentration was sustained for 72 hours. In group 2, application of 2 patches provided inconsistent results; in group 1, application of 1 patch rarely provided measurable serum fentanyl concentrations. No llamas became sedated at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that application of four 75 microg/h fentanyl patches provides consistent, sustained serum fentanyl concentrations without sedation in llamas. However, the serum concentration of fentanyl that provides analgesia in llamas is not known.

Use of chemotherapy for treatment of a mixed-cell thoracic lymphoma in a horse.

A 4-year-old Oldenburg mare was evaluated because of signs of lower airway disease and subsequently developed bilateral pleural effusion. Neoplastic cells were not identified in the fluid sample obtained via the initial thoracocentesis. A thoracic mass was detected radiographically, but its location prevented collection of a tissue sample. A diagnosis of lymphoma was made on the basis of results of immunophenotyping of pleural fluid specimens. Treatment of thoracic lymphoma in horses has been attempted, but there are limited data regarding chemotherapeutic-induced remission. In this horse, remission was achieved by use of a chemotherapeutic protocol consisting of administration of cytarabine, cyclophosphamide, and prednisolone. No adverse drug reactions were encountered during treatment. Immunophenotyping of cells in specimens of pleural fluid could be used to determine lymphocyte lineage and may be a useful alternative diagnostic modality when morphologic and cytologic examination of tissue specimens obtained via invasive techniques is not feasible.

Minimum alveolar concentration of sevoflurane in spontaneously breathing llamas and alpacas.

OBJECTIVE: To determine the minimum alveolar concentration (MAC) of sevoflurane in spontaneously breathing llamas and alpacas. DESIGN: Prospective study. ANIMALS: 6 healthy adult llamas and 6 healthy adult alpacas. PROCEDURE: Anesthesia was induced with sevoflurane delivered with oxygen through a mask. An endotracheal tube was inserted, and a port for continuous measurement of end-tidal and inspired sevoflurane concentrations was placed between the endotracheal tube and the breathing circuit. After equilibration at an end-tidal-to-inspired sevoflurane concentration ratio > 0.90 for 15 minutes, a 50-Hz, 80-mA electrical stimulus was applied to the antebrachium until a response was obtained (ie, gross purposeful movement) or for up to 1 minute. The vaporizer setting was increased or decreased to effect a 10 to 20% change in end-tidal sevoflurane concentration, and equilibration and stimulus were repeated. The MAC was defined as the mean of the lowest end-tidal sevoflurane concentration that prevented a positive response and the highest concentration that allowed a positive response. RESULTS: Mean +/- SD MAC of sevoflurane was 2.29 +/- 0.14% in llamas and 2.33 +/- 0.09% in alpacas. CONCLUSIONS AND CLINICAL RELEVANCE: The MAC of sevoflurane in llamas and alpacas was similar to that reported for other species.

Computed tomographic characterization of the pulmonary system in clinically normal alpacas.

OBJECTIVE: To characterize and quantitatively assess the typical pulmonary anatomy of healthy adult alpacas with multidetector row CT. ANIMALS: 10 clinically normal adult female alpacas. PROCEDURES: CT examination of the thorax was performed before and after IV administration of iodinated contrast medium in sedated alpacas in sternal recumbency. Measurements of the trachea, bronchi and related blood vessels, and selected vertebrae as well as the extent and density of lung parenchyma were performed with a Digital Imaging and Communications in Medicine (DICOM) viewer. Morphometric and quantitative data were summarized. RESULTS: Separation of individual lung lobes could not be identified, except for the accessory lung lobe. In all alpacas, both lungs extended farther caudally at the medial aspect than at the lateral aspect. The right lung extended farther in both cranial and caudal directions than did the left lung. The branching pattern of the bronchial tree varied only slightly among alpacas and consisted of 1 cranial bronchus and 3 caudal bronchi bilaterally, with a right accessory bronchus. Luminal diameters of first-generation bronchi ranged from 3 to 9 mm. Mean ± SD parenchymal lung density was -869 ± 40 Hounsfield units (HU) before contrast injection and -825 ± 51 HU after contrast injection. Mean difference in diameter between bronchi and associated arteries or veins was 0.8 ± 0.9 mm. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of the typical anatomy of the lungs and bronchial tree in healthy alpacas as determined via CT will aid veterinarians in clinical assessment and bronchoscopic evaluation of alpacas.

Listeria associated mural and valvular endocarditis in an alpaca.

An alpaca presented for emergency evaluation of respiratory distress. Physical examination revealed weakness, pyrexia, and a grade V/VI left apical holosystolic murmur. Initial thoracic examination and radiographs were consistent with left sided congestive heart failure. Blood cultures, echocardiographic evaluation, and necropsy findings established a diagnosis of bacterial endocarditis associated with a Listeria monocytogenes infection. Left ventricular endocarditis is uncommon in ruminants, and to the authors' knowledge there are no other reports of L. monocytogenes being the causative agent in an alpaca.

Minimum alveolar concentration of desflurane in llamas and alpacas.

OBJECTIVE: To determine the minimum alveolar concentration (MAC) of desflurane in llamas and alpacas. DESIGN: Prospective study. Animals Six healthy adult llamas and six healthy adult alpacas. PROCEDURE: Anesthesia was induced with desflurane delivered with oxygen through a mask. An endotracheal tube was inserted, and a port for continuous measurement of end-tidal and inspired desflurane concentrations was placed between the endotracheal tube and the breathing circuit. After equilibration at an end-tidal-to-inspired desflurane concentration ratio >0.90 for 15 minutes, a 50-Hz, 80-mA electrical stimulus was applied to the antebrachium until a response was obtained (i.e. gross purposeful movement) or for up to 1 minute. The vaporizer setting was increased or decreased to effect a 10-20% change in end-tidal desflurane concentration, and equilibration and stimulus were repeated. The MAC was defined as the average of the lowest end-tidal desflurane concentration that prevented a positive response and the highest concentration that allowed a positive response. RESULTS: Mean +/- SD MAC of desflurane was 7.99 +/- 0.58% in llamas and 7.83 +/- 0.51% in alpacas. CONCLUSIONS AND CLINICAL RELEVANCE: The MAC of desflurane in llamas and alpacas was in the range of that reported for other species.