Objective—To investigate gene expression of the major proteolytic systems and growth regulators in skeletal muscle of horses with myopathy associated with pituitary pars intermedia dysfunction (PPID).
Animals—14 horses with PPID-associated myopathy and 7 healthy control horses.
Procedures—Horses with PPID and controls were age matched (15 to 28 years old). Muscle biopsy specimens were collected from both groups and processed for RNA and cDNA extraction. Validation of the most stable housekeeping genes for skeletal muscle was performed and used to compare gene expression of the following proteolytic systems: cysteine aspartate protease–dependent systems (caspases), lysosomal-dependent systems (cathepsins), non–lysosomal calcium protease–dependent systems (calpains), and ubiquitin-proteasome–dependent systems (ubiquitins). Gene expression of negative regulators of muscle growth (myostatin and inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α) was also determined.
Results—No significant difference between groups was detected in expression of the major proteolytic systems except for m-calpain, which was greater in horses with PPID. No differences in gene expression of myostatin and interleukin-1β, interleukin-6, and tumor necrosis factor-α were detected between groups.
Conclusions and Clinical Relevance—Greater expression of m-calpain may suggest that calpains play an important role in development of muscle atrophy in horses with PPID. However, because posttranslational events may alter protein activation, inactivation, and functions not studied here, other mechanisms of muscle atrophy cannot be excluded.
Case Description—A 15-year-old Quarter Horse gelding and a 26-year-old Thoroughbred gelding were evaluated because of hematuria of 4 to 6 days' duration following prolonged oral administration of phenylbutazone.
Clinical Findings—The horses had received either treatment with phenylbutazone for 3 months or intermittent long-term phenylbutazone treatment prior to development of hematuria. Each horse was systemically stable but had orthopedic or neurologic problems. Clinicopathologic findings included normochromic normocytic anemia in both horses and hypoalbuminemia and high BUN concentration in 1 horse. In both horses, urinalysis revealed proteinuria and RBCs, but no evidence of WBCs or bacteria. Ulceration and hemorrhage of the urinary bladder with no evidence of uroliths were observed via cystoscopy. Gastric ulceration along the margo plicatus was observed via gastroscopy.
Treatment and Outcome—For each horse, phenylbutazone treatment was discontinued and a synthetic prostaglandin (misoprostol) was administered. The hematuria resolved, and results of a follow-up CBC, serum biochemical analysis, urinalysis, and cystoscopy 25 or 30 days after cessation of phenylbutazone treatment were unremarkable in both cases.
Clinical Relevance—Given the known adverse effects of NSAID treatment in several species, phenylbutazone and its metabolites were suspected to have caused ulceration of the urinary bladder, resulting in hematuria, in the 2 horses. A definitive cause of urinary bladder ulceration was not confirmed in these cases; however, resolution of ulceration after discontinuation of phenylbutazone treatment and administration of synthetic prostaglandins and exclusion of other causes suggested an association between phenylbutazone administration and ulcerative cystitis in these horses.
Objective—To describe ultrasonographic landmarks for use in collection of CSF from the lumbosacral region in equids.
Animals—37 equids (27 with neurologic disease and 10 with nonneurologic disease).
Procedures—Standing equids (n = 17) were sedated with detomidine hydrochloride (0.006 to 0.01 mg/kg [0.003 to 0.005 mg/lb], IV) followed by butorphanol tartrate (0.01 mg/kg, IV) and restrained with a nose twitch for collection of CSF. The CSF was collected from 20 laterally recumbent equids (10 sedated and 10 immediately after euthanasia). Anatomic landmarks were identified ultrasonographically. Height at the dorsal point of the shoulders, body weight, depth of the spinal needle, number of attempts to collect CSF, and cytologic evaluation of CSF were recorded.
Results—Lumbosacral puncture cranial to the cranial border of the most superficial location of both tuber sacrale along the midline was consistently successful for CSF collection (35/37 equids). Two horses had anatomic abnormalities that precluded CSF collection. Mean number of attempts to collect CSF per animal was 1.1. Height and body weight were strongly correlated with needle depth for CSF collection. Pelvic and sacral displacement was observed in several laterally recumbent animals, which resulted in discrepancies of the midline between the cranial and caudal aspects of the vertebral column. In most equids, the spinal needle was aligned on the midline of the caudal aspect of the vertebral column.
Conclusions and Clinical Relevance—Ultrasonography was a useful aid for collection of CSF from the lumbosacral space and decreased the risk of repeated trauma and contamination in equids.
Objective—To describe clinical and clinicopathologic findings and outcome of horses with meningitis and meningoencephalomyelitis.
Design—Retrospective case series.
Procedures—Medical records of horses admitted to the hospital during a 25-year period were reviewed. Horses with a definitive diagnosis of meningitis or meningoencephalomyelitis were included in this study. Information extracted from the medical records included signalment, history, reason for admission, clinical signs, results of clinicopathologic testing and diagnostic procedures, treatment, outcome, and necropsy findings.
Results—22 horses had confirmed infectious disease (19 bacterial, 2 parasitic, and 1 fungal), 4 had suspected infectious disease on the basis of CSF cytologic examination findings, and 2 had noninfectious meningitis or meningoencephalomyelitis. Trauma of the head and vertebral column with disruption of the blood-brain barrier and local ascending or hematogenous spread were the most common routes of infection. Common neurologic signs included abnormal mental status, cranial nerve deficits, vestibular dysfunction, ataxia, tetraparesis, and apparent neck pain. Common hematologic abnormalities included leukocytosis, neutrophilia, lymphopenia, and hyperfibrinogenemia. Cytologic examination of CSF samples revealed moderate to marked suppurative inflammation. Mortality rate was 96.4%. Microbial culture of CSF yielded bacterial growth in 15 of 23 horses (before death [2 horses], after death , and both ).
Conclusions and Clinical Relevance—Results suggested that meningitis and meningoencephalomyelitis are uncommon disorders in horses. Infectious disease was more common than noninfectious disease. Local trauma, ascending infection, or hematogenous spread of infection were the most common causes of meningitis or meningoencephalomyelitis. Neurologic deficits, neutrophilia, lymphopenia, hyperfibrinogenemia, and CSF with neutrophilic pleocytosis were common findings in affected horses.
Objective—To describe the clinical and laboratory findings, diagnostic features, and outcome of tracheal collapse in American Miniature Horses at a referral institution.
Design—Retrospective case series.
Animals—13 American Miniature Horses with tracheal collapse.
Procedures—Medical records of American Miniature Horses with tracheal collapse at a referral hospital were reviewed. Data extracted included signalment, history, clinical signs, laboratory data, diagnostic procedures, outcome, and histologic findings.
Results—Tracheal collapse was documented in 5.6% of American Miniature Horses admitted to this referral hospital. Median age at onset of clinical signs was 11 years with a range of 2 to 15 years. Common complaints and clinical signs included respiratory distress, tachypnea, inspiratory honking noises, and increased abdominal expiratory effort, which were exacerbated by stressful events, pregnancy, exercise, a dusty environment, and eating. Tracheal collapse was confirmed by use of radiography, endoscopy, fluoroscopy, or postmortem examination. Dorsoventral flattening of the extra- or intrathoracic trachea, or both, was more common than lateral collapse. Tracheal chondromalacia was identified histologically in 4 cases, and mortality rate for affected horses was 10 of 13.
Conclusions and Clinical Relevance—Tracheal collapse was relatively common in this study of American Miniature Horses, and outcome was poor. The etiopathogenesis of the disease remains unknown.
Objective—To assess gene expressions of cyclooxygenase-1 and -2 in oral, glandular gastric, and urinary bladder mucosae and determine the effect of oral administration of phenylbutazone on those gene expressions in horses.
Animals—12 healthy horses.
Procedures—Horses were allocated to receive phenylbutazone or placebo (6 horses/group); 1 placebo-treated horse with a cystic calculus was subsequently removed from the study, and those data were not analyzed. In each horse, the stomach and urinary bladder were evaluated for ulceration via endoscopy before and after experimental treatment. Oral, glandular gastric, and urinary bladder mucosa biopsy specimens were collected by use of a skin punch biopsy instrument (oral) or transendoscopically (stomach and bladder) before and after administration of phenylbutazone (4.4 mg/kg, PO, q 12 h) in corn syrup or placebo (corn syrup alone) for 7 days. Cyclooxygenase-1 and -2 gene expressions were determined (via quantitative PCR techniques) in specimens collected before and after the 7-day treatment period and compared within and between groups. Prior to commencement of treatment, biopsy specimens from 7 horses were used to compare gene expressions among tissues.
Results—The cyclooxygenase-1 gene was expressed in all tissues collected. The cyclooxygenase-2 gene was expressed in the glandular gastric and bladder mucosae but not in the oral mucosa. Cyclooxygenase gene expressions were unaffected by phenylbutazone administration.
Conclusions and Clinical Relevance—Cyclooxygenase-2 was constitutively expressed in glandular gastric and bladder mucosae but not in the oral mucosa of healthy horses. Oral administration of phenylbutazone at the maximum recommended dosage daily for 7 days did not affect cyclooxygenase-1 or -2 gene expression.
Case Description—A 4-month-old American Paint filly was evaluated because of sudden onset of ataxia that progressed to recumbency. Five additional horses from the same and neighboring premises developed signs of poor performance, generalized weakness, ataxia, and recumbency; 2 of those horses were also evaluated. A new batch of a commercial feed supplement had been introduced to the horses' diet on each farm within the preceding 3 days.
Clinical Findings—Other than recumbency, findings of physical and neurologic examinations of the foal were unremarkable. The other 2 horses had generalized weakness and mild ataxia, and 1 horse also had persistent tachycardia. The foal had mild leukocytosis with neutrophilia, hyperglycemia, and mildly high serum creatine kinase activity. Results of cervical radiography, CSF analysis, and assessments of heavy metals and selenium concentrations in blood and vitamin E concentration in serum were within reference limits. Feed analysis revealed high concentrations of the ionophore antimicrobial salinomycin.
Treatment and Outcome—The 5 affected horses survived, but the foal was euthanized. At necropsy, a major histopathologic finding was severe vacuolation within neurons of the dorsal root ganglia, which was compatible with ionophore toxicosis. The surviving horses developed muscle atrophy, persistent weakness, and ataxia.
Clinical Relevance—In horses, ionophore toxicosis should be considered as a differential diagnosis for acute weakness, ataxia, recumbency, or sudden death. Furthermore, ionophore toxicosis should be considered as a cause of poor performance, weakness, muscle wasting, and cardiac arrhythmias in horses. Surviving horses may have impaired athletic performance.
Objective—To determine the nucleotide sequence of
the equine intestinal fatty acid binding protein
(I-FABP) gene, its expression in various regions of the
gastrointestinal tract, and the use of measuring
I-FABP in horses with colic.
Animals—86 horses with colic.
Procedure—The mRNA sequence for the I-FABP
gene was obtained by use of a rapid amplification of
complementary DNA ends technique. Comparative
I-FABP gene expression was quantitated by use of a
real-time reverse transcription-polymerase chain reaction
assay. Amounts of I-FABP in abdominal fluid and
plasma were measured by use of an ELISA kit.
Association between I-FABP concentrations and clinical
variables was performed by nonparametric analysis,
and associations of these variables with intestinal
ischemia were determined by the Spearman correlation
Results—The nucleotide sequence had 87% identity
with human I-FABP. The I-FABP gene was highly
expressed in the small intestinal mucosa but had low
expression in the colon. High concentrations of
I-FABP in abdominal fluid correlated with an increase
in protein concentrations in peritoneal fluid and nonsurvival,
whereas plasma I-FABP concentrations correlated
with the necessity for abdominal surgery.
Clinical variables associated with intestinal ischemia
included the color and protein content of abdominal
fluid and serum creatine kinase activity.
Conclusions and Clinical Relevance—
Determination of I-FABP concentrations in abdominal
fluid and plasma may be useful for predicting survival
and the need for abdominal surgical intervention in
horses with colic. Furthermore, serum creatine kinase
activity and color and protein concentrations of
abdominal fluid may be useful in the diagnosis of
intestinal ischemia. (Am J Vet Res 2005;66:223–232)
Objective—To evaluate deafness in American Paint Horses by phenotype, clinical findings, brainstem auditory-evoked responses (BAERs), and endothelin B receptor (EDNBR) genotype.
Design—Case series and case-control studies.
Animals—14 deaf American Paint Horses, 20 suspected-deaf American Paint Horses, and 13 nondeaf American Paint Horses and Pintos.
Procedures—Horses were categorized on the basis of coat color pattern and eye color. Testing for the EDNBR gene mutation (associated with overo lethal white foal syndrome) and BAERs was performed. Additional clinical findings were obtained from medical records.
Results—All 14 deaf horses had loss of all BAER waveforms consistent with complete deafness. Most horses had the splashed white or splashed white–frame blend coat pattern. Other patterns included frame overo and tovero. All of the deaf horses had extensive head and limb white markings, although the amount of white on the neck and trunk varied widely. All horses had at least 1 partially heterochromic iris, and most had 2 blue eyes. Ninety-one percent (31/34) of deaf and suspected-deaf horses had the EDNBR gene mutation. Deaf and suspected-deaf horses were used successfully for various performance events. All nondeaf horses had unremarkable BAER results.
Conclusions and Clinical Relevance—Veterinarians should be aware of deafness among American Paint Horses, particularly those with a splashed white or frame overo coat color pattern, blend of these patterns, or tovero pattern. Horses with extensive head and limb markings and those with blue eyes appeared to be at particular risk.