Efficacy of treatment of equine anhidrosis with acupuncture and Chinese herbs is low but higher in treated horses compared with placebo.

OBJECTIVE: To assess the therapeutic efficacy of acupuncture in combination with Chinese herbs for treatment of horses affected with anhidrosis. ANIMALS: 44 horses affected with anhidrosis for up to 3 years' duration were enrolled. Inclusion required both compatible clinical signs and results of a quantitative intradermal terbutaline sweat test. METHODS: Study horses were randomly allocated into 2 groups. Group 1 (n = 19) was treated with daily Chinese herbs and 4 weekly acupuncture sessions. Group 2 (n = 25) was given daily hay powder as a placebo and 4 weekly sham acupuncture sessions. Horses were tested by quantitative intradermal terbutaline sweat test within 2 days after treatment completion and again 4 weeks following treatment. RESULTS: Terbutaline-induced sweat responses (mg) were not different between groups within 2 days and 4 weeks after treatment. Two days after treatment, ratios of sweat responses (compared to baseline) were higher (P < .05) in the treatment group compared to the placebo group at terbutaline concentrations of 1.0, 100, and 1,000 µg/mL. The number of horses responding to treatment was higher in the treatment group (5/19 [26%]), compared to horses in the placebo group (1/25 [4%]) for 1 of 5 terbutaline concentrations 2 days (10 µg/mL) or 4 weeks (0.1 µg/mL) after treatment. CLINICAL RELEVANCE: Ratios of sweat responses were higher in treatment horses 2 days after treatment, compared to baseline, but not 4 weeks later. The efficacy of a traditional Chinese veterinary medicine protocol for anhidrosis treatment with acupuncture and Chinese herbs was low but higher in treated horses compared with placebo.

Equine Protozoal Myeloencephalitis.

Advances in the understanding of equine protozoal myeloencephalitis (EPM) are reviewed. It is now apparent that EPM can be caused by either of 2 related protozoan parasites, Sarcocystis neurona and Neospora hughesi, although S neurona is the most common etiologic pathogen. Horses are commonly infected, but clinical disease occurs only infrequently; the factors influencing disease occurrence are not well understood. Epidemiologic studies have identified risk factors for the development of EPM, including the presence of opossums and prior stressful health-related events. Attempts to reproduce EPM experimentally have reliably induced antibody responses in challenged horses, but have not consistently produced neurologic disease. Diagnosis of EPM has improved by detecting intrathecal antibody production against the parasite. Sulfadiazine/pyrimethamine (ReBalance) and the triazine compounds diclazuril (Protazil) and ponazuril (Marquis) are effective anticoccidial drugs that are now available as FDA-approved treatments for EPM.

Magnetic resonance imaging of the normal equine pituitary gland.

Magnetic resonance imaging is increasingly available for evaluation of horses with suspected pituitary adenomas; however, published studies describing the MRI features of normal equine pituitary glands are currently lacking. This retrospective, descriptive, anatomic study describes the MRI appearance and size of presumed normal equine pituitary glands and assesses potential correlations between pituitary size, brain size, and patient weight. These findings serve as a reference for MRI evaluation of the equine pituitary gland. Inclusion criteria consisted of adult horses (2-15 years old), over 300 kg with no evidence of Pituitary pars intermedia dysfunction (PPID) and no pituitary abnormalities identified with MRI, yielding 27 horses. Histology was available on seven pituitary glands; all were considered normal by a board-certified anatomic pathologist. Imaging features of the glands were evaluated on T2-weighted and pre- and postcontrast T1-weighted images. Pituitary length, width, and height and brain height and width were measured by two authors on transverse and mid-sagittal plane postcontrast T1 weighted images. The mean ± SD pituitary gland width was 21.0 ± 2.4 mm, height: 10.4 ± 1.9 mm, and length: 24.5 ± 2.7 mm. There were no significant correlations using a Pearson's correlation coefficient between pituitary and brain measurements, pituitary measurement, and body weight, or between brain measurements and body weight. A statistical difference was not identified using an unpaired t-test (p > 0.05) in pituitary and brain measurements between necropsied and non-necropsied horses. Relative to the cerebral white matter, all pituitary glands were isointense to slightly hyperintense on T1-weighted images and isointense on T2-weighted images, with the exception of a focal T1-weighted hyperintensity that was present in the caudal aspect of the pituitary gland in 88% of horses. All pituitary glands were homogenously contrast enhancing. Pituitary dimensions did not correlate with either brain size or body weight in horses.

Plasma l-indospicine and 3-nitropropionic acid in ponies fed creeping indigo: Comparison with results from an episode of presumptive creeping indigo toxicosis.

BACKGROUND: Creeping indigo (Indigofera spicata) toxicosis is an emerging problem among horses in Florida and bordering states. OBJECTIVES: To quantify the putative toxins l-indospicine (IND) and 3-nitropropionic acid (NPA) in creeping indigo collected from multiple sites and to measure plasma toxin concentrations in ponies fed creeping indigo and horses with presumptive creeping indigo toxicosis. STUDY DESIGN: Experimental descriptive study with descriptive observational field investigation. METHODS: Air-dried creeping indigo was assayed for IND and NPA content. Five ponies were fed chopped creeping indigo containing 1 mg/kg/day of IND and trace amounts of NPA for 5 days, then observed for 28 days. Blood samples from these ponies and from horses involved in a presumptive creeping indigo toxicosis were assayed for IND and NPA. RESULTS: IND in creeping indigo plants was 0.4-3.5 mg/g dry matter whereas NPA was <0.01 to 0.03 mg/g. During creeping indigo feeding, clinical and laboratory signs were unchanged except for significant weight loss (median 6%, range 2%-9%; p = .04) and significant increase from baseline plasma protein concentration (median 16 g/L, range 8-25 g/L; p < .001). These changes could not definitively be ascribed to creeping indigo ingestion. Plasma IND rose to 3.9 ± 0.52 mg/L on day 6. Pharmacokinetic modelling indicated an elimination half-life of 25 days and a steady state plasma concentration of 22 mg/L. Plasma IND concentration in sick horses during an incident of creeping indigo toxicosis was approximately twice that of clinically normal pasture mates. Plasma NPA was <0.05 mg/L in all samples. MAIN LIMITATIONS: Creeping indigo used in the feeding trial may not be representative of plants involved in creeping indigo toxicosis. There was no control group without creeping indigo in the feeding trial. CONCLUSIONS: Indospicine can be detected in blood of horses consuming creeping indigo and the toxin accumulates in tissues and clears slowly. The role of NPA in the neurological signs of this syndrome is unclear.

Ion Channel and Ubiquitin Differential Expression during Erythromycin-Induced Anhidrosis in Foals.

Macrolide drugs are the treatment of choice for Rhodococcus equi infections, despite severe side-effects temporary anhidrosis as a. To better understand the molecular biology leading to macrolide induced anhidrosis, we performed skin biopsies and Quantitative Intradermal Terbutaline Sweat Tests (QITSTs) in six healthy pony-cross foals for three different timepoints during erythromycin administration-pre-treatment (baseline), during anhidrosis and post-recovery. RNA sequencing of biopsies followed by differential gene expression analysis compared both pre and post normal sweating timepoints to the erythromycin induced anhidrosis episode. After Bonferroni correction for multiple testing, 132 gene transcripts were significantly differentially expressed during the anhidrotic timepoint. Gene ontology analysis of the full differentially expressed gene set identified over-represented biological functions for ubiquitination and ion-channel function, both biologically relevant to sweat production. These same mechanisms were previously implicated in heritable equine idiopathic anhidrosis and sweat gland function and their involvement in macrolide-induced temporary anhidrosis warrants further investigation.

Horses affected by EPM have increased sCD14 compared to healthy horses.

Equine protozoal myeloencephalitis (EPM) is a debilitating neurologic disease affecting horses across the Americas. Gaps in understanding the inflammatory immune response in EPM-affected horses create difficulties with diagnosis and treatment, subsequently negatively impacting the prognosis of affected horses. The purpose of the current study was to evaluate circulating levels of the inflammatory immune marker soluble CD14 (sCD14), in horses with EPM (n = 7) and determine if they differed from healthy neurologically normal horses (n = 6). Paired sera and cerebrospinal fluid (CSF) samples were analyzed for sCD14. Inclusion criteria for EPM horses consisted of the presence of neurologic signs consistent with EPM, Sarcocystis neurona surface antigens 2, 4/3 (SnSAG 2, 4/3) ELISA serum: CSF antibody ratio ≤ 100, and a postmortem diagnosis of EPM. Control horses were neurologically normal, healthy horses with SnSAG 2, 4/3 ELISA serum: CSF antibody ratios of > 100. Serum anti-Sarcocystis neurona antibodies indicate that healthy control horses were exposed to S. neurona but resistant to developing clinical EPM. EPM cases had significantly greater concentrations of sCD14 in CSF samples compared to control horses and increased serum sCD14 concentrations. A positive correlation between sCD14 serum and CSF concentrations was observed in EPM-affected horses but not healthy horses. Soluble CD14 is an inflammatory marker, and the study results suggest it is elevated in EPM patients. When performed in conjunction with clinical evaluation and standard antibody testing, there may be potential for sCD14 to be utilized as a correlate for EPM.

Genomic Association of Chronic Idiopathic Anhidrosis to a Potassium Channel Subunit in a Large Animal Model.

Similar to humans, the horse relies predominantly on the evaporation of sweat from the skin surface to dissipate excess body heat. Loss of the sweat response or anhidrosis can result in life-threatening hyperthermia. Anhidrosis occurs more frequently in some breeds as well as occurs at an increased frequency among individuals with a family history, suggesting a heritable component to the pathology. Given the natural occurrence and indications of genetic components in the etiology, we utilized genomics to better understand the molecular mechanisms involved in sweat response. We performed a case-control (n = 200) GWAS targeting cases of chronic idiopathic anhidrosis in a controlled genetic background to discover the contributing regions and interrogated gene function for roles in the sweating mechanism. A region containing the KCNE4 gene, which encodes the ß-subunit of a potassium channel protein with a possible function in sweat gland outflow, was associated (P = 1.13 × 10-07) with chronic idiopathic anhidrosis through GWAS. A candidate mutation (NC_009149.3:g.11813731A > G, rs68643109) disrupting the KCNE4 protein structure could explain the disease but requires further investigation in larger populations. We show the potential role of ion channels and cellular damage in sweat response, correlating anhidrosis as a possible effect of congenital channelopathy.

Acid-base disorders in sick goats and their association with mortality: A simplified strong ion difference approach.

OBJECTIVES: To investigate the acid-base status of sick goats using the simplified strong ion difference (sSID) approach, to establish the quantitative contribution of sSID variables to changes in blood pH and HCO3 - and to determine whether clinical, acid-base, and biochemical variables on admission are associated with the mortality of sick goats. ANIMALS: One hundred forty-three sick goats. METHODS: Retrospective study. Calculated sSID variables included SID using 6 electrolytes unmeasured strong ions (USI) and the total nonvolatile buffer ion concentration in plasma (Atot ). The relationship between measured blood pH and HCO3 - , and the sSID variables was examined using forward stepwise linear regression. Cox proportional hazard models were constructed to assess associations between potential predictor variables and mortality of goats during hospitalization. RESULTS: Hypocapnia, hypokalemia, hyperchloremia, hyperlactatemia, and hyperproteinemia were common abnormalities identified in sick goats. Respiratory alkalosis, strong ion acidosis, and Atot acidosis were acid-base disorders frequently encountered in sick goats. In sick goats, the sSID variables explained 97% and 100% of the changes in blood pH and HCO3 - , respectively. The results indicated that changes in the respiratory rate (<16 respirations per minute), USI, and pH at admission were associated with increased hazard of hospital mortality in sick goats. CONCLUSIONS AND CLINICAL IMPORTANCE: The sSID approach is a useful methodology to quantify acid-base disorders in goats and to determine the mechanisms of their development. Clinicians should consider calculation of USI in sick goats as part of the battery of information required to establish prognosis.

Agreement of 2 electrolyte analyzers for identifying electrolyte and acid-base disorders in sick horses.

BACKGROUND: Use of different analyzers to measure electrolytes in the same horse can lead to different interpretation of acid-base balance when using the simplified strong ion difference (sSID) approach. OBJECTIVE: Investigate the level of agreement between 2 analyzers in determining electrolytes concentrations, sSID variables, and acid-base disorders in sick horses. ANIMALS: One hundred twenty-four hospitalized horses. METHODS: Retrospective study using paired samples. Electrolytes were measured using a Beckman Coulter AU480 Chemistry analyzer (PBMA) and a Nova Biomedical Stat Profile (WBGA), respectively. Calculated sSID variables included strong ion difference, SID4 ; unmeasured strong ions, USI; and total nonvolatile buffer ion concentration in plasma (Atot ). Agreement between analyzers was explored using Passing-Bablok regression and Bland-Altman analysis. Kappa (κ) test evaluated the level of agreement between analyzers in detecting acid-base disorders. RESULTS: Methodologic differences were identified in measured Na+ and Cl- and calculated values of SID4 and USI. Mean bias (95% limits of agreement) for Na+ , Cl- , SID4 , and USI were: -1.2 mmol/L (-9.2 to 6.8), 4.4 mmol/L (-4.4 to 13), -5.4 mmol/L (-13 to 2), and -6.2 mmol/L (-14 to 1.7), respectively. The intraclass correlation coefficient for SID4 and USI was .55 (95%CI: -0.2 to 0.8) and .2 (95%CI: -0.15 to 0.48), respectively. There was a poor agreement between analyzers for detection of SID4 (κ = 0.20, 95%CI, 0.1 to 0.31) or USI abnormalities (κ = -0.04, 95%CI, -0.11 to 0.02). CONCLUSIONS AND CLINICAL IMPORTANCE: Differences between analyzer methodology in measuring electrolytes led to a poor agreement between the diagnosis of acid-base disorders in sick horses when using the sSID approach.

Treatment Options for Melanoma of Gray Horses.

All gray horses inherited a single gene mutation, STX17G, that unbalances melanocyte behavior to cause graying and propensities to develop vitiligo and melanoma. The coat color genes ASIPa and MC1RE add risk such that relative likelihood of melanoma based on pregraying coat color is black > bay > chestnut. Melanomas begin at about 4 years. Locoregional control of melanoma masses depends on surgical removal and/or intralesional chemotherapy (possibly with adjunctive hyperthermia or electroporation). Systemic treatment is not evidence based but immunomodulators (cimetidine, levamisole) and vaccines can be tried.

Equine protozoal myeloencephalitis.

Equine protozoal myeloencephalitis (EPM) can be caused by either of 2 related protozoan parasites, Sarcocystis neurona and Neospora hughesi, although S. neurona is the most frequent etiologic pathogen. Horses are commonly infected, but clinical disease occurs infrequently; the factors influencing disease occurrence are not well understood. Risk factors for the development of EPM include the presence of opossums and prior stressful health-related events. Attempts to reproduce EPM experimentally have reliably induced antibody responses in challenged horses but have not consistently produced acute neurologic disease. Diagnosis and options for treatment of EPM have improved over the past decade.

Systemic and anti-nociceptive effects of prolonged lidocaine, ketamine, and butorphanol infusions alone and in combination in healthy horses.

BACKGROUND: Prolonged drug infusions are used to treat horses with severe signs of pain, but can be associated with altered gastrointestinal transit. The purpose of this study was to determine the effects of prolonged constant rate infusions (CRI) of lidocaine (L), butorphanol (B), and ketamine (K) alone and in combination on gastrointestinal transit, behavior, and thermal nociceptive threshold in healthy horses. METHODS: Eight healthy adult horses were used in a randomized, cross-over, blinded, prospective experimental trial. Interventions were saline, L, K, B, LK, LB, BK, and LBK as an intravenous CRI for 96 hours. Drugs were mixed or diluted in saline; following a bolus, CRI rate was 0.15 mL/kg/hr with drug doses as follows: L - 1.3 mg/kg then 3 mg/kg/hr; B - 0.018 mg/kg then 0.013 mg/kg/hr; K - 0.55 mg/kg then 0.5 mg/kg/hr. Two-hundred plastic beads were administered intragastrically by nasogastric tube immediately prior to the bolus. Feces were collected every 2 hours, weighed, and beads manually retrieved. Behavior was scored every 2 hours, vital parameters every 6 hours, and thermal nociceptive threshold every 12 hours for 96 hours. Drug concentrations in the LBK solution were tested every 6 hours for 72 hours. RESULTS: Four of 64 trials (3 LBK, 1 BK) were discontinued early due to signs of abdominal discomfort. There were no apparent differences between groups in vital parameters or thermal threshold. Transit time was delayed for LB and LBK with a corresponding decrease in fecal weight that was most severe in the final 24 hours of infusion. Significant changes in behavior scores, vital parameters, or thermal threshold were not observed. The concentration of each drug in the combined solution declined by less than 31% over the sampling period. CONCLUSIONS: Drug combinations containing butorphanol cause an apparent delay in gastrointestinal transit in healthy horses without substantially affecting somatic nociception at the doses studied. Combinations of lidocaine and ketamine may have less impact on gastrointestinal transit than infusions combined with butorphanol. Further work is needed to determine the effects of these drugs in painful or critically ill patients.

Removal of ureteral calculi in two geldings via a standing flank approach.

CASE DESCRIPTION: Two geldings, aged 11 and 17 years, were examined for treatment of ureteroliths located approximately 10 cm proximal to the bladder. CLINICAL FINDINGS: Ureteral obstruction was an incidental finding in 1 horse that was referred because of urinary tract obstruction and a cystic calculus. This horse did not have clinical or laboratory evidence of renal failure, although severe hydronephrosis was evident on transabdominal ultrasonography. The second patient had a serum creatinine concentration of 6.3 mg/dL (reference range, 0.8 to 2.2 mg/dL) and mild hydronephrosis of the affected left kidney. TREATMENT AND OUTCOME: In both patients, the obstructed ureter was exteriorized through a flank incision as a standing procedure, and the calculus was crushed and removed with a uterine biopsy forceps introduced through a ureterotomy approximately 25 cm proximal to the calculus. The cystic calculus was removed through a perineal urethrostomy by lithotripsy, piecemeal extraction, and lavage. The horse without azotemia developed pyelonephritis in the affected kidney and was euthanatized because of complications of a nephrectomy 13 months later. In the horse with azotemia, the serum creatinine concentration decreased after surgery, and the horse returned to its intended use. However, it was euthanatized approximately 2 years after surgery because of progressive renal failure, and a large nephrolith was found in the previously unobstructed right kidney. CLINICAL RELEVANCE: The technique used for ureterolith removal was successful in both horses in this report, did not require sophisticated equipment, and could be effective in the early stages of ureteral obstruction as a means of restoring urine flow and renal function. The outcome in the horse with advanced unilateral renal disease without azotemia would suggest that nephrectomy should be considered as a treatment in such patients.

An epidemiologic study of anhidrosis in horses in Florida.

OBJECTIVE-To estimate prevalence of and identify factors associated with anhidrosis in horses in Florida. Design-Cross-sectional study and case-control study. ANIMALS-4,620 horses on 500 farms. PROCEDURES-A questionnaire was structured and mailed to farm owners or managers to obtain information related to diagnosis of anhidrosis in horses and exposure factors associated with this condition. The frequency of investigated farm- and animal-level factors was compared between farms and horses affected and not affected with anhidrosis, respectively. RESULTS-The prevalence of anhidrosis was 11% at the farm level and 2% at the animal level. The odds of anhidrosis were 2.13 and 4.40 times as high in farms located in central and southern Florida, respectively, compared with odds for farms in northern Florida. The odds of anhidrosis were 5.26 and 15.40 times as high in show and riding instruction operations, respectively, compared with odds for ranch operations. At the animal level, breed (Thoroughbreds and warmblood horses), foaling place (western or midwestern region of the United States), and family history of anhidrosis were significantly associated with anhidrosis. CONCLUSIONS AND CLINICAL RELEVANCE-This study provides new information on the prevalence of and factors for anhidrosis in horses in Florida. Horses with a family history of anhidrosis should be examined by a veterinarian for diagnosis of this condition before they are exposed to exercise in a hot and humid climate.

Epidemiologic analysis of nosocomial Salmonella infections in hospitalized horses.

OBJECTIVE: To examine the relationship between abdominal surgery and nosocomial Salmonella infections and the relationship between high caseload in combination with abdominal surgery and nosocomial Salmonella infections in hospitalized horses with signs of gastrointestinal tract disease. ANIMALS: 140 horses. DESIGN: Case-control study. PROCEDURES: To accomplish the first objective, 1 to 4 control horses were matched with each nosocomial case horse on the basis of admission date of a primary case horse. The frequency of abdominal surgery and other investigated exposure factors were compared between nosocomial case horses and control horses. For the second objective, 4 control horses were matched with each nosocomial case horse on the basis of year of admission. The frequency of high caseload (>or=26 inpatients), abdominal surgery, and other factors was compared between nosocomial case horses and control horses. RESULTS: The odds of nosocomial Salmonella infection were 8 times as high (odds ratio=8.2; 95% confidence interval=1.11, 60.24) in horses that underwent abdominal surgery, compared with the odds for horses that did not undergo surgery. High caseload alone or in combination with abdominal surgery was not associated with increased risk of nosocomial Salmonella infection. CONCLUSIONS AND CLINICAL RELEVANCE: Abdominal surgery was identified as a risk factor for nosocomial Salmonella infections in horses. Horses that undergo abdominal surgery require enhanced infection control and preventative care. Risk of nosocomial Salmonella infections may be reduced by implementation of biosecurity measures (such as the use of plastic boots, gloves, and footbaths) immediately after surgery.

Effect of intermittent oral administration of ponazuril on experimental Sarcocystis neurona infection of horses.

OBJECTIVE: To evaluate the effect of intermittent oral administration of ponazuril on immunoconversion against Sarcocystis neurona in horses inoculated intragastrically with S neurona sporocysts. ANIMALS: 20 healthy horses that were seronegative for S neurona-specific IgG. PROCEDURES: 5 control horses were neither inoculated with sporocysts nor treated. Other horses (5 horses/group) each received 612,500 S neurona sporocysts via nasogastric tube (day 0) and were not treated or were administered ponazuril (20 mg/kg, PO) every 7 days (beginning on day 5) or every 14 days (beginning on day 12) for 12 weeks. Blood and CSF samples were collected on day - 1 and then every 14 days after challenge for western blot assessment of immunoconversion. Clinical signs of equine protozoal myeloencephalitis (EPM) were monitored, and tissues were examined histologically after euthanasia. RESULTS: Sera from all challenged horses yielded positive western blot results within 56 days. Immunoconversion in CSF was detected in only 2 of 5 horses that were treated weekly; all other challenged horses immunoconverted within 84 days. Weekly administration of ponazuril significantly reduced the antibody response against the S neurona 17-kd antigen in CSF. Neurologic signs consistent with EPM did not develop in any group; likewise, histologic examination of CNS tissue did not reveal protozoa or consistent degenerative or inflammatory changes. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of ponazuril every 7 days, but not every 14 days, significantly decreased intrathecal anti-S neurona antibody responses in horses inoculated with S neurona sporocysts. Protocols involving intermittent administration of ponazuril may have application in prevention of EPM.