A retrospective analysis of renal carcinoma in the horse.

BACKGROUND: Renal carcinoma is a rare tumor of horses. HYPOTHESIS: Presenting complaints and clinical signs of this disease are vague and early diagnosis increases survival time. ANIMALS: Data were collected from the medical records of 4 horses presented to Washington State University as well as the 23 previously published case reports of horses with renal carcinoma. METHODS: Retrospective study. RESULTS: Renal carcinoma affects horses of all ages with most cases observed in geldings and Thoroughbreds. The most common presenting complaints are nonspecific and usually do not occur until late in the course of the disease. Routine laboratory results generally are unremarkable with no evidence of renal dysfunction. Urine and peritoneal fluid analyses are consistently abnormal, but the changes usually are nonspecific. Rectal palpation often allows detection of an abnormal kidney or a mass in the area of the kidney. Renal ultrasound examination is the most rewarding imaging procedure, and when combined with renal biopsy, antemortem diagnosis can be achieved. Renal carcinoma is both locally invasive and metastatic, necessitating careful staging for metastasis using thoracic radiography and abdominal ultrasound examination. If the tumor is localized to 1 kidney, nephrectomy is the treatment of choice. No chemotherapy or radiation treatment for renal carcinoma has been reported in the horse. Median survival for this series of cases was 11 days (0 days-1 year). CONCLUSIONS AND CLINICAL IMPORTANCE: Prognosis is poor to grave.

Pharmacokinetics of butorphanol and evaluation of physiologic and behavioral effects after intravenous and intramuscular administration to neonatal foals.

BACKGROUND: Despite frequent clinical use, information about the pharmacokinetics (PK), clinical effects, and safety of butorphanol in foals is not available. OBJECTIVES: The purpose of this study was to determine the PK of butorphanol in neonatal foals after IV and IM administration; to determine whether administration of butorphanol results in physiologic or behavioral changes in neonatal foals; and to describe adverse effects associated with its use in neonatal foals. ANIMALS: Six healthy mixed breed pony foals between 3 and 12 days of age were used. METHODS: In a 3-way crossover design, foals received butorphanol (IV and IM, at 0.05 mg/kg) and IV saline (control group). Butorphanol concentrations were determined by high-performance liquid chromatography and analyzed using a noncompartmental PK model. Physiologic data were obtained at specified intervals after drug administration. Pedometers were used to evaluate locomotor activity. Behavioral data were obtained using a 2-hour real-time video recording. RESULTS: The terminal half-life of butorphanol was 2.1 hours and C0 was 33.2 +/- 12.1 ng/mL after IV injection. For IM injection, Cmax and Tmax were 20.1 +/- 3.5 ng/mL and 5.9 +/- 2.1 minutes, respectively. Bioavailability was 66.1 +/- 11.9%. There were minimal effects on vital signs. Foals that received butorphanol spent significantly more time nursing than control foals and appeared sedated. CONCLUSIONS AND CLINICAL IMPORTANCE: The disposition of butorphanol in neonatal foals differs from that in adult horses. The main behavioral effects after butorphanol administration to neonatal foals were sedation and increased feeding behavior.

Streptococcus equi Infections in Horses: Guidelines for Treatment, Control, and Prevention of Strangles-Revised Consensus Statement.

This consensus statement update reflects our current published knowledge and opinion about clinical signs, pathogenesis, epidemiology, treatment, complications, and control of strangles. This updated statement emphasizes varying presentations in the context of existing underlying immunity and carrier states of strangles in the transmission of disease. The statement redefines the "gold standard" for detection of possible infection and reviews the new technologies available in polymerase chain reaction diagnosis and serology and their use in outbreak control and prevention. We reiterate the importance of judicious use of antibiotics in horses with strangles. This updated consensus statement reviews current vaccine technology and the importance of linking vaccination with currently advocated disease control and prevention programs to facilitate the eradication of endemic infections while safely maintaining herd immunity. Differentiation between immune responses to primary and repeated exposure of subclinically infected animals and responses induced by vaccination is also addressed.

Parasitemia in an immunocompetent horse experimentally challenged with Sarcocystis neurona sporocysts.

Equine protozoal myeloencephalitis (EPM) is a serious neurological disease of horses in Americans. Most cases are attributed to infection of the central nervous system with Sarcocystis neurona. Parasitemia has not been demonstrated in immunocompetent horses, but has been documented in one immunocompromised foal. The objective of this study was to isolate viable S. neurona from the blood of immunocompetent horses. Horses used in this study received orally administered S. neurona sporocysts (strain SN 37-R) daily for 112 days at the following doses: 100/day for 28 days, followed by 500/day for 28 days, followed by 1000/day for 56 days. On day 98 of the study, six yearling colts were selected for attempted culture of S. neurona from blood, two testing positive, two testing suspect and two testing negative for antibodies against S. neurona on day 84 of the study. Two 10 ml tubes with EDTA were filled from each horse by jugular venipuncture and the plasma fraction rich in mononuclear cells was pipetted onto confluent equine dermal cell cultures. The cultures were monitored weekly for parasite growth for 12 weeks. Merozoites grown from cultures were harvested and tested using S. neurona-specific PCR with RFLP to confirm species identity. PCR products were sequenced and compared to known strains of S. neurona. After 38 days of in vitro incubation, one cell culture from a horse testing positive for antibodies against S. neurona was positive for parasite growth while the five remaining cultures remained negative for parasite growth for all 12 weeks. The Sarcocystis isolate recovered from cell culture was confirmed to be S. neurona by PCR with RFLP. Gene sequence analysis revealed that the isolate was identical to the challenge strain SN-37R and differed from two known strains UCD1 and MIH1. To our knowledge this is the first report of parasitemia with S. neurona in an immunocompetent horse.

Monoclonal antibodies to the equine CD2 T lymphocyte marker, to a pan-granulocyte/monocyte marker and to a unique pan-B lymphocyte marker.

Murine monoclonal antibodies, HB88A, B29A and DH59B separately identify the CD2 T lymphocyte molecule, a unique pan-B lymphocyte surface marker and a pan-granulocyte/monocyte surface molecule, respectively, in the horse. Specificity was shown by two-color immunofluorescent flow cytometry and immunofluorescent microscopy. MAb HB88A reacted with a 52 kDa pan-T lymphocyte molecule present on 75% +/- 7 of peripheral blood lymphocytes (PBL) (n = 15 horses). It also reacted with lymphocytes restricted to T lymphocyte dependent areas of lymph node and spleen. Specificity of mAb HB88A to CD2 was demonstrated by its reactivity to COS7 cells which expressed a transfected 1.5 kb equine lymphocyte c-DNA clone having 77.5% overall sequence homology with human CD2 c-DNA. MAb B29A reacted with a pan-B lymphocyte specific cell surface complex, 143, 72, 50, 40, 27 and 14.5 kDa, present on 19% +/- 7 of PBL (n = 15 horses). This complex has not been described in the horse or other species. MAb DH59B reacted with a 96 kDa pan-granulocyte/monocyte specific surface protein and identified macrophages and Kupffer cells in equine tissue sections. Together these mAbs can be used to identify and quantitate the major constituents of equine leukocytes.

Quantitative characterization of lymphocyte populations in bronchoalveolar lavage fluid and peripheral blood of normal adult Arabian horses.

Bronchoalveolar lavage fluid (BALF) and peripheral blood were obtained from each of 17 adult Arabian mares and absolute numbers and relative lymphocyte proportions were determined for total T lymphocytes, using CD2 as a marker, CD4 + T lymphocytes, CD8 + T lymphocytes, CD5 + lymphocytes, and sIgM + B lymphocytes. The marked variation in BALF cell recovery resulted in wide variation in absolute values for each lymphocyte subset. The relative proportions of gated BALF lymphocytes were much less variable and provided a basis for comparison of lymphocyte subsets between the BALF and peripheral blood in normal horses. The total lymphocyte population was comprised predominantly of T cells in both BALF (83 +/- 11% CD2 + lymphocytes) and peripheral blood (70 +/- 8% CD2 + lymphocytes). There was a significantly greater percentage of total T lymphocytes and a significantly lower percentage of B lymphocytes in BALF as compared with peripheral blood collected at the same time. The increase in total T lymphocytes in BALF reflected a significantly higher percentage of CD8 + T lymphocytes in BALF (39 +/- 7%) as compared with peripheral blood (18 +/- 5%). The mean percentages of CD4 + T lymphocytes (58 +/- 13% in BALF; 62 +/- 8% in peripheral blood) and CD5 + lymphocytes (78 +/- 11% in BALF; 71 +/- 7% in peripheral blood), a population composed primarily of T lymphocytes but also including a subset of sIgM + B lymphocytes, were not significantly different between the two compartments. These normal values in Arabian mares provide a basis for detection of disease associated changes in the lymphocyte populations and for determination of effects of age and breed on lymphocyte subpopulations in the BALF and peripheral blood.

Immunity to Rhodococcus equi: antigen-specific recall responses in the lungs of adult horses.

Rhodococcal pneumonia is an important disease of young horses that is not seen in immunocompetent adults. Since all foals are normally exposed to Rhodococcus equi in their environment, we hypothesized that most develop protective immune responses. Furthermore, these antigen-specific responses were hypothesized to operate throughout adult life to prevent rhodococcal pneumonia. A better understanding of the mechanisms of immune clearance in adult horses would help define the requirements for an effective vaccine in foals. Adult horses were challenged with virulent R. equi by intrabronchial inoculation into the right lung, and pulmonary immune responses were followed for 2 weeks by bronchoalveolar lavage. Local responses in the inoculated right lung were compared to the uninfected left lung and peripheral blood. Challenged horses rapidly cleared R. equi infection without significant clinical signs. Clearance of bacteria was associated with increased mononuclear cells in bronchoalveolar lavage fluid (primarily lymphocytes) and inversion of the normal macrophage:lymphocyte ratio. There was no significant increase in neutrophils at 7 days post-challenge. Flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that clearance correlated with significant increases in pulmonary T-lymphocytes, both CD4+ and CD8+. Prior to challenge, most adult horses demonstrated low proliferative responses when pulmonary lymphocytes were stimulated with soluble R. equi ex vivo. However, clearance was associated with marked increases in lymphoproliferative responses to soluble R. equi antigen and recombinant VapA, a virulence associated protein of R. equi and candidate immunogen. These results are compatible with previous work in mice which showed that both CD4+ and CD8+ T-cells play a role in immune clearance of R. equi. Recognition of VapA in association with clearance lends further support to its testing as an immunogen. Importantly, the cellular responses to R. equi challenge were relatively compartmentalized. Responses were more marked and the sensitivity to antigen dose was increased at the site of challenge. The blood, including peripheral blood mononuclear cells, was an insensitive indicator of local pulmonary responses.

Studies on equine recurrent uveitis. I: Levels of immunoglobulin and albumin in the aqueous humor of horses with and without intraocular disease.

A radioimmunoassay was developed for detection of immunoglobulin in the aqueous of normal horses and horses with intraocular diseases. Levels of albumin were detected by radial immunodiffusion. Results of assays on samples from normal eyes from which aqueous was obtained by paracentesis under anesthesia were 32.10 +/- 21.50 microgram/ml for IgG, 0.05 +/- 0.01 microgram/ml for IgM, 0.04 +/- 0.02 microgram/ml for IgA and 34.0 +/- 38.0 microgram/ml for albumin. Results in 138 normal eyes sampled post mortem were 41.56 +/- 38.65 microgram/ml for IgG, 0.18 +/- 0.43 microgram/ml for IgM, 0.46 +/- 1.45 microgram/ml for IgE and 184 +/- 240 microgram/ml for albumin. Levels in abnormal eyes were some 50-120% greater, and very high levels were noted in cases of clinically documented uveitis. The aqueous to serum ratio of the proteins measured generally varied in relation to the molecular weights and was increased in diseased eyes. The ratio of IgG/albumin in the diseased eyes was less which suggested leakage of protein from an impaired blood/aqueous barrier rather than intraocular antibody synthesis.

Studies on equine recurrent uveitis. II: The role of infection with Leptospira interrogans serovar pomona.

An enzyme linked immunosorbent assay was developed for the detection of immunoglobulin class specific antibodies to Leptospira interrogans serovar pomona in the serum and aqueous humor of horses. Serum antibody was also assayed by microscopic agglutination tests. Although higher levels of antibody were found in sera from horses with signs of uveitis, the association was not statistically significant. Antibodies to pomona were detected in the aqueous of 12 eyes from the 101 horses sampled at a slaughterhouse, and in most instances, a comparison of the aqueous/serum antibody level with that of the total aqueous/serum IgG level indicated intraocular antibody synthesis. Antibodies were also found in 4 aqueous (or vitreous) samples out of 9 obtained from horses with clinically documented uveitis and the above comparison again indicated intraocular antibody synthesis. The data point to an important role for pomona as an etiology of equine recurrent uveitis but also emphasize that the initiating cause for this disease is often obscure in that association with leptospirosis cannot be shown in many instances.

Effects of inhalation of albuterol sulphate, ipratroprium bromide and frusemide on breathing mechanics and gas exchange in healthy exercising horses.

The possibility that pre-exercise inhalation of a bronchodilator by healthy horses could improve their mechanics of breathing and enhance performance was investigated. Ipratropium bromide (0.35 microg/kg bwt; n = 7) was administered by nebulisation 30 min before exercise and frusemide (1 mg/kg bwt; n = 6) was given in the same manner 2 h before exercise. Albuterol sulphate (360 and 720 microg; n = 7) were administered with a metered dose inhaler 2 h before exercise. Each drug was investigated independently of the others using cross-over protocols. Horses completed incremental exercise tests and oxygen consumption, carbon dioxide production, arterial blood gases, heart rate and measures of breathing mechanics including total pulmonary resistance (RL) and nasopharyngeal resistance (RU) were determined for each exercise intensity. The resistance of the lower airways was calculated subsequently from the difference between RL and RU. None of the drugs tested had an effect on any of the variables measured, possibly because maximal bronchodilation is stimulated in healthy horses by the normal sympathoadrenergic response to exercise. Therefore, the pre-exercise inhalation of a bronchodilator by a healthy horse is unlikely to improve performance capacity.

Exercise and immunity: a review with emphasis on the horse.

Exercise has been recognized as a stress, which can significantly alter the host's immune response and, therefore, its susceptibility to disease. Whereas research in this area has previously focused primarily on human subjects and laboratory animals, it has more recently extended to domestic animals, especially the equine athlete. Despite several studies, defining the relationship among exercise, the immune response, and disease has proven difficult due to a number of factors, including the complexity of the immune system and the variable nature of exercise itself. It now appears that exercise has dual effects on the immune system. Suppressive effects, such as a decline in the ratio of CD4+ to CD8+ cells, diminished lymphocyte function, and a decline in the number and cytolytic activity of natural killer cells have been observed in response to brief high-intensity exercise, prolonged exhaustive exercise, and overtraining. In contrast, moderate training generally has beneficial effects on host defense mechanisms. The mechanisms for regulating the dual effects of exercise are complex, involving a network of neuroendocrine hormones and cytokines.

Disseminated hemangiosarcoma in the horse: 35 cases.

Thirty-five cases of disseminated hemangiosarcoma (21 clinical cases and 14 previously reported cases) were reviewed to describe the disease in horses. Hemangiosarcoma occurred in mature, particularly middle-aged horses, with no apparent sex predilection. Thoroughbreds seemed to be overrepresented (13 cases) but a true breed predilection could not be established. The respiratory and musculoskeletal systems were most commonly affected and presenting complaints included dyspnea (26%), subcutaneous or muscular swelling (24%), epistaxis (17%), and lameness (12%). Heart and respiratory rates were usually increased and mucous membrane color was frequently pale or icteric. Capillary refill time and rectal temperature were often normal. Anemia (88%), neutrophilic leukocytosis (62%), and thrombocytopenia (48%) were common. Examination of tissue samples collected by fine-needle aspirate or biopsy established an antemortem diagnosis in 4 horses. The diagnosis was made during postmortem examination in the remaining 31 horses. The lung and pleura (77%), skeletal muscle (46%), and spleen (43%) were most commonly affected. A primary site of tumor involvement could be identified in 22 horses. Hemangiosarcoma should be included as a differential diagnosis for horses with evidence of hemorrhage into body cavities, skeletal muscle, or subcutaneous locations.

Pharmacokinetics of imipramine in narcoleptic horses.

OBJECTIVE: To validate use of high-performance liquid chromatography (HPLC) in determining imipramine concentrations in equine serum and to determine pharmacokinetics of imipramine in narcoleptic horses. ANIMALS: 5 horses with adult-onset narcolepsy. PROCEDURE: Blood samples were collected before (time 0) and 3, 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 3, 4, 6, 8, 12, and 24 hours after IV administration of imipramine hydrochloride (2 or 4 mg/kg of body weight). Serum was analyzed, using HPLC, to determine imipramine concentration. The serum concentration-versus-time curve for each horse was analyzed separately to estimate pharmacokinetic values. RESULTS: Adverse effects (muscle fasciculations, tachycardia, hyperresponsiveness to sound, and hemolysis) were detected in most horses when serum imipramine concentrations were high, and these effects were most severe in horses receiving 4 mg of imipramine/kg. Residual adverse effects were not apparent. Value (mean +/- SD) for area under the curve was 3.9 +/- 0.7 h X microg/ml, whereas volume of distribution was 584 +/- 161.7 ml/kg, total body clearance was 522 +/- 102 ml/kg/h, and mean residence time was 1.8 +/- 0.6 hours. One horse had signs of narcolepsy 6 and 12 hours after imipramine administration; corrresponding serum imipramine concentrations were less than the therapeutic range. CONCLUSIONS AND CLINICAL RELEVANCE: Potentially serious adverse effects may be seen in horses administered doses of imipramine that exceed a dosage of 2 mg/kg. Total body clearance of imipramine in horses is slower than that in humans; thus, the interval between subsequent doses should be longer in horses.

Effects of intravenous administration of formaldehyde on platelet and coagulation variables in healthy horses.

OBJECTIVES: To assess safety and determine effects of IV administration of formaldehyde on hemostatic variables in healthy horses. ANIMALS: 7 healthy adult horses. PROCEDURE: Clinical signs and results of CBC, serum biochemical analyses, and coagulation testing including template bleeding time (TBT) and activated clotting time (ACT) were compared in horses given a dose of 0.37% formaldehyde or lactated Ringer's solution (LRS), IV, in a 2-way crossover design. In a subsequent experiment, horses received an infusion of 0.74% formaldehyde or LRS. In another experiment, horses were treated with aspirin to impair platelet responses prior to infusion of formaldehyde or LRS. RESULTS: Significant differences were not detected in any variable measured between horses when given formaldehyde or any other treatment. Infusion of higher doses of formaldehyde resulted in adverse effects including muscle fasciculations, tachycardia, tachypnea, serous ocular and nasal discharge, agitation, and restlessness. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous infusion of formaldehyde at doses that do not induce adverse reactions did not have a detectable effect on measured hemostatic variables in healthy horses.

Body weight, fluid, electrolyte, and hormonal changes in horses competing in 50- and 100-mile endurance rides.

OBJECTIVE: To investigate effects of prolonged exercise on fluid and electrolyte losses in horses competing in 50- and 100-mile endurance competitions, with emphasis on recovery. ANIMALS: Changes in body weight (BW); PCV; serum osmolality; plasma total protein, lactate, aldosterone, and serum electrolyte concentrations; and exchangeable cation content were measured in 12 and 7 horses before and after and before, during, and after successful completion of 50- and 100-mile endurance rides, respectively. PROCEDURE: BW was measured by use of a portable load bar scale, and blood samples were collected during the hour before ride start, at ride finish, and after approximately 2 and 18 hours (overnight) of recovery for horses competing in the 50-mile ride. For horses competing in the 100-mile ride, BW was measured and blood samples were collected at the start; after 50, 67, and 84 miles of the ride; at the finish; and after approximately 12 hours (overnight) of recovery. RESULTS: BW decreased by (mean +/- SEM) 3.6 +/- 0.0% and 4.9 +/- 0.8% in horses that successfully completed rides of 50 and 100 miles, respectively. After the overnight recovery period, BW was 4.3 +/- 0.5% and 3.9 +/- 0.8% lower than preride values for horses performing the 50- and 100-mile rides, respectively. A decrease in plasma volume during the ride was reflected by an increase in plasma total protein concentration, but both measures returned to preride values after overnight recovery. Serum osmolality and serum electrolyte concentrations decreased and aldosterone concentration increased during prolonged exercise. Aldosterone concentration peaked after overnight recovery. CONCLUSION: Despite apparent rapid return of plasma volume and ionic composition to near normal values, substantial depletion of body fluid and electrolyte stores persists after an overnight recovery period in horses that successfully complete 50 or 100 miles of endurance competition.

Effects of training on maximum oxygen consumption of ponies.

OBJECTIVES: To establish maximum oxygen consumption VO2max) in ponies of different body weights, characterize the effects of training of short duration on VO2max, and compare these effects to those of similarly trained Thoroughbreds. ANIMALS: 5 small ponies, 4 mid-sized ponies, and 6 Thoroughbreds. PROCEDURE: All horses were trained for 4 weeks. Horses were trained every other day for 10 minutes on a 10% incline at a combination of speeds equated with 40, 60, 80, and 100% of VO2max. At the beginning and end of the training program, each horse performed a standard incremental exercise test in which VO2max was determined. Cardiac output (Q), stroke volume (SV), and arteriovenous oxygen content difference (C [a-v] O2) were measured in the 2 groups of ponies but not in the Thoroughbreds. RESULTS: Prior to training, mean VO2max for each group was 82.6 = 2.9, 97.4 +/- 13.2, and 130.6 +/- 10.4 ml/kg/min, respectively. Following training, mean VO2max increased to 92.3 +/- 6.0, 107.8 +/- 12.8, and 142.9 +/- 10.7 ml/kg/min. Improvement in VO2max was significant in all 3 groups. For the 2 groups of ponies, this improvement was mediated by an increase in Q; this variable was not measured in the Thoroughbreds. Body weight decreased significantly in the Thoroughbreds but not in the ponies. CONCLUSIONS AND CLINICAL RELEVANCE: Ponies have a lower VO2max than Thoroughbreds, and larger ponies have a greater VO2max than smaller ponies. Although mass-specific VO2max changed similarly in all groups, response to training may have differed between Thoroughbreds and ponies, because there were different effects on body weight.

Ventricular tachycardia associated with exhaustive exercise in a horse.

Ventricular tachycardia was diagnosed in a 12-year-old unconditioned Appaloosa gelding after a 3-day trail ride. Initial signs were those of abdominal discomfort, ileus, and dehydration. Medical treatment included IV administration of lactated Ringer's solution. During hospitalization, the horse developed ventricular tachycardia. Serum potassium concentrations were within reference limits; however, assessment of total body potassium stores was not performed. Resolution of the arrhythmia occurred with further fluid treatment and potassium supplementation. Cardiac arrhythmias should be considered in horses in which fluid and electrolyte disturbances are evident after exhaustive exercise.

Anorectal lymphadenopathy causing colic, perirectal abscesses, or both in five young horses.

Enlarged anorectal lymph nodes can cause colic in young horses by obstructing the caudal aspect of the rectum. Dyschezia and clinical signs consistent with abdominal pain were the predominant reasons for evaluation of the 5 young (3 to 15 month old) horses of this report. Digital transrectal palpation revealed a firm mass obstructing the caudal aspect of the rectum in each horse. Results of cytologic evaluation of the masses revealed a lymphoid population of cells in 4 of 5 horses. These nodes regressed over time or became abscesses and drained into the rectum. In 1 horse, detection of a mature abscess and concomitant dysuria necessitated immediate surgical drainage of the mass; however, the other 4 horses were successfully managed medically, thereby avoiding risks associated with surgery of the perirectal area. Anorectal lymphadenopathy should be considered as a differential diagnosis in young horses with colic.

Endoscopy of the auditory tube diverticula in four horses with otitis media/interna.

Endoscopic examination of the auditory tube diverticula was a diagnostic aid in the evaluation of 4 horses with otitis media/interna and associated osseous changes of the stylohyoid and petrous temporal. One of the horses was examined because of persistent head shaking; the other 3 were examined because of an acute onset of facial and vestibulocochlear nerve dysfunction. Proliferative lesions involving the petrous temporal bone and proximal portion of the stylohyoid bone were identified endoscopically in all 4 horses. Endoscopy is a noninvasive procedure that provides an alternative to skull radiography and tympanocentesis in the diagnosis of otitis media/interna in horses. In addition, risks associated with general anesthesia are avoided.