Effect of phenylbutazone on insulin secretion in horses with insulin dysregulation.

BACKGROUND: Phenylbutazone is often prescribed to manage pain caused by hyperinsulinemia-associated laminitis, but in diabetic people nonsteroidal anti-inflammatory drugs increase insulin secretion and pancreatic activity. HYPOTHESIS/OBJECTIVES: Investigate the effect of phenylbutazone administration on insulin secretion in horses. It was hypothesized that phenylbutazone will increase insulin secretion in horses with insulin dysregulation (ID). ANIMALS: Sixteen light breed horses, including 7 with ID. METHODS: Randomized cross-over study design. Horses underwent an oral glucose test (OGT) after 9 days of treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). After a 10-day washout period, horses received the alternative treatment, and a second OGT was performed. Insulin and glucose responses were compared between groups (ID or controls) and treatments using paired t test and analyses of variance with P < .05 considered significant. RESULTS: In horses with ID, phenylbutazone treatment significantly decreased glucose concentration (P = .02), glucose area under the curve (2429 ± 501.5 vs 2847 ± 486.1 mmol/L × min, P = .02), insulin concentration (P = .03) and insulin area under the curve (17 710 ± 6676 vs 22 930 ± 8788 µIU/mL × min, P = .03) in response to an OGT. No significant effect was detected in control horses. CONCLUSION AND CLINICAL IMPORTANCE: Phenylbutazone administration in horses with ID decreases glucose and insulin concentrations in response to an OGT warranting further investigation of a therapeutic potential of phenylbutazone in the management of hyperinsulinemia-associated laminitis beyond analgesia.

Clinical effects of a combination of phenylbutazone and omeprazole on chronic lameness in Mongolian horses.

BACKGROUND: Phenylbutazone (PBZ) is the most commonly used drug to treat symptoms of lameness in horses; however, it is associated with adverse effects such as gastric ulcer syndrome (EGUS). Interestingly, many practitioners prescribe omeprazole (OME) concurrently with PBZ to prevent the development of EGUS. However, the efficacy and safety of this practice in Mongolian horses with chronic lameness remain unknown. OBJECTIVES: To evaluate the clinical effects of a combination of PBZ and OME on chronic lameness in Mongolian horses. STUDY DESIGN: Randomised block experimental design. METHODS: Eighteen Mongolian horses with lameness score was ≥3 points, were divided into three treatment groups, with six horses in each group: placebo (CON), PBZ (4.4 mg/kg PO q. 24 h), or PBZ plus OME (4 mg/kg PO q. 24 h; PBZ + OME) in a randomised block design based on the initial lameness score. The horses were treated for 15 days. During this period, weekly gastroscopy, and physiological and biochemical tests were performed. RESULTS: Both PBZ (median 1.0, interquartile range [IQR]: 0.8-1.3; p = 0.01) and PBZ + OME (median 1.0, IQR: 1.0-1.0; p = 0.01) significantly decreased the lameness score compared with before administration. In addition, PBZ significantly increased the equine glandular gastric disease (EGGD) score (3.0 ± 0.6, p < 0.001), GT-17 content (293.4 ± 21.8 pg/mL, p < 0.001), and pepsinogen-1 (PG1) content (295.3 ± 38.3 ng/mL, p < 0.001) compared with CON or PBZ + OME. However, it significantly reduced the total protein (53.6 ± 1.5 g/L, p < 0.05) and albumin (25.5 ± 1.8 g/L, p < 0.05) contents. Nevertheless, compared with PBZ, PBZ + OME significantly decreased the EGGD score (0.3 ± 0.5, p < 0.001) and significantly increased the gastric fluid pH (7.3 ± 0.5, p < 0.001), total protein content (62.5 ± 4.6 g/L, p = 0.009), and albumin content (29.4 ± 1.1 g/L, p = 0.004). Meanwhile, they significantly diminished the gastrin 17 (GT-17) (162.0 ± 21.0 pg/mL, p < 0.001) and PG1 (182.4 ± 22.5 ng/mL, p < 0.001) contents. MAIN LIMITATIONS: Individual differences in horses were larger, but the sample size was small. There was larger interval between observations for each index. CONCLUSIONS: Compared with PBZ alone, PBZ + OME had no therapeutic effect on chronic lameness; however, it reduced the occurrence of EGGD in Mongolian horses. Horses may be protected against chronic lameness and PBZ-induced EGGD by increasing the pH value, decreasing serum PG1 and GT-17 content, and preventing the reduction of myeloperoxidase content.

Preliminary evaluation of hepatitis A virus cell receptor 1/kidney injury molecule 1 in healthy horses treated with phenylbutazone.

OBJECTIVES: To investigate if hepatitis A virus cell receptor 1/kidney injury molecule 1 (HAVCR1/KIM1) in urine is detectable concurrently with increases in serum creatinine concentrations in horses receiving a recommended dose of phenylbutazone (PBZ) for 7 days. DESIGN: Preliminary study. METHODS: Ten clinically healthy horses with normal physical examination and laboratory work were randomly assigned to PBZ or placebo groups (5 each). The PBZ group received PBZ at 4.4 mg/kg mixed with corn syrup orally every 12 hours. The placebo group received corn syrup orally every 12 hours. Both groups were treated for 7 days. Kidney ultrasonography was performed, and venous blood and urine samples were collected prior to commencement and at the end of treatment. Samples from 1 additional healthy horse, 3 horses with acute kidney failure, and 1 horse with chronic kidney failure were also evaluated. RESULTS: None of the 10 horses had detectable HAVCR1/KIM1 in urine at baseline. Serum creatinine concentrations in placebo group did not increase, and HAVCR1/KIM1 was undetectable in urine. At the end of treatment, 3 of 5 horses receiving PBZ developed increases in serum creatinine of >26.5 µmol/L (>0.3 mg/dL), and HAVCR1/KIM1 was detectable in urine, despite normal findings on kidney ultrasonography in all horses. CONCLUSIONS: HAVCR1/KIM1 is detectable in urine and is associated with increases in serum creatinine concentrations of >26.5 µmol/L in horses following treatment with PBZ for 7 consecutive days. Thus, HAVCR1/KIM1 might aid in the early detection of acute kidney injury in horses.

Effects of Intravenous Flunixin Meglumine, Phenylbutazone, and Acupuncture on Ocular Pain Scores in the Horse: A Pilot Study.

In this controlled, blinded, randomized block pilot study, the main objective was to evaluate the effectiveness of intravenous flunixin meglumine, phenylbutazone, and acupuncture on ocular pain relief using a multifactorial pain scale in the horse. Four experimental horses underwent corneal epithelial debridement in four sessions, when a randomly selected treatment or a control was used. All horses were pain scored before corneal wounding, then at 18 time points, when 11 parameters were allocated. Differences in the area under the curve of pain scores between the treatment groups were analyzed using a paired t-test. Corneal pain was significantly reduced by the third postoperative day (P = .03) when all 11 parameters were considered. Five ocular signs showed significant differences between treatments and proved to be good indicators of ocular pain. The other parameters (heart rate, corneal touch threshold, respond to palpation, and three behavioral parameters) were determined to be irrelevant when evaluating the degree of pain. When considering the five ocular signs, the lowest pain score was attributed to the flunixin meglumine group (1114), followed by the electroacupuncture group (1356), the phenylbutazone group (1397), and the control group (1580). There were significantly lower pain scores (P = .01) in the flunixin meglumine group when compared with those recorded in the control group during the first 46 hours. Flunixin meglumine was the most effective treatment at reducing ocular pain in the horse. In the future, a reduction in the number of pain score parameters and more precisely defined image evaluation criteria could be used.

Phenylbutazone (Bute, PBZ, EPZ): one drug across two species.

In this article we explore the different trajectories of this one drug, phenylbutazone, across two species, humans and horses in the period 1950-2000. The essay begins by following the introduction of the drug into human medicine in the early 1950s. It promised to be a less costly alternative to cortisone, one of the "wonder drugs" of the era, in the treatment of rheumatic conditions. Both drugs appeared to offer symptomatic relief rather than a cure, and did so with the risk of side effects, which with phenylbutazone were potentially so severe that it was eventually banned from human use, for all but a few diseases, in the early 1980s. Phenylbutazone had been used with other animals for many years without the same issues, but in the 1980s its uses in veterinary medicine, especially in horses, came under increased scrutiny, but for quite different reasons. The focus was primarily the equity, economics, and ethics of competition in equine sports, with differences in cross-species biology and medicine playing a secondary role. The story of phenylbutazone, a single drug, shows how the different biologies and social roles of its human/animal subjects resulted in very different and changing uses. While the drug had a seemingly common impact on pain and inflammation, there were inter-species differences in the drug's metabolism, the conditions treated, dosages, and, crucially, in intended clinical outcomes and perceptions of its benefits and risks.

CLINICAL MANAGEMENT OF BILATERAL CUTANEOUS SQUAMOUS CELL CARCINOMA OF THE HIND FEET PADS IN A SOUTHERN WHITE RHINOCEROS (CERATOTHERIUM SIMUM SIMUM).

The current report describes the temporary regression, due to intensive symptomatic treatment, of ulcerative skin lesions caused by squamous cell carcinoma in a white rhinoceros. A captive, 40-yr-old southern white rhinoceros (Ceratotherium simum simum) developed profound, ulcerative skin lesions on the pads of both hind feet. At the peak of the disease, at least one quarter of the pads was affected. A diagnosis of squamous cell carcinoma was made via biopsy. Treatment included anti-inflammatory drugs, antibiotics, and local care. The lesions regressed on both feet until they seemed clinically healed. It was presumed that long-term, anti-inflammatory treatment and local bandaging had induced the temporary regression of the lesions. Two years later, however, a small ulcerative lesion reappeared on one pad and post mortem examination confirmed that the carcinoma was also histologically present in the clinically intact tissue. No metastasis was found and computed tomography showed normal digital bones.

Comminuted fracture of the accessory carpal bone removed via an arthroscopic-assisted arthrotomy.

A 16-year-old American paint horse gelding was presented for evaluation of a left forelimb lameness grade III/V. Radiographs and computed tomography revealed a comminuted fracture of the accessory carpal bone involving the entire articulation with the distal radius and the proximal aspect of the articulation with the ulnar carpal bone. Multiple fragments were present in the palmar pouch of the antebrachiocarpal joint. An arthroscopic-assisted open approach was necessary to remove all fractured fragments. Subsequently the horse was re-admitted for lameness and was treated successfully with antibiotics and long-term supportive bandaging.

Fracture comminutive de l'os du carpe accessoire enlevé à l'aide d'une arthrotomie assistée par arthroscopie. Un cheval American Paint Horse âgé de 16 ans a été présenté pour l'évaluation d'une boiterie de la jambe avant gauche de grade III/V. Les radiographies et la tomodensitométrie ont révélé une fracture comminutive de l'os du carpe accessoire touchant toute l'articulation avec le radius distal et l'aspect proximal de l'articulation avec l'os du carpe cubital. Des fragments multiples étaient présents dans la poche palmaire de l'articulation antébrachio-carpienne. Une approche ouverte assistée par arthroscopie a été nécessaire pour retirer tous les fragments fracturés. Le cheval a ensuite été réadmis pour boiterie et a été traité avec succès à l'aide d'antibiotiques et de pansements de soutien à long terme.(Traduit par Isabelle Vallières).

In vivo effects of phenylbutazone on inflammation and cartilage-derived biomarkers in equine joints with acute synovitis.

Although phenylbutazone (PBZ) is commonly used in equine orthopaedic practice, little is known about its in vivo effects on joint inflammation and cartilage turnover. This study investigates the effects of PBZ on inflammatory parameters, matrix metalloproteinase (MMP) activity and cartilage biomarkers in equine joints with acute synovitis. In a two-period cross-over study, transient synovitis was induced at T = 0 h in the middle carpal joint of seven ponies by lipopolysaccharide (LPS) injection. Ponies received PBZ (2 mg/kg PO twice daily) or placebo for 1 week, starting at T = 2 h. Arthroscopic assessment of the middle carpal joint was performed at T = -504, 48 and 672 h. Synovial fluid (SF) was sampled at T = -504, 0, 8, 24, 48, 168, 336 and 672 h and analysed for leukocytes and total protein, substance P, general MMP activity, glycosaminoglycans (GAG), collagen II cleavage marker C2C and synthesis marker CPII. Markers in PBZ- vs. placebo-treated joints were compared over time using a linear mixed model. LPS injection caused marked transient synovitis without visible cartilage changes. Substance P and general MMP activity were not significantly reduced by PBZ treatment, nor were SF GAG or C2C concentrations at any time point. Concentration of CPII was significantly lower at T = 24 and 168 h in PBZ treated joints compared to placebo. Although PBZ is clinically effective in treating acute synovitis, it does not limit inflammation-induced cartilage catabolism and may transiently reduce collagen anabolism as evidenced by SF markers.

Enthesopathy and desmitis of the medial collateral ligament of the cubital joint in 4 horses.

CASE DESCRIPTION: 4 horses with enthesopathy and desmitis of the medial collateral ligament of the cubital joint were examined. CLINICAL FINDINGS: All 4 horses had a history of acute, severe, unilateral forelimb lameness and had signs of pain during manipulation of the affected upper forelimb; 2 also had swelling in the axillary region. There was no improvement in lameness after diagnostic local analgesia below the carpal region, and 1 of 4 horses had mild improvement after cubital joint analgesia. Radiography revealed enthesophyte formation on the radial tuberosity and linear mineralization of the medial collateral ligament in 2 horses and periosteal reaction on the humeral condyle in all 4 horses. One horse had mild osteoarthritis of the cubital joint, and 3 had osteophytosis of the cranial aspect of the radius. Although all horses were initially examined because of an acute onset of lameness, all had chronic abnormalities visible on imaging. Ultrasonography revealed an irregular boney contour and enthesopathy at the insertion of the short medial collateral ligament to the radial tuberosity and desmitis of the short medial collateral ligament. Two horses had radiographic evidence of similar but less severe lesions of the contralateral cubital joint. TREATMENT AND OUTCOME: All horses received phenylbutazone and rest. All horses were free of lameness after a median of 3 months (range, 2 to 4 months) and returned to previous use after a median of 6 months (range, 3 to 8 months). CONCLUSIONS AND CLINICAL RELEVANCE: The results of the present report suggested that performance horses with enthesopathy and desmitis of the medial collateral ligament of the cubital joint may have a good prognosis for return to previous use following appropriate treatment.

Upregulation of articular synovial membrane µ-opioid-like receptors in an acute equine synovitis model.

Intra-articular injection of opioids provides analgesia in painful equine joints and µ-opioid receptors (MORs) have been demonstrated in equine synovial membranes. The aim of this study was to determine whether acute inflammatory conditions will lead to up-regulation of MOR in equine synovial membranes and whether anti-inflammatory treatment can prevent any such upregulation. In a two-period, blinded, placebo-controlled randomised cross-over design, lipopolysaccharide (LPS, 1.0 ng) was injected into the left or right middle carpal joint of seven healthy ponies. Arthroscopy and synovial membrane biopsy was performed under general anaesthesia at baseline, 48 h (T48) and 672 h (T672) after LPS injection, with ponies assigned to receive either phenylbutazone (PBZ 2.2mg/kg PO BID) or placebo from 2h post-LPS. Ponies were scored for pain and lameness. Repeated synovial fluid samples were obtained and the degree of synovitis scored both macroscopically and microscopically. The density and staining pattern of MOR-like protein in synovial membrane biopsies over the course of the synovitis with or without PBZ treatment was evaluated using immunohistochemical techniques. LPS injection consistently induced a severe transient synovitis. Pain and lameness were significantly attenuated by treatment with PBZ. Up-regulation of MOR-like protein in the inflamed equine synovial membrane could be demonstrated in the placebo treated animals, but not in the PBZ-treated animals overall, although there were no significant differences at any individual time-point between the two groups. It was concluded that acute inflammation will up-regulate MOR, while anti-inflammatory treatment will attenuate this response.

The use of phenylbutazone in the horse.

This review presents a brief historical prospective of the genesis of regulated medication in the US racing industry of which the nonsteroidal anti-inflammatory drug (NSAID) phenylbutazone (PBZ) is the focus. It presents some historical guideposts in the development of the current rules on the use of PBZ by racing jurisdictions in the US. Based on its prevalent use, PBZ remains a focus of attention. The review examines the information presented in a number of different models used to determine the effects and duration of PBZ in the horse. They include naturally occurring lameness and reversible-induced lameness models that directly examine the effects and duration of the administration of various doses of PBZ. The review also examines indirect plasma and tissue models studying the suppression of the release of arachidonic acid-derived mediators of inflammation. The majority of studies suggest an effect of PBZ at 24 h at 4.4 mg/kg. This reflects and substantiates the opinion of many clinical veterinarians, many of whom will not perform a prepurchase lameness examination unless the horse is free of NSAID. This remains the opinion of many regulatory veterinarians responsible for the prerace examination of race horses that they wish to examine a horse without the possibility of an NSAID interfering with the examination and masking possible musculoskeletal conditions. Based on scientific studies, residual effects of PBZ remain at 24 h. The impact of sustained effect on the health and welfare of the horse and its contribution to injuries during competition remains problematic.

Quiste subcondral a nivel de la articulación interfalángicaproximal en una potranca criolla colombiana: reporte de caso / Subchondral cyst in the proximal interphalangeal joint in a paso fino colombian horse: a case report / Cisto subcondral na articulação proximal interfalângicaem um potro crioulo colombiano: relato de caso

Se reporta el caso de una paciente equina, evaluada por Especial•Vet práctica privada, la cual presentaba alexamen clínico ortopédico un grado de claudicación II/V en ambos miembros posteriores (según clasificaciónde la AAEP), la cual no presento mejoría después de realizar un tratamiento médico de tipo parenteral confenilbutazona. Posteriormente se realizó un nuevo examen clínico ortopédico en el cual se realizó bloqueoanestésico perineural abaxial en ambos miembros posteriores encontrando una mejoría del 90% con respectoal grado de claudicación inicial. Se realizó evaluación radiológica digital, con las siguientes proyecciones:dorso plantar y lateromedial en las cuales se evidenció un área radiolúcida circunscrita a nivel del terciodistal de la primera falange, con comunicación a la articulación interfalángica proximal en ambos miembros posteriores, seguidamente se realizó evaluación ultrasonográfica en la cual se observa un área anecóica y lafalta de continuidad de la superficie ósea a nivel de la articulación interfalángica proximal de ambos miembrosposteriores. Estableciendo de esta forma como diagnóstico definitivo quiste subcondral a nivel del tercio distalde la primera falange, con comunicación a la articulación interfalángica proximal. Se realizó infiltración conacetato de triamcinolona, betametasona y ácido hialurónico a nivel intrarticular; antibioterapia de maneraprofiláctica al procedimiento, descanso en pesebrera por 4 semanas y reincorporación al ejercicio de maneraprogresiva, suministro de complementos condroprotectores de manera enteral (Flexequin® 40 gr/día VO yCortaflex® 20 ml/día VO). Al momento de la publicación de este artículo, la paciente no presenta ningún gradode claudicación y se encuentra realizando un trabajo físico y atlético normal.

We report the case of an equine patient, assessed by Especial Vet private practice, whose orthopedic clinicalexamination showed a degree of lameness II / V in both hind limbs (according to AAEP classification), whichdemonstrated no improvement after medical treatment with parenteral phenylbutazone. Subsequently a neworthopedic clinical examination was performed in which an abaxial, perineural anesthetic block was applied to both hind legs, which produced 90% improvement compared to the initial degree of lameness. Digital radiographicevaluation was performed with the following results: dorsal-plantar and lateral-medial images which showeda circumscribed, radiolucent area at the level of the distal third of the first phalanx, with communication to theproximal interphalangeal joint on both hind limbs. Following, an ultrasound evaluation was carried out in whichthere was an anechoic area and lack of continuity of the bone surface at the proximal interphalangeal joint of bothhind limbs. These findings established a definitive diagnosis of a subchondral bone cyst at the distal third of the firstphalanx, with communication to the proximal interphalangeal joint. Intra-articular infiltration was performed with triamcinolone acetonide, betamethasone and hyaluronic acid; antibiotics as prophylaxis, rest in a stable for 4 weekswith a gradual return to exercise, and provision of enteral, chondroprotective supplements (p.o. Flexequin ® 40 gr/day and p.o. Cortaflex ® 20ml/day). At the time of publication of this article, the patient does not present any degreeof lameness and is performing normal athletic and physical activity.

Relatamos um caso de um paciente eqüino, avaliado pela prática privada Especial Vet, cujo exame clínicoortopédico mostrou um grau de claudicação II / V em ambos os membros posteriores (de acordo com aclassificação do AAEP), o qual não demonstrou melhora após o tratamento médico com fenilbutazona parenteral.Após a aplicação de um bloqueio anestésico perineural abaxial em ambas as pernas traseiras, foi realizadoum novo exame clínico ortopédico, mostrando uma melhora de 90% em comparação com o grau inicial declaudicação. Realizou-se também uma avaliação radiográfica digital obtendo-se os seguintes resultados: imagensdorso-plantar e latero-medial que mostrou uma área radiolúcida circunscrita ao nível do terço distal da primeirafalange, com comunicação para a articulação interfalângica proximal em ambos os membros posteriores. E após,a realização de um ultra-som, verificou-se que houve uma área anecóica e falta de continuidade da superfície óssea ao nível da articulação interfalângica proximal dos dois membros posteriores. Desta forma estabeleceu umdiagnóstico definitivo de um cisto ósseo subcondral no terço distal da primeira falange, com comunicação para aarticulação interfalângica proximal. Uma infiltração intra-articular foi realizada com acetato de triamcinolona,betametasona e ácido hialurônico; antibióticos como profilaxia, um descanso em estábulo durante 4 semanas, com um retorno gradual aos exercícios, e administração de suplementos condroprotetores de maneira enteral(Flexequin® 40 gr/día VO e Cortaflex® 20 ml/día VO). No momento da publicação deste artigo, o paciente nãoapresenta qualquer grau de claudicação e está realizando atividades atléticas e físicas normais.

Phenylbutazone and flunixin meglumine used singly or in combination in experimental lameness in horses.

REASON FOR PERFORMING STUDY: Using an adjustable heart bar shoe model of foot pain, the objective of this study was to test the hypothesis that the combined use of phenylbutazone (PBZ) and flunixin meglumine (FM) would prove more efficacious in alleviating lameness than either drug alone. MATERIALS AND METHODS: One hour after induction of lameness at weekly intervals, 8 healthy adult Thoroughbred horses randomly underwent one of 4 i.v. treatments: saline (SAL) placebo (1 ml/45 kg bwt), PBZ (4.4 mg/kg bwt), FM (1.1 mg/kg bwt) or PBZ+FM (at the same dosages as given individually). Heart rate (HR) and lameness score (LS) responses were assessed in a blinded manner every 20 min for 5 h after lameness induction and then hourly for 12 h after treatment. Jugular venous blood samples were obtained at -1, 0, 0.05, 1, 2, 4, 6, 8, 10 and 12 h and subsequently analysed for drug concentrations. Repeated measures ANOVA and post hoc Tukey's test were used to identify analgesic effects at a significance level of P<0.05. RESULTS: Heart rate was lower in all nonsteroidal anti-inflammatory drug (NSAID)-treated trials from 2 h to 10 h post treatment (P<0.05). Analgesic effects of FM and PBZ+FM, as evidenced by decreases in HR, lasted for 12 h post treatment (P<0.05). Lameness score decreased earlier in PBZ and PBZ+FM trials than in FM trials (P<0.05) and the analgesic effect on LS lasted for 12 h post treatment for all NSAID trials (P<0.05). Peak PBZ plasma concentration was 73.7 ± 6.0 and 77.9 ± 5.5 µg/ml. Peak FM concentration was 12.0 ± 0.8 and 13.7 ± 1.0 µg/ml. CONCLUSIONS: It was concluded that the combination of PBZ+FM was not more effective than either PBZ or FM alone. These data do not support the hypothesis that the combination is more efficacious at these dosages than either drug alone in this model of acute foot pain.

Ulcerative cystitis associated with phenylbutazone administration in two horses.

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.

Efficacy of single-dose intravenous phenylbutazone and flunixin meglumine before, during and after exercise in an experimental reversible model of foot lameness in horses.

REASONS FOR PERFORMING STUDY: Objective blinded efficacy data during exercise are lacking on the use of single-dose i.v. nonsteroidal anti-inflammatory drugs (NSAIDs) before, during and after exercise. HYPOTHESIS: Single i.v. doses of either phenylbutazone (PBZ) or flunixin meglumine (FM) would prove more efficacious than negative saline control (SAL) before, during and after exercise in a reversible model of foot lameness. METHODS: Six Quarter Horse mares had lameness induced by tightening a set screw against a heart bar shoe 1 h prior to treatment. Randomised blinded treatments included PBZ (4.4 mg/kg bwt i.v.), FM (1.1 mg/kg bwt i.v.), and SAL (1 ml/45 kg i.v.). Heart rate and lameness score (LS) were recorded at rest; every 20 min after lameness induction for 5 h and at the end of 2 min treadmill workloads of 2 and 4 m/s. Heart rate was also recorded from 0.5-60 min post exercise. Results were compared using RM ANOVA and Student-Newman-Keul's test (HR) and Wilcoxon signed rank test (%ΔLS) with significance set at P < 0.05. RESULTS: Pre-exercise mean HR was decreased for both NSAIDs compared to SAL from 1:20-4 h post treatment (P < 0.05). Pre-exercise mean %ΔLS was decreased for PBZ (1:20-4 h) and FM (1-4 h) compared to SAL (P < 0.01). With exercise, there were no HR differences between treatments (P > 0.05), but mean %ΔLS was decreased for both NSAIDs compared to SAL (P < 0.01). Mean recovery HR was decreased for PBZ and FM from 1-60 min compared to SAL (P < 0.05). CONCLUSIONS: PBZ and FM demonstrated definitive clinical efficacy after single i.v. doses before, during and after exercise. Use of single i.v. doses during competition may mask lameness and may affect the ability of judges in determining the soundness of horses in competition.