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Background: Clinically, flunixin meglumine (FM) and phenylbutazone (PBZ) are preferentially selected for the treatment of visceral and musculoskeletal pain, respectively, in horses. In donkeys, there is no information to support or refute this conventional conjecture., Objectives: To compare postoperative outcomes in a group of jennies treated with intravenous FM or oral PBZ., Animals: Fourteen jennies unilaterally ovariectomised by standing left flank laparotomy., Study Design: Retrospective cohort study., Methods: Data from medical records of ovariectomised jennies (case details, weight, non-steroidal anti-inflammatory drug [NSAID] protocol, surgery duration, operative sequence, anaesthesia protocol, physical examination findings and outcomes) were collected. From collated data, postoperative adverse events were defined as fever, tachycardia, tachypnea, inappetence, altered mentation, abnormal oral mucous membranes, bruxism, colic, incisional complications (i.e., drainage, oedema, peri-incisional emphysema and pain) and non-survival, then further divided into occurrence during the early (≤24 h) or late (>24 h) postoperative period for data analysis using R software. Chi-squared test was used to compare individual adverse events between groups (PBZ vs. FM) and moments (early vs. late). Significance was set at p ≤ 0.05., Results: PBZ treatment (8/14) was associated with (odds ratio, 95% confidence interval) more total (2.93, 1.97-4.36), early (3.01, 1.87-4.84) and late (2.69, 1.28-5.63) adverse events than FM treatment (6/14). Tachycardia (37.83, 2.21-646.66), tachypnoea (0.29, 0.13-0.66), altered mentation (2.78, 1.01-7.67), altered mucous membranes (18.38, 1.04-325.23), incisional oedema (44.33, 2.60-754.5) and incisional pain (47.78, 2.81-811.61) were significantly different between groups. Early adverse events significantly different between groups included tachycardia (50.2, 2.9-877.0), altered mentation (3.33, 1.08-10.29) and incisional pain (21.0, 1.2-374.5), with late adverse events being tachypnea (0.07, 0.01-0.62), incisional oedema (32.92, 1.85-584.28) and incisional pain (28.92, 1.62-515.68). Colic (2/8) and non-survival (1/8) were rare events that only occurred in the PBZ cohort and could not be further evaluated for differences., Main Limitations: Small sample size; retrospective study; treatment bias; varied administration routes., Conclusions: Oral PBZ may be inappropriate to use following abdominal surgery in donkeys., Clinical Relevance: More prospective and case-controlled studies are needed to evaluate the clinical efficacy of these two NSAIDs in donkeys., (© 2024 EVJ Ltd.)

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., (© 2023 EVJ Ltd.)

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., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

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., (© Veterinary Emergency and Critical Care Society 2023.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

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.

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.

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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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., (© 2011 Blackwell Publishing Ltd.)

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., (© 2011 EVJ Ltd.)

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.

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., (© 2010 EVJ Ltd.)

Objective: To compare the analgesic efficacy of administration of butorphanol tartrate, phenylbutazone, or both drugs in combination in colts undergoing routine castration., Design: Randomized controlled clinical trial., Animals: 36 client-owned colts., Procedures: Horses received treatment with butorphanol alone (0.05 mg/kg [0.023 mg/lb], IM, prior to surgery and then q 4 h for 24 hours), phenylbutazone alone (4.4 mg/kg [2.0 mg/lb], IV, prior to surgery and then 2.2 mg/kg [1.0 mg/lb], PO, q 12 h for 3 days), or butorphanol and phenylbutazone at the aforementioned dosages (12 horses/group). For single-drug-treated horses, appropriate placebos were administered to balance treatment protocols among groups. All horses were anesthetized, and lidocaine hydrochloride was injected into each testis. Physical and physiological variables, plasma cortisol concentration, body weight, and water consumption were assessed before and at intervals after surgery, and induction of and recovery from anesthesia were subjectively characterized. Observers assessed signs of pain by use of a visual analogue scale and a numerical rating scale., Results: Significant changes in gastrointestinal sounds, fecal output, and plasma cortisol concentrations were evident in each treatment group over time, compared with preoperative values. At any time point, assessed variables and signs of pain did not differ significantly among groups, although the duration of recumbency after surgery was longest for the butorphanol-phenylbutazone-treated horses., Conclusions and Clinical Relevance: With intratesticular injections of lidocaine, administration of butorphanol to anesthetized young horses undergoing routine castration had the same apparent analgesic effect as phenylbutazone treatment. Combined butorphanolphenylbutazone treatment was not apparently superior to either drug used alone.

Reasons for Performing Study: In horses, it has been demonstrated that suxibuzone (SBZ) has a lower gastric ulcerogenic effect than phenylbutazone (PBZ). However, no field trials have been reported comparing the efficacy of the drugs in alleviating lameness., Objectives: To compare the therapeutic effect of SBZ to that of PBZ when administered orally in lame horses. Acceptability of both products was also compared., Methods: Lame horses (n = 155) were used in a multicentre, controlled, randomised and double-blinded clinical trial. Horses were treated orally with either SBZ or PBZ at equivalent therapeutic dosages. PBZ was given to 79 horses at a dose of 4.4 mg/kg bwt/12 h for 2 days, followed by 2.2 mg/kg bwt/12 h for 6 days. SBZ was given to 76 horses at 6.6 mg/kg bwt/12 h for 2 days, followed by 3.3 mg/kg bwt/ 12 h for 6 days. Efficacy of treatments was evaluated by clinicians in equine practices according to lameness progression throughout the study. Product ingestion was checked daily to evaluate product acceptability., Results: Although SBZ showed a statistically significant tendency to have a better efficacy than PBZ (Odds ratio = 2.7; P = 0.016), significance dissipated once the analysis was adjusted for some imbalanced baseline covariates, confirming that they were actually related to the apparent advantage of SBZ over PBZ. Product acceptability was significantly higher in the SBZ group than in the PBZ group (96.1% vs. 77.2%; P = 0.001)., Conclusions: SBZ and PBZ did not show significant differences in alleviating lameness in horses. However, SBZ had better product acceptability when administered orally with some food., Potential Relevance: SBZ is a good therapeutic alternative to PBZ in horses since there is no significant difference in alleviating lameness between the 2 therapies.

There are several choices of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating dogs that have osteoarthritis. However, fewer drugs are available for cats. Like people, there may be greater differences among individuals in their response than there are differences among the drugs. In past practice, veterinarians often selected aspirin or phenylbutazone as an initial drug, and then progressed to off-label human drugs or other agents as an alternative. Now we have the advantage of several approved NSAIDs for which there are excellent published studies and US Food and Drug Administration or foreign approval to guide clinical use and safe dosages.

A 15 year old Oldenburger gelding was treated during 3 weeks for laminitis with the anticoagulant phenprocoumone (27 mg orally, once daily) and concurrent administration of phenylbutazone (2-4 g orally, twice daily). After this treatment the animal was presented to the Equine Clinic University of Zurich with a history of acute colic and advanced symptoms of shock. On the basis of the clinical signs and laboratory values, a diagnosis of combined drug induced coagulopathy was made. The horse was treated with the antidote Vitamine-K1 (0.5 mg/kg, subcutaneously). Eventually, the general condition of the animal worsened and it was therefore euthanized. Necropsy revealed profound, multifocal hemorrhagic diathesis of the serosal surface of the viscera, as well as bleeding into the visceral cavities. This case shows that concurrent administration of phenprocoumone and phenylbutazone may lead to drug interactions that increase the anticoagulation effect of the coumarine-derivative. Simultaneous use of coumarine-derivatives and phenylbutazone is therefore contraindicated due to the higher risk of bleeding. A reasonable treatment of horses with anticoagulants requires regular monitoring with constant evaluation of coagulation status and special attention to potential drug interactions.

Hemophagocytic lymphohistiocytosis (HLH) is a complex inflammatory disease with multiple diagnostic and therapeutic pitfalls. The congenital form, referred to as familial hemophagocytic lymphohistiocytosis (FHL), is often associated with cerebromeningeal involvement, whereas neurological complications are not characteristic of the adult form of secondary HLH (sHLH). Here we report the case of a 20-year-old woman with adult-onset Still's disease (AOSD), retinal microangiopathy and concurrent macrophage activation syndrome (MAS), in the context of sHLH. Following treatment with etanercept, ibuprofen, methylprednisolone, and phenylbutazone for 3 weeks, MAS deteriorated and fatal cerebral edema occurred within only 24 h. The clinical signs and neuropathological findings are discussed with special emphasis on possible relationships between the aggravation of MAS and therapeutic interventions for AOSD. In conclusion, even the slightest sign of mental decline in a patient with AOSD must be considered central nervous system MAS which can be rapidly fatal., (Copyright 2008 Wiley-Liss, Inc.)

We report 6 additional observations of a drug/hormone assay interaction between serum testosterone and phenylbutazone intake. This interaction had been described previously only once. We discuss its potential mechanisms, based upon our experimental findings, and its clinical implications.

The objective was to test the hypothesis that phenylbutazone (PBZ) alleviates lameness in an adjustable heart bar shoe model of equine foot pain. Eight Quarter Horse mares underwent 4-weekly treatments randomly: 0.9% saline placebo (SAL: 1 mL/45 kg body weight i.v.) with no lameness; SAL with lameness; PBZ (4.4 mg/kg body weight i.v.) with no lameness; and PBZ with lameness. Blinded heart rate (HR) and lameness score (LS) were assessed every 20 min for 2 h and then hourly through 9 h. At 1 h SAL or PBZ was administered. Jugular venous samples were obtained at hours 0, 1, 2, 4, 6, and 8 and were evaluated for packed cell volume (PCV), cortisol, and drug concentrations. Repeated measures anova and t-tests were used to identify PBZ effects at a significance level of P<0.05. PBZ-treated LS was lower 2-8 h post-treatment, and HR was lower from 2 through 6 h post-treatment (P<0.05). Phenylbutazone did not change PCV and had minimal effect on cortisol. Mean plasma PBZ and oxyphenbutazone concentrations 7 h after treatment were 7.2-7.5 and 1.6-1.9 microg/mL, respectively. It was concluded that PBZ was efficacious in alleviating lameness in this model. Cortisol and PCV were not discriminating enough to distinguish between PBZ-treated and SAL-treated trials.

Objective: To determine the effectiveness of administering multiple doses of phenylbutazone alone or a combination of phenylbutazone and flunixin meglumine to alleviate lameness in horses., Animals: 29 adult horses with naturally occurring forelimb and hind limb lameness., Procedures: Lameness evaluations were performed by use of kinematic evaluation while horses were trotting on a treadmill. Lameness evaluations were performed before and 12 hours after administration of 2 nonsteroidal anti-inflammatory drug (NSAID) treatment regimens. Phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days, or phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days in combination with flunixin meglumine administered at 1.1 mg/kg, IV, every 12 hours for 5 days., Results: Alleviation of lameness was greater after administration of the combination of NSAIDs than after oral administration of phenylbutazone alone. Improvement in horses after a combination of NSAIDs did not completely mask lameness. Five horses did not improve after either NSAID treatment regimen. All posttreatment plasma concentrations of NSAIDs were less than those currently allowed by the United States Equestrian Federation Inc for a single NSAID. One horse administered the combination NSAID regimen died of acute necrotizing colitis during the study., Conclusions and Clinical Relevance: Administration of a combination of NSAIDs at the dosages and intervals used in the study reported here alleviated the lameness condition more effectively than did oral administration of phenylbutazone alone. This may attract use of combinations of NSAIDs to increase performance despite potential toxic adverse effects.

Objective: To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis., Design: Randomized controlled clinical trial., Animals: 253 client-owned horses with naturally occurring osteoarthritis., Procedures: Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined reduction of at least 3 points in scores for pain during manipulation or palpation, joint swelling, joint circumference, and range of motion., Results: Proportion of horses clinically improved on day 14 for the firocoxib group (104/123 [84.6%]) was not significantly different from the proportion for the phenylbutazone group (103/119 [86.6%]). Proportion of horses that were improved on day 14 was significantly greater for horses treated with firocoxib than for horses treated with phenylbutazone with regard to score for pain on manipulation or palpation (P = 0.028), joint circumference score (P = 0.026), and range of motion score (P = 0.012), but not for overall lameness score or joint swelling score. No direct treatment-related adverse effects were detected during the study., Conclusions and Clinical Relevance: Results suggested that overall clinical efficacy of a paste formulation of firocoxib in horses with naturally occurring osteoarthritis was comparable to efficacy of a paste formulation of phenylbutazone.

Reason for Performing Study: Common methods used to treat back problems in horses need to be assessed objectively., Objectives: To measure spinal mechanical nociceptive thresholds (MNTs) and evaluate the effects of chiropractic, massage and phenylbutazone, compared with active and inactive control groups., Methods: Baseline MNTs at 7 sites within the thoracolumbar and sacral regions were measured in 38 healthy mature horses exhibiting no clinical signs of lumbar pain. Horses were assigned to one of 3 treatment groups: instrument-assisted chiropractic treatment, therapeutic massage and phenylbutazone; or 2 control groups: ridden exercise (active control) or routine paddock turnout with no ridden exercise (inactive control). MNT measurements were repeated at 1, 3 and 7 days post treatment. The percentage change from baseline MNT values was calculated within groups., Results: On Day 7, the median MNT had increased by 27, 12 and 8% in the chiropractic, massage and phenylbutazone groups, respectively. MNT changes of <1% were seen within the active and inactive control groups., Conclusions: Chiropractic treatment and massage therapy increased spinal MNTs within horses not exhibiting signs of lumbar pain., Potential Relevance: Pressure algometry provides an objective tool to evaluate the effects of commonly used, but currently unproven treatment modalities on spinal MNTs. Future studies need to evaluate combined treatment effects and longer-term MNT changes in horses with documented back pain.

Cervical spine involvement is common but usually delayed in patients with psoriatic arthritis. We report two cases with early and predominant involvement of the upper cervical spine. Synovitis of the atlanto-odontoid joint and fusion of multiple facet joints were noted in one patient. In the other patient, the main finding was atlanto-axial subluxation with erosions of the odontoid process and anterior arch of C1. No abnormalities were noted in the peripheral joints, sacroiliac joints, or thoracolumbar spine. Analgesics and conventional antiinflammatory agents were only minimally effective. TNFalpha antagonist therapy (infliximab followed by etanercept) in one patient and phenylbutazone therapy in the other improved the symptoms and led to shrinkage of the pannus.

Background: Equine herpesvirus type 1 (EHV-1) infection causes neurologic disease in horses. However, risk factors for the disease and long-term prognosis are poorly characterized., Hypothesis: There are identifiable risk factors for equine herpes-1 myeloencephalopathy., Animals: The entire population of 135 horses housed within the equestrian facility., Methods: A descriptive study investigated the clinical, serologic, virologic, and management aspects of an outbreak of EHV-1 myeloencephalopathy., Results: Out of 135 horses at the facility, 117 displayed signs of EHV-1 infection. Forty-six horses developed neurologic deficits characterized by symmetrical hind limb ataxia and weakness. Twelve horses that developed neurologic deficits became recumbent and did not survive. The development of severe neurologic deficits during the outbreak was associated with the presence of residual deficits at the 6-month examination. Within 1 year of the outbreak onset, all horses that survived had returned to an exercise level comparable to that experienced before the outbreak. Factors associated with the development of neurologic disease included age of > 5 years, location in the south or arena stall areas, and highest rectal temperature on day 3 or later of the febrile period., Conclusions and Clinical Importance: Being > 5 years of age, having had a rectal temperature of > 103.5 degrees F, and highest rectal temperature occurring on or after the 3rd day of the febrile period were the factors most predictive of the development of neurologic disease and death. Data obtained during this outbreak substantiate previous findings relating to clinical aspects and diagnosis of EHV-1 myeloencephalopathy. The prophylactic and therapeutic use of acyclovir during this outbreak is described.

To evaluate the effect of Calotropis G in various experimental animal models. The anti-inflammatory activity was evaluated using carrageenin-induced kaolin -induced rat paw oedema for acute and cotton-pellet granuloma, adjuvant-induced arthritis model for chronic inflammation. Antipyretic activity was carried out using yeast induced pyresis method. Phenylquinone--induced writhing method in mice was used for analgesic activity. Test compounds exhibited variable anti-inflammatory activity and peak activity of the test compounds were reached at 2 h. Alkaloid fraction possesses comparatively high initial anti-inflammatory activity. The residual anti-inflammatory activity of alkaloid fraction of Calotropis G suggest either a greater protein binding nature of the compound there by providing a slow released pool of active drug molecule in the system or non available of possible bioactive metabolites to retain the activity profile relation.

Ornithine transcarbamylase deficiency is the most common inherited urea cycle disorder. Its clinical manifestations as lethargy, vomites, coma and cerebral edema are the effect of the higher concentration of the ammonia in plasma. Hyperammonemia, caused by mutation in ornithine transcarbamylase gene, is often considered as a reason of coma by pediatricians but skipped by internist, although it is the third reason of hepatic coma in adults. This article is the recapitulation of published studies and their implication on everyday clinical practice.

An eighteen-month old quarter horse gelding was diagnosed with chip fractures from the distal lateral trochlear ridge of the talus. The horse presented with the symptom of persistent synovitis. The diagnosis was based on radiographic evidence. The horse was treated initially with arthroscopic surgery. He was given a non-steroidal anti-inflammatory agent, and a chondroprotective agent to prevent further damage to, and aid in the healing of, the damaged joint.

Objective: To evaluate use of electroacupuncture for treatment of horses with signs of chronic thoracolumbar pain., Design: Prospective study., Animals: 15 horses with signs of chronic thoracolumbar pain., Procedure: Horses were randomly allocated to 1 of 3 treatment groups. Horses in group 1 received electroacupuncture stimulation (once every 3 days for 5 treatments), those in group 2 received phenylbutazone (2.2 mg/kg [1 mg/lb], PO, q 12 h, for 5 days), and those in group 3 received saline (0.9% NaCl) solution (20 mL, PO, q 12 h, for 5 days). Thoracolumbar pain scores (TPSs) were evaluated before (baseline) and after each treatment., Results: Mean +/- SE TPSs in horses receiving phenylbutazone or saline solution did not change significantly during the study. After the third treatment, mean +/- SE TPS (2.1 +/- 0.6) in horses receiving electroacupuncture stimulation was significantly lower than baseline (6.0 +/- 0.6) TPS. Mean +/- SE TPSs in horses receiving electroacupuncture stimulation were significantly lower than baseline TPSs and TPSs in horses receiving phenylbutazone or saline solution after the third treatment to 14 days after the last treatment., Conclusions and Clinical Relevance: TPSs are useful for evaluating the efficacy of various analgesic methods used for treatment of thoracolumbar pain in horses. Electroacupuncture was effective for treatment of chronic thoracolumbar pain in horses. Results provided evidence that 3 sessions of electroacupuncture treatment can successfully alleviate signs of thoracolumbar pain in horses. The analgesic effect induced by electroacupuncture can last at least 2 weeks. Phenylbutazone administered PO did not effectively alleviate signs of thoracolumbar pain in horses in this study.

Objective: To quantitatively compare 3 commonly used treatments for navicular syndrome (NS) in horses: heel-elevation shoeing alone, heel-elevation shoeing and phenylbutazone administration, heel-elevation shoeing and injection of the distal interphalangeal joint (DIPJ) with triamcinolone acetonide (TA), and all 3 treatments in combination., Animals: 12 horses with NS., Procedure: A force plate was used to measure baseline peak vertical ground reaction force (PVGRF) of the forelimbs. Each horse's forelimbs were shod with 3 degrees heel-elevation horseshoes; PVGRF was measured 24 hours and 14 days after shoeing. Fourteen days after shoeing (following data collection), phenylbutazone (4.4 mg/kg, i.v., q 12 h) was administered (5 treatments). Two hours after the fifth treatment, PVGRF was measured; TA (6 mg) was injected into the DIPJ of the forelimb that generated the lower baseline PVGRF Fourteen days later, PVGRF was measured. Phenylbutazone was administered as before, and PVGRF was measured. Percentage body weight of force (%BWF) was calculated from PVGRF measurements and used for comparisons., Results: 14 days after shoeing, mean %BWF in both forelimbs significantly increased from baseline; additional administration of phenylbutazone significantly increased %BWF applied from the more lame forelimb. Compared with shoeing alone, there was no significant change in %BWF after injection of the DIPJ with TA in shod horses., Conclusions and Clinical Relevance: Heel-elevation shoeing alone and in combination with phenylbutazone administration quantitatively decreased lameness in horses with NS. Although not significant, additional DIPJ injection with TA resulted in further quantitative decrease in lameness, compared with that achieved via shoeing alone.

A 12-year-old American Saddlebred gelding was referred to a veterinary teaching hospital for evaluation of a chronic lameness problem in the right radiocarpal joint. The horse had been treated for osteoarthritis of the right radiocarpal joint with multiple injections of cortisone during the past 3 years. The horse was severely lame on the right forelimb at a trot. Radiography and computed tomography revealed a 3 x 2-cm lytic defect in the distal portion of the radius and periarticular bone proliferation around the right radiocarpal joint. Ultrasonography of the distal portion of the radius revealed a soft tissue mass in the palmarolateral aspect of the joint. Proliferative synovium with a large amount of fibrin was observed in the dorsal and palmar aspects of the joint via arthroscopic examination of the right radiocarpal joint. Histologic examination of synovial biopsy specimens revealed proliferative granulomatous synovitis with giant cells. Mycobacterium avium complex was cultured from the synovial fluid. Infection with M avium complex should be considered in horses with chronic recurring arthritis associated with granulomatous synovitis.

Objective: To compare analgesic effects of phenylbutazone administered at a dosage of 4.4 mg/kg/d (2 mg/lb/d) or 8.8 mg/kg/d (4 mg/lb/d) in horses with chronic lameness., Design: Controlled crossover study. Animals-9 horses with chronic forelimb lameness., Procedure: Horses were treated i.v. with phenylbutazone (4.4 mg/kg/d or 8.8 mg/kg/d) or saline (0.9% NaCl) solution once daily for 4 days. All horses received all 3 treatments with a minimum of 14 days between treatments. Mean peak vertical force (mPVF) was measured and clinical lameness scores were assigned before initiation of each treatment and 6, 12, and 24 hours after the final dose for each treatment., Results: Compared with values obtained after administration of saline solution, mPVF was significantly increased at all posttreatment evaluation times when phenylbutazone was administered. Clinical lameness scores were significantly decreased 6 and 12 hours after administration of the final dose when phenylbutazone was administered at the low or high dosage but were significantly decreased 24 hours after treatment only when phenylbutazone was administered at the high dosage. No significant differences in mPVF and clinical lameness scores were found at any time when phenylbutazone was administered at the low versus high dosage., Conclusions and Clinical Relevance: Results suggest that the high dosage of phenylbutazone was not associated with greater analgesic effects, in terms of mPVF or lameness score, than was the low dosage. Considering that toxicity of phenylbutazone is related to dosage, the higher dosage may not be beneficial in chronically lame horses.

The symptoms and signs of ornithine transcarbamylase deficiency are discussed. When the condition occurs among males in the neonatal period it is likely to be lethal. Pathological findings are non-specific. The diagnosis should be considered if coma with cerebral oedema and respiratory alkalosis occurs for no obvious reason. When hyperammonaemia is found, enzyme assay on a liver biopsy should be considered. A useful clue in an asymptomatic patient is a voluntary adoption of a vegetarian diet. Provocative tests, such as the allopurinol test can be used, but the method most frequently applied is mutation analysis. In the case of prenatal diagnosis this is possible on a chorionic villus sample. The prognosis of ornithine transcarbamylase deficiency is better for those with an onset after infancy, but morbidity from brain damage does not appear to be linked to the number of episodes of hyperammonaemia that have occurred. The syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase which catalyses the conversion of ornithine and carbamoyl phosphate to citrulline. The gene responsible for this enzyme is located on Xp21.1, and is expressed in the liver and gut. Mutations can be divided into two groups: those with neonatal onset with all enzyme activity abolished, and those with later onset with partial and varying enzyme deficiency. There can be a variety of precipitating causes, for example sodium valproate. Treatment can be given with a low protein diet, and with alternate pathway drugs such as sodium benzoate and phenylbutyrate. Liver transplant can be considered when symptoms are life-threatening, although there may be severe complications.Gene replacement therapy is the hope of the future.

Two patients with severe bleeding complications under oral anticoagulant treatment are presented, in one case caused by pharmacokinetic drug interference (phenylbutazone), in the other by genetic predisposition to bleeding induced by coumarin anticoagulants. Another patient with decreasing INR due to drug interference (rifampicin) is presented as well. The possibility of drug interferences with coumarin anticoagulants has to be anticipated, whenever the medication of an orally anticoagulated patient is changed. A founder mutation of the factor IX propeptide constitutes a genetic predisposition to bleeding in patients put on coumarins. Its presence should be excluded in any patient suffering from hemorrhagic complications after starting anticoagulation when INR values are in the target range.