A study of the pharmacokinetics and thromboxane inhibitory activity of a single intramuscular dose of carprofen as a means to establish its potential use as an analgesic drug in white rhinoceros.

The alleviation of pain and prevention of suffering are key aspects of animal welfare. Unfortunately, analgesic drugs are not available for all species. White rhinoceros (Ceratotherium simum), representing one of such species, which survive poaching attempts inflicted with severe facial injuries and gunshot wounds, nonetheless require analgesic support. To improve treatment conditions, this study explored the use of carprofen for the treatment of pain and inflammation in white rhinoceros. The pharmacokinetics of 1 mg/kg intramuscular carprofen was evaluated in six healthy white rhinoceros. The half-life of λz and mean residence time was 105.71 ± 15.67 and 155.01 ± 22.46 hr, respectively. The area under the curve and the maximum carprofen concentration were 904.61 ± 110.78 µg ml-1  hr-1 and 5.77 ± 0.63 µg/ml, respectively. Plasma TXB2 inhibition demonstrated anti-inflammatory properties and indicated that carprofen may be effective for a minimum of 48 hr in most animals. With its long half-life further indicating that a single dose could be effective for several days, we suggest that carprofen may be a useful drug for the treatment of white rhinoceros.

Risk Factors for Equine Gastric Glandular Disease: A Case-Control Study in a Finnish Referral Hospital Population.

BACKGROUND: Equine gastric glandular disease (EGGD) is a term used to classify erosive and ulcerative diseases of the glandular mucosa of the equine stomach. Epidemiologic studies of risk factors for EGGD have not been reported. OBJECTIVE: To determine risk factors for EGGD. ANIMALS: Cases (n = 83) had endoscopic evidence of EGGD; controls (n = 34) included healthy horses and horses with equine squamous gastric disease (ESGD) without EGGD. METHODS: Retrospective case-control study. The data were analyzed by multivariable logistic regression modeling. Analysis was performed on the full dataset. An additional analysis compared horses with glandular lesions (n = 43) against healthy horses (n = 22). RESULTS: On first analysis, Warmblood breed (OR = 13.9, 95% CI 2.2-90.9, P = .005) and an increasing number of caretakers (OR = 7.3, 95% CI 0.98-55.6, P = .053) were associated with an increased risk of EGGD. On analysis of the subset of data, Warmblood breed (OR = 28.6, 95% CI 2.96-250.0, P = .004) and increasing number of riders (OR = 12.99, 95% CI 0.94-166.7, P = .056) were risk factors. The presence of sand in the colon appeared to have a protective effect against EGGD (OR = 0.195, 95% CI 0.04-1.0, P = .051 for sand versus not having sand). CONCLUSIONS AND CLINICAL IMPORTANCE: This study suggests that Warmbloods are predisposed to EGGD and multiple handlers/riders might increase the risk of EGGD. Identification of risk factors allows speculation on potential pathophysiological mechanisms of EGGD.

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

REASONS FOR PERFORMING STUDY: Infiltrative disease of the intestine is an important cause of weight loss in the horse. Infiltration of inflammatory or neoplastic cells into the intestinal wall and intestinal fibrosis cause changes in the integrity of the intestinal wall. This may lead to altered intestinal permeability which can be measured using the contrast medium iohexol. OBJECTIVES: To determine if iohexol intestinal permeability, as evaluated by serum iohexol concentration, could be used to differentiate between healthy horses and horses with infiltrative disease of the large colon. STUDY DESIGN: Prospective non-randomised controlled clinical trial. METHODS: Six healthy adult horses and 4 horses with chronic infiltrative disease of the large colon were used in the study. Infiltrative disease was confirmed on post mortem in all cases, and included alimentary lymphoma and mycobacterial granulomatous enterocolitis. Following a 16-h fast, each horse was dosed with 1.0 ml/kg bwt of iohexol as a 10% solution via nasogastric intubation. Blood samples were collected at 0, 30, 60, 120, 180, 240, 300, 360, 420 and 480 min after dosing. Iohexol concentration was determined using HPLC-UV and the differences between the groups were analysed with a repeated measures ANOVA. RESULTS: There was a statistically significant difference in iohexol serum concentration between the diseased and nondiseased horses (P = 0.001). The overall difference in the mean iohexol concentration between the 2 groups was 6.07 (95% CI 3.19-8.96) µg/ml, however there appeared to be a trend towards increasing difference at later time points (240, 300, 360 min). CONCLUSIONS: The iohexol permeability test has potential as a diagnostic tool for estimation of intestinal permeability in horses with infiltrative intestinal disease. Further studies are warranted to determine whether the test can be used to determine the site of intestinal pathology, predict the prognosis and potentially evaluate the response to treatment. ACKNOWLEDGEMENTS: The authors thank Professor Riitta-Mari Tulamo and Professor Thomas Spillmann and the staff of Equine College Ypäjä and the University of Helsinki Equine Teaching Hospital. The cooperation of horse owners is gratefully acknowledged. Ethical animal research: The study protocol was approved by the National Animal Experiment Board of Finland (Eläinkoelautakunta ELLA, Request for Animal Experiments, ref. no. ESAVI-2010-06567/Ym-23). For client-owned animals, owner informed consent was obtained. SOURCE OF FUNDING: This study was funded by the Faculty of Veterinary Medicine, University of Helsinki, Finland. Competing interests: None declared.

Investigations of the reliability of observational gait analysis for the assessment of lameness in horses.

The objectives of this study were to assess the reliability of a numerical rating scale (NRS) and a verbal rating scale (VRS) for the assessment of lameness in horses and to determine whether they can be used interchangeably. Sixteen independent observers graded the severity of lameness in 20 videotaped horses, and the agreement between and within observers, correlation and bias were determined for each scale. The observers agreed with each other in 56 per cent of the observations with the NRS and in 60 per cent of the observations with the VRS, and the associated Kendall coefficient of concordance was high. Similar trends were evident in the agreement between two observations by each observer. The correlation between and within observers was high for both scales. There were no significant differences (bias) among the observers' mean scores when using either scale. There was a significant correlation between the lameness scores attributed when using the two scales, but the differences between the scores when plotted against their overall mean were unacceptable for clinical purposes. The results indicate that the NRS and VRS are only moderately reliable when used to assess lameness severity in the horse, and that they should not be used interchangeably.

Sucrose concentration in blood: a new method for assessment of gastric permeability in horses with gastric ulceration.

A urine sucrose test has recently been reported to be a reliable method of detecting gastric ulcers in horses; however, technical difficulties associated with urine collection have limited the practical value of the test. The objective of this pilot study was to determine whether gastric sucrose permeability, as evaluated by serum sucrose concentration, could be used to detect gastric mucosal injury in horses. Twelve adult horses with naturally acquired gastric ulceration were studied. After a 20-hour nonfeeding period, each horse was dosed with 250 g of sucrose via nasogastric intubation. Blood samples were collected at 0, 15, 30, 45, 60, and 90 minutes, and horses underwent gastroscopy 4 hours later. The severity of gastric ulceration in each horse was defined by means of a 4-point ulcer-scoring system, and the relationship with serum sucrose concentration was analyzed by means of a linear mixed-effects model. Serum sucrose concentration was measured by liquid chromatography operating in tandem with electrospray mass spectrometry. After nasogastric administration of table sugar, horses with moderate to severe gastric ulceration had significant increase in serum sucrose concentration at 30, 45, 60, and 90 minutes, relative to earlier times (P < .05). Peak sucrose concentration was observed at 45 minutes, and was correlated with ulcer severity (Spearman's rank correlation coefficient = 0.898, P < .05). These data indicate that determination of sucrose concentration in equine serum may be a useful test for identifying horses with endoscopically visible gastric ulceration and has potential use as a noninvasive method for screening and monitoring horses engaged in racing training and other performance-related disciplines.

Rupture of the flexor tendons of a horse secondary to a non-responsive digital sheath sepsis.

A 12-year-old hunter gelding became severely lame as a result of a laceration to the sheath of the digital flexor tendons of its left hindlimb, but there was no apparent damage to the tendons. The injury became chronically infected with Pseudomonas and Streptococcus species and Escherichia coli which did not respond to antibiotic treatment, and the horse remained lame. A postmortem examination revealed that the tendons had ruptured.

An economic evaluation of the use of granulocyte colony-stimulating factor after bone marrow transplantation in children.

Studies that have assessed the use of granulocyte colony-stimulating factor (G-CSF) following bone marrow transplantation have shown a significantly reduced time to neutrophil recovery with the use of this agent, which may translate into a reduced duration of antimicrobial therapy and hospitalisation. We performed a pharmacoeconomic study evaluating the elective use of G-CSF after bone marrow transplantation in children. 22 consecutive children who underwent bone marrow transplantation and received G-CSF 5 micrograms/kg/day were compared with 18 such children (control group) who did not receive G-CSF. Despite a significant reduction in time to recovery of the absolute neutrophil count (ANC) to > 0.5 x 10(9)/L in G-CSF recipients compared with the control group (14 days vs 20.9 days; p < 0.0001), there was only a trend towards a reduction in the duration of intravenous antimicrobial therapy (14.5 days vs 18.6 days; p = 0.15), and there was no significant difference in the duration of hospitalisation (25.3 days vs 29.8 days). Reasons for prolonged hospitalisation beyond ANC recovery included continued use of total parenteral nutrition, treatment of graft-versus-host disease and treatment of ongoing infection. Overall, the mean total cost for patients receiving G-CSF was Pounds 15001, compared with Pounds 15482 for the control group (1995 values). In conclusion, while there appears to be no benefit in financial terms, the release of a child from strict isolation as a result of early ANC recovery must be taken into consideration.

An economic evaluation of peripheral blood stem cell transplantation as an alternative to autologous bone marrow transplantation in multiple myeloma.

Autologous peripheral blood stem cell transplantation (PBSCT) is increasingly being utilised as an alternative to autologous bone marrow transplantation (ABMT) in the treatment of malignant diseases. We have performed a pharmacoeconomic study using cost-minimisation analysis to evaluate the two techniques in a population of multiple myeloma patients undergoing PBSCT (n = 37) or ABMT (n = 14). In the PBSCT group, the time to > 0.5 x 10(9)/l neutrophils was significantly shorter (16 vs 22 days; P = 0.0019) as was the time to > 50 x 10(9)/l platelets (19 vs 27 days; P = 0.0019). The faster haematopoietic recovery resulted in a reduced period of intravenous antibiotic therapy (12 vs 19 days; P < 0.0001), reduced requirements for platelet transfusions (12 vs 31.5 units; P = 0.0005), and ultimately, a significant reduction in duration of hospitalisation (19 vs 27.5 days; P < 0.0001). These clinical benefits translated into economic benefits such that the total cost in the PBSCT group was 27.5% less than in the ABMT group (< Pounds 7995 vs < Pounds 11026; P = 0.0001). We conclude that the use of PBSCT as an alternative to ABMT in patients with multiple myeloma is associated with demonstrable economic advantages in addition to clinical benefits.

Costs of antifungal prophylaxis after bone marrow transplantation. A model comparing oral fluconazole, liposomal amphotericin and oral polyenes as prophylaxis against oropharyngeal infections.

We used a costs model to compare alternative modes of prophylaxis against oropharyngeal fungal infections in patients with leukaemia or myeloma who had undergone bone marrow transplantation (BMT). We compared 2 innovative pharmaceutical options (oral fluconazole and intravenous liposomal amphotericin) with existing standard practice (oral polyenes). Costs were measured over a 12-week treatment period, and were compared with the 2 effectiveness measures: (i) the avoidance of colonisation or infection; and (ii) the patients' ability to continue with prophylaxis in an uninfected state. The costs and effectiveness of BMT itself were not considered in this evaluation. The costs per successfully treated patient over a 12-week period were 28,956 pounds (1 pound = $US1.60, June 1995) for oral fluconazole, 53,225 pounds for liposomal amphotericin and 32,768 pounds for oral polyenes. Sensitivity analysis showed that the costs of liposomal amphotericin always exceeded those of the oral comparators, reflecting its high acquisition, preparation and administration costs.

Results of a double blind placebo controlled study of ondansetron as an antiemetic during total body irradiation in patients undergoing bone marrow transplantation.

Total body irradiation (TBI) is a highly emetogenic component of the majority of conditioning regimens in use for bone marrow transplantation. Conventional antiemetic therapy fails to control nausea and vomiting induced by single fraction TBI in as many as 50% of patients. In a double blind study of 20 patients undergoing marrow transplantation, a single 8 mg ondansetron dose was compared with placebo given immediately prior to TBI. Our routine premedication of phenobarbitone and corticosteroid was also administered to all patients. All patients had received high dose melphalan the previous evening. Only 1 of the 10 patients in the ondansetron group experienced an emetic event compared with 5 of the 10 in the comparison group (p = 0.029). No significant adverse events were observed. Ondansetron appears to have extremely useful antiemetic activity during single fraction low dose rate TBI.