Investigations into the analysis of intact drug conjugates in animal sport doping control - Development and assessment of a rapid and economical approach for screening greyhound urine.

Animal sport doping control laboratories are constantly reviewing ways in which they can improve their service offering whilst ensuring that they remain economically viable. This paper describes the development and assessment of a rapid and economical method for the detection of intact glucuronide conjugates of three anabolic steroids and their metabolites along with three corticosteroids in canine urine. The analysis of intact drug conjugates for animal sport doping control is generally not performed routinely as it presents a number of analytical challenges, not least of which is the lack of availability of appropriate reference standards. Here, we report the development of a UHPLC-MS/MS method using APCI in the negative ion mode for the detection of intact phase II conjugates, including the importance of in vitro incubations in order to provide appropriate reference materials. Cross-validation of the developed method demonstrated that the detection capability of the intact phase II conjugates of stanozolol, boldenone, nandrolone, and their metabolites along with the corticosteroids dexamethasone and methylprednisolone was equivalent to that achieved in routine race-day screens. The new process has been in operation for approximately 2 years and has been used to analyze in excess of 13500 canine urine samples, resulting in a number of positive screening findings. To the best of our knowledge, this is the first reported use of a routine screen for intact drug conjugates within animal sport doping control.

The pharmacokinetics of orally administered butylscopolamine in greyhound dogs.

The oral tablet formulation of butylscopolamine, which is available without prescription, is commonly used by trainers of racing greyhounds to treat functional urethral obstruction. As medication control of butylscopolamine is therefore required for such use to ensure the integrity of greyhound racing, an administration study was performed in six greyhounds to determine the pharmacokinetics of orally administered butylscopolamine. A single dose of one 10 mg butylscopolamine tablet was administered orally to simulate this use in greyhound racing. Blood, urine and faeces were collected at regular intervals from the greyhounds for up to 9 days and butylscopolamine concentrations determined. There was some, but very limited, absorption of butylscopolamine, with rapid elimination from plasma with a mean half-life of 2 hr. Urine concentrations initially declined in a similar manner to the plasma pharmacokinetics but then entered a much longer half-life of approximately 50 hr. Faecal concentrations declined to very low levels between 48 and 120 hr. The use of orally administered butylscopolamine for functional urethral obstruction in greyhounds is unjustified due to this very limited drug absorption. Medication control of butylscopolamine's antispasmodic effect on the digestive tract is possible by setting screening limits based on the urinary and faecal drug levels as determined in this study.

Comparison of pulmonary artery catheter, echocardiography, and arterial waveform analysis monitoring in predicting the hemodynamic state during and after cardiac surgery.

OBJECTIVE: The aim of this trial was to determine whether Flotrac Vigileo™ (FV™) provides a reliable representation of the hemodynamic state of a cardiac surgical patient population when compared to pulmonary artery catheter (PAC) and echocardiography in the peril-operative period. DESIGN: This was a prospective observational trial comparing perioperative hemodynamic states using transesophageal echocardiography (TEE), transthoracic echocardiography (TTE), FV™ and PAC during and post cardiothoracic surgery. SETTING: Tertiary regional hospital Intensive Care Unit (ICU). PARTICIPANTS: 50 consecutive adult cardiothoracic patients with written consent provided. INTERVENTION: Comparison of the perioperative hemodynamic states using echocardiography, FV™ and PAC was performed. Evaluation of the hemodynamic state (HDS) was performed using TEE, TTE, PAC and FV™ during and after cardiac surgery. Data were compared between the three hemodynamic assessment modalities. MAIN OUTCOME MEASURE: Predicted hemodynamic state. RESULTS: FV™ and PAC were shown to correlate poorly with TEE/TTE assessment of the hemodynamic state. Both PAC and FV™ showed significant discordance with echocardiographic assessment of the hemodynamic state. CONCLUSIONS: In this trial, FV™ and PAC were shown to agree poorly with TTE/TEE assessment of the HDS in an adult cardiothoracic population. Agreement between the FV™ and PAC was also poor. Caution is recommended in interpreting isolated hemodynamic monitoring data. All hemodynamic monitoring devices have inherent sources of error. Caution is advised in interpreting any single device or measurement as a gold standard. We suggest that hemodynamic measuring devices such as FV™/PAC may act as triggers for a global hemodynamic assessment including consideration of TTE/TEE.

The Effectiveness and Safety of Tranexamic Acid in Orthotopic Liver Transplantation Clinical Practice: A Propensity Score Matched Cohort Study.

BACKGROUND: Randomized trials have demonstrated the efficacy of tranexamic acid (TXA) in reducing blood loss and transfusion requirements during liver transplantation. However, clinical utilization is limited due to a perceived lack of generalizable effectiveness and concerns regarding its thromboembolic risks. The aim of this study was to describe the clinical use of TXA and to provide a pragmatic reappraisal of its effectiveness and safety. METHODS: After ethics approval, data were collected from 1799 consecutive liver transplant recipients between January 1, 2002, and December 31, 2015, using retrospectively collected electronic databases. Propensity matching was used to account for confounders of transfusion and thrombotic risk. Exposure was defined as a total TXA dose greater than 10 mg/kg for 50% of the operative duration. RESULTS: After propensity matching, 367 unique pairs were well balanced in terms of all measured covariates. In the matched pairs, patients exposed to TXA received less red blood cell (3 [0, 6] vs 4 [1, 7] P = 0.003) and frozen plasma (6 [2, 10] vs 6 [2, 12], P = 0.032) transfusions. There were no differences in thromboembolic events between the groups (22 [6.0%] vs 36 [9.8%]). CONCLUSIONS: TXA appears effective in reducing red blood cell transfusion requirements without increasing the risk of thromboembolic events across a wide variety of liver transplant recipients, including those at low risk of bleeding or high risk of thromboembolic complications. We did not detect evidence of an increased risk of thrombotic complications with TXA exposure.

Removal of a bullet in the pericardial cavity by video-assisted thoracoscopic surgery.

The use of video-assisted thoracoscopic surgery (VATS) in dealing with thoracic trauma has been well established. VATS avoids a thoracotomy and offers excellent visualization of the entire pleural cavity. The removal of bullets from the pleural cavity using VATS has also been reported, but, to our knowledge, this is the first time a bullet has been removed from the pericardial cavity using VATS.