Modified Broström With and Without Suture Tape Augmentation: A Systematic Review.

The Modified Broström has become the gold standard for operative management of chronic lateral ankle instability. Despite overall good clinical outcomes with this procedure, recent biomechanical data have called into question the strength and durability of this technique. Accordingly, the addition of suture tape to the Modified Broström construct has been described in an attempt to more closely recreate the natural biomechanical properties of the ankle lateral ligament complex. We performed a systematic review of the literature was using PubMed, Embase, and CINAHL to identify English-language articles from 2009 to present discussing outcomes with the augmented Modified Broström technique. A total of 4 studies (2 retrospective cohort studies, 2 case series) involving 156 patients with Modified Broström with augmentation met inclusion criteria. Average follow-up time was 13.8 months. Of the 3 studies reporting patient-reported outcome measures both pre- and postoperatively, there was a significant improvement in all measures (p < .05). Two studies compared the Modified Broström directly with and without augmentation, one of which found a statistically significant difference in the Foot and Ankle Ability Measure in favor of the augmentation group (93.1 vs 90.5, p = .027), while American Orthopaedic Foot and Ankle Society score was not significantly different (p > .05) between the 2 procedures across studies. There were no significant differences in complications between techniques. Modified Broström with suture tape augmentation for chronic lateral ankle instability can produce good short-term clinical outcomes with few complications, comparable to the Modified Broström alone.

Clinical Outcomes After Extracorporeal Shock Wave Therapy for Chronic Plantar Fasciitis in a Predominantly Active Duty Population.

Chronic plantar fasciitis is a common cause of foot pain, with conservative treatment providing relief for most patients. However, because of the common occurrence of this pathology, this leaves many patients dissatisfied. The purpose of the present study was to determine the effectiveness of extracorporeal shock wave therapy (ESWT) to treat chronic plantar fasciitis (PF) in a largely active duty population. A review of 82 patients (115 heels) who had undergone ESWT for chronic PF was performed. Outcome data were obtained by patient telephone interviews. All ESWT was conducted at 24 kV for 2000 shocks. Of the 82 patients (115 heels), 76 (93%; 111 heels) agreed to participate. Their mean age was 42 ± 10 years, with 41 males (54%) and 35 females (46%). The mean follow-up period was 42 ± 22 months. Of the patients, 73.6% were active duty military personnel. The mean preoperative pain score of 7.8 ± 2 had improved to 2.5 ± 2 at the last follow-up visit (p <.0001). Active duty patients reported a mean improvement in pain of 4.8 ± 3 compared with 6.8 ± 3 in non-active duty patients (p = .005). Of the 76 patients, 75 (98%) underwent 1 ESWT session, and 1 (2%) requiring 2 sessions. Overall, 74% of patients rated the outcome of their procedure as either good or excellent, with 87% stating that ESWT was successful. Ten patients (18%) left the military because of continued foot pain, with 76% able to return to running. For patients with chronic PF, these results support the use of ESWT to relieve pain in >85% of patients, with a preponderance for better pain relief in patients who are not active duty military personnel.

Angular control of optical cavities in a radiation-pressure-dominated regime: the Enhanced LIGO case.

We describe the angular sensing and control (ASC) of 4 km detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO). Enhanced LIGO, the culmination of the first generation LIGO detectors, operated between 2009 and 2010 with about 40 kW of laser power in the arm cavities. In this regime, radiation-pressure effects are significant and induce instabilities in the angular opto-mechanical transfer functions. Here we present and motivate the ASC design in this extreme case and present the results of its implementation in Enhanced LIGO. Highlights of the ASC performance are successful control of opto-mechanical torsional modes, relative mirror motions of ≤ 1×10(-7) rad rms, and limited impact on in-band strain sensitivity.

Botox as an adjuvant to tendon transfer for foot drop.

The authors' hypothesis was that weakening the gastrocnemius muscle at the time of tendon transfer will reduce the risk of rupture and facilitate faster rehabilitation with increased active dorsiflexion and improved overall outcome, because the transferred tendon is spared the antagonistic effect of the gastrocnemius during the early recovery period. A retrospective chart review identified 12 patients who underwent a tibialis posterior tendon (PTT) transfer with gastrocnemius Botox injection for foot drop. All statistical analyses were conducted using SAS version 9.2 (SAS Institute, Inc., Cary, North Carolina). There were no failures or tendon ruptures. All patients had zero dorsiflexion (DF) strength preoperatively, and those with DF strength documented postoperatively had a mean DF strength at final clinical evaluation of 3.9 (p < .001) with a mean active DF of 4°. It was concluded that gastrocnemius chemodenervation with Botox at the time of PTT transfer is a safe and effective means of restoring active dorsiflexion.

Racial and Gender Diversity of Physicians Accepted to American Military Orthopaedic and Surgical Residencies: An 18-Year Analysis.

Orthopaedic surgery ranks among the least racially and gender diverse medical/surgical specialties. United States military surgeons train in military or military-funded residency positions to care for a markedly diverse population; however, the composition and diversity of these training programs have not been previously assessed. The purpose of this study was to analyze the trends of physician diversity in military orthopaedics in comparison with other surgical specialties over time. Methods: We performed a retrospective cohort study evaluating matriculation into first year of residency training in US military surgical training programs between 2002 and 2020. In total, 9,124 applicants were reviewed. We collected matriculant self-reported race/ethnicity and sex and the medical/specialty program. We considered under-represented minorities as those who reported their race as African American, Indian/Alaskan Native, and Native, other, or who reported ethnicity as Hispanic. We calculated changes in persons accepted to training positions over time and used linear regression to model trends in diversity among orthopaedic matriculating residents when compared with other surgical subspecialities over time. Results: Across all surgical subspecialities, the average change in percent women was 0.94% per year for the study period (p < 0.01). The average annual percent women entering orthopaedic surgery residency programs was 14% for the 18-year study period. Across all surgical subspecialties, the average change for accepted applicants from groups underrepresented in medicine (URiM) was 1.01% per year for the study period (p < 0.01). The average annual percent URiM entering orthopaedic surgery residency programs was 17% for the 18-year study period. The annual change of women and URiM entering military orthopaedic residencies was 0.10% and 1.52%, respectively. Conclusions: Despite statistically significant improvements, recruitment efforts as used to date fall far short of reversing sexual, racial, and ethnic disparities in military orthopaedic residencies. Orthopaedics has a lower representation of both women and physicians with minority backgrounds when compared with many surgical subspecialties. Additional interventions are still necessary to increase diversity for military orthopaedic surgeons.

Toltrazuril sulfone sodium salt: synthesis, analytical detection, and pharmacokinetics in the horse.

Toltrazuril sulfone (ponazuril) is a triazine-based antiprotozoal agent with clinical application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In this study, we synthesized and determined the bioavailability of a sodium salt formulation of toltrazuril sulfone that can be used for the treatment and prophylaxis of EPM in horses. Toltrazuril sulfone sodium salt was rapidly absorbed, with a mean peak plasma concentration of 2400 ± 169 (SEM) ng/mL occurring at 8 h after oral-mucosal dosing and was about 56% bioavailable compared with the i.v. administration of toltrazuril sulfone in dimethylsulfoxide (DMSO). The relative bioavailability of toltrazuril sulfone suspended in water compared with toltrazuril sulfone sodium salt was 46%, indicating approximately 54% less oral bioavailability of this compound suspended in water. In this study, we also investigated whether this salt formulation of toltrazuril sulfone can be used as a feed additive formulation without significant reduction in oral bioavailability. Our results indicated that toltrazuril sulfone sodium salt is relatively well absorbed when administered with feed with a mean oral bioavailability of 52%. Based on these data, repeated oral administration of toltrazuril sulfone sodium salt with or without feed will yield effective plasma and cerebrospinal fluid (CSF) concentrations of toltrazuril sulfone for the treatment and prophylaxis of EPM and other protozoal diseases of horses and other species. As such, toltrazuril sulfone sodium salt has the potential to be used as feed additive formulations for both the treatment and prophylaxis of EPM and various other apicomplexan diseases.

Effect of increased weight on ankle mechanics and spatial temporal gait mechanics in healthy controls.

BACKGROUND: Ankle osteoarthritis has been associated with trauma, instability, and inflammatory arthritis. Limited literature exists examining the effect of body weight on ankle joint loading. The purpose of this study was to examine the relationship between increased weight and gender on ankle kinematics and kinetics. METHODS: Fifty-three (28 male, 25 female) subjects were recruited for the study. All subjects underwent a standard level walking gait analysis in four different weight conditions (normal, 10%, 15%, and 20% increased body weight). Testing order was randomized. A series of mixed-factor, repeated-measures analyses of variance (weight by gender) were used to determine statistical differences between the groups (p < .05). RESULTS: Walking speed was not significantly different between gender or weight conditions. No significant differences existed for step length, step time, stride length, swing time, or sagittal plane ankle kinematics and kinetics. A significant increase in plantarflexion moment existed for the males (p < .05). The peak plantarflexion moment increased as weight increased. Single support time (p = .042) was significantly different between the no weight and the 15% and 20% increased weight conditions. In addition, double support time was significantly longer in the males compared with females (p < .001) and significantly increased for each weight condition (p < .001). CONCLUSION: Increasing weight alters spatial temporal mechanics and sagittal plane ankle kinetics in a healthy control population. The effect of increasing weight appears to be similar between genders. CLINICAL RELEVANCE: The findings of the present study may be relevant for future studies to assess the role of weight as a potential covariate on postoperative outcomes and gait mechanics.

Development of Policy-Relevant Indicators for Injury Prevention in British Columbia by the Key Decision-Makers.

Indicators can help decision-makers evaluate interventions in a complex, multi-sectoral injury system. We aimed to create indicators for road safety, seniors falls, and 'all-injuries' to inform and evaluate injury prevention initiatives in British Columbia, Canada. The indicator development process involved a five-stage mixed methodology approach, including an environmental scan of existing indicators, generating expert consensus, selection of decision-makers and conducting a survey, selection of final indicators, and specification of indicators. An Indicator Reference Group (IRG) reviewed the list of indicators retrieved in the environmental scan and selected candidate indicators through expert consensus based on importance, modifiability, acceptance, and practicality. Key decision-makers (n = 561) were invited to rank each indicator in terms of importance and actionability (online survey). The IRG applied inclusion criteria and thresholds to survey responses from decision-makers, which resulted in the selection of 47 road safety, 18 seniors falls, and 33 all-injury indicators. After grouping "like" indicators, a final list of 23 road safety, 8 seniors falls, and 13 all-injury indicators were specified. By considering both decision-maker ranking and expert opinion, we anticipate improved injury system performance through advocacy, accountability, and evidence-based resource allocation in priority areas. Our indicators will inform a data management framework for whole-system reporting to drive policy and funding for provincial injury prevention improvement.

Generating the American Shoulder and Elbow Surgeons Score Using Multivariable Predictive Models and Computer Adaptive Testing to Reduce Survey Burden.

BACKGROUND: The preferred patient-reported outcome measure for the assessment of shoulder conditions continues to evolve. Previous studies correlating the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests (CATs) to the American Shoulder and Elbow Surgeons (ASES) score have focused on a singular domain (pain or physical function) but have not evaluated the combined domains of pain and physical function that compose the ASES score. Additionally, previous studies have not provided a multivariable prediction tool to convert PROMIS scores to more familiar legacy scores. PURPOSE: To establish a valid predictive model of ASES scores using a nonlinear combination of PROMIS domains for physical function and pain. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 3. METHODS: The Military Orthopaedics Tracking Injuries and Outcomes Network (MOTION) database is a prospectively collected repository of patient-reported outcomes and intraoperative variables. Patients in MOTION research who underwent shoulder surgery and completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at varying time points were included in the present analysis. Nonlinear multivariable predictive models were created to establish an ASES index score and then validated using "leave 1 out" techniques and minimal clinically important difference /substantial clinical benefit (MCID/SCB) analysis. RESULTS: A total of 909 patients completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at presurgery, 6 weeks, 6 months, and 1 year after surgery, providing 1502 complete observations. The PROMIS CAT predictive model was strongly validated to predict the ASES (Pearson coefficient = 0.76-0.78; R2 = 0.57-0.62; root mean square error = 13.3-14.1). The MCID/SCB for the ASES was 21.7, and the best ASES index MCID/SCB was 19.4, suggesting that the derived ASES index is effective and can reliably re-create ASES scores. CONCLUSION: The PROMIS CAT predictive models are able to approximate the ASES score within 13 to 14 points, which is 7 points more accurate than the ASES MCID/SCB derived from the sample. Our ASES index algorithm, which is freely available online (https://osf.io/ctmnd/), has a lower MCID/SCB than the ASES itself. This algorithm can be used to decrease patient survey burden by 11 questions and provide a reliable ASES analog to clinicians.

Do intraoperative radiographs in scoliosis surgery reflect radiographic result?

UNLABELLED: It is often difficult to predict postoperative radiographic curve magnitude and balance parameters while performing intraoperative correction during scoliosis surgery. We asked whether there was a radiographic correlation between intraoperative long-cassette scoliosis film and postoperative standing radiographs of adolescent idiopathic scoliosis with pedicle screw instrumentation. We retrospectively reviewed 44 patients with adolescent idiopathic scoliosis who underwent posterior instrumentation with pedicle screws. We made preoperative, intraoperative (after instrumentation and correction), and standing postoperative radiographic measurements (eg, curve magnitudes, coronal and sagittal balance, disc angles) and compared those for the intra- and postoperative radiographs. The intraoperative long-cassette scoliosis film correlated with the immediate postoperative standing film for all curve correction and balance parameters. The routine use of a long-cassette intraoperative scoliosis film provides the surgeon with a valuable tool to guide intraoperative decision-making and foreshadows the correction and balance obtained on the immediate postoperative film. LEVEL OF EVIDENCE: Level IV, retrospective study. See Guidelines for Authors for a complete description of levels of evidence.

ESI+ MS/MS confirmation of canine ivermectin toxicity.

Ivermectin is a semisynthetic macrocyclic lactone anthelmintic of the avermectin family derived from Streptomyces fermentation products. Avermectins are used as antiparasitic agents in domestic animals; although considered relatively safe, one must consider animal species, breed, weight, and age in dosage determinations.In January 2006, two canines were presented to the UK Livestock Disease Diagnostic Center after dying from suspected ivermectin overdoses [30-50 mg/kg body weight]. To confirm this clinical diagnosis we developed a rapid, sensitive semiquantitative ElectroSpray Ionization-Mass Spectrometry (ESI/MS) method for ivermectin in canine tissue samples. Pharmaceutical ivermectin contains two ivermectins differing by a single methyl group, and each compound forms interpretation-confounding adducts with tissue Na(+) and K(+) ions. We now report that ivermectin administration was clearly confirmed by comparison with standard and dosage forms of ivermectin, and simple proportionalities based on mass spectral intensity of respective molecular ions allowed semiquantitative estimates of injection site tissue concentrations of 20 and 40 microg/g tissue (wet weight) in these animals, consistent with the history of ivermectin administration and the clinical signs observed.There is a distinct need for both rapid detection and confirmation of toxic exposures in veterinary diagnostics, whether for interpretation of clinical cases antemortem or for forensic reasons postmortem. It is vital that interpreters of analytical results have appropriate guidance in the scientific literature and elsewhere so as to enable clear-cut answers. The method presented here is suitable for routine diagnostic work in that it allows rapid extraction of ivermectin from tissue samples, avoids the need for high-performance liquid chromatography and allows ready interpretation of the multiple ivermectin species seen by ESI(+) MS/MS in samples originating from veterinary dosage forms.

Pheromone orientation: role of internal control mechanisms.

Male American cockroaches walk a zigzag path upwind toward a source of female sex pheromone. Although the maximum width of the pathway is regulated by the width of an odor plume, many turns are made before the edge of a wide plume is encountered. In addition to the pheromone regulation of the insect's orientation movements, an internal mechanism appears to influence the zigzag turning pattern.

Synthesis and detection of toltrazuril sulfone and its pharmacokinetics in horses following administration in dimethylsulfoxide.

Triazine-based antiprotozoal agents are known for their lipophylic characteristics and may therefore be expected to be well absorbed following oral administration. However, although an increase in lipid solubility generally increases the absorption of chemicals, extremely lipid-soluble chemicals may dissolve poorly in gastrointestinal (GI) fluids, and their corresponding absorption and bioavailability would be low. Also, if the compound is administered in solid form and is relatively insoluble in GI fluids, it is likely to have limited contact with the GI mucosa, and therefore, its rate of absorption will be low. Based on the above considerations, we sought a solvent with low or no toxicity that would maintain triazine agents in solution. As the oral route is most preferred for daily drug therapy, such a solvent would allow an increased rate of absorption following oral administration. In present study, it was demonstrated that dimethylsulfoxide (DMSO) increased the oral bioavailability of toltrazuril sulfone (Ponazuril) threefold, relative to oral administrations of toltrazuril sulfone suspended in water. The cross-over study of toltrazuril sulfone formulated in DMSO indicated that the absolute oral bioavailability of toltrazuril sulfone in DMSO is 71%. The high bioavailability of the DMSO-preparation suggests that its daily oral administration will routinely yield effective plasma and cerebral spinal fluid (CSF) concentrations in all horses treated. Also, this improved formulation would allow clinicians to administer loading doses of toltrazuril sulfone in acute cases of Equine Protozoal Myeloencephalitis. Another option would involve administration of toltrazuril sulfone in DMSO mixed with feed (1.23 kg daily dose) meeting the US Food and Drug Administration (FDA) recommendations for the levels of DMSO permissible in pharmaceutical preparations.

Pyrilamine in the horse: detection and pharmacokinetics of pyrilamine and its major urinary metabolite O-desmethylpyrilamine.

Pyrilamine is an antihistamine used in human and veterinary medicine. As antihistamines produce central nervous system effects in horses, pyrilamine has the potential to affect the performance of racehorses. In the present study, O-desmethylpyrilamine (O-DMP) was observed to be the predominant equine urinary metabolite of pyrilamine. After intravenous (i.v.) administration of pyrilamine (300 mg/horse), serum pyrilamine concentrations declined from about 280 ng/mL at 5 min postdose to about 2.5 ng/mL at 8 h postdose. After oral administration of pyrilamine (300 mg/horse), serum concentrations peaked at about 33 ng/mL at 30 min, falling to <2 ng/mL at 8 h postdose. Pyrilamine was not detected in serum samples at 24 h postdosing by either route. After i.v. injection of pyrilamine (300 mg/horse) O-DMP was recovered at a level of about 20 microg/mL at 2 h postdose thereafter declining to about 2 ng/mL at 168 h postdose. After oral administration, the O-DMP recovery peaked at about 12 microg/mL at 8 h postdose and declined to <2 ng/mL at 168 h postdose. These results show that pyrilamine is poorly bioavailable orally (18%), and can be detected by sensitive enzyme-linked immunosorbent assay tests in urine for up to 1 week after a single administration. Care should be taken as the data suggest that the withdrawal time for pyrilamine after repeated oral administrations is likely to be at least 1 week or longer.

Nonsteroidal anti-inflammatory agents and musculoskeletal injuries in Thoroughbred racehorses in Kentucky.

Injuries sustained by horses during racing have been considered as an unavoidable part of horse racing. Many factors may be associated with the musculoskeletal injuries of Thoroughbred race horses. This study surveyed the amounts of nonsteroidal anti-inflammatory agents (NSAIDs) in injured horse's biological system (plasma) at Kentucky racetracks from January 1, 1995 through December 31, 1996. During that period, there were 84 catastrophic cases (euthanized horses) and 126 noncatastrophic cases. Plasma concentrations of NSAIDs were determined by High Performance Liquid Chromatography in injured and control horses. The possible role of anti-inflammatory agents in musculoskeletal injuries of Thoroughbred race horses was investigated by comparing the apparent concentrations of NSAIDs in injured horses to concentrations in control horses. The plasma concentrations of phenylbutazone and flunixin were higher in injured horses than in control horses. Most injured and control horses did not have a detectable level of naproxen in their plasma samples. Further studies must be carried out to determine whether horses with higher plasma concentrations of NSAIDs have an altered risk of musculoskeletal injuries compared with other horses.

Variability in plasma concentrations of methylprednisolone 6 days after intrasynovial injection of methylprednisolone acetate in racing horses: A field study.

BACKGROUND: Methylprednisolone (MP) acetate is a commonly used corticosteroid for suppression of inflammation in synovial structures in horses. Its use is often regulated in equine sports by plasma MP concentrations. OBJECTIVES: To describe variability in MP plasma concentrations after MP acetate injection in different synovial structures and with co-administration with hyaluronic acid (HA). STUDY DESIGN: Field study in actively racing horses in three disciplines (Thoroughbred, Standardbred and Quarter Horse). METHODS: Seventy-six horses (15 Thoroughbreds, 20 Standardbreds and 41 Quarter Horses) were included in the study. Injection of any synovial structure with a total body dose of 100 mg MP acetate was permitted, data were grouped according to the synovial structure injected and co-administration with HA. Plasma was collected before injection and at 6 days post-injection. Per cent censored data (below the limit of quantification) for each synovial structure were determined, and summary statistics generated by Robust Regression on Order. Differences between synovial structures and co-administration with HA were identified by ANOVA with Tukey's post hoc testing. RESULTS: The MP plasma concentration at 6 days for injection for the entire group (mean ± standard deviation [s.d.], pg/mL) was 96 ± 104. Metacarpophalangeal (MCP) plasma concentrations contained 86% censored data and could not be included in the statistical analysis. The carpal joints (CJO) group had a lower plasma MP concentration (P<0.05) than the distal tarsal joints (DTJ) or medial femorotibial (MFT), the no HA (NHA) group had a lower plasma MP concentration (P<0.05) than HA. MAIN LIMITATIONS: The synovial structures injected varied by racing discipline, so this study was unable to identify any differences between disciplines. CONCLUSIONS: Practitioners should be aware that injection of DTJ, CS and MFT joints, and combining MP acetate with HA may prolong its clearance, and withdrawal times for competition in regulated equine sports.

Plasma and urinary concentrations of trimetoquinol by LC-MS-MS following intravenous and intra-tracheal administration to horses with heaves.

Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 microg/kg) and intra-tracheal (IT, 2 microg/kg) routes. TMQ was administered to six horses affected with heaves (RAO - Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at -20 degrees C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)-LC-MS-MS (ElectroSpray Ionization, positive mode - Liquid Chromatography - Mass Spectrometry - Mass Spectrometry); with a Limit of Detection (LOD) estimated at 1 pg/mL. Following IV administration, TMQ plasma levels peaked at 1 min at 707 pg/mL, and at 9 min at 306 pg/mL following IT administration. Our results show that TMQ plasma concentrations decline rapidly following IV administration, which is consistent with the fast onset and short duration of TMQ effect that was observed in our previous studies. On the other hand, IT administration showed a very unique plasma concentration pattern. From a regulatory standpoint, the current available TMQ ELISA kit was also used in an attempt to detect TMQ from the plasma and urine samples. We report that the ELISA kit was unable to detect TMQ from any of the samples generated in these studies.

Gabapentin in horses: validation of an analytical method for gabapentin quantitation.

Gabapentin [1-(aminomethyl)cyclohexaneacetic acid, Neurontin], is a new anticonvulsant used as adjunctive therapy in the treatment of partial seizures in humans not controlled with standard antiseizure drugs, and it has also been used in veterinary medicine. In performance horses, gabapentin is listed as a class 3 performance-enhancing substance by the Association of Racing Commissioners International, and thus is considered to have the potential to influence the outcome of races. Therefore, we developed and validated a sensitive gas chromatographic-mass spectrometric (GC-MS) method for gabapentin detection. Gamma-aminobutyric acid-d(2) (GABA-d(2)) was used as an internal standard during solid-phase extraction; lacking the cyclohexyl ring of gabapentin, GABA-d(2) formed a lactam structure to only a minor extent. Gabapentin, on the other hand, readily formed a lactam on thermal exposure during trimethylsilyl-derivatization and/or GC analysis; electrospray-ionization MS was employed to verify that the original compound was present as the expected 171 m.w. compound. Extraction efficiency for the assay was about 60%, and a curvilinear standard curve ranging from 50 ng/mL to 3000 ng/mL provided excellent within-run and between-run coefficients of variation and accuracies over a range of low, medium, and high values. The limit of detection, defined as the concentration calculated from the mean response at zero concentration plus two times the standard deviation, was calculated at 7.6 ng/mL; the limit of quantitation, defined as the concentration calculated from the mean of the zero responses plus five times the standard deviation, was calculated at 17 ng/mL. This method will enable accurate quantification of gabapentin in equine biological fluids for use in both pharmacokinetic and forensic studies.

Trimetoquinol: bronchodilator effects in horses with heaves following aerosolised and oral administration.

REASON FOR PERFORMING STUDY: The bronchodilator effects of trimetoquinol (TMQ) have been studied when administered i.v. or intratracheally, but not in an aerosolised form. OBJECTIVES: To define the relationship between the therapeutic and adverse responses (therapeutic index) of TMQ when administered as an aerosol or by the oral route. METHODS: Increasing doses of TMQ were administered to horses with heaves as an aerosol and by the oral route. Dose ranged 100-1000 microg/horse for aerosolised TMQ and from 6-60 microg/kg bwt for the oral route. Airway and cardiac effects were assessed by measurement of maximal change in pleural pressure (deltaPplmax) and heart rate (HR), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action of aerosolised (1000 pg/horse) and oral (6-60 microg/kg bwt) TMQ was evaluated over 6 h. RESULTS: Aerosol administration of TMQ caused dose-dependent bronchodilation but did not change HR or cause other observable side effects. When 1000 microg/horse was administered via aerosol, TMQ produced a 2-phase bronchodilation; an immediate effect lasting up to 30 min and a second phase between 2 and 4 h. Oral TMQ was therapeutically ineffective. CONCLUSION: Aerosol administration of TMQ is a safe and effective method of producing bronchodilation in horses.

Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with 'heaves'.

REASON FOR PERFORMING STUDY: Trimetoquinol (TMQ) is a potent beta-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with 'heaves'. OBJECTIVES: To assess the pharmacodynamics of TMQ in horses with 'heaves' to determine potential therapeutic effects. METHODS: Increasing doses of TMQ were administered to horses with 'heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001-0.2 microg/kg bwt i.v. and 0.01-2 microg/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural pressure (deltaPplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 microg/kg bwt) and i.t. (2 microg/kg bwt) TMQ was evaluated over 6 h. RESULTS: Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 microg/kg bwt, and was still increasing after administration of highest dose, 0.2 microg/kg bwt. Airway bronchodilation, measured as a decrease in deltaPplmax, also commenced at 0.01 microg/kg bwt. By the i.t. route, TMQ was 50-100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h. CONCLUSION: When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with 'heaves'. Further studies of TMQ by oral and aerosol routes are necessary. POTENTIAL RELEVANCE: In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of 'heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other beta-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of 'heaves'.