Selected nitrostyrene compounds demonstrate potent activity in chronic lymphocytic leukaemia cells, including those with poor prognostic markers.

The nitrostyrene scaffold was previously identified as a lead target structure for the development of effective compounds targeting Burkitt's lymphoma. The present study aimed to develop these compounds further in haematological malignancies, including chronic lymphocytic leukaemia (CLL). Cellular viability, flow cytometry and lactate dehydrogenase assays, amongst others, were used to examine the effects of nitrostyrene compounds on CLL cells, including a cell line representing disease with poor prognosis (HG­3) and in ex vivo CLL patient samples (n=14). The results demonstrated that two representative nitrostyrene compounds potently induced apoptosis in CLL cells. The pro­apoptotic effects of the compounds were found to be reactive oxygen species and caspase­dependent, and had minimal effects on the viability of normal donor peripheral blood mononuclear cells. Nitrostyrene compounds exhibited synergistic augmentation of apoptosis when combined with the phosphatidylinositol 3­kinase inhibitor idelalisib and demonstrated potent toxicity in ex vivo CLL cells, including those co­cultured with bone marrow stromal cells, making them more resistant to apoptosis (n=8). These compounds also demonstrated activity in samples from patients with poor prognostic indicators; unmutated immunoglobulin heavy chain genes, expression of CD38 and deletions in chromosomes 17p and 11q. These results suggest that this class of pharmaceutically active compounds offer potential in the treatment of CLL.

Buckling down on torus fractures: has evolving evidence affected practice?

PURPOSE: The purpose of this study was to evaluate the management of paediatric torus fractures of the distal forearm in current practice in light of growing evidence supporting a 'minimalist' approach with splint immobilization and limited follow-up. We hypothesized that 'traditional' cast-based management has persisted despite alternative evidence. METHODS: A retrospective review was performed of a consecutive series of paediatric patients diagnosed with torus fractures of the distal forearm between 2011 and 2014. Records were reviewed to abstract the type of immobilization (splint versus cast) prescribed at each visit, number of radiographic exams, duration of immobilization, number of clinical visits and complications. The primary outcome was the proportion of patients exclusively managed in splints. Injuries were grouped based on treatment into a cast group (CG) and a splint group (SG) for statistical analyses. Additionally, injuries were grouped by epoch of time to determine if immobilization usage patterns evolved. RESULTS: A total of 240 forty injuries met criteria for inclusion. Of these, 16 (6.7%) were exclusively splinted (SG). Relative to the CG, the SG had fewer clinical visits (p < 0.001), fewer radiographic exams (p < 0.001) and a shorter total encounter time (p = 0.015). No change in immobilization use occurred over the study period. In all, 21 (9.4%) of the CG experienced complications. No clinically significant displacements occurred in either group. CONCLUSION: Cast utilization and frequent radiographic follow-up remain prevalent at our institution in the management of paediatric torus fractures. Splint-only management was associated with fewer clinical visits, fewer radiographic exams and a shorter total encounter time. LEVEL OF EVIDENCE LEVEL III: Therapeutic retrospective cohort study.

Clinical Implications and Hospital Outcome of Immune-Mediated Myositis in Horses.

BACKGROUND: Immune-mediated myositis (IMM) is a cause of rhabdomyolysis, stiffness, and muscle atrophy predominantly affecting Quarter horses. Limited information is available with regard to outcome, prognostic indicators, and associations with concurrent diseases. HYPOTHESIS/OBJECTIVES: To report outcomes and associations between outcome and clinical and laboratory parameters, and presence of concurrent illness. ANIMALS: Sixty-eight horses; 52 Quarter horses and related breeds and 16 other breeds. METHODS: Retrospective cohort study (1991-2014). Medical records of horses with histological diagnosis of IMM were reviewed. Data recovery included signalment, laboratory variables, therapy, and outcome. Logistic regression was used to quantify the association between potential prognostic factors and survival to discharge. RESULTS: Quarter horses were younger (mean < 4 years, range 3 months-21 years) than other breeds (mean < 10 years, range 1-23 years). Pathogens causing concurrent or recent infection included S. equi equi, S. equi zooepidemicus, C. pseudotuberculosis, Anaplasma phagocytophilum, herpes virus-1, and influenza. The most common clinical signs consisted of rapidly progressive diffuse symmetrical muscle atrophy (80%), stiff gait (74%), and fever (44%). All horses that received medical therapy immediately upon admission survived to discharge (survival proportion = 87%). Leucocytosis was a common finding (60%). Horses with concurrent fever and other illness had a poor prognosis for hospital discharge. CONCLUSIONS AND CLINICAL IMPORTANCE: Horses with IMM can have a favorable outcome. Horses with concurrent fever and another illness had decreased probability of survival to discharge.

Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines.

Microtubules are currently ranked one of the most validated targets for chemotherapy; with clinical use of microtubule targeting agents (MTAs) extending beyond half a century. Recent research has focused on the development of novel MTAs to combat drug resistance and drug associated toxicities. Of particular interest are compounds structurally different to those currently used within the clinic. The pyrrolo-1, 5-benzoxazepines (PBOXs) are a structurally distinct novel group of anti-cancer agents, some of which target tubulin. Herein, we review the chemistry, mechanism of action, preclinical development of the PBOXs and comparisons with clinically relevant chemotherapeutics. The PBOXs induce a range of cellular responses including; cell cycle arrest, apoptosis, autophagy, anti-vascular and anti-angiogenic effects. The apoptotic potential of the PBOXs extends across a wide spectrum of cancer-derived cell lines, by targeting tubulin and multiple molecular pathways frequently deregulated in human cancers. Extensive experimental data suggest that combining the PBOXs with established chemotherapeutics or radiation is therapeutically advantageous. Pre-clinical highlights of the PBOXs include; cancer specificity and improved therapeutic efficacy as compared to some current first line therapeutics.

Neurologic Deficits Including Auditory Loss and Recovery of Function in Horses with Temporohyoid Osteoarthropathy.

BACKGROUND: Auditory loss is a common deficit in horses with temporohyoid osteoarthropathy (THO), however, recovery of function is unknown. HYPOTHESIS/OBJECTIVES: To investigate neurologic function with emphasis in audition in horses with THO after treatment. To describe anatomical alterations of the petrous temporal bone that might result in auditory loss. ANIMALS: Twenty-four horses with a clinical diagnosis of THO. METHODS: Prospective study. A brainstem auditory evoked response (BAER) study was done as part of the criteria for inclusion in horses with a clinical diagnosis of THO from the years of 2005 to 2014. Physical and neurologic status and BAER findings were recorded. Brainstem auditory evoked response variables were compared by using Wilcoxon sign test. Fisher's exact test was also used. Significance was set at P < 0.05. RESULTS: The most common signs included auditory loss (100% of horses), vestibular and facial nerve dysfunction (83%), and exposure ulcerative keratitis (71%). Concurrent left laryngeal hemiparesis was observed in 61% of horses through endoscopy. Auditory dysfunction was bilateral in 50% of the cases (complete and partial), and unilateral affecting more commonly the right ear (R = 8, L = 4). Short- and long-term follow-up revealed persistent auditory loss in all horses based on abnormal response to sound, and further confirmed through a BAER in 8 horses. CONCLUSIONS AND CLINICAL IMPORTANCE: Auditory dysfunction appears to be a permanent neurologic deficit in horses diagnosed with THO despite overall neurologic improvement.

Electroencephalogram of Healthy Horses During Inhaled Anesthesia.

BACKGROUND: Previous study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings. OBJECTIVES: To determine the effects of 2 inhalation anesthetics on the EEG of healthy horses. ANIMALS: Six healthy horses. METHODS: Prospective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded during controlled ventilation, spontaneous ventilation, and nerve stimulation. RESULTS: Burst suppression was observed with isoflurane, along with EEG events that resembled epileptiform discharges. Halothane results were variable between horses, with epileptiform-like discharges and bursts of theta, alpha, and beta recorded intermittently. One horse died and 2 were euthanized as the result of anesthesia-related complications. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study indicate that the effects of halothane and isoflurane on EEG activity in the normal horse can be quite variable, even when used in the absence of other drugs. It is recommended that equine EEG be performed without the use of these inhalation anesthetics and that general anesthesia be induced and maintained by other contemporary means.

Qualitative and Quantitative Characteristics of the Electroencephalogram in Normal Horses during Administration of Inhaled Anesthesia.

BACKGROUND: The effects of anesthesia on the equine electroencephalogram (EEG) after administration of various drugs for sedation, induction, and maintenance are known, but not that the effect of inhaled anesthetics alone for EEG recording. OBJECTIVE: To determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses. ANIMALS: Six healthy horses. METHODS: Prospective study. Digital EEG with video and quantitative EEG (qEEG) were recorded after the administration of one of the 2 anesthetics, isoflurane or halothane, at 3 alveolar doses (1.2, 1.4 and 1.6 MAC). Segments of EEG during controlled ventilation (CV), spontaneous ventilation (SV), and with peroneal nerve stimulation (ST) at each MAC multiple for each anesthetic were selected, analyzed, and compared. Multiple non-EEG measurements were also recorded. RESULTS: Specific raw EEG findings were indicative of changes in the depth of anesthesia. However, there was considerable variability in EEG between horses at identical MAC multiples/conditions and within individual horses over segments of a given epoch. Statistical significance for qEEG variables differed between anesthetics with bispectral index (BIS) CV MAC and 95% spectral edge frequency (SEF95) SV MAC differences in isoflurane only and median frequency (MED) differences in SV MAC with halothane only. CONCLUSIONS AND CLINICAL IMPORTANCE: Unprocessed EEG features (background and transients) appear to be beneficial for monitoring the depth of a particular anesthetic, but offer little advantage over the use of changes in mean arterial pressure for this purpose.

Electrophysiologic Study of a Method of Euthanasia Using Intrathecal Lidocaine Hydrochloride Administered during Intravenous Anesthesia in Horses.

BACKGROUND: An intravenous (IV) overdose of pentobarbital sodium is the most commonly used method of euthanasia in veterinary medicine. However, this compound is not available in many countries or rural areas resulting in usage of alternative methods such as intrathecal lidocaine administration after IV anesthesia. Its safety and efficacy as a method of euthanasia have not been investigated in the horse. HYPOTHESIS/OBJECTIVES: To investigate changes in mean arterial blood pressure and electrical activity of the cerebral cortex, brainstem, and heart during intrathecal administration of lidocaine. Our hypothesis was that intrathecal lidocaine affects the cerebral cortex and brainstem before affecting cardiovascular function. ANIMALS: Eleven horses requiring euthanasia for medical reasons. METHODS: Prospective observational study. Horses were anesthetized with xylazine, midazolam, and ketamine; and instrumented for recording of electroencephalogram (EEG), electrooculogram (EOG), brainstem auditory evoked response (BAER), and electrocardiogram (ECG). Physical and neurological (brainstem reflexes) variables were monitored. Mean arterial blood pressure was recorded throughout the study. RESULTS: Loss of cerebro-cortical electrical activity occurred up to 226 seconds after the end of the infusion of lidocaine solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of BAER occurred subsequently. Undetectable heart sounds, nonpalpable arterial pulse, and extremely low mean arterial blood pressure supported cardiac death; a recordable ECG was the last variable to disappear after the infusion (300-1,279 seconds). CONCLUSIONS AND CLINICAL IMPORTANCE: Intrathecal administration of lidocaine is an effective alternative method of euthanasia in anesthetized horses, during which brain death occurs before cardiac death.

Cerebral and brainstem electrophysiologic activity during euthanasia with pentobarbital sodium in horses.

BACKGROUND: An overdose of pentobarbital sodium administered i.v. is the most commonly used method of euthanasia in veterinary medicine. Determining death after the infusion relies on the observation of physical variables. However, it is unknown when cortical electrical activity and brainstem function are lost in a sequence of events before death. HYPOTHESIS/OBJECTIVES: To examine changes in the electrical activity of the cerebral cortex and brainstem during an overdose of pentobarbital sodium solution for euthanasia. Our testing hypothesis is that isoelectric pattern of the brain in support of brain death occurs before absence of electrocardiogram (ECG) activity. ANIMALS: Fifteen horses requiring euthanasia. METHODS: Prospective observational study. Horses with neurologic, orthopedic, and cardiac illnesses were selected and instrumented for recording of electroencephalogram, electrooculogram, brainstem auditory evoked response (BAER), and ECG. Physical and neurologic (brainstem reflexes) variables were monitored. RESULTS: Loss of cortical electrical activity occurred during or within 52 seconds after the infusion of euthanasia solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of the BAER happened subsequently. Despite undetectable heart sounds, palpable arterial pulse, and mean arterial pressure, recordable ECG was the last variable to be lost after the infusion (5.5-16 minutes after end of the infusion). CONCLUSIONS AND CLINICAL IMPORTANCE: Overdose of pentobarbital sodium solution administered i.v. is an effective, fast, and humane method of euthanasia. Brain death occurs within 73-261 seconds of the infusion. Although absence of ECG activity takes longer to occur, brain death has already occurred.

Electrophysiologic confirmation of heterogenous motor polyneuropathy in young cats.

BACKGROUND: Reports of motor polyneuropathies in young cats are scarce. Further, in-depth electrophysiologic evaluation to confirm a motor polyneuropathy in young cats of various breeds other than 2 Bengal cats is lacking. HYPOTHESIS/OBJECTIVES: To confirm a motor polyneuropathy in young cats of various breeds. ANIMALS: Five young cats with heterogenous chronic or relapsing episodes of weakness. METHODS: Retrospective case series. Cats were presented for evaluation of generalized neuromuscular disease and underwent electrophysiologic examination including electromyography, nerve conduction, and repetitive nerve stimulation. Minimum database and muscle and nerve biopsy analyses were carried out. Descriptive statistics were performed. RESULTS: Disease onset was at 3 months to 1 year of age and in 5 breeds. The most common clinical sign (5 of 5 cats) was weakness. Additional neurologic deficits consisted of palmigrade and plantigrade posture (4/4), low carriage of the head and tail (4/4), and variable segmental reflex deficits (5/5). Motor nerve conduction studies were abnormal for the ulnar (4/4), peroneal (5/5), and tibial (2/2) nerves (increased latencies, reduced amplitudes, slow velocities). A marked decrement was observed on repetitive nerve stimulation of the peroneal nerve in 3 cats for which autoimmune myasthenia gravis was ruled out. All sensory nerve conduction studies were normal. Histologic evaluation of muscle and nerve biopsies supported heterogenous alterations consistent with motor polyneuropathy with distal nerve fiber loss. CONCLUSIONS AND CLINICAL IMPORTANCE: Heterogenous motor polyneuropathies should be considered in young cats of any breed and sex that are presented with relapsing or progressive generalized neuromuscular disease.

Brainstem auditory evoked responses in an equine patient population. Part II: foals.

BACKGROUND: Reports of the use of brainstem auditory evoked response (BAER) as a diagnostic modality in foals have been limited. HYPOTHESIS/OBJECTIVES: To describe BAER findings and associated causes of hearing loss in foals. ANIMALS: Study group 18 foals (15 neonatal, 3 nonneonatal), control group (5 neonatal foals). METHODS: Retrospective. BAER records from the Clinical Neurophysiology Laboratory were reviewed from the years of 1982 to 2013. Peak latencies, amplitudes, and interpeak intervals were measured when visible. Clinical data were extracted from the medical records. Foals were grouped under disease categories. Descriptive statistics were performed. RESULTS: Ten neonatal foals had complete absence of BAER bilaterally and 5 had findings within reference range. Abnormalities were associated with common neonatal disorders such as sepsis, neonatal encephalopathy, neonatal isoerythrolysis, and prematurity. BAER loss also was observed in foals with specific coat color patterns such as completely or mostly white with blue irides or lavender with pale yellow irides. An American Miniature foal with marked facial deformation also lacked BAER bilaterally. One nonneonatal foal with an intracranial abscess had no detectable BAER peaks bilaterally, and 2 older foals, 1 with presumed equine protozoal myeloencephalitis and the other with progressive scoliosis and ataxia, had BAER within normal limits. CONCLUSIONS AND CLINICAL IMPORTANCE: In neonatal foals, BAER deficits commonly are complete and bilateral, and associated with common neonatal disorders and certain coat and eye color patterns. Sepsis, hypoxia, bilirubin toxicity, and prematurity should be investigated as potential causes of auditory loss in neonatal foals.

Brainstem auditory evoked responses in an equine patient population: part I--adult horses.

BACKGROUND: Brainstem auditory evoked response has been an underused diagnostic modality in horses as evidenced by few reports on the subject. HYPOTHESIS/OBJECTIVES: To describe BAER findings, common clinical signs, and causes of hearing loss in adult horses. ANIMALS: Study group, 76 horses; control group, 8 horses. METHODS: Retrospective. BAER records from the Clinical Neurophysiology Laboratory were reviewed from the years of 1982 to 2013. Peak latencies, amplitudes, and interpeak intervals were measured when visible. Horses were grouped under disease categories. Descriptive statistics and a posthoc Bonferroni test were performed. RESULTS: Fifty-seven of 76 horses had BAER deficits. There was no breed or sex predisposition, with the exception of American Paint horses diagnosed with congenital sensorineural deafness. Eighty-six percent (n = 49/57) of the horses were younger than 16 years of age. The most common causes of BAER abnormalities were temporohyoid osteoarthropathy (THO, n = 20/20; abnormalities/total), congenital sensorineural deafness in Paint horses (17/17), multifocal brain disease (13/16), and otitis media/interna (4/4). Auditory loss was bilateral and unilateral in 74% (n = 42/57) and 26% (n = 15/57) of the horses, respectively. The most common causes of bilateral auditory loss were sensorineural deafness, THO, and multifocal brain disease whereas THO and otitis were the most common causes of unilateral deficits. CONCLUSIONS AND CLINICAL IMPORTANCE: Auditory deficits should be investigated in horses with altered behavior, THO, multifocal brain disease, otitis, and in horses with certain coat and eye color patterns. BAER testing is an objective and noninvasive diagnostic modality to assess auditory function in horses.

Synthesis and antiproliferative action of a novel series of maprotiline analogues.

The synthesis of a diverse library of compounds structurally related to maprotiline, a norepinephrine reuptake transporter (NET) selective antidepressant which has recently been identified as a novel in vitro antiproliferative agent against Burkitt's lymphoma (BL) cell lines is reported. A series of 9,10-dihydro-9,10-ethanoanthracenes were synthesised with modifications to the bridge of the dihydroethanoanthracene structure and with alterations to the basic side chain. A number of compounds were found to reduce cell viability to a greater extent than maprotiline in BL cell lines. In addition a related series of novel 9-substituted anthracene compounds were investigated as intermediates in the synthesis of 9,10-dihydro-9,10-ethanoanthracenes. These compounds proved the most active from the screen and were found to exert a potent caspase-dependant apoptotic effect in the BL cell lines, while having minimal effect on the viability of peripheral blood mononuclear cells (PBMCs). Compounds also displayed activity in multi-drug resistant (MDR) cells.

Sensory nerve conduction and somatosensory evoked potentials of the trigeminal nerve in horses with idiopathic headshaking.

BACKGROUND: Idiopathic headshaking (HSK) in horses is a distressing disorder in which the etiology and pathophysiology are unknown. HYPOTHESIS: Differences in sensory function of the trigeminal nerve exist between healthy and affected horses. ANIMALS: Six healthy mature geldings and 6 mature geldings with idiopathic HSK. METHODS: Prospective study. Sensory nerve action and somatosensory evoked potentials studies were performed. The stimulus site comprised the gingival mucosa dorsal to the maxillary canine. A pair of recording electrodes was placed along the sensory pathway of the trigeminal complex at the infraorbital nerve (R1), maxillary nerve (R2), spinal tract of trigeminal (R3), and somatosensory cortex (R4). Sensory nerve action potential latency (ms), amplitude (µV), duration (ms), area under the curve (µVms), and conduction velocity (m/s) were calculated. RESULTS: Threshold for activation of the infraorbital branch of the trigeminal nerve was significantly different between 5 affected (≤ 5 mA) and 6 control horses (≥ 10 mA). After initiation of an action potential, there were no differences in all parameters measured and no differences between left and right sides. A horse with seasonal HSK tested during a time of no clinical manifestations showed a threshold for activation similar to control horses. CONCLUSIONS AND CLINICAL IMPORTANCE: This study confirms involvement of the trigeminal nerve hyperexcitability in the pathophysiology of disease. Further, results might support a functional rather than a structural alteration in the sensory pathway of the trigeminal complex that can be seasonal. The horse could serve as a natural animal model for humans with idiopathic trigeminal neuralgia.

A de novo mutation in KIT causes white spotting in a subpopulation of German Shepherd dogs.

Although variation in the KIT gene is a common cause of white spotting among domesticated animals, KIT has not been implicated in the diverse white spotting observed in the dog. Here, we show that a loss-of-function mutation in KIT recapitulates the coat color phenotypes observed in other species. A spontaneous white spotting observed in a pedigree of German Shepherd dogs was mapped by linkage analysis to a single locus on CFA13 containing KIT (pairwise LOD = 15). DNA sequence analysis identified a novel 1-bp insertion in the second exon that co-segregated with the phenotype. The expected frameshift and resulting premature stop codons predicted a severely truncated c-Kit receptor with presumably abolished activity. No dogs homozygous for the mutation were recovered from multiple intercrosses (P = 0.01), suggesting the mutation is recessively embryonic lethal. These observations are consistent with the effects of null alleles of KIT in other species.

Qualitative and quantitative characteristics of the electroencephalogram in normal horses after sedation.

BACKGROUND: The administration of certain sedatives has been shown to promote sleep in humans. Related agents induce sleep-like behavior when administered to horses. Interpretation of electroencephalograms (EEGs) obtained from sedated horses should take into account background activity, presence of sleep-related EEG events, and the animal's behavior. HYPOTHESIS: Sedatives induce states of vigilance that are indistinguishable on EEGs from those that occur naturally. ANIMALS: Six healthy horses. METHODS: Digital EEG with video was recorded after administration of 1 of 4 sedatives (acepromazine, butorphanol, xylazine, or detomidine). Serum drug concentrations were measured. Recordings were reviewed, states were identified, and representative EEG samples were analysed. These data were compared with data previously obtained during a study of natural sleep. RESULTS: Butorphanol was associated with brief episodes resembling slow wave sleep in 1 horse. Acepromazine led to SWS in 3 horses, including 1 that also exhibited rapid eye movement sleep. Periods of SWS were observed in all horses afer xylazine or detomidine administration. Normal sleep-related EEG events and heart block, occurred in association with SWS regardless of which sedative was used. Spectral data varied primarily by state, but some differences were observed between sedative and natural data. CONCLUSIONS AND CLINICAL IMPORTANCE: Qualitatively, EEG findings appeared identical whether sedation-induced or naturally occurring. The startle response and heart block associated with some sedatives may be related to sleep. Alpha(2) agonists can be used to obtain high quality EEGs in horses, but acepromazine does not promote a relaxed state in all animals.

Chemical characterization of the fine particle emissions from commercial aircraft engines during the Aircraft Particle Emissions eXperiment (APEX) 1 to 3.

This paper addresses the need for detailed chemical information on the fine particulate matter (PM) generated by commercial aviation engines. The exhaust plumes of seven turbofan engine models were sampled as part of the three test campaigns of the Aircraft Particle Emissions eXperiment (APEX). In these experiments, continuous measurements of black carbon (BC) and particle surface-bound polycyclic aromatic compounds (PAHs) were conducted. In addition, time-integrated sampling was performed for bulk elemental composition, water-soluble ions, organic and elemental carbon (OC and EC), and trace semivolatile organic compounds (SVOCs). The continuous BC and PAH monitoring showed a characteristic U-shaped curve of the emission index (EI or mass of pollutant/mass of fuel burned) vs fuel flow for the turbofan engines tested. The time-integrated EIs for both elemental composition and water-soluble ions were heavily dominated by sulfur and SO(4)(2-), respectively, with a ∼2.4% median conversion of fuel S(IV) to particle S(VI). The corrected OC and EC emission indices obtained in this study ranged from 37 to 83 mg/kg and 21 to 275 mg/kg, respectively, with the EC/OC ratio ranging from ∼0.3 to 7 depending on engine type and test conditions. Finally, the particle SVOC EIs varied by as much as 2 orders of magnitude with distinct variations in chemical composition observed for different engine types and operating conditions.

Repetitive stimulation of the common peroneal nerve as a diagnostic aid for botulism in foals.

BACKGROUND: Botulism is a potentially fatal paralytic disorder for which definitive diagnosis is difficult. OBJECTIVES: To determine if repetitive stimulation of the common peroneal nerve will aid in the diagnosis of botulism in foals. ANIMALS: Four control and 3 affected foals. METHODS: Validation of the test in healthy foals for its comparison in foals with suspected botulism. Controls were anesthetized and affected foals were sedated to avoid risks of anesthesia. The common peroneal nerve was chosen for its superficial location and easy access. Stimulating electrodes were placed along the common peroneal nerve. For recording, the active and reference electrodes were positioned over the midpoint and distal end of the extensor digitorum longus muscle, respectively. Repeated supramaximal stimulation of the nerve was performed utilizing a range of frequencies (1-50 Hz). Data analysis consisted of measuring the amplitude and area under the curve for each M wave and converting these values into percentages of decrement or increment based on the comparison of subsequent potentials to the initial one (baseline) within each set. RESULTS: A decremental response was seen at all frequencies in control foals. Decremental responses also were observed in affected foals at low frequencies. An incremental response was seen in all affected foals at 50 Hz. CONCLUSIONS AND CLINICAL IMPORTANCE: Decreased baseline M wave amplitudes with incremental responses at high rates are supportive of botulism. Repetitive nerve stimulation is a safe, simple, fast, and noninvasive technique that can aid in the diagnosis of suspected botulism in foals.