Arachidonic acid metabolites and enzyme transcripts in asthma are altered by cigarette smoking.

BACKGROUND: Arachidonic acid metabolites are implicated in the pathogenesis of asthma although only limited information is available on the impact of current smoking history on these metabolites. The aim of the study was to examine the effect of smoking status on urinary, sputum, and plasma eicosanoid concentrations and relevant enzyme transcripts in asthma. METHODS: In 108 smokers and never smokers with asthma and 45 healthy controls [smokers and never smokers], we measured urinary tetranor prostaglandin (PG)D2 (PGDM) and leukotriene (LT)E4 , induced sputum fluid LTB4 , LTE4 , PGD2 , and PGE2 , plasma secretory phospholipase A2 (sPLA2 ), and 11ß prostaglandin F2α (11ßPGF2α ), and, in a subgroup with severe asthma, airway leukocyte and epithelial cell mRNA expression levels of arachidonic acid metabolic enzymes. RESULTS: Smokers with asthma had higher urinary LTE4 ; 83 (59, 130) vs 59 (40, 90) pg/mg creatinine, P = 0.008, and PGDM; 60 (35, 100) vs 41 (28, 59) ng/mg creatinine, P = 0.012 concentrations, respectively, and lower sputum PGE2 concentrations 80 (46, 157) vs 192 (91, 301) pg/ml, P = 0.001 than never smokers with asthma. Sputum LTB4 (P = 0.013), and plasma 11ßPGF2α (P = 0.032), concentrations, respectively, were increased in smokers with asthma compared with healthy smokers. Asthma-specific and smoking-related increases (>1.5-fold expression) in arachidonate 15-lipoxygenase and gamma-glutamyltransferase transcripts were demonstrated. CONCLUSIONS: Several arachidonic acid metabolites and enzyme transcripts involving both lipoxygenase and cyclooxygenase pathways are increased in smokers with asthma and differ from never smokers with asthma. Possibly targeting specific lipoxygenase and cyclooxygenase pathways that are activated by asthma and cigarette smoking may optimize therapeutic responses.

Subclinical ultrasonographic abnormalities of the suspensory ligament branch of the athletic horse: A survey of 60 Thoroughbred racehorses.

REASONS FOR PERFORMING STUDY: Ultrasonographic (US) abnormalities of the suspensory ligament branch (SLB) have been poorly investigated but can have considerable impact on market value and career path when encountered in athletic horses. There is a need for determination of the prevalence and relationship to clinical injury of these US abnormalities in the Thoroughbred (TB) racehorse. OBJECTIVES: To establish the prevalence of, and the repeatability of an US grading system for, subclinical US abnormalities of the forelimb SLB in a population of UK TB flat racehorses. METHODS: Ultrasonographic assessment of the forelimb SLBs of 60 TB racehorses free from history and clinical indication of SLB desmopathy in a single UK training yard was performed. Images were viewed independently by 2 blinded observers and graded for US abnormality. Interobserver agreement was assessed using Cohen's kappa statistic with 95% confidence intervals (95% CI). RESULTS: Prevalence of horses with subclinical US abnormality of the forelimb SLB of moderate severity was 6.7%. Medial branches were overrepresented. Inter observer agreement was substantial for US grade (kappa = 0.743; 95% CI 0.652-0.834) and almost perfect for appearance of sesamoid bone at ligament insertion (kappa = 0.817; 95% CI 0.66-0.98). CONCLUSIONS: The study reveals that a proportion of TB racehorses in flat training free from history or clinical signs of SLB injury have US abnormalities that could negatively impact on market value and career path. POTENTIAL RELEVANCE: Clinicians should be aware that US abnormalities of the SLB may not always be related to clinical desmopathy. Further longitudinal studies are required to determine whether such findings are predictive for future injury.

The role of mast cells and their mediators in reproduction, pregnancy and labour.

BACKGROUND: Mast cells (MCs) are the classical mediators of allergy, however, their importance in the development of innate and adaptive immune responses is increasingly being recognized. Herein, the present MC literature is summarized, with particular focus on studies of MCs in the endometrium and myometrium, and their involvement in fertility, implantation, pregnancy and labour. METHODS: Recent developments in MC biology were identified by systematic searches of PubMed, Medline and Google Scholar from 2000 to November 2009. To specifically examine the role of MCs in fertility and pregnancy, we then performed a systematic review of English literature cited in the PubMed, Medline and Google Scholar databases, but extended the search period, from 1980 to January 2010 RESULTS: MCs can respond to immunoglobulin E-independent innate immune stimuli and are present within the endometrium, with activation and release of mediators occurring prior to menstruation and in association with endometriosis. With respect to pregnancy, MCs are redundant during blastocyst implantation and although their mediators can induce myometrial contractility, there is no epidemiological link of preterm birth with allergy, suggesting a non-essential role or robust regulation. In males, MCs are present in the testes and are increased in oligo- and azoospermia, with MC mediators directly suppressing sperm motility in a potentially reversible manner. CONCLUSIONS: MCs are prevalent in the female and male reproductive tract. However, whether MCs are absolutely required for a successful pregnancy or are fundamental to reproductive pathology, and thereby a therapeutic target, remains to be determined.

Standing magnetic resonance imaging detection of bone marrow oedema-type signal pattern associated with subcarpal pain in 8 racehorses: a prospective study.

REASON FOR PERFORMING STUDY: The proximal metacarpal region is a common site of origin of lameness in the performance horse. A number of disease entities are recognised as causes of proximal metacarpal lameness but a definitive diagnosis is often elusive. Magnetic resonance imaging (MRI) is hypothesised to offer advantages over traditional imaging modalities in the investigation of proximal metacarpal pain. OBJECTIVE: To describe clinical and imaging features of cases of lameness in racehorses arising from the proximal metacarpal region in which standing MRI identified 'bone marrow oedema-type' (BMO-type) signal patterns. METHODS: Records for all horses undergoing standing MRI of the proximal metacarpus/distal carpus from September 2006 to December 2008 were reviewed. Cases underwent a standardised protocol for diagnostic analgesia, radiography and ultrasonography of the proximal metacarpus and distal carpus. Cases with proximal metacarpal lameness displaying a characteristic BMO-type signal pattern on MRI were identified and outcomes analysed. RESULTS: Eight cases were identified with characteristic MRI findings of extensive hyperintensity on T2* gradient echo and short tau inversion fast spin echo sequences and corresponding hypointensity on T1 gradient echo images within the palmaroproximal aspect of the third metacarpal bone. Follow-up information was available for all cases; at the time of writing 7/8 had returned to full work and were free from lameness. CONCLUSIONS: The BMO-type signal patterns visible on MR images in these cases may signal the existence of a previously under-diagnosed pathological process associated with proximal metacarpal lameness in racehorses. This finding is postulated to be associated with a stress reaction and possible prodromal stress fracture of the palmaroproximal metacarpus not appreciable radiographically or ultrasonographically. POTENTIAL RELEVANCE: MRI of the proximal metacarpal region permits detection of pathological processes, which may elude conventional imaging and, therefore, has important therapeutic and prognostic implications in these cases.

Lower respiratory tract disease in Thoroughbred racehorses: analysis of endoscopic data from a UK training yard.

REASON FOR PERFORMING STUDY: There has been much research directed at potential causative agents and the epidemiology of lower respiratory tract disease (LRTD), but few reports of the clinical progression and outcome. OBJECTIVES: To define clinical features of LRTD in racehorses, including association with age and average duration of disease, through the analysis of endoscopic data. METHODS: A retrospective analysis of records from a single training yard of endoscopic examinations undertaken over a 2-year period was performed. Horses were subjected to regular endoscopic examination for a variety of reasons, and all horses placed on antibiotic therapy for lower respiratory tract disease were rescoped following treatment. Data analysed included a 0-8 tracheal mucus score based on visible endoscopic mucus and gross tracheal lavage turbidity, as well as age and treatment duration and type. RESULTS: A total of 522 endoscopic examinations undertaken on 123 horses and tracking 169 episodes of lower respiratory tract disease were recorded. Mean duration of disease episode was 15.5 days (median = 11 days, range = 4-61 days). Horses age 2 years were significantly more likely than those age > or=3 years to have at least one episode of respiratory disease (P<0.001). There was a direct association between initial tracheal mucus score and rescope score after treatment. CONCLUSIONS: Lower respiratory tract disease was more common in 2-year-olds than in older horses. Affected horses had endoscopic evidence of increased tracheal mucus accumulation for an average of 15.5 days per episode, a considerably shorter period than that suggested by previous studies. POTENTIAL RELEVANCE: Endoscopic examinations permit longitudinal tracking of lower respiratory tract disease in Thoroughbred racehorses. A prolonged duration of disease, sometimes extending for months, can be expected in a small proportion of cases, some of which appear to be refractory to treatment. There is a clear need for evidence-based analysis of treatment regimes to assist clinicians in decision making when managing disease in both individual and group situations.

Polarization observations with the Cosmic Background Imager.

Polarization observations of the cosmic microwave background with the Cosmic Background Imager from September 2002 to May 2004 provide a significant detection of the E-mode polarization and reveal an angular power spectrum of polarized emission showing peaks and valleys that are shifted in phase by half a cycle relative to those of the total intensity spectrum. This key agreement between the phase of the observed polarization spectrum and that predicted on the basis of the total intensity spectrum provides support for the standard model of cosmology, in which dark matter and dark energy are the dominant constituents, the geometry is close to flat, and primordial density fluctuations are predominantly adiabatic with a matter power spectrum commensurate with inflationary cosmological models.

The efficacy of dantrolene sodium in controlling exertional rhabdomyolysis in the Thoroughbred racehorse.

REASONS FOR PERFORMING STUDY: Dantrolene sodium (Dantrium) has been used extensively for the treatment of myopathies in man and anecdotal evidence suggests it is of clinical benefit in the control of exercise-induced rhabdomyolysis (ER) in racehorses, although data to support this are currently lacking. OBJECTIVES: To investigate the efficacy of oral dantrolene sodium in controlling ER in a randomised, double-blind, placebo-controlled crossover trial involving 77 Thoroughbred racehorses in Newmarket, UK. METHODS: Horses were treated on 2 occasions 1 week apart, with treatment days coinciding with a return to exercise following 2 days box rest on each occasion. For the first treatment, each horse was randomly selected to receive either 800 mg dantrolene sodium or a colour-matched placebo administered orally 1 h before exercise. This was followed by crossover to the other treatment on the second occasion, with each horse thereby acting as its own control. Degree of ER was assessed using rising serum creatine kinase (CK) levels, by subtracting pre-exercise blood CK levels from those measured in 6 h post exercise blood samples. For each horse, the difference in change between pre- and post exercise CK values between placebo and dantrolene treatments was calculated, with positive values indicating a greater rise with placebo than with dantrolene sodium treatment. RESULTS: The overall mean difference for all horses was +104.8 iu/l and the null hypothesis, that there was no true difference in non-normally distributed post exercise rises in CK values between placebo and dantrolene treatments, was rejected (P = 0.0013) using the nonparametric Wilcoxon signed rank test. Additionally, no horses given dantrolene sodium showed clinical signs of ER, whereas 3 horses given the placebo developed ER following exercise. The incidence of ER in the study was 4% (3/77). CONCLUSIONS: The results confirmed that oral administration of dantrolene sodium, 1 h before exercise, had a statistically significant effect on reducing the difference between pre- and post exercise plasma CK levels compared with a placebo in the same animals, and preventing clinical ER in susceptible individuals. POTENTIAL RELEVANCE: This study suggested that dantrolene sodium is of use in controlling ER in the Thoroughbred racehorse. Further investigation into pre- and post exercise myoplasmic calcium levels and the repeat of the study late in the season when horses receive a much higher energy ration and more strenuous exercise would appear to be warranted.

The application of a scintigraphic grading system to equine tibial stress fractures: 42 cases.

REASONS FOR PERFORMING STUDY: Tibial stress fractures are an important cause of lameness in the Thoroughbred racehorse. While it is recognised that these injuries can vary in clinical presentation and radiographic or scintigraphic appearance, little has been done to quantify lesion severity. By contrast the scintigraphic grading of tibial stress fractures in human athletes is widely reported and assists in the selection of appropriate management regimes. OBJECTIVES: To determine the relationship between scintigraphic grade, clinical severity and radiographic appearance of tibial stress fractures. METHODS: The current study involved the retrospective analysis of records from 42 Thoroughbreds with abnormal tibial scintigraphic activity. RESULTS: There was a significant association between lesion site and scintigraphic grade and good correlation of scintigraphic scoring between investigators. No significant association was found between scintigraphic grade and either radiographic grade or degree of lameness. CONCLUSIONS: The study confirmed that radiographic appearance is an unreliable measure of clinical severity or stage of progression of lesions. The scintigraphic grading system used in the study was not of use in defining stress fracture severity in the equine tibia. POTENTIAL RELEVANCE: Despite this finding, there is clearly a need for prospective investigations to explore the potential for targeted management regimes for tibial injuries based on lesion site or clinical criteria.

Effect of infused angiotensin II on the bronchoconstrictor activity of inhaled endothelin-1 in asthma.

STUDY OBJECTIVES: Endothelin (ET)-1 is a potent bronchoconstrictor, and asthmatics demonstrate bronchial hyperresponsiveness to ET-1 given by inhalation. Angiotensin II (Ang II) is increased in plasma in acute severe asthma, causes bronchoconstriction in asthmatics, and potentiates contractions induced by ET-1 in bovine bronchial smooth muscle in vitro, and contractions induced by methacholine both in vitro and in vivo. We wished to examine any potentiation of the bronchoconstrictor activity of inhaled ET-1 by infused Ang II at subbronchoconstrictor doses. DESIGN: Double-blind randomized placebo-controlled study. SETTING: Asthma research unit in university hospital. PATIENTS: Eight asthmatic subjects with baseline FEV1 88% predicted, bronchial hyperreactivity (geometric mean, concentration of methacholine producing 20% fall, methacholine PC20 2.5 mg/mL), and mean age 37.1 years. INTERVENTIONS: We examined the effect of subbronchoconstrictor doses of infused Ang II (1 ng/kg/min and 2 ng/kg/min) or placebo on bronchoconstrictor responses to inhaled ET-1 (dose range, 0.96 to 15.36 nmol). MEASUREMENTS: Oxygen saturation, noninvasive BP, and spirometric measurements were made throughout the study visits. Blood was sampled for plasma Ang II levels at baseline and before and after ET-1 inhalation. RESULTS: Ang II infusion did not produce bronchoconstriction per se at either dose prior to ET-1 challenge. Bronchial challenge with inhaled ET-1 produced dose-dependent bronchoconstriction, but there was no difference in bronchial responsiveness to ET-1 comparing infusion of placebo with Ang II at 1 ng/kg/min or 2 ng/kg/min (geometric mean, concentration of ET-1 producing 15% fall, 5.34 nmol, 4.95 nmol, and 4.96 nmol, respectively) (analysis of variance, p > 0.05). There was an increase in systolic and diastolic BP at the higher dose of Ang II compared to placebo (mean 136/86 vs 117/75 mm Hg, respectively). Plasma Ang II was elevated following infusion of both doses of Ang II compared to placebo. CONCLUSIONS: In contrast to the potentiating effect on methacholine-induced bronchoconstriction, Ang II at subbronchoconstrictor doses does not potentiate ET-1-induced bronchoconstriction in asthma.

Fracture of the wing of the ilium, adjacent to the sacroiliac joint, in thoroughbred racehorses.

During a two year period, sagittal fractures of the wing of the ilium were diagnosed in 10 Thoroughbred horses. All were spontaneous fractures sustained during normal exercise in training and racing, with no history of inciting trauma. When ultrasound scans of the surface of the pelvis were performed, the fracture was clearly visible as a discontinuity of the sacral wing of the ilium. In 3 horses, an irregular contour suggestive of periosteal callus was seen in the vicinity of the acute fracture. All horses examined by gamma scintigraphy had a focal increase in uptake of isotope just lateral to the tuber sacrale. Nine of the horses were treated conservatively by rest. The other horse had bilateral fractures and was subjected to euthanasia at the time of the injury. Six horses returned to full training, and 2 subsequently won, without recurrence of lameness.

Lung abscesses mimicking multiple pulmonary metastases.

Five patients receiving chemotherapy for cancer through Hickman central venous catheters had lung lesions detected by plain chest radiography or computed tomography. In each case these were initially misdiagnosed as metastases, although they ultimately proved to be staphylococcal abscesses. Because of the grave implications of an erroneous diagnosis of metastatic malignant disease, clinicians are urged to consider abscesses in the differential diagnosis of radiological chest abnormalities in such patients.