Effect of Dexamethasone and Fluticasone on Airway Hyperresponsiveness in Horses With Inflammatory Airway Disease.

BACKGROUND: Airway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC75 RL ) or hyperreactivity (slope of the histamine dose-response curve), is a feature of inflammatory airway disease (IAD) or mild equine asthma in horses. Glucocorticoids are used empirically to treat IAD. OBJECTIVES: To determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 µg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD. METHODS: A randomized crossover study design was used. Eight horses with IAD were assigned to a treatment group with either DEX or FLUT. Measured outcomes included lung mechanics during bronchoprovocative challenges, bronchoalveolar lavage fluid (BALF) cytology, and scoring of clinical signs during exercise. RESULTS: Dexamethasone and FLUT abolished the increase in RL by 75% at any histamine bronchoprovocative dose in all horses after the first week of treatment. However, after 2 weeks of FLUT treatment, 1 horse redeveloped hypersensitivity. There was a significant decrease in the number of lymphocytes after treatment with both DEX and FLUT (P = .039 for both) but no significant differences in other BALF cell types or total cell counts (P > .05). There was no difference in the scoring of the clinical signs during each treatment and washout period (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Both DEX and FLUT treatments significantly inhibit airway hypersensitivity and hyperreactivity in horses with IAD. There are no significant effects on the clinical signs or the number of inflammatory cells (except lymphocytes) in BALF. The treatments have no residual effect 3 weeks after discontinuation.

Trichodysplasia spinulosa: a polyomavirus infection specifically targeting follicular keratinocytes in immunocompromised patients.

Trichodysplasia spinulosa (TS) is a rare skin disease, caused by a specific polyomavirus, occurring in immunocompromised patients. The pathophysiological mechanisms of TS are not yet fully understood. By using polymerase chain reaction and skin biopsy immunostaining we report evidence, in a paediatric case, of follicular keratinocytes being the primary target of trichodysplasia spinulosa-associated polyomavirus.

Bronchial collapse during bronchoalveolar lavage in horses is an indicator of lung inflammation.

REASONS FOR PERFORMING STUDY: The bronchoalveolar lavage (BAL) procedure can return variable volumes of fluid, possibly depending on the presence of bronchial collapse during fluid aspiration and on the severity of lung inflammation. OBJECTIVES: We tested the hypothesis that horses with bronchial collapse during BAL are at higher risk of having severe lung inflammation. STUDY DESIGN: Prospective field study. METHODS: Bronchial collapse was graded using a new simple scoring method (0, 1 or 2) during a standardised BAL procedure in the field on 131 horses with normal, mild/moderate or severe lower airway inflammation on cytology of BAL fluid. RESULTS: Of the 131 horses, 37 (28%), 55 (42%) and 39 (30%) horses had bronchial collapse scores of 0, 1 and 2, respectively. There was a difference in collapse scores between all the BAL inflammation categories (P<0.001). Severe collapse had a positive predictive value of 0.95 for both mild/moderate and severe BAL inflammation, with a prevalence of 63% and 20%, respectively. The BAL fluid return volume in the horses with severe collapse scores was lower than volumes in the partial (score 1/2) and no collapse (score 0/2) groups (P<0.001). The BAL fluid volume was negatively correlated with BAL neutrophil percentage (P<0.001). CONCLUSIONS: Airway collapse during BAL is associated with airway inflammation and neutrophilia. POTENTIAL RELEVANCE: During a standardised BAL procedure, clinicians can expect lung inflammation in horses that have bronchial collapse and bronchial collapse in horses with lung inflammation. Lung inflammation may be a contributing factor in the mechanism of bronchial collapse during BAL in horses.

Radiosensitising nanoparticles as novel cancer therapeutics--pipe dream or realistic prospect?

The field of high atomic number nanoparticle radiosensitising agents is reviewed. After a brief discussion of the new mode of physicochemical action implied by irradiation of high atomic number nanoparticles embedded in biological systems, a series of exemplars are discussed. Silver-, gadolinium- and gold-based nanoparticles are discussed in order of increasing atomic number with functionalisation strategies being outlined. In vitro and in vivo evidence for radio-enhancement and the mechanisms attributed to the increased biological effect are discussed.

Endoscopic assessment of airway inflammation in horses.

BACKGROUND: Comprehensive endoscopic scoring of the upper and lower airways for inflammation has not been critically assessed among a large population of horses. The relationship between upper and lower airways described in humans by the "one airway, one disease" concept might also apply to horses. HYPOTHESIS/OBJECTIVES: To evaluate if an association exists between endoscopic inflammatory scores and mucus scores of upper and lower airways and to investigate if endoscopic findings correlate with the lower airway inflammation measured by bronchoalveolar lavage (BAL) cytology. METHODS: Prospective field study. Pharyngitis, pharyngeal mucus, tracheal mucus, tracheal septum thickness, and bronchial mucus were scored using new and previously described scoring systems on a convenience sample of 128 horses with and without lung inflammation. Based on BAL fluid cytology, horses were categorized as having normal, moderate, or severe inflammation of the lower airways. RESULTS: All 5 endoscopy scores showed excellent interobserver agreement. Tracheal mucus (P < .001), tracheal septum thickness (P = .036), and bronchial mucus (P = .037) were significantly increased in horses with severe inflammation BALs and were correlated among themselves but not with upper airways scores. BAL neutrophils percentage was correlated with tracheal mucus (r(s) = 0.41, P < .001), bronchial mucus (r(s) = 0.27, P = .003), and had a weak negative correlation with pharyngitis (r(s) = -0.25, P = .004). CONCLUSIONS AND CLINICAL IMPORTANCE: Lower airway endoscopy scores are reflective of lower airway inflammation; however, upper and lower airways are independent in terms of severity of inflammation. Therefore, observing upper airway inflammation is not an indication to test for lower airway inflammation.

Evaluation of a risk-screening questionnaire to detect equine lung inflammation: results of a large field study.

REASONS FOR PERFORMING STUDY: The diagnosis of equine recurrent airway obstruction (RAO) and inflammatory airway disease (IAD) is based on clinical signs and increased inflammatory cell percentages in the bronchoalveolar lavage (BAL) fluid. Since a BAL is an invasive procedure, a risk-screening questionnaire (RSQ) would be a valuable screening tool for lung inflammation. OBJECTIVE: To evaluate the accuracy of a RSQ to detect lower airway inflammation (LAI) in a large population of horses. METHODS: A standardised BAL was performed in the field on 167 horses in Alberta, Canada. Horses were separated into 3 categories: 1) BAL normal; 2) BAL mild to moderate LAI (MLAI), and 3) BAL severe LAI (SLAI). The horse owners were asked to complete a RSQ. The RSQ scores were compared to the BAL results to determine the likelihood of a horse having MLAI, SLAI or no LAI. RESULTS: Based on BAL cytology, 28 (17%) horses were normal and 139 (83%) were abnormal, with 110 (66%) showing MLAI and 29 (17%) SLAI. Horses with SLAI and MLAI had a mean RSQ score of 0.95 and 0.70, respectively, compared to 0.60 for normal BAL horses. Horses with SLAI showed more clinical signs than normal and MLAI horses. The sensitivity and negative predictive values of the RSQ for detecting SLAI using a cut-off score of 0.87, were excellent at 0.90 (95%CI 0.73-0.98) and 0.96 (95%CI 0.82-1.00). Questions on the clinical signs typically found in RAO cases differed significantly between horses with BAL SLAI and those with BAL normal. CONCLUSIONS: Prevalence of MLAI was high in this population. Although the RSQ did not allow differentiating normal horses from horses with MLAI, it has a high sensitivity to detect horses with SLAI and is therefore a good screening tool for SLAI.

Fusarium culmorum is a single phylogenetic species based on multilocus sequence analysis.

Fusarium culmorum is a major pathogen of wheat and barley causing head blight and crown rot in cooler temperate climates of Australia, Europe, West Asia and North Africa. To better understand its evolutionary history we partially sequenced single copy nuclear genes encoding translation elongation factor 1-α (TEF), reductase (RED) and phosphate permease (PHO) in 100 F. culmorum isolates with 11 isolates of Fusarium crookwellense, Fusarium graminearum and Fusarium pseudograminearum. Phylogenetic analysis of multilocus sequence (MLS) data using Bayesian inference and maximum parsimony analysis showed that F. culmorum from wheat is a single phylogenetic species with no significant linkage disequilibrium and little or no lineage development along geographic origin. Both MLS and TEF and RED gene sequence analysis separated the four Fusarium species used and delineated three to four groups within the F. culmorum clade. But the PHO gene could not completely resolve isolates into their respective species. Fixation index and gene flow suggest significant genetic exchange between the isolates from distant geographic regions. A lack of strong lineage structure despite the geographic separation of the three collections indicates a frequently recombining species and/or widespread distribution of genotypes due to international trade, tourism and long-range dispersal of macroconidia. Moreover, the two mating type genes were present in equal proportion among the F. culmorum collection used in this study, leaving open the possibility of sexual reproduction.

Field test of a novel detection device for Mycobacterium tuberculosis antigen in cough.

BACKGROUND: Tuberculosis is a highly infectious disease that is spread from person to person by infected aerosols emitted by patients with respiratory forms of the disease. We describe a novel device that utilizes immunosensor and bio-optical technology to detect M. tuberculosis antigen (Ag85B) in cough and demonstrate its use under field conditions during a pilot study in an area of high TB incidence. METHODS: The TB Breathalyzer device (Rapid Biosensor Systems Ltd) was field tested in the outpatient clinic of Adama Hospital, Ethiopia. Adults seeking diagnosis for respiratory complaints were tested. Following nebulization with 0.9% saline patients were asked to cough into a disposable collection device where cough aerosols were deposited. Devices were then inserted into a portable instrument to assess whether antigen was present in the sample. Demographic and clinical data were recorded and all patients were subjected to chest radiogram and examination of sputum by Ziehl-Nielsen microscopy. In the absence of culture treatment decisions were based on smear microscopy, chest x-ray and clinical assessment. Breathalyzer testing was undertaken by a separate physician to triage and diagnostic assessment. RESULTS: Sixty individuals were each subjected to a breathalyzer test. The procedure was well tolerated and for each patient the testing was completed in less than 10 min. Positive breath test results were recorded for 29 (48%) patients. Of 31 patients with a diagnosis of tuberculosis 23 (74%; 95% CI 55-87) were found positive for antigen in their breath and 20 (64%; 95% CI 45-80) were smear positive for acid fast bacilli in their sputum. Six patients provided apparent false positive breathalyzer results that did not correlate with a diagnosis of tuberculosis. CONCLUSIONS: We propose that the breathalyzer device described warrants further investigation as a tool for studying exhalation of M. tuberculosis. The portability, simplicity of use and speed of the test device suggest it may also find use as a tool to aid early identification of infectious cases. We recommend studies be undertaken to determine the diagnostic sensitivity and specificity of the device when compared to microbiological and clinical indicators of tuberculosis disease.

Effect of different potting systems; inoculation time; nematode density and sources of cereal cyst nematode (Heterodera filipjevi) on juvenile penetration into wheat root system.

Investigations were designed to optimize testing systems for screening wheat breeding lines for resistance to Heterodera filipjevi. The effects of: 1) plant potting systems 2) inoculum level and time of inoculation 3) and type of inoculum of H. filipjevi on detection accuracy were examined in growth chamber experiments in Turkey. The rate of nematode penetration in the highly susceptible variety Bezostaya was used as the base measurement of efficacy. The results showed that the highest level of penetration coupled with high level of germination was obtained in plastic tubes (13 cm long x 3 cm in diam.) when compared to both small flower pots (400 cm3) and smaller plastic tubes (10.2 cm long x 0.8 cm in diam.). The highest rate of nematode penetration into wheat root system was obtained by inoculating the seedlings with 1000 J2 per plant. However, inoculation with 200 J2 at sowing or 200 J2 at sowing plus an additional 200 J2 after germination improved percent penetration when compared to inoculation with 600 or 1000 J2/plant at sowing. The test on the optimum form of inoculum showed that inoculating the seedling with J2's gave the highest rate of nematode penetration over inoculum with eggs or cysts. The results of these experiments demonstrated that screening wheat for resistance can be optimized by raising the seedlings in plastic tubes and inoculating them with 400 J2.

The global importance of the cereal cyst nematode (Heterodera spp.) on wheat and international approaches to its control.

The Cereal Cyst Nematodes (CCNs) are a group of several closely related species which have been documented to cause economic yield loss on rainfed wheat production systems in several part of the world including North Africa, West Asia, China, India, Australia, America and several countries in Europe. The most commonly reported species is Heterodera avenae, however there are at least two other species H. filipjevi and H. latipons are implicated. It is well appreciated that plants under water and nutrient stress suffer greater yield loss. Control of CCNs requires maintaining nematode populations below economic thresholds. Chemicals are not environmentally sustainable or economic and the major emphasis on control has been with host genetic resistance applied with other integrated pest managent options. Unfortunately due to the number of species and pathotype variation genetic control of Cereal Cyst Nematode with plant resistance is complex. Turkey is one of the top ten wheat producers in the world and has identified these nematode as a major biotic constraint in their rainfed wheat systems. In 2001 a new joint intiative was established between CIMMYT International, the Turkish Ministry of Agriculture and (Ukurova University in Adana to understand i) the distribution of cereal nematodes on wheat; ii) assess the economic importance and improve our understanding of the population dynamics iii) culture, screen and assess known sources of resistance and identify new sources to both groups of nematodes; iv) integrate new sources of resistance into bread wheat cultivars for Turkey and International germplasm using conventional and molecular tools; v) investigate other integrated control options such as rotation and different wheat management strategies and finally vi) capacity build scientists to work in this important area. Some highlights of this work will be presented and the newly formed ICCNI - International Cereal Cyst Nematode Initative introduced.

Serum electrolyte concentrations and hydration status are not associated with exercise associated muscle cramping (EAMC) in distance runners.

OBJECTIVES: To determine whether acute exercise associated muscle cramping (EAMC) in distance runners is related to changes in serum electrolyte concentrations and hydration status. METHODS: A cohort of 72 runners participating in an ultra-distance road race was followed up for the development of EAMC. All subjects were weighed before and immediately after the race. Blood samples were taken before the race, immediately after the race, and 60 minutes after the race. Blood samples were analysed for glucose, protein, sodium, potassium, calcium, and magnesium concentrations, as well as serum osmolality, haemoglobin, and packed cell volume. Runners who suffered from acute EAMC during the race formed the cramp group (cramp, n = 21), while runners with no history of EAMC during the race formed the control group (control, n = 22). RESULTS: There were no significant differences between the two groups for pre-race or post-race body weight, per cent change in body weight, blood volume, plasma volume, or red cell volume. The immediate post-race serum sodium concentration was significantly lower (p = 0.004) in the cramp group (mean (SD), 139.8 (3.1) mmol/l) than in the control group (142.3 (2.1) mmol/l). The immediate post-race serum magnesium concentration was significantly higher (p = 0.03) in the cramp group (0.73 (0.06) mmol/l) than in the control group (0.67 (0.08) mmol/l). CONCLUSIONS: There are no clinically significant alterations in serum electrolyte concentrations and there is no alteration in hydration status in runners with EAMC participating in an ultra-distance race.

Duplex Scorpion primers in SNP analysis and FRET applications.

Scorpions are fluorogenic PCR primers with a probe element attached at the 5'-end via a PCR stopper. They are used in real-time amplicon-specific detection of PCR products in homogeneous solution. Two different formats are possible, the 'stem-loop' format and the 'duplex' format. In both cases the probing mechanism is intramolecular. We have shown that duplex Scorpions are efficient probes in real-time PCR. They give a greater fluorescent signal than stem-loop Scorpions due to the vastly increased separation between fluorophore and quencher in the active form. We have demonstrated their use in allelic discrimination at the W1282X locus of the ABCC7 gene and shown that they can be used in assays where fluorescence resonance energy transfer is required.

Semantic factors in the production of number agreement.

This paper examines the role of semantic factors in the production of subject-verb number agreement. As an ostensibly grammatical process, number agreement provides an interesting case for examining the flow and interaction of semantic and syntactic information through the language-production system. Using a sentence-completion task, agreement errors can be elicited from subjects by presenting them with sentence fragments containing a complex noun-phrase, in which the nonhead noun is plural (e.g., The key to the cabinets ... WERE missing.). Previous research has demonstrated that the probability of making an error can be affected by varying the properties of the nouns in the complex noun phrase. By investigating which variables do and do not affect error rates, constraints on the flow of information through the production system can be inferred. In three experiments, we investigated the possible effects of three different semantic manipulations of the nouns in the complex NP: animacy, semantic overlap, and plausibility of modification by the sentence predicate. We found that both animacy and semantic relatedness had reliable effects on error rates, indicating that the mechanism involved in implementing agreement cannot be blind to semantic information. However, the plausibility with which each noun could serve as the subject of the sentence predicate had no effect on error rates. Taken together, these results suggest that while semantic information is visible to the agreement mechanism, there are still constraints on when this information can affect the process. Specifically, it may be the case that only information contained within the complex NP is considered for the purposes of implementing agreement.

Word frequency effects on the processing of subject-verb number agreement.

This paper examines the role of word frequency in the computation of subject-verb number agreement. Previous research in both production and comprehension has demonstrated that processing difficulties can arise in sentence structures containing a singular subject noun followed by a plural "distractor" noun, as in The key to the cabinets.... A whole sentence reading task was employed to determine whether the relative frequency with which the distractor noun appears in its singular or plural form would affect the degree of processing difficulty experienced by readers. Results suggest that the agreement process is, indeed, sensitive to this factor and this finding is compatible with activation-based accounts of the implementation of number agreement.

A research registry: uses, development, and accuracy.

Many studies of population health, clinical epidemiology, and health services can be supported by a population-based research registry. Such a registry accurately defines the health insurance status for each individual over many years, magnifying the effectiveness of a cross-sectional registry (typically relevant for only a short duration) used in the administration of a health insurance plan. A research registry can distinguish between "well" individuals (no contact with the health care system), loss to follow-up (ineligibility associated with leaving the insurance plan), loss of continuity (two or more unlinked registrations over time for the same person), and mortality. The Manitoba research registry was developed to facilitate longitudinal studies; working within strict confidentiality controls, identifiers for each individual known to Manitoba Health since 1970 can be retrieved and a single unique identifier assigned. Careful reporting of changes in family registration numbers has enabled tracing area of residence, marital status, and family characteristics; results are equivalent to a daily census of the province. This article provides details on source materials, design, and quality of the registry, highlighting its value both for the development of integrated population health information systems and for research in general.

Yield Loss Caused by Pratylenchus thornei on Wheat in South Australia.

A two-year field trial with 130 plots was conducted at Tanunda, South Australia. Ten cereal cultivars differing in susceptibility to Pratylenchus thornei, two poor host crops (non-leguminous), and a bare fallow treatment were used to manipulate the numbers of nematodes in the plots in the first year. Initial and final densities were determined for each plot and varied from 0 to 9,400 nematodes/200 g oven-dried soil at the beginning of the second year. A highly susceptible wheat cultivar, Warigal, and two wheat lines known to have some resistance to P. thornei, GS50A and AUS4930, were planted in the second year. High densities of P. thornei caused more extensive lesions and severe cortical degradation in roots of Warigal than in GS50A or AUS4930. There was a significant linear relationship between initial density of P. thornei and Warigal grain yield (t/ha), with the estimated regression equation Y = 1.86 - 0.0000557x, where Y is the grain yield in t/ha and x is the number of P. thornei/200 g oven-dried soil. High initial densities (9,000 P. thornei/200 g oven-dried soil) caused up to 27% yield loss of this commercial Australian wheat. In contrast, the yield of the two resistant lines was not affected by initial density, suggesting that both were tolerant as well as resistant in the field.

Separating hierarchical relations and word order in language production: is proximity concord syntactic or linear?

In this paper we address the question whether hierarchical relations and word order can be separated in sentence production. In two experiments, we assess whether subject-verb agreement errors (such as 'The time for fun and games are over') require linear proximity of a so-called 'local' noun ('games' in the example) to the verb. In the first experiment, we found a proximity effect when participants were asked to complete sentential beginnings of the kind: 'The helicopter for the flights'. In the second experiment, we asked participants to produce a question such as 'Is the helicopter for the flights safe?'. The syntactic relation between the subject noun and the local noun is the same in the two experiments, but the linear position of the local noun is different. The distribution of agreement errors was similar in the two experiments. We argue that these data provide evidence for a stage in language production in which a syntactic structure is built prior to a stage in which words are assigned to their linear position. Agreement is computed during the first stage.

What can prosody tell a parser?

In this paper, I consider how a sentence processor might use specific prosodic cues at various points in the processing of particular sentences containing (at least temporary) syntactic ambiguity. In principle, the usefulness of prosodic information depends on what a given cluster of prosodic cues typically signifies, and on which syntactic options exist for a given string: in only some instances can prosodic information provide useful disambiguating information.

Tourists as inpatients in Queensland regional hospitals.

This study analysed medical record data from seven regional hospitals in Queensland to determine the types of medical conditions and injuries that resulted in overseas and interstate tourists being admitted to hospital. From a total of 135,128 admissions to the participating hospitals, 695 (0.51 per cent) were identified as overseas tourists and 3479 (2.57 per cent) were from interstate. The main reasons for admission of overseas tourists, based on principal diagnoses, were injuries and poisonings (37.6 per cent), circulatory disorders (11.7 per cent), digestive conditions (9.8 per cent), and genito-urinary disorders (8.8 per cent). For interstate tourists, the main reasons for admission were genito-urinary disorders (19.8 per cent), injuries and poisonings (15.4 percent), neoplasms (11.4 per cent) and circulatory disorders (10.6 per cent). These findings are discussed in relation to current literature in the field of travel medicine, emphasising the burden of care placed on the admitting hospital's resources, and the growing number of visitors to Queensland needing health care.

Effects of clausal structure on subject-verb agreement errors.

This paper explores the effect of manipulating the internal structure of a complex subject on the incidence of subject--verb agreement errors. Using the sentence completion task (Bock & Miller, 1991), this study followed up on Vigliocco and Nicol's (1995) finding that the syntactic distance between a head noun and a number-mismatching noun contained within a modifier has an impact on error incidence: the greater the distance, the lower the error rate. The study presented in this paper investigated whether this distance effect is purely syntactic; if so, then it would be expected that there would be fewer errors following The owner of the house which charmed the realtors... than following The owner of the house who charmed the realtors..., since in the latter, the mismatch is syntactically nearer the head noun. Results show no hint of a difference between the two, suggesting that the distance effect is more likely due to temporal distance rather than syntactic distance per se.