Utilization of the validated Psoriasis Epidemiology Screening Tool to identify signs and symptoms of psoriatic arthritis among those with psoriasis: a cross-sectional analysis from the US-based Corrona Psoriasis Registry.

BACKGROUND: Despite increasing awareness of the disease, rates of undiagnosed psoriatic arthritis (PsA) are high in patients with psoriasis (PsO). The validated Psoriasis Epidemiology Screening Tool (PEST) is a five-item questionnaire developed to help identify PsA at an early stage. OBJECTIVES: To assess the risk of possible undiagnosed PsA among patients with PsO and characterize patients based on PEST scores. METHODS: This study included all patients enrolled in the Corrona PsO Registry with data on all five PEST questions. Demographics, clinical characteristics and patient-reported outcomes were compared in Corrona PsO Registry patients with PEST scores ≥3 and <3 using t-tests for continuous variables and chi-squared tests for categorical variables; scores ≥3 may indicate PsA. RESULTS: Of 1516 patients with PsO, 904 did not have dermatologist-reported PsA; 112 of these 904 patients (12.4%) scored ≥3 and were significantly older, female, less likely to be working, and had higher BMI than patients with scores <3. They also had significantly longer PsO duration, were more likely to have nail PsO and had worse health status, pain, fatigue, Dermatology Life Quality Index and activity impairment. CONCLUSIONS: Improved PsA screening is needed in patients with PsO because the validated PEST identified over one-tenth of registry patients who were not noted to have PsA as having scores ≥3, who could have had undiagnosed PsA. Appropriate, earlier care is important because these patients were more likely to have nail PsO, worse health-related quality of life and worse activity impairment.

The effect of bolus volume on laryngeal closure and UES opening in swallowing: Kinematic analysis using 320-row area detector CT study.

This study investigated the effects of three different volumes of honey-thick liquid on the temporal characteristics of swallowing. Twenty-six healthy subjects (15 males, 11 females) underwent 320-row area detector CT scan while swallowing 3, 10 and 20 mL of honey-thick liquid barium. Three-dimensional images were created at 10 images/s. Kinematic events involving six structures (velopharynx, hyoid bone, epiglottis, laryngeal vestibule (LV), true vocal cords (TVC), upper esophageal sphincter (UES)) and timing of bolus movement were timed using frame by frame analysis. The overall sequence of events did not differ across three volumes; however, increasing bolus volume significantly changed the onset and termination of events. The bolus head reached to pharynx and esophagus earlier and the duration of bolus passing through UES was significantly longer in 10 and 20 mL compared to 3 mL (P < .05). Consequently, the onset of UES opening was significantly earlier with increased volume (P < .05). LV and TVC closure occurred later in 20 mL compared to 3 mL (P < .05). These changes in motion of pharynx and larynx appeared to promote swallow safety by preventing aspiration, suggesting that anatomical structure movements adapt in response to bolus volume. Our findings also suggest that the pharyngeal swallow behaviours may be modified by afferents in the oral cavity. The three-dimensional visualization and quantitative measurements provided by 320-ADCT provide essential benchmarks for understanding swallowing, both normal and abnormal.

Anatomy of the larynx and pharynx: effects of age, gender and height revealed by multidetector computed tomography.

Although oropharyngeal and laryngeal structures are essential for swallowing, the three-dimensional (3D) anatomy is not well understood, due in part to limitations of available measuring techniques. This study uses 3D images acquired by 320-row area detector computed tomography ('320-ADCT'), to measure the pharynx and larynx and to investigate the effects of age, gender and height. Fifty-four healthy volunteers (30 male, 24 female, 23-77 years) underwent one single-phase volume scan (0.35 s) with 320-ADCT during resting tidal breathing. Six measurements of the pharynx and two of larynx were performed. Bivariate statistical methods were used to analyse the effects of gender, age and height on these measurements. Length and volume were significantly larger for men than for women for every measurement (P < 0.05) and increased with height (P < 0.05). Multiple regression analysis was performed to understand the interactions of gender, height and age. Gender, height and age each had significant effects on certain values. The volume of the larynx and hypopharynx was significantly affected by height and age. The length of pharynx was associated with gender and age. Length of the vocal folds and distance from the valleculae to the vocal folds were significantly affected by gender (P < 0.05). These results suggest that age, gender and height have independent and interacting effects on the morphology of the pharynx and larynx. Three-dimensional imaging and morphometrics using 320-ADCT are powerful tools for efficiently and reliably observing and measuring the pharynx and larynx.

A questionnaire-based survey of perioperative blood conservation practice for revision hip arthroplasty in Scotland.

The aim of this study was to describe current blood conservation practice during revision hip surgery in Scotland and document practice variation. Revision hip surgery is associated with a high likelihood of blood transfusion. A decrease in the proportion of patients requiring blood transfusion has been documented, but the reasons for this are unclear. Various blood conservation practices are available to clinicians, but the extent to which these are used in Scottish hospitals is not known. A cross-sectional postal survey was sent to all consultant orthopaedic surgeons and consultant anaesthetists participating in revision hip surgery in Scottish hospitals. Responses were received from 92 of 120 (77%) surgeons, and 174 of 216 (81%) anaesthetists (62/92). A total of 62 of 92 (67%) surgeons and 78 of 174 (45%) anaesthetists surveyed participated in revision hip surgery. Blood conservation practice varied widely: 34 of 78 (44%) anaesthetists routinely assessed revision hip patients >or=1 week prior to surgery; 10 of 62 (16%) surgeons and 24 of 78 (31%) anaesthetists routinely used cell salvage; 7 of 78 (9%) anaesthetists and 2 of 62 (3%) surgeons routinely used tranexamic acid; and 45 of 62 (73%) surgeons use a transfusion protocol. A wide variation in the use of blood conservation strategies exists during revision hip surgery in Scotland.

Cyclic motion of the soft palate in feeding.

The soft palate moves rhythmically during feeding, but the timing and frequency of this motion are not known. We tested the hypothesis that cyclic soft palate motion is temporally linked to cyclic jaw movement. Nine healthy, asymptomatic human subjects with normal dentition ate solid food coated with barium. Videofluorographic recordings showed that rhythmic motions of the soft palate during mastication were linked temporally to jaw motion. Soft palate motion occurred in every recording but not in every jaw cycle. The soft palate moved upward as the jaw opened, but the nasopharynx was not sealed. During swallowing, however, the soft palate invariably elevated during the intercuspal phase of jaw motion, sealing the nasopharynx. The frequency of soft palate cycles was lowest early in a feeding sequence and gradually increased as the sequence progressed from ingestion to swallowing. We conclude that cyclic movement of the soft palate in feeding is temporally linked to jaw motion.

Comparison of adult and fetal cytokine secretion during mixed lymphocyte reactions.

Umbilical cord blood transplants are associated with a lower incidence of graft-versus-host disease (GVHD) than adult marrow or peripheral blood stem cell transplants, and this could be related to a difference in cytokine production between fetal and adult mononuclear cells after allogeneic stimulation. Mixed lymphocyte reactions (MLRs) involving adult cells were associated with greater interferon-gamma (IFNgamma) secretion than MLRs between cord blood cells, although IL-2 secretion was similar. Experiments in which T cells were separated from accessory cells then recombined in artificial combinations indicated that differences in T cells were primarily responsible for the greater [IFNgamma]:[IL-2] ratios generally found after MLRs involving adult cells compared to fetal cells, but accessory cells also influenced this ratio. The cellular basis for the observed difference was not established, but mononuclear cell preparations from cord blood contained significantly higher proportions of CD16(+)56(-) NK-type cells and a CD19(+)1c(+) B cell subset, as well as more CD45 RA-expressing nai;ve T cells.

The effect of airway epithelium on smooth muscle contractility in bovine trachea.

In bovine tracheal smooth muscle the presence of airway epithelium significantly reduced the sensitivity and maximum contractile response to histamine, 5-hydroxytryptamine (5-HT) or acetylcholine. Muscle contraction induced by K+ and electrical field stimulation was of similar magnitude both in the presence or absence of adherent epithelium. The effect of epithelium on smooth muscle contractility was unaffected by pretreatment with indomethacin (10(-6) M) or mepacrine (5 X 10(-5) M). The relaxant response to isoprenaline was enhanced in the presence of epithelium, although this was significant only in the case of precontraction with 5-HT. It is concluded that the bronchial epithelium may produce a relaxant factor which is not a cyclooxygenase or lipoxygenase product. The production of this factor may be reduced or lost following epithelial damage and this may be important in the pathogenesis of bronchial hyperresponsiveness in asthma.

Calcitonin gene-related peptide is localised to human airway nerves and potently constricts human airway smooth muscle.

In human airways synthetic human sequence calcitonin gene-related peptide (hCGRP), a novel peptide produced by alternative processing of mRNA from the calcitonin gene, caused concentration-dependent contraction of human bronchi (EC50 4.9 X 10(-9) M) and was significantly more potent than substance P or carbachol. The contractile response was unaffected by atropine (2 X 10(-6) M), propranolol (10(-6) M), indomethacin (10(-5) M), tetrodotoxin (3 X 10(-6) M), chlorpheniramine (10(-4) M), cimetidine (10(-5) M), or FPL55712 (10(-4) M) suggesting a direct effect of CGRP on airways smooth muscle. CGRP was detected in human airways by radioimmunoassay with highest concentrations in cartilaginous airways. CGRP was localised by immunocytochemistry to both nerves and ganglia in human airways. CGRP, is a potent constrictor of human airways and may have important effects on airway function and be implicated in the pathogenesis of bronchial hyper-responsiveness and asthma.

Clinical efficacy, tolerance and pharmacokinetics of temocillin in patients with respiratory tract infections.

In this study 13 patients with a history of chronic respiratory disease were treated with temocillin for severe infection of the lower respiratory tract. Eleven patients were clinically improved or cured at the end of treatment and 4 remained free of infection at follow up. However, the 2 remaining patients failed to respond clinically and bacteriologically to temocillin. Blood and sputum pharmacokinetics were studied in patients receiving temocillin at 12-hourly intervals in doses of either 1g by intravenous bolus or 2g by intravenous infusion. On the first day of treatment the mean peak serum concentration was 102 mg/L for the 1g dose and 220 mg/L for the 2g dose, falling to 11 mg/L (1g) and 18.8 mg/L (2g) at 12 hours. Similar results were recorded on the last day of treatment. Temocillin concentrations in the sputum ranged from 1.5 to 2.8 mg/L, with no difference being found in the sputum concentrations of the 2 doses. Temocillin was well tolerated and was found to be an effective treatment for Gram-negative bacterial infections of the lower respiratory tract.

VIP and PHM and their role in nonadrenergic inhibitory responses in isolated human airways.

There is increasing evidence in many species that vasoactive intestinal peptide (VIP) may be a neurotransmitter in nonadrenergic inhibitory nerves. We have studied the effect of electrical field stimulation (EFS), exogenous VIP, and isoproterenol (Iso) on human airways in vitro. We have also studied a related peptide, peptide histidine methionine (PHM), which coexists with VIP in human airway nerves, and in separate experiments studied fragments of the VIP amino acid sequence (VIP1-10 and VIP16-28) for agonist and antagonist activity. Human airways were obtained at thoracotomy and studied in an organ bath. In bronchi EFS gave an inhibitory response that was unaltered by 10(-6) M propranolol but was blocked by tetrodotoxin, whereas in bronchioles there was little or no nonadrenergic inhibitory response. VIP, PHM, and Iso all caused dose-dependent relaxation of bronchi, VIP and PHM being approximately 50-fold more potent than Iso. VIP, but not Iso, mimicked the time course of nonadrenergic inhibitory nerve stimulation. In contrast bronchioles relaxed to Iso but not to VIP or PHM. Neither propranolol nor indomethacin altered the relaxant effects of VIP or PHM, suggesting a direct effect of these peptides on airway smooth muscle. Neither of the VIP fragments showed either agonist or antagonist activity. We conclude that VIP and PHM are more potent bronchodilators of human bronchi than Iso and that the association between the relaxant effects of these peptides and nonadrenergic inhibitory responses suggests that they may be possible neurotransmitters of nonadrenergic inhibitory nerves in human airways.

The heterogeneity of the 5q--chromosome marker in refractory anemia.

A patient presenting with an unusual case of refactory anemia is described in whom acquired markers originating from chromosomes No. 5 and 8 are identified by G- and sequential C-banding. Comparison with various published illustrations of chromosome No. 5 deletions in this general broad category of disease raises the possibility that karyotypic misclassification in cases of absent or substandard banding (typical of bone marrow) may help to explain the considerable variation in size and morphology of the 5q--marker.

The efficacy and tolerability of inhaled salmeterol and individually dose-titrated, sustained-release theophylline in patients with reversible airways disease.

In a double-blind, double-dummy, cross-over, multicentre study, 141 patients with moderate reversible airways disease were randomized to receive either 50 micrograms salmeterol via a metered dose inhaler or individually dose-titrated oral theophylline, both twice daily for a 2-week period. Just over half (n = 77) the patients had received theophylline before, but 64 patients were new to theophylline therapy. Efficacy was based on lung function data and symptom scores. Salmeterol produced significantly higher increase in mean morning peak expiratory flow (PEF) of 161 min-1 (P < 0.001; 95% Confidence Interval (CI); 8-241 min-1) and mean evening PEF of 151 min-1 (p < 0.001; 95% CI; 7-221 min-1) compared with theophylline therapy. Further analysis of the data revealed that the increase in PEF with salmeterol compared with theophylline was highest in a sub-group of patients new to theophylline therapy. Patients on salmeterol had significantly less night-time awakenings than those on theophylline (P = 0.011) and significantly less daytime symptoms (P = 0.017). There was also a significant increase in the number of nights (P = 0.013) and days (P < 0.001) on salmeterol when no additional salbutamol was required compared with theophylline. Theophylline produced a higher incidence of adverse events compared with salmeterol. The results of this study show that inhaled salmeterol is more effective and better tolerated than individually dose-titrated oral theophylline over a 2-week study period in patients with moderate asthma.

Inhaled salmeterol in the treatment of patients with moderate to severe reversible obstructive airways disease--a 3-month comparison of the efficacy and safety of twice-daily salmeterol (100 micrograms) with salmeterol (50 micrograms).

Three-hundred and fifty patients with moderate to severe reversible obstructive airways disease (forced expiratory volume in 1 s or peak expiratory flow rate < or = 50% predicted, a 15% reversibility to inhaled salbutamol and symptomatic) were recruited into a multi-centre, multinational, double-blind, parallel-group randomized study. Two-hundred and eighty-three patients were randomized to receive 50 micrograms salmeterol twice daily or 100 micrograms salmeterol twice daily administered from a metered-dose inhaler for 3 months. Salbutamol (100 micrograms per metered actuation) was provided for symptomatic relief. Morning and evening peak expiratory flow rate (PEFR), day-time and night-time asthma symptoms and additional bronchodilator usage were recorded by the patient on a daily basis. Lung function and patient/physician assessment of treatment efficacy were recorded at scheduled clinic visits. Safety was determined by monitoring adverse events and standard biochemical, haematological and cardiovascular parameters. Salmeterol 100 micrograms twice daily was consistently superior to salmeterol 50 micrograms twice daily in morning and evening PEFR measurements (mean differences between the treatments: 10-14 l min-1 for morning, 95% CI-0, 22 l min-1, P = 0.047; and 10-15 l min-1 for evening, 95% CI 2, 22 l min-1, P = 0.023). The improvement in PEFR was independent of concurrent steroid usage, with the most marked improvement being seen in the more severe asthmatics requiring concurrent oral corticosteroids (mean differences between the treatments: 27-31 l min-1, 95% CI: 3,55 l m-1, P = 0.027).(ABSTRACT TRUNCATED AT 250 WORDS)

Salmeterol provides prolonged protection against exercise-induced bronchoconstriction in a majority of subjects with mild, stable asthma.

In patients with asthma, exercise-induced symptoms are well recognized and frequently limiting. Currently available beta 2-receptor agonists have a short duration of action and breakthrough symptoms may occur. We studied the efficacy of the recently developed long acting inhaled beta 2-agonist salmeterol with respect to protection against exercise-induced bronchoconstriction. Twelve patients with mild to moderate, stable asthma were recruited (age range 21-33 years). They each underwent treadmill exercise tests, with target heart rate of approximately 90% of predicted maximum, 1, 6 and 12 h after a single dose of salmeterol 50 micrograms, salbutamol 200 micrograms and placebo. Patients breathed through a two-way valve, inspiring dry air from a compressed air cylinder via a Douglas bag to maintain constant humidity. The primary efficacy variable analysed was the maximum percentage fall in FEV1 and FVC from pre-exercise readings within the first 30 min post-exercise. At 1 h post-dose there was significant protection in terms of fall in mean +/- SEM FEV1 in response to exercise challenge after either salmeterol (0.83 +/- 6.2%) or salbutamol (3.8 +/- 5.5%) as compared with placebo (27.1 +/- 7.3%). At 6 h post-dose, fall in FEV1 on salmeterol was 11.3 +/- 3.8% as compared with salbutamol, 28.0 +/- 5.7% and placebo, 32.0 +/- 7.0%. At 12 h post-dosing there was still significant protection in terms of fall in FEV1 in the salmeterol treated group, 12.8 +/- 4.9%, as compared with salbutamol, 28.7 +/- 4.9% and placebo, 25.4 +/- 7.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Motions of the posterior pharyngeal wall in swallowing.

The motions of the posterior pharyngeal wall during swallowing were studied in four asymptomatic males using a new method for videoradiography. Radiopaque markers of 4 mm diameter were affixed to the pharyngeal wall by suction. Ventrodorsal and axial components of motion were measured frame by frame. Large axial motions occurred during the pharyngeal stage of swallowing. Cephalad displacement of each marker occurred early and was followed by caudad motion. Within the pharyngoesophageal segment, there were cephalocaudal motions measuring as much as 25 mm. A late caudad motion beyond the reference position was observed in this segment in two participants. This late motion may play a role in passing the bolus through the pharyngoesophageal segment. The findings support the concept of an "engulfment" mechanism in pharyngeal kinesiology.

Tongue-jaw linkages in human feeding: a preliminary videofluorographic study.

Motions of the tongue and jaw are closely coupled during feeding in mammals, but this relation has not been studied in humans. A videofluorographic method for measuring tongue movement relative to jaw motion using small radiopaque markers affixed to the tongue with dental adhesive was developed and tested in five individuals. Sagittal movements of the anterior tongue marker (ATM) and the lower jaw were measured for complete feeding sequences with a computerized image-analysis system. The ATM and jaw moved in loosely linked, semirhythmic cycles. Vertical and horizontal maxima of ATM motion were determined for each motion cycle in relation to maximum and minimum gape (greatest jaw opening and closing, respectively). The amplitude of tongue movements and their timing differed between hard and soft foods (p < 0.001). For both food types, motions varied as the feeding sequence progressed from ingestion to terminal swallow (p < 0.001). A basic temporal sequence was found in 70% of the 224 cycles analysed. On average, the ATM reached its most inferior position just after maximum gape, its most posterior during jaw closing, its most superior just after minimum gape, and its most anterior during jaw opening (p < 0.001). This study confirms that tongue and jaw movements are linked during human feeding, as they are in other mammals.

Ontogeny of postnatal hyoid and larynx descent in humans.

Postnatal descent of the hyoid and larynx relative to the palate and mandible, which occurs uniquely in humans, is an anatomical prerequisite for quantal speech. This study tested the hypothesis that spatial constraints related to deglutition impose greater restrictions on the rate and degree of hyo-laryngeal descent than do adaptations for vocalization. Ontogenetic data on changes in the size and shape of the pharynx, the vocal tract, and the spatial positions of the larynx, hyoid, mandible and hard palate relative to each other and to the oral cavity were obtained for 15 males and 13 females from a longitudinal series of lateral radiographs (the Denver Growth Study) taken between the ages of 1 month and 14 years. To establish growth patterns, nine linear dimensions of the pharynx and 15 different pharyngeal and vocal-tract proportions were regressed against percentage growth. The results demonstrate that certain aspects of vocal-tract shape change markedly during ontogeny, especially in the first postnatal year and during the adolescent growth spurt. The ratio of pharynx height to oral cavity length (which is important for speech) decreases significantly (P<0.001) from 1.5 to 1.0 between birth and 6-8 years, after which it remains stable. In contrast, regression analyses indicated that superoinferior spatial relations between the positions of the vocal folds, the hyoid body, the mandible and the hard palate do not change significantly throughout the entire postnatal growth period (P<0.05). Sexual dimorphism in pharyngeal shape and size before the age of 14 years is very limited. The results suggest that the descent of the hyoid and larynx relative to the mandible is constrained by muscle function related to deglutition, highlighting the different functional roles of the hyoid during speech and oral transport.

Effects of pollution on swallowing: how little we know.

Swallowing is an essential function of the upper alimentary tract. It is highly complex, requiring precise coordination of numerous nerves and muscles of the oral cavity, pharynx, larynx, and esophagus. Swallowing is integrated with other physiologic functions, including mastication and respiration. Impairments of swallowing may result from many different structural or physiologic disorders. Little is currently known about the direct effects of pollution on swallowing. Structures critical to swallowing, however, are vulnerable to damage by environmental hazards such as exposure to ionizing radiation or intake of toxins by ingestion or inhalation. The relationship of swallowing to environmental lung disease is an area of particular interest because impaired swallowing may result in aspiration of food particles into the lung, and because pollutants may hamper airway defense mechanisms. In this article, we discuss the possible impact of selected environmental agents on swallowing and suggest future directions for research.

ORION laser target diagnostics.

The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

Effects of respiration on soft palate movement in feeding.

Cyclic soft palate elevation is temporally associated with masticatory jaw movement. However, the soft palate is normally lowered during nasal breathing to maintain retropalatal airway patency. We tested the hypothesis that the frequency and amplitude of soft palate elevation associated with mastication would be reduced during inspiration. Movements of radiopaque soft palate markers were recorded by videofluorography while 11 healthy volunteers ate solid foods. Breathing was monitored with plethysmography. Masticatory sequences were divided into processing and stage II transport cycles (food transport to the oropharynx before swallowing). In food processing, palatal elevation was less frequent and its displacement was smaller during inspiration than expiration. In stage II transport, the soft palate was elevated less frequently during inspiration than expiration. These findings suggest that masticatory soft palate movement is diminished during inspiration. The control of breathing appears to have a significant effect on soft palate elevation in mastication.