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, , 459-462. Upper oesophageal sphincter yield pressure was measured in 26 normal subjects and in 69 patients with gastro-oesophageal reflux, using a system of continuously perfused catheters. There was no significant difference between the two groups. Perfusion of the oesophagus with hydrochloric acid produced no change in sphincter pressure. The resting sphincter pressure was not related to the degree of oesophagitis nor to the severity of reflux as measured by 15-hour pH recordings. There were significant differences in sphincter pressure recorded by the three catheters either when their orifices were set 5 cm apart longitudinally or when they were at the same level, equidistant around the circumference of a circle. This indicates that spatial orientation of catheter tips influences the pressure recorded from a sphincter. [ABSTRACT FROM PUBLISHER]

Viruses, such as Rhinovirus, are a major cause of asthma exacerbations. Pellino1 was identified as an interleukin 1 receptor associated kinase binding partner and has shown to act as an E3-ubiquitin ligase that is involved in Lysine-63 polyubiquitination of interleukin 1 receptor associated kinase 1/4 and RIP1, which are key mediators of the Toll-like receptor and interleukin 1 receptor (IL-1R) signalling pathways. As such, these pathways are implicated in responses to both bacterial and viral infections. However, the functional importance of Pellino proteins in regulating immune responses and their role in airway inflammatory diseases is yet to be elucidated. We hypothesised that Pellino1 would play a critical role in regulating the inflammatory response in the lung airway epithelium. Pellino1 was knocked down in the human bronchial airway epithelial cell line BEAS2B and primary human bronchial epithelial cells (PBECs) using targeted siRNA. Knockdown of Pellino1 at the transcriptional level was measured using qPCR. Pellino1 knockdown cells were stimulated with Toll-like receptor/IL-1R agonists or the natural pathogen rhinovirus 1B (RV1B) and cytokine release was measured using ELISA. Signalling pathways were explored by western blotting. Pellino1 was expressed in BEAS2B and primary bronchial epithelial cells. Pellino1 mRNA transcript level was knocked down by 78% in BEAS2B and 94% in PBECs. Pellino1 knockdown led to reduced IL-8 generation in response to IL-1β and a viral mimic Poly (I:C) stimulation in BEAS2B, however RANTES production was unchanged. In contrast to the BEAS2B, the primary bronchial epithelial cells exhibited preserved IL-1 signalling. However, these cells also showed a reduction in IL-8 production in response to both Poly (I:C) stimulation and RV1B infection. Pellino1 knockdown had no effect on the interferon-stimulated gene RANTES production. Pellino1 knockdown leads to reduced IL-8 production in response to a viral mimic Poly (I:C) in lung airway epithelial cells and RV1B in PBECs. These data indicate that Pellino1 regulates proinflammatory responses in airway epithelium and may be a feasible target to downregulate neutrophillic airway inflammation while retaining antiviral immunity, which would be highly beneficial in the treatment of chronic airway inflammatory disorders such as asthma and COPD. These studies were supported by an MRC/Asthma UK PhD studentship. [ABSTRACT FROM AUTHOR]

Introduction Currently the same threshold value is used to identify a positive D-dimer result for all patients presenting to our ambulatory clinic with suspected pulmonary emboli (PE). It has been suggested that adjusting the threshold value according to the pre-test probability would exclude PE in more patients than using the same cutoff point regardless of clinical probability. Methods Data from 362 consecutive patients presenting to the ambulatory PE clinic was collected. A pre-test probability of PE was recorded for all patients and those with a high pre-test probability had radiological investigations. Patients with a low or intermediate pre-test probability had a latex agglutination D-dimer test. If this result was =0.5 µg/ml they had further investigations, otherwise they were discharged. The diagnosis of PE was made if a VQ scan showed ventilation/perfusion mismatch or CTPA report demonstrated PE. Receiver operating characteristic curve analysis was performed separately for patients with low and intermediate probability and the optimum cut-off value to exclude PE determined. Sensitivity, specificity, negative predictive value and positive predictive value for different cut-off points were determined. Results 362 patients were included in the analysis, 207 (57%) had low, 129 (36%) intermediate and 26 (7%) high pre-test probability. Prevalence of PE was 2% in the low probability group, 14% in the intermediate probability group and 42% in the high probability group. No patients with a D-dimer of <0.5 µg/ml who were discharged without further tests have re-presented with similar symptoms. In the low pre-test probability group, a cut-off point of 1.07 improved the specificity from 64% to 89% while maintaining a sensitivity of 100% and negative predictive value of 100%. Analysis in patients in the intermediate risk group suggested that a cut-off of 0.5 µg/ml was appropriate. By adjusting the D-dimer threshold to >1.0 µg/ml in the low probability group, a further 53 patients could have been discharged home without need for radiological investigation. Conclusion The diagnostic accuracy of D-dimer testing may be improved in patients with a low pre-test probability by adjusting the cut-off threshold. [ABSTRACT FROM AUTHOR]

Introduction Suspected Pulmonary Embolism (PE) is a significant cause of admission to hospital. The objective of this study was to establish the feasibility and safety of managing suspected and proven PE in an out-patient setting. Methods Criteria for low risk patients with suspected PE suitable for treatment in an ambulatory setting were established based on modified Pulmonary Embolism Severity Score (PESI) criteria. Patients deemed low risk were referred to a nurse-led clinic. Clinical pre-test probability of PE was recorded for all patients and those with a low/intermediate probability had D-dimer testing. Patients with a high pre-test probability or D-dimer=0.5 µg/ml had radiological investigations. Data were collected prospectively. Missing information was completed from pathology, imaging systems and case-note review. Results 362 patients (Median age 46, Female 70%) with suspected PE were referred to the ambulatory clinic in 12 months from June 2010. 269 (74%) patients presented with chest pain. 145 patients (40%) had a negative D-dimer and were discharged. 210 patients (58%) had subsequent imaging in the form of 65 (31%) VQ scan, 138 (66%) CT scan, 7 (3%) both. Median time to imaging was 1 day (range 0-5 days). 34 patients were diagnosed with PE (9%). 11 patients (3%) were admitted, of which 5 (45%) were due to right heart strain. Likelihood of PE correlated strongly to clinical probability (low 2%, intermediate 14%, high 42%). One patient with a negative D-Dimer and intermediate clinical probability was diagnosed with PE. 294 (81%) patients were discharged with no follow-up, 28 (8%) patients were followed-up by consultant care. One patient admitted as they did not meet criteria for ambulatory care (tachycardia) had a cardiorespiratory arrest as an inpatient due to massive PE but was successfully resuscitated. To date three patients have (0.8%) died since attending the clinic, no death was related to PE. Savings to PCTs were estimated at £120 000 over 12 months. Conclusion Selected patients with suspected and proven PE may be managed safely in an ambulatory PE clinic setting resulting in significant savings to the healthcare community. [ABSTRACT FROM AUTHOR]