Primary care summary of the British Thoracic Society Guideline on the management of non-cystic fibrosis bronchiectasis.

The British Thoracic Society (BTS) has recently published a guideline for the management of non-cystic fibrosis (non-CF) bronchiectasis in children and adults. This paper summarises the key recommendations applicable to the primary care setting. The key points are: • Think of the diagnosis of bronchiectasis in adults and children who present with a chronic productive cough or unexplained haemoptysis, and in children with asthma which responds poorly to treatment; • High resolution computed tomography (HRCT) scanning is needed to confirm the diagnosis • Sputum culture should be obtained at the start of an exacerbation prior to initiating treatment with antibiotics; Treatment should be started whilst awaiting the sputum result and should be continued for 14 days; • Patients with bronchiectasis have significant morbidity.

Electrophoretic transfer protein zymography.

Zymography detects and characterizes proteolytic enzymes by electrophoresis of protease-containing samples into a nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel containing a copolymerized protein substrate. The usefulness of zymography for molecular weight determination and proteomic analysis is hampered by the fact that some proteases exhibit slower migration through a gel that contains substrate protein. This article introduces electrophoretic transfer protein zymography as one solution to this problem.

Mapping the sequence of conformational changes underlying selectivity filter gating in the K(v)11.1 potassium channel.

The potassium channel selectivity filter both discriminates between K(+) and sodium ions and contributes to gating of ion flow. Static structures of conducting (open) and nonconducting (inactivated) conformations of this filter are known; however, the sequence of protein rearrangements that connect these two states is not. We show that closure of the selectivity filter gate in the human K(v)11.

In-vehicle extremity injuries from improvised explosive devices: current and future foci.

The conflicts in Iraq and Afghanistan have been epitomized by the insurgents' use of the improvised explosive device against vehicle-borne security forces. These weapons, capable of causing multiple severely injured casualties in a single incident, pose the most prevalent single threat to Coalition troops operating in the region. Improvements in personal protection and medical care have resulted in increasing numbers of casualties surviving with complex lower limb injuries, often leading to long-term disability.

Blast-related fracture patterns: a forensic biomechanical approach.

Improved protective measures and medical care has increased the survivability from battlefield injuries. In an attempt to reduce the debilitating consequences of blast injury, understanding and mitigating the effects of explosion on the extremities is key. In this study, forensic biomechanical analyses have been applied to determine mechanisms of injury after the traumatic event.

Safety and efficacy of CURB65-guided antibiotic therapy in community-acquired pneumonia.

Objectives: To determine whether the introduction of a community-acquired pneumonia (CAP) severity assessment tool to guide antibiotic selection could reduce broad-spectrum antibiotic prescribing without compromising patient safety.

Methods: A prospective before and after evaluation study. Empirical antibiotic prescribing was studied for 18 months from June 2006 to January 2008 (pre-intervention) and then for 18 months following the implementation of a CURB65-guided antibiotic therapy guideline in June 2008.

Impact of mannose-binding lectin insufficiency on the course of cystic fibrosis: A review and meta-analysis.

Mannose-binding lectin (MBL) is an innate immune protein produced by the liver. MBL binds to glycoconjugates containing mannose, fucose or N-acetylglucosamine that are present in a wide variety of bacteria, viruses and fungi. Upon binding, MBL may active the lectin pathway of complement or directly opsonize organisms to enhance phagocytosis.

A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis.

Rationale: Bronchiectasis is a chronic debilitating disease with few evidence-based long-term treatments.

Objectives: A randomized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non-cystic fibrosis bronchiectasis.

Methods: Sixty-five patients were randomized to either twice-daily nebulized gentamicin, 80 mg, or nebulized 0.

Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia. Systematic review and meta-analysis.

Introduction: International guidelines recommend a severity-based approach to management in community-acquired pneumonia. CURB65, CRB65 and the Pneumonia Severity Index (PSI) are the most widely recommended severity scores. The aim of this study was to compare the performance characteristics of these scores for predicting mortality in community-acquired pneumonia.

An improved curvilinear gradient method for parameter optimization in complex biological models.

Mathematical modeling is an often used approach in biological science which, given some understanding of a system, is employed as a means of predicting future behavior and quantitative hypothesis testing. However, as our understanding of processes becomes more in depth, the models we use to describe them become correspondingly more complex. There is a paucity of effective methods available for sampling the vast objective surfaces associated with complex multiparameter models while at the same time maintaining the accuracy needed for local evaluation of minima-all in a practical time period.

Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels.

Potassium channels embedded in cell membranes employ gates to regulate K+ current. While a specific constriction in the permeation pathway has historically been implicated in gating, recent reports suggest that the signature ion selectivity filter located in the outer membrane leaflet may be equally important. Inwardly rectifying K+ channels also control the directionality of flow, using intracellular polyamines to stem ion efflux by a valve-like action.

Assay development and screening of human DGAT1 inhibitors with an LC/MS-based assay: application of mass spectrometry for large-scale primary screening.

Many attractive targets for therapeutic intervention are enzymes that catalyze biological reactions involving small molecules such as lipids, fatty acids, amino acid derivatives, nucleic acid derivatives, and cofactors. Some of the reactions are difficult to detect by methods commonly used in high-throughput screening (HTS) without specific radioactive or fluorescent labeling of substrates. In addition, there are instances when labeling has a detrimental effect on the biological response.

Statins in community acquired pneumonia: Evidence from experimental and clinical studies.

Statins are widely used to lower cholesterol and prevent complications of cardiovascular disease. The non-lipid lowering (pleiotropic) effects of statins may also have applications to the management of infections. These include effects on endothelial function, inflammation and coagulation pathways.

Incidence and prognostic implications of acute kidney injury on admission in patients with community-acquired pneumonia.

Background: A consensus definition of acute kidney injury (AKI)-the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification-predicts mortality in general hospital and ICU populations. We aimed to assess its value on admission in patients with community-acquired pneumonia (CAP).

Methods: A prospective observational study with CAP was carried out.

Do processing time and storage of sputum influence quantitative bacteriology in bronchiectasis?

This study aimed to establish whether the bacterial density of spontaneous sputum is affected by the time and mode of sample storage. Ten patients with bronchiectasis collected all sputum expectorated over 45 min. The samples were aliquoted and processed at 25 degrees C for qualitative and quantitative bacteriology at 1, 2, 4 and 6 h from expectoration.

Right ventricular dilation on CT pulmonary angiogram independently predicts mortality in pulmonary embolism.

Background: The aim of this study was to determine the prognostic significance of right ventricular dilation on CT pulmonary angiogram in acute pulmonary embolism and to distinguish if this feature predicts mortality independently of the Pulmonary Embolism Severity Index, an established admission severity score.

Methods: A retrospective study of patients admitted with pulmonary embolism confirmed by CT pulmonary angiogram to three teaching hospitals in East Scotland between January 2005 and July 2007. Two radiologists judged presence of right ventricular dilation on CT pulmonary angiogram independently.

Sarcoidosis Presenting as a Proximal Phalangeal Bony Swelling-a Case and Review of the Literature.

We report a case of a 27-year-old man who presented with a progressive painful swelling at the base of his left index finger, with radiographs and a computed tomography scan revealing a lytic lesion of the proximal phalanx. Following further investigation, the patient underwent a bone biopsy that revealed a florid noncaseating granulomatous chronic inflammatory infiltrate, compatible with sarcoidosis. Osseous sarcoidosis of the hand is uncommon and, in the absence of significant systemic disease, is rarely the primary presenting feature.

Not all hERG pore domain mutations have a severe phenotype: G584S has an inactivation gating defect with mild phenotype compared to G572S, which has a dominant negative trafficking defect and a severe phenotype.

Introduction: Mutations in the pore domain of the human ether-a-go-go-related gene (hERG) potassium channel are associated with higher risk of sudden death. However, in many kindreds clinical presentation is variable, making it hard to predict risk. We hypothesized that in vitro phenotyping of the intrinsic severity of individual mutations can assist with risk stratification.

The compressive behavior of the human glenoid labrum may explain the common patterns of SLAP lesions.

Purpose: The aim of the study was to define the normalized compressive stiffness (modulus) of the glenoid labrum around its circumference and to characterize the difference in modulus between different areas.

Methods: Sixteen fresh-frozen cadaveric shoulders were harvested and dissected down to the glenoid labrum. Any specimens with significant degenerative changes were discarded, leaving 8 labra for testing.

The range of axial rotation of the glenohumeral joint.

There is a paucity of data in the literature on the restraining effects of the glenohumeral (GH) ligaments; cadaveric testing is one of the best methods for determining the function of these types of tissues. The aim of this work was to commission a custom-made six degrees of freedom (dof) joint loading apparatus and to establish a protocol for laxity testing of cadaveric shoulder specimens. Nine cadaveric shoulder specimens were used in this study and each specimen had all muscle resected leaving the scapula, humerus (transected at mid-shaft) and GH capsule.

Admission D-dimer can identify low-risk patients with community-acquired pneumonia.

Study Objective: Severity assessment is an important component of the management of community-acquired pneumonia. Clinicians are increasingly searching for biomarkers to aid in clinical decisions. Coagulation disorders can accompany severe pneumonia.

Stable bronchiectasis is associated with low serum L-ficolin concentrations.

Background And Aims: Bronchiectasis is a common chronic respiratory condition with recurrent cough and sputum production and recurrent chest infections. It is characterised by pathological dilatation of the bronchi thought to result from infection and inflammation. It was hypothesised that impaired innate immunity might influence susceptibility to this disease process.

Human ether-a-go-go related gene (hERG) K+ channels: function and dysfunction.

The human Ether-a-go-go Related Gene (hERG) potassium channel plays a central role in regulating cardiac excitability and maintenance of normal cardiac rhythm. Mutations in hERG cause a third of all cases of congenital long QT syndrome, a disorder of cardiac repolarisation characterised by prolongation of the QT interval on the surface electrocardiogram, abnormal T waves, and a risk of sudden cardiac death due to ventricular arrhythmias. Additionally, the hERG channel protein is the molecular target for almost all drugs that cause the acquired form of long QT syndrome.

Predicting the need for mechanical ventilation and/or inotropic support for young adults admitted to the hospital with community-acquired pneumonia.

The UK Department of Health has published concerns that pneumonia severity scores determined at hospital admission may underestimate the severity of pneumonia in young adults. SMART-COP (systolic blood pressure, multilobar chest radiography involvement, albumin level, respiratory rate, tachycardia, confusion, oxygenation, and arterial pH) was superior to both the CURB65 (confusion, urea, respiratory rate, systolic or diastolic blood pressure, and age >or=65 years) score and the Pneumonia Severity Index in predicting the need for mechanical ventilation and/or inotropic support, but SMART-COP would still incorrectly stratify 15% of patients.