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Diane Lefaudeux, Bertrand De Meulder, Matthew J Loza, Nancy Peffer, Anthony Rowe, Frédéric Baribaud, Aruna T Bansal, Rene Lutter, Ana R Sousa, Julie Corfield, Ioannis Pandis, Per S Bakke, Massimo Caruso, Pascal Chanez, Sven-Erik Dahlén, Louise J Fleming, Stephen J Fowler, Ildiko Horvath, Norbert Krug, Paolo Montuschi, Marek Sanak, Thomas Sandstrom, Dominic E Shaw, Florian Singer, Peter J Sterk, Graham Roberts, Ian M Adcock, Ratko Djukanovic, Charles Auffray, Kian F Chung
BACKGROUND: Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalised management approach can be provided. OBJECTIVES: We stratified patients with moderate-to-severe asthma based on clinico-physiological parameters and performed an -omics analysis of sputum. METHODS: Partition-around-medoid clustering was applied to a training set of 266 asthma participants from the European U-BIOPRED adult cohort using 8 pre-specified clinic-physiological variables...
October 20, 2016: Journal of Allergy and Clinical Immunology
Kate E George, Dorothy M Ryan, Brian Keevil, Robert Niven, Stephen J Fowler
There is currently no direct measure of measuring adherence to inhaled corticosteroids in asthma. In this study we were able to detect fluticasone propionate and budesonide in the serum of treatment-adherent patients with severe asthma.
October 11, 2016: Journal of Allergy and Clinical Immunology
Sarah A F Chamberlain Mitchell, Rachel Garrod, Lynne Clark, Abdel Douiri, Sean M Parker, Jenny Ellis, Stephen J Fowler, Siobhan Ludlow, James H Hull, Kian Fan Chung, Kai K Lee, H Bellas, Anand Pandyan, Surinder S Birring
BACKGROUND: Physiotherapy, and speech and language therapy are emerging non-pharmacological treatments for refractory chronic cough. We aimed to investigate the efficacy of a physiotherapy, and speech and language therapy intervention (PSALTI) to improve health-related quality of life (HRQoL) and to reduce cough frequency in patients with refractory chronic cough. METHODS: In this multicentre randomised controlled trial, patients with refractory chronic cough were randomised to four weekly 1:1 sessions of either PSALTI consisting of education, laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and psychoeducational counselling or control intervention consisting of healthy lifestyle advice...
September 28, 2016: Thorax
Jack S Elder
Undescended testis (UDT) is the most common disorder of sexual development in boys and affects 3.5% of male newborns. Although approximately half of newborn UDTs descend spontaneously, some boys develop an ascending testis later in childhood. Recent guideline recommendations advocate orchiopexy by 18 months of age to maximize potential for fertility and perhaps reduce the risk for testicular carcinoma in the future. For palpable testes, a standard inguinal approach is appropriate. However, the prescrotal approach is often effective for low inguinal testes and reduces surgical time and patient discomfort with an equivalent success rate in boys with an ascending testis...
October 2016: European Journal of Pediatric Surgery
Lieuwe D Bos, Peter J Sterk, Stephen J Fowler
Exhaled breath contains thousands of volatile organic compounds that reflect the metabolic process occurring in the host both locally in the airways and systemically. They also arise from the environment and airway microbiome. Comprehensive analysis of breath volatile organic compounds (breathomics) provides opportunities for noninvasive biomarker discovery and novel mechanistic insights. Applications in patients with obstructive lung diseases, such as asthma and chronic obstructive pulmonary disease, include not only diagnostics (especially in children and other challenging diagnostic areas) but also identification of clinical treatable traits, such as airway eosinophilia and risk of infection/exacerbation, that are not specific to diagnostic labels...
October 2016: Journal of Allergy and Clinical Immunology
Richard Boulding, Rebecca Stacey, Rob Niven, Stephen J Fowler
Dysfunctional breathing is a term describing breathing disorders where chronic changes in breathing pattern result in dyspnoea and other symptoms in the absence or in excess of the magnitude of physiological respiratory or cardiac disease. We reviewed the literature and propose a classification system for the common dysfunctional breathing patterns described. The literature was searched using the terms: dysfunctional breathing, hyperventilation, Nijmegen questionnaire and thoraco-abdominal asynchrony. We have summarised the presentation, assessment and treatment of dysfunctional breathing, and propose that the following system be used for classification...
September 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
Chih-Hsi Scott Kuo, Stelios Pavlidis, Matthew Loza, Fred Baribaud, Anthony Rowe, Ioannis Pandis, Uruj Hoda, Christos Rossios, Ana Sousa, Susan J Wilson, Peter Howarth, Barbro Dahlen, Sven-Erik Dahlen, Pascal Chanez, Dominick Shaw, Norbert Krug, Thomas Sandström, Bertrand De Meulder, Diane Lefaudeux, Stephen Fowler, Louise Fleming, Julie Corfield, Charles Auffray, Peter J Sterk, Ratko Djukanovic, Yike Guo, Ian M Adcock, Kian Fan Chung
RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes. METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement...
August 31, 2016: American Journal of Respiratory and Critical Care Medicine
James H Hull, Vibeke Backer, Peter G Gibson, Stephen J Fowler
The larynx is one of the most highly innervated organs in humans and serves a number of vitally important, complex and highly-evolved biological functions. On a day-to-day basis, the larynx functions autonomously, addressing several roles including airway protection, swallowing and phonation. In some situations the larynx appears to adopt a functional state that could be considered maladaptive or 'dysfunctional'. This laryngeal dysfunction can underpin and account for a number of respiratory symptoms that otherwise appear incongruous with a clinical disease state and/or contribute to the development of symptoms that appear 'refractory' to treatment...
August 30, 2016: American Journal of Respiratory and Critical Care Medicine
Kar Lai Poon, Xingang Wang, Ashley S Ng, Wei Huang Goh, Claudia McGinnis, Stephen Fowler, Tom J Carney, Haishan Wang, Phillip W Ingham
Understanding and predicting whether new drug candidates will be safe in the clinic is a critical hurdle in pharmaceutical development, that relies in part on absorption, distribution, metabolism, excretion and toxicology studies in vivo. Zebrafish is a relatively new model system for drug metabolism and toxicity studies, offering whole organism screening coupled with small size and potential for high-throughput screening. Through toxicity and absorption analyses of a number of drugs, we find that zebrafish is generally predictive of drug toxicity, although assay outcomes are influenced by drug lipophilicity which alters drug uptake...
August 2, 2016: Archives of Toxicology
Imran Satia, Nikolaos Tsamandouras, Kimberley Holt, Huda Badri, Mark Woodhead, Kayode Ogungbenro, Timothy W Felton, Paul M O'Byrne, Stephen J Fowler, Jaclyn A Smith
BACKGROUND: Cough in asthmatic patients is a common and troublesome symptom. It is generally assumed coughing occurs as a consequence of bronchial hyperresponsiveness and inflammation, but the possibility that airway nerves are dysfunctional has not been fully explored. OBJECTIVES: We sought to investigate capsaicin-evoked cough responses in a group of patients with well-characterized mild-to-moderate asthma compared with healthy volunteers and assess the influences of sex, atopy, lung physiology, inflammation, and asthma control on these responses...
June 15, 2016: Journal of Allergy and Clinical Immunology
Andrew Higham, Nicholas J W Rattray, Jennifer A Dewhurst, Drupad K Trivedi, Stephen J Fowler, Royston Goodacre, Dave Singh
BACKGROUND: The use of electronic cigarettes (e-cigs) is increasing and there is widespread perception that e-cigs are safe. E-cigs contain harmful chemicals; more research is needed to evaluate the safety of e-cig use. Our aim was to investigate the effects of e-cigs on the inflammatory response of human neutrophils. METHODS: Neutrophils were exposed to e-cig vapour extract (ECVE) and the expression of CD11b and CD66b was measured by flow cytometry and MMP-9 and CXCL8 by ELISA...
2016: Respiratory Research
John Farrant, Henry Brice, Stephen Fowler, Robert Niven
BACKGROUND: Fungal sensitisation is an important factor in severe asthma, not only for allergic bronchopulmonary aspergillosis (ABPA) but also the more recently described severe asthma with fungal sensitisation (SAFS). It is not known whether these diseases are driven by the presence of airway fungal colonisation. We aimed to determine if both SAFS and ABPA were associated with airway isolation of Aspergillus fumigatus and whether the frequency of isolation changed following anti-fungal treatment...
September 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
Joanne K Marcario, Gurudutt Pendyala, Mariam Riazi, Kandace Fleming, Janet Marquis, Shannon Callen, Steven J Lisco, Stephen C Fowler, Paul D Cheney, Shilpa J Buch
The abuse of opiates such as morphine in synergy with HIV infection not only exacerbates neuropathogenesis but significantly impacts behavioral attributes in HIV infected subjects. Thus, the goal of the current study was to characterize behavioral perturbations in rhesus macaques subjected to chronic morphine and SIV infection. Specifically, we assessed three behavioral tasks: motor skill (MS), forelimb force (FFT) and progressive ratio (PR) tasks. After collecting baseline control data (44 weeks) and data during the morphine-only dependency period (26 weeks), a subset of animals were productively infected with neurovirulent strains of SIVmac (R71/E17) for an additional 33 weeks...
June 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Nurullah Hamidi, Onur Telli, Uygar Bagci, Baris Esen, Mehmet Ali Karagoz, Ahmet Metin Hascicek, Tarkan Soygur, Berk Burgu
PURPOSE: To date, laparoscopy has gradually become the gold standard for treatment of non-palpable testicles (NPT) with different success and complication rates. In this study, we aimed to evaluate outcomes of laparoscopic approaches for NPT. MATERIALS AND METHODS: We reviewed data of 82 consecutive patients who underwent laparoscopic treatment for unilateral NPT at two institutions by two high volume surgeons from 2004 January to 2014 December. Laparoscopic-assisted orchidopexy (LAO) and two-stage Fowler-Stephens technique (FST) was performed for 45 and 37 patients, respectively...
2016: Frontiers in Pediatrics
Paul A Marsden, Imran Satia, Baharudin Ibrahim, Ashley Woodcock, Lucy Yates, Iona Donnelly, Lisa Jolly, Neil C Thomson, Stephen J Fowler, Jaclyn A Smith
BACKGROUND: Cough is recognized as an important troublesome symptom in the diagnosis and monitoring of asthma. Asthma control is thought to be determined by the degree of airway inflammation and hyperresponsiveness but how these factors relate to cough frequency is unclear. The goal of this study was to investigate the relationships between objective cough frequency, disease control, airflow obstruction, and airway inflammation in asthma. METHODS: Participants with asthma underwent 24-h ambulatory cough monitoring and assessment of exhaled nitric oxide, spirometry, methacholine challenge, and sputum induction (cell counts and inflammatory mediator levels)...
June 2016: Chest
Dorothy M Ryan, Stephen J Fowler, Robert M Niven
No abstract text is available yet for this article.
July 2016: Journal of Allergy and Clinical Immunology
Sameh Shehata, Rafik Shalaby, Maged Ismail, Mohamed Abouheba, Ahmed Elrouby
BACKGROUND: We present the midterm results of the novel technique of two-stage laparoscopic traction orchiopexy (SLTO) for the high intraabdominal testis (IAT) for elongation of the testicular vessels without division. PATIENTS AND METHODS: Boys with IAT proven by laparoscopy were selected for the technique between September 2009 and April 2013 in 2 Egyptian pediatric surgery units. Boys <6months or >9years were excluded. The technique entails fixation of the testis to a point one inch above and medial to the contralateral anterior superior iliac spine for 12weeks...
February 2016: Journal of Pediatric Surgery
Diana K Bowen, Richard S Matulewicz, Edward M Gong
BACKGROUND: Laparoscopic management of remnant uterine structures for patients with persistent müllerian duct syndrome (PMDS) and bilateral intra-abdominal testes include supracervical hysterectomy or splitting of the uterine structure to facilitate orchiopexy. A laparoscopic uterine-sparing approach, however, has not been described in the literature. METHODS: We present a case of a 10-year-old male with PMDS who underwent laparoscopic two-step Fowler-Stephens orchiopexy (FSO) with uterine preservation...
February 2016: Journal of Pediatric Urology
Ben Dhaou Mahdi, Chtourou Rahma, Jallouli Mohamed, Zitouni Hayet, Mhiri Riadh
PURPOSE: We review the literature and describe our technique for laparoendoscopic single-site orchidopexy using a glove port and rigid instruments. We assessed the feasibility and outcomes of this procedure. MATERIALS AND METHODS: We retrospectively reviewed the case records of all children who had undergone laparoendoscopic single-site orchidopexy by use of a surgical glove port and conventional rigid instruments for a nonpalpable intraabdominal testis between January 2013 and September 2014...
November 2015: Korean Journal of Urology
Russell Jones, Michaela Marschmann, Michael Keller, Na Hong Qiu, Stephen Fowler, Thomas Singer, Franz Schuler, Christoph Funk, Simone Schadt
1. In recent years, the minipig is increasingly used as a test species in non-clinical assessment of drug candidates. While there is good scientific evidence available concerning cytochrome P450-mediated metabolism in minipig, the knowledge of other metabolic pathways is more limited. 2. The aim of this study was to provide an understanding of when, why, and how drug metabolism in minipig differs from other species commonly used in non-clinical studies. In-house cross-species metabolite profile comparisons in hepatocytes and microsomes of 38 Roche development compounds were retrospectively analyzed to compare the metabolism among minipig, human, rat, dog, monkey, rabbit and mouse...
2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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