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https://www.readbyqxmd.com/read/28102831/biomarkers-in-adult-asthma-a-systematic-review-of-8-isoprostane-in-exhaled-breath-condensate
#1
Adam M Peel, Christina-Jane Crossman-Barnes, Jonathan Tang, Stephen Fowler, Gwyneth Davies, Andrew Wilson, Yoon Loke
OBJECTIVES: We aimed to assess the evidence for the use of 8-isoprostane in exhaled breath condensate (EBC) as a biomarker in adult asthma. DESIGN: A systematic review and meta-analysis of EBC 8-isoprostane. METHODS: We searched a number of online databases (including PubMed, Embase and Scopus) in January 2016. We included studies of adult non-smokers with EBC collection and asthma diagnosis conducted according to recognised guidelines. We aimed to pool data using random effects meta-analysis and assess heterogeneity using I2...
January 19, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/28099872/assessment-of-gait-and-sensorimotor-deficits-in-the-d1ct-7-mouse-model-of-tourette-syndrome
#2
Stephen C Fowler, Laura J Mosher, Sean C Godar, Marco Bortolato
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and phonic tics. While TS patients have been also shown to exhibit subtle abnormalities of sensorimotor integration and gait, animal models of this disorder are seldom tested for these functions. To fill this gap, we assessed gait and sensorimotor integration in the D1CT-7 mouse, one of the best-validated animal models of TS. D1CT-7 mice exhibit spontaneous tic-like manifestations, which, in line with the clinical phenomenology of TS, are markedly exacerbated by environmental stress...
January 15, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28050713/metabolic-profiling-of-human-long-term-liver-models-and-hepatic-clearance-predictions-from-in-vitro-data-using-nonlinear-mixed-effects-modeling
#3
Nicole A Kratochwil, Christophe Meille, Stephen Fowler, Florian Klammers, Aynur Ekiciler, Birgit Molitor, Sandrine Simon, Isabelle Walter, Claudia McGinnis, Johanna Walther, Brian Leonard, Miriam Triyatni, Hassan Javanbakht, Christoph Funk, Franz Schuler, Thierry Lavé, Neil J Parrott
Early prediction of human clearance is often challenging, in particular for the growing number of low-clearance compounds. Long-term in vitro models have been developed which enable sophisticated hepatic drug disposition studies and improved clearance predictions. Here, the cell line HepG2, iPSC-derived hepatocytes (iCell®), the hepatic stem cell line HepaRG™, and human hepatocyte co-cultures (HμREL™ and HepatoPac®) were compared to primary hepatocyte suspension cultures with respect to their key metabolic activities...
January 3, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28049457/breathdx-molecular-analysis-of-exhaled-breath-as-a-diagnostic-test-for-ventilator-associated-pneumonia-protocol-for-a-european-multicentre-observational-study
#4
Pouline M P van Oort, Tamara Nijsen, Hans Weda, Hugo Knobel, Paul Dark, Timothy Felton, Nicholas J W Rattray, Oluwasola Lawal, Waqar Ahmed, Craig Portsmouth, Peter J Sterk, Marcus J Schultz, Tetyana Zakharkina, Antonio Artigas, Pedro Povoa, Ignacio Martin-Loeches, Stephen J Fowler, Lieuwe D J Bos
BACKGROUND: The diagnosis of ventilator-associated pneumonia (VAP) remains time-consuming and costly, the clinical tools lack specificity and a bedside test to exclude infection in suspected patients is unavailable. Breath contains hundreds to thousands of volatile organic compounds (VOCs) that result from host and microbial metabolism as well as the environment. The present study aims to use breath VOC analysis to develop a model that can discriminate between patients who have positive cultures and who have negative cultures with a high sensitivity...
January 3, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27889491/pramipexole-enhances-disadvantageous-decision-making-lack-of-relation-to-changes-in-phasic-dopamine-release
#5
Romina Pes, Sean C Godar, Andrew T Fox, Lauren M Burgeno, Hunter J Strathman, David P Jarmolowicz, Paola Devoto, Beth Levant, Paul E Phillips, Stephen C Fowler, Marco Bortolato
Pramipexole (PPX) is a high-affinity D2-like dopamine receptor agonist, used in the treatment of Parkinson's disease (PD) and restless leg syndrome. Recent evidence indicates that PPX increases the risk of problem gambling and impulse-control disorders in vulnerable patients. Although the molecular bases of these complications remain unclear, several authors have theorized that PPX may increase risk propensity by activating presynaptic dopamine receptors in the mesolimbic system, resulting in the reduction of dopamine release in the nucleus accumbens (NAcc)...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27867845/current-management-of-non-palpable-testes-a-literature-review-and-clinical-results
#6
REVIEW
Ximena Sepúlveda, Pedro-José López Egaña
Cryptorchidism is a common pathology that occurs in 3% in full term newborns, and it decreases to 0.8-1.2% at 1 year of age. Nearly a 20% of undescended testes are non-palpable. Various surgical treatments have been described, but its management is still controversial. A literature review was made of non-palpable testes, analysing diagnostic tools, treatment and its results. Additionally we reviewed non-palpable testes cases treated in our centre in the last 20 years. Different techniques are described for the management of non-palpable testes; with or without section of the spermatic vessels and/or in 1 or 2 stages...
October 2016: Translational pediatrics
https://www.readbyqxmd.com/read/27845220/staged-fowler-stephens-and-single-stage-laparoscopic-orchiopexy-for-intra-abdominal-testes-is-there-a-difference-a-single-institution-experience
#7
Alireza Alam, Joan C Delto, Ruben Blachman-Braun, George Wayne, Angela G Mittal, Miguel Castellan, Kristin Kozakowski, Andrew Labbie, Rafael Gosalbez
OBJECTIVE: To compare single-stage laparoscopic orchiopexy (SSLO) and staged Fowler-Stephens (SFS) procedures in the management of intra-abdominal undescended testes, and to analyze postoperative atrophy and malpositioning as end points. MATERIALS AND METHODS: A retrospective chart review identified laparoscopic orchiopexy patients with intra-abdominal testes between November 2006 and November 2014. Of 167 patients who had laparoscopic orchiopexy, 73 (85 testes) were identified as having laparoscopic orchiopexy...
November 11, 2016: Urology
https://www.readbyqxmd.com/read/27821711/low-potential-of-basimglurant-to-be-involved-in-drug-drug-interactions-influence-of-non-michaelis-menten-p450-kinetics-on-fraction-metabolized
#8
Stephen Fowler, Elena Guerini, NaHong Qiu, Yumi Cleary, Neil Parrott, Gerard Greig, Navita L Mallalieu
Basimglurant, a novel mGlu5-negative allosteric modulator under development for the treatment of major depressive disorder, is cleared via cytochrome P450 (P450)-mediated oxidative metabolism. Initial enzyme phenotyping studies indicated that CYP3A4/5 dominates basimglurant metabolism and highlights a risk for drug-drug interactions when it is comedicated with strong CYP3A4/5 inhibitors or inactivators; however, a clinical drug-drug interaction (DDI) study using the potent and selective CYP3A4/5 inhibitor ketoconazole resulted in an area under the curve (AUC) AUCi/AUC ratio of only 1...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27773852/u-biopred-clinical-adult-asthma-clusters-linked-to-a-subset-of-sputum-omics
#9
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 Fan 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 personalized management approach can be provided. OBJECTIVES: We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum. METHODS: Partition-around-medoids clustering was applied to a training set of 266 asthmatic participants from the European Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) adult cohort using 8 prespecified clinic-physiologic variables...
October 20, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27742392/a-pilot-study-to-investigate-the-use-of-serum-inhaled-corticosteroid-concentration-as-a-potential-marker-of-treatment-adherence-in-severe-asthma
#10
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
https://www.readbyqxmd.com/read/27682331/physiotherapy-and-speech-and-language-therapy-intervention-for-patients-with-refractory-chronic-cough-a-multicentre-randomised-control-trial
#11
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
https://www.readbyqxmd.com/read/27631723/surgical-management-of-the-undescended-testis-recent-advances-and-controversies
#12
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
https://www.readbyqxmd.com/read/27590400/breathomics-in-the-setting-of-asthma-and-chronic-obstructive-pulmonary-disease
#13
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
https://www.readbyqxmd.com/read/27581828/dysfunctional-breathing-a-review-of-the-literature-and-proposal-for-classification
#14
REVIEW
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
https://www.readbyqxmd.com/read/27580351/a-transcriptome-driven-analysis-of-epithelial-brushings-and-bronchial-biopsies-to-define-asthma-phenotypes-in-u-biopred
#15
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
https://www.readbyqxmd.com/read/27575803/laryngeal-dysfunction-assessment-and-management-for-the-clinician
#16
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...
November 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27485346/humanizing-the-zebrafish-liver-shifts-drug-metabolic-profiles-and-improves-pharmacokinetics-of-cyp3a4-substrates
#17
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
https://www.readbyqxmd.com/read/27444176/capsaicin-evoked-cough-responses-in-asthmatic-patients-evidence-for-airway-neuronal-dysfunction
#18
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
https://www.readbyqxmd.com/read/27184092/electronic-cigarette-exposure-triggers-neutrophil-inflammatory-responses
#19
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
https://www.readbyqxmd.com/read/27043956/fungal-sensitisation-in-severe-asthma-is-associated-with-the-identification-of-aspergillus-fumigatus-in-sputum
#20
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
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