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Sample records for fibrosis current usefulness

  1. The Role of Current and Historical Alcohol Use in Hepatic Fibrosis Among HIV-Infected Individuals.

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    Kim, H Nina; Crane, Heidi M; Rodriguez, Carla V; Van Rompaey, Stephen; Mayer, Kenneth H; Christopoulos, Katerina; Napravnik, Sonia; Chander, Geetanjali; Hutton, Heidi; McCaul, Mary E; Cachay, Edward R; Mugavero, Michael J; Moore, Richard; Geng, Elvin; Eron, Joseph J; Saag, Michael S; Merrill, Joseph O; Kitahata, Mari M

    2016-12-29

    We examined risk factors for advanced hepatic fibrosis [fibrosis-4 (FIB)-4 >3.25] including both current alcohol use and a diagnosis of alcohol use disorder among HIV-infected patients. Of the 12,849 patients in our study, 2133 (17%) reported current hazardous drinking by AUDIT-C, 2321 (18%) had a diagnosis of alcohol use disorder, 2376 (18%) were co-infected with chronic hepatitis C virus (HCV); 596 (5%) had high FIB-4 scores >3.25 as did 364 (15%) of HIV/HCV coinfected patients. In multivariable analysis, HCV (adjusted odds ratio (aOR) 6.3, 95% confidence interval (CI) 5.2-7.5), chronic hepatitis B (aOR 2.0, 95% CI 1.5-2.8), diabetes (aOR 2.3, 95% CI 1.8-2.9), current CD4 500 copies/mL (aOR 1.3, 95% CI 1.0-1.6) were significantly associated with advanced fibrosis. A diagnosis of an alcohol use disorder (aOR 1.9, 95% CI 1.6-2.3) rather than report of current hazardous alcohol use was associated with high FIB-4. However, among HIV/HCV coinfected patients, both current hazardous drinkers (aOR 1.6, 95% CI 1.1-2.4) and current non-drinkers (aOR 1.6, 95% CI 1.2-2.0) were more likely than non-hazardous drinkers to have high FIB-4, with the latter potentially reflecting the impact of sick abstainers. These findings highlight the importance of using a longitudinal measure of alcohol exposure when evaluating the impact of alcohol on liver disease and associated outcomes.

  2. Nephrogenic systemic fibrosis: Current concepts

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    Prasanta Basak

    2011-01-01

    Full Text Available Nephrogenic systemic fibrosis (NSF was first described in 2000 as a scleromyxedema-like illness in patients on chronic hemodialysis. The relationship between NSF and gadolinium contrast during magnetic resonance imaging was postulated in 2006, and subsequently, virtually all published cases of NSF have had documented prior exposure to gadolinium-containing contrast agents. NSF has been reported in patients from a variety of ethnic backgrounds from America, Europe, Asia and Australia. Skin lesions may evolve into poorly demarcated thickened plaques that range from erythematous to hyperpigmented. With time, the skin becomes markedly indurated and tethered to the underlying fascia. Extracutaneous manifestations also occur. The diagnosis of NSF is based on the presence of characteristic clinical features in the setting of chronic kidney disease, and substantiated by skin histology. Differential diagnosis is with scleroderma, scleredema, scleromyxedema, graft-versus-host disease, etc. NSF has a relentlessly progressive course. While there is no consistently successful treatment for NSF, improving renal function seems to slow or arrest the progression of this condition. Because essentially all cases of NSF have developed following exposure to a gadolinium-containing contrast agent, prevention of this devastating condition involves the careful avoidance of administering these agents to individuals at risk.

  3. Current Strategies for Quantitating Fibrosis in Liver Biopsy

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    Yan Wang

    2015-01-01

    Full Text Available Objective: The present mini-review updated the progress in methodologies based on using liver biopsy. Data Sources: Articles for study of liver fibrosis, liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014. Study Selection: Key articles were selected mainly according to their levels of relevance to this topic and citations. Results: With the recently mounting progress in chronic liver disease therapeutics, comes by a pressing need for precise, accurate, and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients. Histopathological information is recognized as the most valuable data for fibrosis assessment. Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility. Morphometric assessment by computer assist digital image analysis, such as collagen proportionate area (CPA, detects change of fibrosis amount in tissue section in a continuous variable, and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis. Due to its evident sensitivity to sampling variances, morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort. Combining state-of-art imaging technology and fundamental principle in Tissue Engineering, structure-based quantitation was recently initiated with a novel proof-of-concept tool, qFibrosis. qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis, but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging. Conclusions: With input from multidisciplinary innovation, liver biopsy assessment as a new "gold standard" is anticipated to substantially support the accelerated

  4. Current Strategies for Quantitating Fibrosis in Liver Biopsy

    Institute of Scientific and Technical Information of China (English)

    Yan Wang; Jin-Lin Hou

    2015-01-01

    Objective:The present mini-review updated the progress in methodologies based on using liver biopsy.Data Sources:Articles for study of liver fibrosis,liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014.Study Selection:Key articles were selected mainly according to their levels of relevance to this topic and citations.Results:With the recently mounting progress in chronic liver disease therapeutics,comes by a pressing need for precise,accurate,and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients.Histopathological information is recognized as the most valuable data for fibrosis assessment.Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility.Morphometric assessment by computer assist digital image analysis,such as collagen proportionate area (CPA),detects change of fibrosis amount in tissue section in a continuous variable,and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis.Due to its evident sensitivity to sampling variances,morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort.Combining state-of-art imaging technology and fundamental principle in Tissue Engineering,structure-based quantitation was recently initiated with a novel proof-of-concept tool,qFibrosis.qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis,but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging.Conclusions:With input from multidisciplinary innovation,liver biopsy assessment as a new "gold standard" is anticipated to substantially support the accelerated progress of Hepatology medicine.

  5. Stage scoring of liver fibrosis using Mueller matrix microscope

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    Zhou, Jialing; He, Honghui; Wang, Ye; Ma, Hui

    2016-10-01

    Liver fibrosis is a common pathological process of varied chronic liver diseases including alcoholic hepatitis, virus hepatitis, and so on. Accurate evaluation of liver fibrosis is necessary for effective therapy and a five-stage grading system was developed. Currently, experienced pathologists use stained liver biopsies to assess the degree of liver fibrosis. But it is difficult to obtain highly reproducible results because of huge discrepancy among different observers. Polarization imaging technique has the potential of scoring liver fibrosis since it is capable of probing the structural and optical properties of samples. Considering that the Mueller matrix measurement can provide comprehensive microstructural information of the tissues, in this paper, we apply the Mueller matrix microscope to human liver fibrosis slices in different fibrosis stages. We extract the valid regions and adopt the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters for quantitative analysis. We also use the Monte Carlo simulation to analyze the relationship between the microscopic Mueller matrix parameters and the characteristic structural changes during the fibrosis process. The experimental and Monte Carlo simulated results show good consistency. We get a positive correlation between the parameters and the stage of liver fibrosis. The results presented in this paper indicate that the Mueller matrix microscope can provide additional information for the detections and fibrosis scorings of liver tissues and has great potential in liver fibrosis diagnosis.

  6. Idiopathic pulmonary fibrosis: current and future directions.

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    Soo, E; Adamali, H; Edey, A J

    2017-01-21

    Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and is increasingly recognised. Prior to the advent of effective therapies, achieving an early diagnosis was arguably of little prognostic consequence given IPF was considered an untreatable and uniformly fatal disease. The advent of new drug treatments has given hope for the future and raised the profile of IPF. International management guidelines highlight the critical role of radiology as part of an interstitial lung disease multidisciplinary team approach in reaching an accurate and early diagnosis of IPF. The diagnostic criteria and levels of diagnostic confidence for the radio-pathological pattern associated with the clinical syndrome of IPF, usual interstitial pneumonia (UIP), appear seemingly straightforward; however, with increasing research and recognition of radiopathological interobserver variability, limitations of this classification model are becoming increasingly apparent. This review describes ancillary radiological features, comorbidities, and emerging new entities that potentially co-exist with IPF. Beyond diagnosis radiology is developing as a key prognostic tool to inform longitudinal patient evaluation. These diagnostic and prognostic clinical challenges and the future role of radiology in IPF are discussed.

  7. Using Cystic Fibrosis Therapies for Non-Cystic Fibrosis Bronchiectasis.

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    ElMaraachli, Wael; Conrad, Douglas J; Wang, Angela C C

    2016-03-01

    Non-cystic fibrosis bronchiectasis (NCFB) is an increasingly prevalent disease that places a significant burden on patients and health systems globally. Although many of the therapies used to treat NCFB were originally developed as cystic fibrosis (CF) therapies, not all of them have been demonstrated to be efficacious in NCFB and some may even be harmful. This article explores the evidence for which therapeutic strategies used to treat CF have been translated into the care of NCFB. The conclusion is that therapies for adult NCFB cannot be simply extrapolated from CF clinical trials, and in some instances, doing so may actually result in harm.

  8. Using ultrasound Nakagami imaging to assess liver fibrosis in rats.

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    Ho, Ming-Chih; Lin, Jen-Jen; Shu, Yu-Chen; Chen, Chiung-Nien; Chang, King-Jen; Chang, Chien-Cheng; Tsui, Po-Hsiang

    2012-02-01

    This study explored the feasibility of using the ultrasound Nakagami image to assess the degree of liver fibrosis in rats. The rat has been widely used as a model in investigations of liver fibrosis. Ultrasound grayscale imaging makes it possible to observe fibrotic rat livers in real time. Statistical analysis of the envelopes of signals backscattered from rat livers may provide useful clues about the degree of liver fibrosis. The Nakagami-model-based image has been shown to be useful for characterizing scatterers in tissues by reflecting the echo statistics, and hence the Nakagami image may serve as a functional imaging tool for quantifying rat liver fibrosis. To validate this idea, fibrosis was induced in each rat liver (n=21) by an intraperitoneal injection of 0.5% dimethylnitrosamine. Livers were excised from rats for in vitro ultrasound scanning using a single-element transducer. The backscattered-signal envelopes of the acquired raw ultrasound signals were used for Nakagami imaging. The Metavir score determined by a pathologist was used to histologically quantify the degree of liver fibrosis. It was found that the Nakagami image could be used to distinguish different degrees of liver fibrosis in rats, since the average Nakagami parameter increased from 0.55 to 0.83 as the fibrosis score increased from 0 (i.e., normal) to 4. This correlation may be due to liver fibrosis in rats involving an increase in the concentration of local scatterers and the appearance of the periodic structures or clustering of scatterers that would change the backscattering statistics. The current findings indicate that the ultrasound Nakagami image has great potential as a functional imaging tool to complement the use of the conventional B-scan in animal studies of liver fibrosis.

  9. Current and novel drug therapies for idiopathic pulmonary fibrosis

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    Adamali HI

    2012-09-01

    Full Text Available Huzaifa I Adamali,1 Toby M Maher1–31Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; 2National Heart and Lung Institute, Imperial College London, London, UK; 3Centre for Respiratory Research, University College London, London, UKAbstract: Over the past decade, there has been a cohesive effort from patients, physicians, clinical and basic scientists, and the pharmaceutical industry to find definitive treatments for idiopathic pulmonary fibrosis (IPF. As understanding of disease behavior and pathogenesis has improved, the aims of those treating IPF have shifted from reversing the disease to slowing or preventing progression of this chronic fibrotic illness. It is to be hoped that by slowing disease progression, survival will be improved from the current dismal median of 3.5 years following diagnosis. In Europe and Asia, a milestone has recently been reached with the licensing of the first IPF-specific drug, pirfenidone. This review assesses the current treatment modalities available for IPF, including pirfenidone. It also turns an eye to the future and discusses the growing number of promising compounds currently in development that it is hoped, in time, will make their way into the clinic as treatments for IPF.Keywords: interstitial lung disease, pirfenidone, clinical trials, usual interstitial pneumonia, acute exacerbations

  10. Cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis: current perspectives

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    Schmidt BZ

    2016-09-01

    Full Text Available Béla Z Schmidt,1 Jérémy B Haaf,2 Teresinha Leal,2 Sabrina Noel,2 1Stem Cell Biology and Embryology, Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, 2Louvain Center for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Brussels, Belgium Abstract: Mutations of the CFTR gene cause cystic fibrosis (CF, the most common recessive monogenic disease worldwide. These mutations alter the synthesis, processing, function, or half-life of CFTR, the main chloride channel expressed in the apical membrane of epithelial cells in the airway, intestine, pancreas, and reproductive tract. Lung disease is the most critical manifestation of CF. It is characterized by airway obstruction, infection, and inflammation that lead to fatal tissue destruction. In spite of great advances in early and multidisciplinary medical care, and in our understanding of the pathophysiology, CF is still considerably reducing the life expectancy of patients. This review highlights the current development in pharmacological modulators of CFTR, which aim at rescuing the expression and/or function of mutated CFTR. While only Kalydeco® and Orkambi® are currently available to patients, many other families of CFTR modulators are undergoing preclinical and clinical investigations. Drug repositioning and personalized medicine are particularly detailed in this review as they represent the most promising strategies for restoring CFTR function in CF. Keywords: high-throughput screening, drug repositioning, personalized medicine, precision medicine, potentiators, correctors

  11. [Nutritional status of adults with cystic fibrosis - current methods of assessment].

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    Szabla, Anna; Skorupa, Wojciech; Milewska, Magdalena; Weker, Halina

    2015-11-01

    Cystic fibrosis (CF) is one of the most frequent monogenic disease in the Caucasian population, inherited in an autosomal recessive pattern. This is a multiple organ disease and its main manifestations include pulmonary and gastrointestinal dysfunction. The exocrine pancreatic deficiency results in impaired digestion and absorption what may lead to malnutrition and vitamins and minerals deficiencies. The life expectancy of cystic fibrosis patients has been increasing over the past years, so there is a need to verify usefulness of existing or create new methods of nutritional status assessment. The aim of this paper was presentation current data on the methods of assessment and monitoring of nutritional status. Particular attention has been paid to appropriate nutritional support in prevention and treatment of malnutrition patients with cystic fibrosis. On the basis of recent literature we can conclude that the advanced nutritional status assessment is recommended in patient with CF by using anthropometrical methods, body composition analysis and biochemical data. Good nutritional status is connected with pulmonary functions, quality and life length.

  12. Regenerative medicine in the treatment of idiopathic pulmonary fibrosis: current position

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    Álvarez D

    2015-04-01

    Full Text Available Diana Álvarez,1,2 Melanie Levine,1 Mauricio Rojas1–3 1Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, 2Pulmonary, Allergy, and Critical Care Medicine, 3McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Abstract: Idiopathic pulmonary fibrosis (IPF is a progressive, irreversible disease of the lung that has no lasting option for therapy other than transplantation. It is characterized by replacement of the normal lung tissue by fibrotic scarring, honeycombing, and increased levels of myofibroblasts. The underlying causes of IPF are still largely unknown. The focus of the current review is the possible use of stem cell therapy, specifically mesenchymal stem cells (MSCs, a multipotent stromal cell population, which have demonstrated promising data in multiple animal models of pulmonary fibrosis (PF. The most studied source of MSCs is the bone marrow, although they can be found also in the adipose tissue and umbilical cord, as well as in the placenta. MSCs have immunomodulatory and tissue-protective properties that allow them to manipulate the local environment of the injured tissue, ameliorating the inflammation and promoting repair. Because IPF primarily affects older patients, the issue of aging is intrinsically linked to many aspects of the disease, including the age of the stem cells. Animal models have shown the success of MSC therapy in mitigating the fibrotic effects of bleomycin-induced PF. However, bleomycin, the most commonly used model for PF, is imperfect in mimicking IPF as it presents in humans, as the duration of the illness is not parallel or reversible, and honeycombing is not produced. Furthermore, the time of MSC dosage has proven to be critical in determining whether the cells will ultimately have a positive or negative effect on disease progression, since it has been demonstrated that the maximal beneficial effect of MSCs occurs during the early

  13. Complementary and alternative medicine use in children with cystic fibrosis.

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    Giangioppo, Sandra; Kalaci, Odion; Radhakrishnan, Arun; Fleischer, Erin; Itterman, Jennifer; Lyttle, Brian; Price, April; Radhakrishnan, Dhenuka

    2016-11-01

    To estimate the overall prevalence of complementary and alternative medicine use among children with cystic fibrosis, determine specific modalities used, predictors of use and subjective helpfulness or harm from individual modalities. Of 53 children attending the cystic fibrosis clinic in London, Ontario (100% recruitment), 79% had used complementary and alternative medicine. The most commonly used modalities were air purifiers, humidifiers, probiotics, and omega-3 fatty acids. Family complementary and alternative medicine use was the only independent predictor of overall use. The majority of patients perceived benefit from specific modalities for cystic fibrosis symptoms. Given the high frequency and number of modalities used and lack of patient and disease characteristics predicting use, we recommend that health care providers should routinely ask about complementary and alternative medicine among all pediatric cystic fibrosis patients and assist patients in understanding the potential benefits and risks to make informed decisions about its use. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Fibrosis assessment: impact on current management of chronic liver disease and application of quantitative invasive tools.

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    Wang, Yan; Hou, Jin-Lin

    2016-05-01

    Fibrosis, a common pathogenic pathway of chronic liver disease (CLD), has long been indicated to be significantly and most importantly associated with severe prognosis. Nowadays, with remarkable advances in understanding and/or treatment of major CLDs such as hepatitis C, B, and nonalcoholic fatty liver disease, there is an unprecedented requirement for the diagnosis and assessment of liver fibrosis or cirrhosis in various clinical settings. Among the available approaches, liver biopsy remains the one which possibly provides the most direct and reliable information regarding fibrosis patterns and changes in the parenchyma at different clinical stages and with different etiologies. Thus, many endeavors have been undertaken for developing methodologies based on the strategy of quantitation for the invasive assessment. Here, we analyze the impact of fibrosis assessment on the CLD patient care based on the data of recent clinical studies. We discuss and update the current invasive tools regarding their technological features and potentials for the particular clinical applications. Furthermore, we propose the potential resolutions with application of quantitative invasive tools for some major issues in fibrosis assessment, which appear to be obstacles against the nowadays rapid progress in CLD medicine.

  15. Imaging of Myocardial Fibrosis in Patients with End-Stage Renal Disease: Current Limitations and Future Possibilities

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    Patel, A. S.; Marsh, A.-M.; McAdam, J.; McCann, G. P.; Burton, J. O.

    2017-01-01

    Cardiovascular disease in patients with end-stage renal disease (ESRD) is driven by a different set of processes than in the general population. These processes lead to pathological changes in cardiac structure and function that include the development of left ventricular hypertrophy and left ventricular dilatation and the development of myocardial fibrosis. Reduction in left ventricular hypertrophy has been the established goal of many interventional trials in patients with chronic kidney disease, but a recent systematic review has questioned whether reduction of left ventricular hypertrophy improves cardiovascular mortality as previously thought. The development of novel imaging biomarkers that link to cardiovascular outcomes and that are specific to the disease processes in ESRD is therefore required. Postmortem studies of patients with ESRD on hemodialysis have shown that the extent of myocardial fibrosis is strongly linked to cardiovascular death and accurate imaging of myocardial fibrosis would be an attractive target as an imaging biomarker. In this article we will discuss the current imaging methods available to measure myocardial fibrosis in patients with ESRD, the reliability of the techniques, specific challenges and important limitations in patients with ESRD, and how to further develop the techniques we have so they are sufficiently robust for use in future clinical trials.

  16. How to avoid nephrogenic systemic fibrosis: current guidelines in Europe and the United States

    DEFF Research Database (Denmark)

    Thomsen, Henrik S

    2009-01-01

    Views vary about how to avoid nephrogenic systemic fibrosis (NSF). In Europe, it is contraindicated to use gadodiamide, gadopentetate dimeglumine, and gadovertisamide in patients who have a glomerular filtration rate (GFR) of less than 30 mL/min, and these agents may only be used with caution in ...

  17. Current and Emerging Therapies for the Treatment of Cystic Fibrosis or Mitigation of Its Symptoms.

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    Murphy, Mark P; Caraher, Emma

    2016-03-01

    Clinical presentation of the chronic, heritable condition cystic fibrosis (CF) is complex, with a diverse range of symptoms often affecting multiple organs with varying severity. The primary source of morbidity and mortality is due to progressive destruction of the airways attributable to chronic inflammation arising from microbial colonisation. Antimicrobial therapy combined with practises to remove obstructive mucopurulent deposits form the cornerstone of current therapy. However, new treatment options are emerging which offer, for the first time, the opportunity to effect remission from the underlying cause of CF. Here, we discuss these therapies, their mechanisms of action, and their successes and failures in order to illustrate the shift in the nature of how CF will likely be managed into the future.

  18. Current approaches to the diagnosis and treatment of idiopathic pulmonary fibrosis in Europe: the AIR survey

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    Vincent Cottin

    2014-06-01

    Full Text Available This review presents the results of the 2013 Advancing IPF Research (AIR survey, which assessed current approaches to the diagnosis and treatment of idiopathic pulmonary fibrosis (IPF by experienced physicians. A total of 149 physicians, predominantly from European countries, replied to the 28-question survey. The results of the AIR survey were compared with a similar survey of 509 French pulmonologists conducted by the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. A number of positive findings emerged from the AIR survey, including the high level of multidisciplinary team involvement in both diagnosis and management. This survey, when taken together with the French survey, suggests that there is still a need to improve earlier diagnosis of IPF.

  19. Pharmacological Treatment of Idiopathic Pulmonary Fibrosis: Current Approaches, Unsolved Issues, and Future Perspectives

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    Michael Kreuter

    2015-01-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a devastating condition with a 5-year survival of approximately 20%. The disease primarily occurs in elderly patients. IPF is a highly heterogeneous disorder with a clinical course that varies from prolonged periods of stability to episodes of rapid deterioration. In the last decade, improved understanding of disease mechanisms along with a more precise disease definition has allowed the design and completion of a number of high-quality clinical trials. Yet, until recently, IPF was essentially an untreatable disease. Finally, pirfenidone and nintedanib, two compounds with antifibrotic properties, have consistently proven effective in reducing functional decline and disease progression in IPF. This is a major breakthrough for patients and physicians alike, but there is still a long way to go. In fact, neither pirfenidone nor nintedanib is a cure for IPF, and most patients continue to progress despite treatment. As such, comprehensive care of patients with IPF, including management of comorbidities/complications and physical debility and timely referral for palliative care or, in a small number of highly selected patients, lung transplantation, remains essential. Several agents with high potential are currently being tested and many more are ready to be evaluated in clinical trials.

  20. Idiopathic pulmonary fibrosis: current treatment options and critical appraisal of nintedanib

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    Bonella F

    2015-12-01

    Full Text Available Francesco Bonella,1 Susanne Stowasser,2 Lutz Wollin3 1Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, 3Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany Abstract: Idiopathic pulmonary fibrosis (IPF is the most common type of idiopathic interstitial pneumonia and is characterized by a poor prognosis, with an estimated 5-year survival of approximately 20%. Progressive and irreversible lung functional impairment leads to chronic respiratory insufficiency with a severely impaired quality of life. In the last 2 decades, novel treatments for IPF have been developed as a consequence of an increasing understanding of disease pathogenesis and pathobiology. In IPF, injured dysfunctional alveolar epithelial cells promote fibroblast recruitment and proliferation, resulting in scarring of the lung tissue. Recently, pirfenidone and nintedanib have been approved for the treatment of IPF, having shown efficacy to slow functional decline and disease progression. This article focuses on the pharmacologic characteristics and clinical evidence supporting the use of nintedanib, a potent small-molecule tyrosine kinase inhibitor, as therapy for IPF. After introducing the mechanism of action and pharmacokinetics, an overview of the safety and efficacy results from the most recent clinical trials of nintedanib in IPF is presented. Keywords: tyrosine kinase, disease progression, treatment outcome, usual interstitial pneumonia, therapeutics

  1. Lumacaftor and ivacaftor in the management of patients with cystic fibrosis: current evidence and future prospects.

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    Kuk, Kelly; Taylor-Cousar, Jennifer L

    2015-12-01

    Cystic fibrosis (CF) is a genetic disorder that causes multiorgan morbidity and premature death, most commonly from pulmonary dysfunction. Mutations in the CF transmembrane conductance regulator (CFTR) gene, of which almost 2000 have been described, result in a dysfunctional CFTR protein. This protein is an adenosine triphosphate binding anion channel, present primarily at the surface of epithelial cells. Loss of function mutations in this anion channel result in decreased or absent chloride/bicarbonate transport. The subsequent abnormal salt and water transport at epithelial cell surfaces leads to thickened secretions, and infection or inflammation in affected organs. In the last 20 years, therapeutics have been developed to treat the signs and symptoms of CF. However, in 2012, the small molecule drug, ivacaftor, became the first approved therapy that addresses the basic defect in CF. Ivacaftor is a potentiator of CFTR channels defective in their chloride/bicarbonate gating/conductance, but present at the epithelial cell surface. It is only approved for 10 mutations carried by approximately 7% of the population of patients with CF. F508del is the most common CFTR mutation, present in homozygosity in approximately 50% of patients with CF. The F508del mutation results in multiple CFTR channel defects that require both correction (stabilization of misfolded CFTR and trafficking to the epithelial cell membrane) and potentiation. This article reviews the in vitro and clinical trial data for the potential use of the potentiator, ivacaftor, and the corrector, lumacaftor, in patients with CF.

  2. Bacteriophage-based therapy in cystic fibrosis-associated Pseudomonas aeruginosa infections: rationale and current status

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    Hraiech, Sami; Brégeon, Fabienne; Rolain, Jean-Marc

    2015-01-01

    Pulmonary infections involving Pseudomonas aeruginosa are among the leading causes of the deterioration of the respiratory status of cystic fibrosis (CF) patients. The emergence of multidrug-resistant strains in such populations, favored by iterative antibiotic cures, has led to the urgent need for new therapies. Among them, bacteriophage-based therapies deserve a focus. One century of empiric use in the ex-USSR countries suggests that bacteriophages may have beneficial effects against a large range of bacterial infections. Interest in bacteriophages has recently renewed in Western countries, and the in vitro data available suggest that bacteriophage-based therapy may be of significant interest for the treatment of pulmonary infections in CF patients. Although the clinical data concerning this specific population are relatively scarce, the beginning of the first large randomized study evaluating bacteriophage-based therapy in burn infections suggests that the time has come to assess the effectiveness of this new therapy in CF P. aeruginosa pneumonia. Consequently, the aim of this review is, after a brief history, to summarize the evidence concerning bacteriophage efficacy against P. aeruginosa and, more specifically, the in vitro studies, animal models, and clinical trials targeting CF. PMID:26213462

  3. Bacteriophage-based therapy in cystic fibrosis-associated Pseudomonas aeruginosa infections: rationale and current status.

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    Hraiech, Sami; Brégeon, Fabienne; Rolain, Jean-Marc

    2015-01-01

    Pulmonary infections involving Pseudomonas aeruginosa are among the leading causes of the deterioration of the respiratory status of cystic fibrosis (CF) patients. The emergence of multidrug-resistant strains in such populations, favored by iterative antibiotic cures, has led to the urgent need for new therapies. Among them, bacteriophage-based therapies deserve a focus. One century of empiric use in the ex-USSR countries suggests that bacteriophages may have beneficial effects against a large range of bacterial infections. Interest in bacteriophages has recently renewed in Western countries, and the in vitro data available suggest that bacteriophage-based therapy may be of significant interest for the treatment of pulmonary infections in CF patients. Although the clinical data concerning this specific population are relatively scarce, the beginning of the first large randomized study evaluating bacteriophage-based therapy in burn infections suggests that the time has come to assess the effectiveness of this new therapy in CF P. aeruginosa pneumonia. Consequently, the aim of this review is, after a brief history, to summarize the evidence concerning bacteriophage efficacy against P. aeruginosa and, more specifically, the in vitro studies, animal models, and clinical trials targeting CF.

  4. Pharmacological Treatment of Idiopathic Pulmonary Fibrosis: Current Approaches, Unsolved Issues, and Future Perspectives

    NARCIS (Netherlands)

    M. Kreuter (Michael); F. Bonella (Francesco); M.S. Wijsenbeek (Marlies); T.M. Maher (Toby M.); P. Spagnolo (Paolo)

    2015-01-01

    textabstractIdiopathic pulmonary fibrosis (IPF) is a devastating condition with a 5-year survival of approximately 20%. The disease primarily occurs in elderly patients. IPF is a highly heterogeneous disorder with a clinical course that varies from prolonged periods of stability to episodes of rapid

  5. Contemporary use of elastography in liver fibrosis and portal hypertension

    DEFF Research Database (Denmark)

    Thiele, Maja; Kjærgaard, Maria; Thielsen, Peter

    2017-01-01

    significant portal hypertension, techniques and limitations. Four types of ultrasound elastography exist, but there is scarce evidence comparing the different techniques. The majority of experience concern transient elastography for diagnosing fibrosis and cirrhosis in patients with chronic viral hepatitis C...

  6. Bacteriophage-based therapy in cystic fibrosis-associated Pseudomonas aeruginosa infections: rationale and current status

    Directory of Open Access Journals (Sweden)

    Hraiech S

    2015-07-01

    Full Text Available Sami Hraiech,1,2 Fabienne Brégeon,1,3 Jean-Marc Rolain1 1Institut Hospitalo-Universitaire Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, 2Réanimation Médicale – Détresses Respiratoires et Infections Sévères, APHM, CHU Nord, 3Service d’Explorations Fonctionnelles Respiratoires, APHM, CHU Nord, Marseille, France Abstract: Pulmonary infections involving Pseudomonas aeruginosa are among the leading causes of the deterioration of the respiratory status of cystic fibrosis (CF patients. The emergence of multidrug-resistant strains in such populations, favored by iterative antibiotic cures, has led to the urgent need for new therapies. Among them, bacteriophage-based therapies deserve a focus. One century of empiric use in the ex-USSR countries suggests that bacteriophages may have beneficial effects against a large range of bacterial infections. Interest in bacteriophages has recently renewed in Western countries, and the in vitro data available suggest that bacteriophage-based therapy may be of significant interest for the treatment of pulmonary infections in CF patients. Although the clinical data concerning this specific population are relatively scarce, the beginning of the first large randomized study evaluating bacteriophage-based therapy in burn infections suggests that the time has come to assess the effectiveness of this new therapy in CF P. aeruginosa pneumonia. Consequently, the aim of this review is, after a brief history, to summarize the evidence concerning bacteriophage efficacy against P. aeruginosa and, more specifically, the in vitro studies, animal models, and clinical trials targeting CF. Keywords: pneumonia, pulmonary infection, bacterial infection, multidrug resistance

  7. Assessment of Myocardial Fibrosis in Mice Using a T2*-Weighted 3D Radial Magnetic Resonance Imaging Sequence

    NARCIS (Netherlands)

    van Nierop, Bastiaan J.; Bax, Noortje A. M.; Nelissen, Jules L.; Arslan, Fatih; Motaal, Abdallah G.; de Graaf, Larry; Zwanenburg, Jaco J. M.; Luijten, Peter R.; Nicolay, Klaas; Strijkers, Gustav J.

    2015-01-01

    Background Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using

  8. Pirfenidone: a review of its use in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Kim, Esther S; Keating, Gillian M

    2015-02-01

    Pirfenidone (Esbriet®) is an orally administered, synthetic, pyridone compound that is approved for the treatment of adults with mild to moderate idiopathic pulmonary fibrosis (IPF) in the EU, and for the treatment of IPF in the USA. This article summarizes pharmacological, efficacy and tolerability data relevant to the use of pirfenidone in these indications. In the randomized, double-blind, placebo-controlled, multinational CAPACITY trials in patients with mild to moderate IPF, a significant reduction in the rate of decline in forced vital capacity (FVC) was seen with pirfenidone versus placebo in study 004 but not in study 006. Pirfenidone also reduced the rate of decline in FVC to a significantly greater extent than placebo in the randomized, double-blind, multinational ASCEND trial in this patient population. In addition, pirfenidone showed a significant treatment effect on the 6-min walking test distance and progression-free survival in the ASCEND trial and in a pooled analysis of the CAPACITY trials. Pirfenidone had a manageable tolerability profile in all three studies. Gastrointestinal and skin-related events (e.g. nausea, rash, photosensitivity reaction), which were the most commonly occurring treatment-emergent adverse events, were generally mild to moderate in severity. In addition, a prespecified mortality analysis across all three studies demonstrated a significant reduction in IPF-related and all-cause mortality with pirfenidone. In conclusion, oral pirfenidone is a valuable agent for use in patients with IPF.

  9. [National consensus regarding azithromycin use in cystic fibrosis].

    Science.gov (United States)

    Abely, M; Jubin, V; Bessaci-Kabouya, K; Chiron, R; Bui, S; Fayon, M

    2015-06-01

    To propose a formalized consensus agreement regarding the prescription of azithromycin in cystic fibrosis (CF). Application of the Delphi method in 5 thematic fields: indications, contra-indications, dosage, precautions for use and treatment follow-up. Thirty identified French CF centers participated in the process on 49 (61%), which comprised 3 rounds. Experts validated azithromycin as a long-term anti-inflammatory agent in children aged over 6 years, presenting with the classical form of CF, irrespective of the bacteriological status of the patient (except for non-tuberculous mycobacteria). Azithromycin administration should not be routine in the milder forms of the disease, and avoided in the presence of severe hepatic or renal involvement. In children whose weight is below 40 kg, a strong consensus recommended a single daily oral dose, administered three times weekly. However, in adults, the level of agreement was weaker. Minimal duration of treatment is 6 months, after which the drug should be discontinued if no observable effect is noted on clinical parameters, exacerbation rate and/or FEV1. Clinical monitoring of treatment tolerance is recommended (nausea, diarrhea, skin rash, tinnitus, deafness, arthropathy), without increasing the frequency of surveillance of sputum bacteria. However, it is essential to monitor sputum for fungi (expectoration, Aspergillus, broncho-pulmonary allergic aspergillosis). This consensus statement defines an area for the prescription of azithromycin in CF, with the aim of better harmonization of its use. Published by Elsevier Masson SAS.

  10. Acoustic structure quantification by using ultrasound Nakagami imaging for assessing liver fibrosis

    OpenAIRE

    Po-Hsiang Tsui; Ming-Chih Ho; Dar-In Tai; Ying-Hsiu Lin; Chiao-Yin Wang; Hsiang-Yang Ma

    2016-01-01

    Acoustic structure quantification (ASQ) is a recently developed technique widely used for detecting liver fibrosis. Ultrasound Nakagami parametric imaging based on the Nakagami distribution has been widely used to model echo amplitude distribution for tissue characterization. We explored the feasibility of using ultrasound Nakagami imaging as a model-based ASQ technique for assessing liver fibrosis. Standard ultrasound examinations were performed on 19 healthy volunteers and 91 patients with ...

  11. Challenges with current inhaled treatments for chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    Greally, Peter

    2012-06-01

    Pseudomonas aeruginosa (Pa) is the predominant pathogen infecting the airways of patients with cystic fibrosis (CF). Initial colonization is usually transient and associated with non-mucoid strains, which can be eradicated if identified early. This strategy can prevent, or at least delay, chronic Pa infection, which eventually develops in the majority of patients by their late teens or early adulthood. This article discusses the management and latest treatment developments of Pa lung infection in patients with CF, with a focus on nebulized antibiotic therapy.

  12. A functional CFTR assay using primary cystic fibrosis intestinal organoids

    NARCIS (Netherlands)

    Dekkers, J.F.; Wiegerinck, C.L.; de Jonge, H.R.; Bronsveld, I.; Janssens, H.M.; de Winter-de Groot, K.M.; Brandsma, A.M.; de Jong, N.W.; Bijvelds, M.J.; Scholte, B.J.; Nieuwenhuis, E.E.; van den Brink, S.; Clevers, H.; van der Ent, C.K.; Middendorp, S.; Beekman, J.M.

    2013-01-01

    We recently established conditions allowing for long-term expansion of epithelial organoids from intestine, recapitulating essential features of the in vivo tissue architecture. Here we apply this technology to study primary intestinal organoids of people suffering from cystic fibrosis, a disease ca

  13. [Causal relationship between the use of gadolinium based contrast media and nephrogenic systemic fibrosis].

    Science.gov (United States)

    Varela, Cristian U; Prieto-Rayo, Juan Carlos

    2014-12-01

    Nephrogenic systemic fibrosis (NSF) is a severe iatrogenic disease that affect patients with impaired renal function exposed to gadolinium-based contrast agents. Clinically, symptoms develop within days or weeks after the exposure and mimic a scleromyxedema. The causal relationship between use of gadolinium-based contrast agents and NSF led to develop clinical guidelines aiming to limit the use of this contrast medium in high risk patients. These guidelines decreased the incidence of NSF in the last years. Unfortunately there is no specific treatment for NSF yet. Thus, strict adherence to current guidelines is key to prevent new cases. Renal dysfunction is increasingly common in our population. Therefore, practicing physicians should be aware of this potential complication of the use of gadolinium based contrast media.

  14. Oral Submucous Fibrosis Caused Due to Long Term Tobacco Use - A Case Report

    Directory of Open Access Journals (Sweden)

    Arun V Subramaniam

    2003-01-01

    Full Text Available A case of a middle aged male patient afflicted with oral submucous fibrosis was noticed by the department of Oral Medicine, Bharari Vidyapeeth′s Dental College & Hospital,Pune , when the patient reported to the department with the chief complaint of a painful lower left molar. On clinical examination, oral submucous fibrosis was diagnosed. The only positive history of tissue abuse habit given by the patient was of the use of tobacco containing toothpaste since many years.

  15. Early detection of liver fibrosis in rats using 3-D ultrasound Nakagami imaging: a feasibility evaluation.

    Science.gov (United States)

    Ho, Ming-Chih; Tsui, Po-Hsiang; Lee, Yu-Hsin; Chen, Yung-Sheng; Chen, Chiung-Nien; Lin, Jen-Jen; Chang, Chien-Cheng

    2014-09-01

    We investigated the feasibility of using 3-D ultrasound Nakagami imaging to detect the early stages of liver fibrosis in rats. Fibrosis was induced in livers of rats (n = 60) by intraperitoneal injection of 0.5% dimethylnitrosamine (DMN). Group 1 was the control group, and rats in groups 2-6 received DMN injections for 1-5 weeks, respectively. Each rat was sacrificed to perform 3-D ultrasound scanning of the liver in vitro using a single-element transducer of 6.5 MHz. The 3-D raw data acquired at a sampling rate of 50 MHz were used to construct 3-D Nakagami images. The liver specimen was further used for histologic analysis with hematoxylin and eosin and Masson staining to score the degree of liver fibrosis. The results indicate that the Metavir scores of the hematoxylin and eosin-stained sections in Groups 1-4 were 0 (defined as early liver fibrosis in this study), and those in groups 5 and 6 ranged from 1 to 2 and 2 to 3, respectively. To quantify the degree of early liver fibrosis, the histologic sections with Masson stain were analyzed to calculate the number of fiber-related blue pixels. The number of blue pixels increased from (2.36 ± 0.79) × 10(4) (group 1) to (7.68 ± 2.62) × 10(4) (group 4) after DMN injections for 3 weeks, indicating that early stages of liver fibrosis were successfully induced in rats. The Nakagami parameter increased from 0.36 ± 0.02 (group 1) to 0.55 ± 0.03 (group 4), with increasing numbers of blue pixels in the Masson-stained sections (p-value Nakagami imaging has potential in the early detection of liver fibrosis in rats and may serve as an image-based pathologic model to visually track fibrosis formation and growth.

  16. Use of exercise in the management of cystic fibrosis: short communication about a survey of cystic fibrosis referral centers.

    Science.gov (United States)

    Kaplan, T A; ZeBranek, J D; McKey, R M

    1991-01-01

    A survey of 47 cystic fibrosis referral centers was conducted to study the use of exercise in the management of patients with cystic fibrosis (CF). A questionnaire with 5 brief questions concerning the prescription and application of exercise therapy was sent to the first 47 centers (38.5%) listed in the 1988 CF Foundation Directory, and 46 (97.9%) were returned. While all but one of the respondents recommend exercise at least to selected patients, and while 80.4% of the centers refer patients to summer camp programs, only 43.5% offer exercise stress testing and only 21.7% offer an exercise program for their patients. Most of the respondents who recommend exercise prescribe aerobic exercise, swimming being the most frequently chosen type. Although there is a large discrepancy between those centers that acknowledge the benefits of exercise and those that have arranged for regularly available exercise services, inroads have been made in utilizing this therapeutic tool for patients with CF.

  17. Evaluating the efficacy of potential drugs for intestinal fibrosis using precision-cut tissue slices

    NARCIS (Netherlands)

    Iswandana, Raditya; Pham, B.T.; van Haaften, Wouter; Oosterhuis, Dorenda; Mutsaers, Henricus; Olinga, Peter

    2015-01-01

    Intestinal fibrosis (IF) is a common complication in Crohn's disease. Currently, there are no drugs registered to treat IF and the sole therapy is intestinal resection. Transforming growth factor (TGF)-beta and platelet-derived growth factor (PDGF) play a key role in IF and are the main targets for

  18. Rattlesnake Phospholipase A2 Increases CFTR-Chloride Channel Current and Corrects ∆F508CFTR Dysfunction: Impact in Cystic Fibrosis.

    Science.gov (United States)

    Faure, Grazyna; Bakouh, Naziha; Lourdel, Stéphane; Odolczyk, Norbert; Premchandar, Aiswarya; Servel, Nathalie; Hatton, Aurélie; Ostrowski, Maciej K; Xu, Haijin; Saul, Frederick A; Moquereau, Christelle; Bitam, Sara; Pranke, Iwona; Planelles, Gabrielle; Teulon, Jacques; Herrmann, Harald; Roldan, Ariel; Zielenkiewicz, Piotr; Dadlez, Michal; Lukacs, Gergely L; Sermet-Gaudelus, Isabelle; Ollero, Mario; Corringer, Pierre-Jean; Edelman, Aleksander

    2016-07-17

    Deletion of Phe508 in the nucleotide binding domain (∆F508-NBD1) of the cystic fibrosis transmembrane regulator (CFTR; a cyclic AMP-regulated chloride channel) is the most frequent mutation associated with cystic fibrosis. This mutation affects the maturation and gating of CFTR protein. The search for new high-affinity ligands of CFTR acting as dual modulators (correctors/activators) presents a major challenge in the pharmacology of cystic fibrosis. Snake venoms are a rich source of natural multifunctional proteins, potential binders of ion channels. In this study, we identified the CB subunit of crotoxin from Crotalus durissus terrificus as a new ligand and allosteric modulator of CFTR. We showed that CB interacts with NBD1 of both wild type and ∆F508CFTR and increases their chloride channel currents. The potentiating effect of CB on CFTR activity was demonstrated using electrophysiological techniques in Xenopus laevis oocytes, in CFTR-HeLa cells, and ex vivo in mouse colon tissue. The correcting effect of CB was shown by functional rescue of CFTR activity after 24-h ΔF508CFTR treatments with CB. Moreover, the presence of fully glycosylated CFTR was observed. Molecular docking allowed us to propose a model of the complex involving of the ABCβ and F1-like ATP-binding subdomains of ΔF508-NBD1. Hydrogen-deuterium exchange analysis confirmed stabilization in these regions, also showing allosteric stabilization in two other distal regions. Surface plasmon resonance competition studies showed that CB disrupts the ∆F508CFTR-cytokeratin 8 complex, allowing for the escape of ∆F508CFTR from degradation. Therefore CB, as a dual modulator of ΔF508CFTR, constitutes a template for the development of new anti-CF agents.

  19. Therapeutic targets in liver fibrosis.

    Science.gov (United States)

    Fallowfield, Jonathan A

    2011-05-01

    Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points.

  20. Acoustic structure quantification by using ultrasound Nakagami imaging for assessing liver fibrosis.

    Science.gov (United States)

    Tsui, Po-Hsiang; Ho, Ming-Chih; Tai, Dar-In; Lin, Ying-Hsiu; Wang, Chiao-Yin; Ma, Hsiang-Yang

    2016-09-08

    Acoustic structure quantification (ASQ) is a recently developed technique widely used for detecting liver fibrosis. Ultrasound Nakagami parametric imaging based on the Nakagami distribution has been widely used to model echo amplitude distribution for tissue characterization. We explored the feasibility of using ultrasound Nakagami imaging as a model-based ASQ technique for assessing liver fibrosis. Standard ultrasound examinations were performed on 19 healthy volunteers and 91 patients with chronic hepatitis B and C (n = 110). Liver biopsy and ultrasound Nakagami imaging analysis were conducted to compare the METAVIR score and Nakagami parameter. The diagnostic value of ultrasound Nakagami imaging was evaluated using receiver operating characteristic (ROC) curves. The Nakagami parameter obtained through ultrasound Nakagami imaging decreased with an increase in the METAVIR score (p Nakagami imaging is a model-based ASQ technique that can be beneficial for the clinical diagnosis of early liver fibrosis.

  1. Liver fibrosis and tissue architectural change measurement using fractal-rectified metrics and Hurst's exponent

    Institute of Scientific and Technical Information of China (English)

    Nicola Dioguardi; Fabio Grizzi; Barbara Franceschini; Paola Bossi; Carlo Russo

    2006-01-01

    AIM: To provide the accurate alternative metrical means of monitoring the effects of new antiviral drugs on the reversal of newly formed collagen.METHODS: Digitized histological biopsy sections taken from 209 patients with chronic C virus hepatitis with different grade of fibrosis or cirrhosis, were measured by means of a new, rapid, user-friendly, fully computeraided method based on the international system meter rectified using fractal principles.RESULTS: The following were described: geometric perimeter, area and wrinkledness of fibrosis; the collation of the Knodell, Sheuer, Ishak and METAVIR scores with fractal-rectified metric measurements; the meaning of the physical composition of fibrosis in relation to the magnitude of collagen islets; the intra- and inter-biopsy sample variability of these parameters; the "staging"of biopsy sections indicating the pathway covered by fibrosis formation towards its maximum known value;the quantitative liver tissue architectural changes with the Hurst exponent.CONCLUSION: Our model provides the first metrical evaluations of the geometric properties of fibrosis and the quantitative architectural changes of the liver tissue.The representativeness of histological sections of the whole liver is also discussed in the light of the results obtained with the Hurst coefficient.

  2. Liver Fibrosis progression using Fibroscan in HIV/HCV coinfected patients with undetectable HIV viral load

    Directory of Open Access Journals (Sweden)

    Laura Perez-Martinez

    2014-11-01

    Full Text Available Introduction: Several factors such as duration of infection, age, male gender, consumption of alcohol, HIV infection and low CD4 count have been associated with fibrosis progression rate. However, it is relatively scarce, the knowledge about the liver fibrosis progression rate in HIV-infected patients with undetectable HIV viral load (VL. For this reason, we performed the present study. Materials and Methods: Observational and multicenter study (2008–2012 conducted in four hospitals of the northern Spain. HIV/HCV (hepatitis c virus coinfected patients ≥18 years on stable combination antiretroviral therapy (cART (≥6 months and with a HIV VL <50 copies/mL were selected to analyze their liver fibrosis progression. Fibrosis progression was assessed using a Fibroscan® (502 STEP 3 model and measuring a basal test and a second one at least 12 months apart from baseline. This evolution was compared with different variables such as duration of HIV/HCV coinfection, gender, age, previous treatment for HCV, HCV genotype, CD4 lymphocyte counts and the cART employed at the basal test. Results: A total of 608 patients were included (median age 29.4 years, 71.7% men. Of these, 463 patients met the inclusion criteria. In these patients, the liver fibrosis progression was nearly flat and the only variables related to a higher liver fibrosis progression were the increasing age of the patients (p=0.02 and the duration of the coinfection (p=0.001. CD4 lymphocyte counts showed a tendency to improved liver fibrosis (p=0.056. Conclusions: In HIV/HCV coinfected patients on stable cART and HIV undetectable VL, the increase in liver fibrosis rate progression was nearly flat, although it was significantly associated with the duration of the coinfection and the age of the patient. The beneficial effects of the cART were independent of the antiretroviral drug employed. A tendency to a lower fibrosis progression was observed in those patients with a higher CD4 count.

  3. The Use of Home Spirometry in Pediatric Cystic Fibrosis Patients

    Science.gov (United States)

    Shakkottai, Aarti; Nasr, Samya Z.

    2017-01-01

    Medication adherence is poor among pediatric cystic fibrosis (CF) patients, with adolescents having one of the lowest adherence rates. We wanted to identify an adherence intervention that would be acceptable to CF adolescents and assess its feasibility. We surveyed 40 adolescents with CF and asked about barriers to and motivators for their own adherence and to generate ideas for potential adherence interventions. Since most of the respondents chose frequent spirometry at home and medication reminders for interventions, we selected 5 subjects, 10 to 14 years of age, with CF to test the feasibility of home spirometry and medication reminders in pediatric CF patients. This article summarizes the results of both the survey and the feasibility pilot study. PMID:28229102

  4. Using Geometry To Sense Current.

    Science.gov (United States)

    McCaughan, Adam N; Abebe, Nathnael S; Zhao, Qing-Yuan; Berggren, Karl K

    2016-12-14

    We describe a superconducting three-terminal device that uses a simple geometric effect known as current crowding to sense the flow of current and actuate a readout signal. The device consists of a "Y"-shaped current combiner, with two currents (sense and bias) entering separately through the top arms of the "Y", intersecting, and then exiting together through the bottom leg of the "Y". When current is added to or removed from one of the arms (e.g., the sense arm), the superconducting critical current in the other arm (i.e., the bias arm) is modulated. The current in the sense arm can thus be determined by measuring the critical current of the bias arm, or inversely, the sense current can be used to modulate the state of the bias arm. The dependence of the bias critical current on the sense current occurs due to the geometric current crowding effect, which causes the sense current to interact locally with the bias arm. Measurement of the critical current in the bias arm does not break the superconducting state of the sense arm or of the bottom leg, and thus, quantized currents trapped in a superconducting loop were able to be repeatedly measured without changing the state of the loop. Current crowding is a universal effect in nanoscale superconductors, and so this device has potential for applicability across a broad range of superconducting technologies and materials. More generally, any technology in which geometrically induced flow crowding exists in the presence of a strong nonlinearity might make use of this type of device.

  5. Airway clearance techniques used by people with cystic fibrosis in the UK.

    Science.gov (United States)

    Hoo, Z H; Daniels, T; Wildman, M J; Teare, M D; Bradley, J M

    2015-12-01

    To describe the current use of airway clearance techniques among people with cystic fibrosis (CF) in the UK, and the baseline characteristics for users of different airway clearance techniques. Analysis of the UK CF Registry 2011 data. All people with CF in the UK aged ≥11 years (n=6372). Of the 6372 people on the UK CF registry in 2011, 89% used airway clearance techniques. The most commonly used primary techniques were forced expiratory techniques (28%) and oscillating positive expiratory pressure (PEP) (23%). Postural drainage and high-frequency chest wall oscillation were used by 4% and 1% of people with CF, respectively. The male:female ratio of individuals who used exercise as their primary airway clearance technique was 2:1, compared with 1:1 for other techniques. Individuals with more severe lung disease tended to use devices such as non-invasive ventilation or high-frequency chest wall oscillation. Forced expiratory techniques and oscillating PEP are the most common airway clearance techniques used by people with CF in the UK, and postural drainage and high-frequency chest wall oscillation are the least common techniques. This is significant in terms of planning airway clearance technique trials, where postural drainage has been used traditionally as the comparator. The use of airway clearance techniques varies between countries, but the reasons for these differences are unknown. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  6. Automated biphasic morphological assessment of hepatitis B-related liver fibrosis using second harmonic generation microscopy

    Science.gov (United States)

    Wang, Tong-Hong; Chen, Tse-Ching; Teng, Xiao; Liang, Kung-Hao; Yeh, Chau-Ting

    2015-08-01

    Liver fibrosis assessment by biopsy and conventional staining scores is based on histopathological criteria. Variations in sample preparation and the use of semi-quantitative histopathological methods commonly result in discrepancies between medical centers. Thus, minor changes in liver fibrosis might be overlooked in multi-center clinical trials, leading to statistically non-significant data. Here, we developed a computer-assisted, fully automated, staining-free method for hepatitis B-related liver fibrosis assessment. In total, 175 liver biopsies were divided into training (n = 105) and verification (n = 70) cohorts. Collagen was observed using second harmonic generation (SHG) microscopy without prior staining, and hepatocyte morphology was recorded using two-photon excitation fluorescence (TPEF) microscopy. The training cohort was utilized to establish a quantification algorithm. Eleven of 19 computer-recognizable SHG/TPEF microscopic morphological features were significantly correlated with the ISHAK fibrosis stages (P 0.82 for liver cirrhosis detection. Since no subjective gradings are needed, interobserver discrepancies could be avoided using this fully automated method.

  7. Exploring Cystic Fibrosis Using Bioinformatics Tools: A Module Designed for the Freshman Biology Course

    Science.gov (United States)

    Zhang, Xiaorong

    2011-01-01

    We incorporated a bioinformatics component into the freshman biology course that allows students to explore cystic fibrosis (CF), a common genetic disorder, using bioinformatics tools and skills. Students learn about CF through searching genetic databases, analyzing genetic sequences, and observing the three-dimensional structures of proteins…

  8. Exploring Cystic Fibrosis Using Bioinformatics Tools: A Module Designed for the Freshman Biology Course

    Science.gov (United States)

    Zhang, Xiaorong

    2011-01-01

    We incorporated a bioinformatics component into the freshman biology course that allows students to explore cystic fibrosis (CF), a common genetic disorder, using bioinformatics tools and skills. Students learn about CF through searching genetic databases, analyzing genetic sequences, and observing the three-dimensional structures of proteins…

  9. Assessment of Airway Microbiota and Inflammation in Cystic Fibrosis Using Multiple Sampling Methods

    OpenAIRE

    Edith T Zemanick; Brandie D Wagner; Robertson, Charles E.; Stevens, Mark J.; Szefler, Stanley J; Accurso, Frank J.; Sagel, Scott D; Harris, J. Kirk

    2015-01-01

    Rationale: Oropharyngeal (OP) swabs and induced sputum (IS) are used for airway bacteria surveillance in nonexpectorating children with cystic fibrosis (CF). Molecular analyses of these airway samples detect complex microbial communities. However, the optimal noninvasive sampling approach for microbiota analyses and the clinical relevance of microbiota, particularly its relationship to airway inflammation, is not well characterized.

  10. Is the raised volume rapid thoracic compression technique ready for use in clinical trials in infants with cystic fibrosis?

    NARCIS (Netherlands)

    Matecki, Stefan; Kent, Lisa; de Boeck, Kris; Le Bourgeois, Muriel; Zielen, Stefan; Braggion, Cesare; Arets, H. G M; Bradley, Judy; Davis, Stephanie; Sermet, Isabelle; Reix, Philippe

    2016-01-01

    The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a revie

  11. Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations.

    Science.gov (United States)

    Li, Li; Somerset, Shawn

    2016-08-01

    An increased prevalence of cystic fibrosis (CF) related complications such as impaired bone health and diabetes has accompanied increased survival of patients with CF. This review was conducted to determine the extent to which adults with CF are meeting current nutrition recommendations for micronutrients in association with CF-related complications management. Although dietary intake and nutritional status in CF has improved significantly in recent decades, micronutrient status seems to have diverged. While vitamin A and E intakes appear adequate, frequent vitamin D and K deficiency/insufficiency and compromised bone health in CF, occurs despite supplementation. Although deficiency of water-soluble vitamins and minerals is uncommon, ongoing surveillance will enhance overall health outcomes, particularly in cases of CF-related liver disease and deteriorated lung function and bone health. Salt and fluid status in CF may also need attention due to diminished thirst sensation and voluntary rehydration. Further investigation in micronutrient status optimisation in CF will inform the development of more effective and targeted nutrition therapies to enable integration of more refined recommendations for micronutrient intakes in CF based on individual needs and disease progression.

  12. Fault current limiters using superconductors

    Science.gov (United States)

    Norris, W. T.; Power, A.

    Fault current limiters on power systems are to reduce damage by heating and electromechanical forces, to alleviate duty on switchgear used to clear the fault, and to mitigate disturbance to unfaulted parts of the system. A basic scheme involves a super-resistor which is a superconductor being driven to high resistance when fault current flows either when current is high during a cycle of a.c. or, if the temperature of the superconductive material rises, for the full cycle. Current may be commuted from superconductor to an impedance in parallel, thus reducing the energy dispersed at low temperature and saving refrigeration. In a super-shorted transformer the ambient temperature primary carries the power system current; the superconductive secondary goes to a resistive condition when excessive currents flow in the primary. A super-transformer has the advantage of not needing current leads from high temperature to low temperature; it behaves as a parallel super-resistor and inductor. The supertransductor with a superconductive d.c. bias winding is large and has small effect on the rate of fall of current at current zero; it does little to alleviate duty on switchgear but does reduce heating and electromechanical forces. It is fully active after a fault has been cleared. Other schemes depend on rapid recooling of the superconductor to achieve this.

  13. Nephrogenic systemic fibrosis: UK survey of the use of gadolinium-based contrast media

    Energy Technology Data Exchange (ETDEWEB)

    Rees, O., E-mail: owenrees1@gmail.co [Wrexham Maelor Hospital, Wrexham (United Kingdom); Agarwal, S.K. [Wrexham Maelor Hospital, Wrexham (United Kingdom)

    2010-08-15

    Aim: To identify the current practice of administration of gadolinium-based contrast media (Gd-CM) within the UK with respect to the European Society of Urogenital Radiology (ESUR) guidelines on nephrogenic systemic fibrosis (NSF). Materials and methods: One hundred and fifty-two institutions were contacted to request details regarding the use of Gd-CM at their institution, their awareness of NSF, and of the ESUR guidelines, and their departmental policy on the administration of Gd-CM agents associated with NSF (high-risk agents) in patients with diminished renal function. Results: Of the 100 institutions that replied, 72% used a cyclic agent as a first-line Gd-CM. The majority of institutions used more than one Gd-CM, and 57% used a high-risk Gd-CM. Seventy percent were aware of the ESUR guidelines, and of the 57% that used a high-risk Gd-CM, 9% did not check renal function at all prior to administration. The course of action of the remaining 48% was varied in patients with diminished renal function with some changing to a low-risk Gd-CM and others electing not to use Gd-CM at all. Five percent continued to use a high-risk Gd-CM with an estimated glomerular filtration rate <30 ml/min. Conclusion: The present survey shows that the majority of institutions use a low-risk Gd-CM as a first-line agent; however, a number of institutions do use a high-risk Gd-CM and their course of action for patients with diminished renal function is varied. Given current evidence, it is advisable to use a low-risk Gd-CM, such as a cyclic agent, in patients with diminished renal function.

  14. Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.

    Directory of Open Access Journals (Sweden)

    Juho Pirhonen

    Full Text Available Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD. We tested whether second-harmonic generation (SHG and coherent anti-Stokes Raman scattering (CARS microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD.We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0-4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals.We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III.This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading.

  15. Prevalence of liver fibrosis and risk factors in a general population using non-invasive biomarkers (FibroTest

    Directory of Open Access Journals (Sweden)

    Bismut Françoise

    2010-04-01

    Full Text Available Abstract Background FibroTest and elastography have been validated as biomarkers of liver fibrosis in the most frequent chronic liver diseases and in the fibrosis screening of patients with diabetes. One challenge was to use them for estimating the prevalence of fibrosis, identifying independent risk factors and to propose screening strategies in the general population. Methods We prospectively studied 7,463 consecutive subjects aged 40 years or older. Subjects with presumed advanced fibrosis (FibroTest greater than 0.48 were re-investigated in a tertiary center. Results The sample characteristics were similar to those of the French population. FibroTest was interpretable in 99.6%. The prevalence of presumed fibrosis was 2.8%, (209/7,463, including cirrhosis in 0.3% (25/7,463; 105/209 (50% subjects with presumed fibrosis accepted re-investigation. Fibrosis was confirmed in 50, still suspected in 27, indeterminate in 25 and not confirmed with false positive FibroTest or false negative elastography in 3 subjects. False negative rate of FibroTest estimated using elastography was 0.4% (3/766. The attributable causes for confirmed fibrosis were both alcoholic and nonalcoholic fatty liver disease (NAFLD in 66%, NAFLD in 13%, alcohol in 9%, HCV in 6%, and other in 6%. Factors independently associated (all P Conclusions Biomarkers have permitted to estimate prevalence of advanced fibrosis around 2.8% in a general population aged 40 years or older, and several risk factors which may be used for the validation of selective or non-selective screening strategies.

  16. Is it better to use two elastographic methods for liver fibro-sis assessment?

    Institute of Scientific and Technical Information of China (English)

    Ioan Sporea; Roxana (S)irli; Alina Popescu; Simona Bota; Radu Badea; Monica Lup(s)or; Mircea Foc(s)a; Mirela D(a)nil(a)

    2011-01-01

    AIM: To find out if by combining 2 ultrasound based elastographic methods: acoustic radiation force impulse (ARFI) elastography and transient elastography (TE), we can improve the prediction of fibrosis in patients with chronic hepatitis C.METHODS: Our study included 197 patients with chronic hepatitis C. In each patient, we performed, in the same session, liver stiffness (LS) measurements by means of TE and ARFI, respectively, and liver biopsy (LB), assessed according to the Metavir score. 10 LS measurements were performed both by TE and ARFI; median values were calculated and expressed in kilopascals (kPa) and meters/second (m/s), respectively. Only TE and ARFI measurements with IQR < 30% and SR ≥ 60% were considered reliable. RESULTS: On LB 13 (6.6%) patients had F0, 32 (16.2%) had F1, 52 (26.4%) had F2, 47 (23.9%) had F3, and 53 (26.9%) had F4. A direct, strong correlation was found between TE measurements and fibrosis (r = 0.741), between ARFI and fibrosis (r = 0.730) and also between TE and ARFI (r = 0.675). For predicting significant fibrosis (F ≥ 2), for a cut-off of 6.7 kPa, TE had 77.5% sensitivity (Se) and 86.5% specificity (Sp) [area under the receiver operating characteristic curve (AUROC) 0.87] and for a cut-off of 1.2 m/s, ARFI had 76.9% Se and 86.7% Sp (AUROC 0.84). For predicting cirrhosis (F = 4), for a cut-off of 12.2 kPa, TE had 96.2% Se and 89.6% Sp (AUROC 0.97) and for a cut-off of 1.8 m/s, ARFI had 90.4% Se and 85.6% Sp (AUROC 0.91). When both elastographic methods were taken into consideration, for predicting significant fibrosis (F ≥ 2), (TE ≥ 6.7 kPa and ARFI ≥ 1.2 m/s) we obtained 60.5% Se, 93.3% Sp, 96.8% positive predictive value (PPV), 41.4% negative predictive value (NPV) and 68% accuracy, while for predicting cirrhosis (TE ≥ 12.2 kPa and ARFI ≥ 1.8 m/s) we obtained 84.9% Se, 94.4% Sp, 84.9% PPV, 94.4% NPV and 91.8% accuracy.CONCLUSION: TE used in combination with ARFI is highly specific for predicting significant

  17. Sparse Logistic Regression for Diagnosis of Liver Fibrosis in Rat by Using SCAD-Penalized Likelihood

    Directory of Open Access Journals (Sweden)

    Fang-Rong Yan

    2011-01-01

    Full Text Available The objective of the present study is to find out the quantitative relationship between progression of liver fibrosis and the levels of certain serum markers using mathematic model. We provide the sparse logistic regression by using smoothly clipped absolute deviation (SCAD penalized function to diagnose the liver fibrosis in rats. Not only does it give a sparse solution with high accuracy, it also provides the users with the precise probabilities of classification with the class information. In the simulative case and the experiment case, the proposed method is comparable to the stepwise linear discriminant analysis (SLDA and the sparse logistic regression with least absolute shrinkage and selection operator (LASSO penalty, by using receiver operating characteristic (ROC with bayesian bootstrap estimating area under the curve (AUC diagnostic sensitivity for selected variable. Results show that the new approach provides a good correlation between the serum marker levels and the liver fibrosis induced by thioacetamide (TAA in rats. Meanwhile, this approach might also be used in predicting the development of liver cirrhosis.

  18. Novel Therapeutics Identification for Fibrosis in Renal Allograft Using Integrative Informatics Approach

    Science.gov (United States)

    Li, Li; Greene, Ilana; Readhead, Benjamin; Menon, Madhav C.; Kidd, Brian A.; Uzilov, Andrew V.; Wei, Chengguo; Philippe, Nimrod; Schroppel, Bernd; He, John Cijiang; Chen, Rong; Dudley, Joel T.; Murphy, Barbara

    2017-01-01

    Chronic allograft damage, defined by interstitial fibrosis and tubular atrophy (IF/TA), is a leading cause of allograft failure. Few effective therapeutic options are available to prevent the progression of IF/TA. We applied a meta-analysis approach on IF/TA molecular datasets in Gene Expression Omnibus to identify a robust 85-gene signature, which was used for computational drug repurposing analysis. Among the top ranked compounds predicted to be therapeutic for IF/TA were azathioprine, a drug to prevent acute rejection in renal transplantation, and kaempferol and esculetin, two drugs not previously described to have efficacy for IF/TA. We experimentally validated the anti-fibrosis effects of kaempferol and esculetin using renal tubular cells in vitro and in vivo in a mouse Unilateral Ureteric Obstruction (UUO) model. Kaempferol significantly attenuated TGF-β1-mediated profibrotic pathways in vitro and in vivo, while esculetin significantly inhibited Wnt/β-catenin pathway in vitro and in vivo. Histology confirmed significantly abrogated fibrosis by kaempferol and esculetin in vivo. We developed an integrative computational framework to identify kaempferol and esculetin as putatively novel therapies for IF/TA and provided experimental evidence for their therapeutic activities in vitro and in vivo using preclinical models. The findings suggest that both drugs might serve as therapeutic options for IF/TA. PMID:28051114

  19. Pharmacokinetic optimisation of antibacterial treatment in patients with cystic fibrosis. Current practice and suggestions for future directions

    NARCIS (Netherlands)

    Touw, D J; Vinks, A A; Mouton, J W; Horrevorts, A M

    1998-01-01

    Antibacterials play a central role in the medical management of patients with cystic fibrosis (CF). Administration of adequate dosages of antibacterials results in pronounced beneficial effects on the morbidity and mortality of this patient group. The dosage of the antibacterial that is needed for o

  20. Symbols: historic and current uses.

    Science.gov (United States)

    Bailey, Emilee

    2008-01-01

    From hieroglyphs to barcodes, symbols have been used throughout history. Symbols can be observed on traffic signs, warning signs that are affixed to building fronts, doors of public restrooms to show gender-specific usage, and caution signs on caustic or poisonous chemicals; even Braille, a system of writing and printing for the blind, is a symbol form. This article includes a brief discussion on the psychology of symbols, history of symbols, symbols used by alchemists and pharmacists, and the current use of symbols.

  1. Identification of key metabolic changes in renal interstitial fibrosis rats using metabonomics and pharmacology

    Science.gov (United States)

    Zhao, Liangcai; Dong, Minjian; Liao, Shixian; Du, Yao; Zhou, Qi; Zheng, Hong; Chen, Minjiang; Ji, Jiansong; Gao, Hongchang

    2016-01-01

    Renal fibrosis is one of the important pathways involved in end-stage renal failure. Investigating the metabolic changes in the progression of disease may enhance the understanding of its pathogenesis and therapeutic information. In this study, 1H-nuclear magnetic resonance (NMR)-based metabonomics was firstly used to screen the metabolic changes in urine and kidney tissues of renal interstitial fibrotic rats induced by unilateral ureteral obstruction (UUO), at 7, 14, 21, and 28 days after operation, respectively. The results revealed that reduced levels of bioenergy synthesis and branched chain amino acids (BCAAs), as well as elevated levels of indoxyl sulfate (IS) are involved in metabolic alterations of renal fibrosis rats. Next, by pharmacological treatment we found that reduction of IS levels could prevent the renal fibrotic symptoms. Therefore, we suggested that urinary IS may be used as a potential biomarker for the diagnosis of renal fibrosis, and a therapeutic target for drugs. Novel attempt combining metabonomics and pharmacology was established that have ability to provide more systematic diagnostic and therapeutic information of diseases. PMID:27256510

  2. Longitudinal Transient Elastography Measurements Used in Follow-up for Patients with Cystic Fibrosis.

    Science.gov (United States)

    Van Biervliet, Stephanie; Verdievel, Hugo; Vande Velde, Saskia; De Bruyne, Ruth; De Looze, Danny; Verhelst, Xavier; Geerts, Anja; Robberecht, Eddy; Van Vlierberghe, Hans

    2016-04-01

    Cystic fibrosis-related liver disease (CFLD) is diagnosed using a combination of criteria. Transient elastography (TE), an ultrasonographic method to evaluate liver stiffness, can differentiate patients with and without liver disease. This retrospective study (2007-2013) aimed to detect developing CFLD using consequent TE measurements. All cystic fibrosis patients with TE measurements between 2007 and 2013 (n = 150, median age 17 (9-24) y) were included, of which 118 had a median of three (range, 2-4) measurements with an interval of 1 (1-2) y. Twenty (14%) had CFLD at the first TE measurement; five (3%) developed CFLD during follow-up. The median TE value in CFLD was 14 kPa (8.7-32.2) compared with 5.3 (4.9-5.7) in cystic fibrosis patients without liver disease (CFnoLD; p = 0.0001). In CFnoLD, TE was correlated with age (p = 0.031). A TE result >6.8 kPa had a sensitivity of 91.5% and a specificity of 91.7% in predicting CFLD, according to the receiver operating characteristics analysis. It also has a positive predictive value of 88.6% and a negative predictive value of 86.9%, increasing to 91.7% and 98%, respectively, in patients at risk (<14 y) for developing CFLD. Patients with developing CFLD had progressively increasing consecutive TE measurements.

  3. Idiopathic pulmonary fibrosis: treatment update.

    LENUS (Irish Health Repository)

    O'Connell, Oisin J

    2011-11-01

    Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. Despite multiple recent clinical trials, there is no strong evidence supporting a survival advantage for any agent in the management of patients with IPF. The limited effectiveness of current treatment regimes has led to a search for novel therapies including antifibrotic strategies. This article reviews the evidence supporting the treatments currently used in the management of IPF.

  4. Pulmonary Fibrosis

    Science.gov (United States)

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This ... blood may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ...

  5. 细胞自噬在肝纤维化中的作用%Current perspectives on the role of autophagy in liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    丁剑波; 李秀惠

    2013-01-01

    细胞自噬是细胞内的一种代谢过程,通过细胞内的膜结构包裹部分胞质和细胞内需降解的细胞器、蛋白质等形成自噬小体,然后与溶酶体融合降解其所包裹内容物,其降解产物氨基酸、游离脂肪酸等可供细胞物质能量循环,细胞自噬在肝脏疾病的发生发展中有重要的作用,最近研究表明,细胞自噬可以通过降解脂滴为肝星状细胞的活化提供能量从而促进肝纤维化的发生.%Liver disease, especially liver fibrosis, remains a major health challenge in China. In order to develop effective preventive and therapeutic interventions of liver fibrosis, the related etiologies and key pathogenic mechanisms must be understood. Upon liver damage, the hepatic stellate cells (HSCs) are activated and secrete robust amounts of inflammatory cytokines and extracellular matrix proteins, leading to fibrosis. A recently recognized mediator of HSC activation is autophagy, a necessary metabolic process of protein cycling for energy production. More recently, however, a role for autophagy in HSC - mediated 1 ver fibrosis has been suggested. This review summarizes the reported evidence of increased autophagy and HSC activation in fibrosis and discusses the potential role of autophage - degraded lipid droplets as energy sources for activating HSCs. In addition, the review briefly highligh s the current research of autophagy and HSCs in relation to hepatitis virus infection, a major etiology of liver disease and fibrosis in China. By gaining a comprehensive and detailed understanding of the role of autophagy in liver disease, novel and improved therapies may be developed, targeting physiological pathways of the patients liver or immune system or of an invading pathogen, such as hepatitis virus replication.

  6. Extended-Interval Aminoglycoside Use in Cystic Fibrosis Exacerbation in Children and Young Adults

    Science.gov (United States)

    Safi, Khalid H.; Damiani, Justina M.; Sturza, Julie; Nasr, Samya Z.

    2016-01-01

    This is a prospective quality improvement project for patients with cystic fibrosis who are 5 years of age and older who were admitted for intravenous antibiotic administration as part of treatment of cystic fibrosis exacerbation. The goal of this project was to compare the pharmacokinetics of once-daily versus thrice-daily aminoglycoside use when treating cystic fibrosis exacerbation in different age groups. Of the total of 119 patient encounters, 82.4% were started on once-daily dosing, and the remainder were started on thrice-daily dosing. Patients with pharmacokinetics allowing the continuation of once-daily dosing differed from patients who required a switch to thrice-daily dosing in terms of baseline forced expiratory volume in 1 second, forced expiratory flow from 25% to 75% of vital capacity, age, and body mass index (BMI) but were similar in BMI percentiles. The once-daily dosing group had higher mean 18-hour level, higher mean half-life, higher mean area under the curve, and lower mean elimination constant. This study showed that aminoglycoside clearance is higher in younger children. PMID:27336007

  7. Analysis of disease-associated protein expression using quantitative proteomics—fibulin-5 is expressed in association with hepatic fibrosis.

    Science.gov (United States)

    Bracht, Thilo; Schweinsberg, Vincent; Trippler, Martin; Kohl, Michael; Ahrens, Maike; Padden, Juliet; Naboulsi, Wael; Barkovits, Katalin; Megger, Dominik A; Eisenacher, Martin; Borchers, Christoph H; Schlaak, Jörg F; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara

    2015-05-01

    Hepatic fibrosis and cirrhosis are major health problems worldwide. Until now, highly invasive biopsy remains the diagnostic gold standard despite many disadvantages. To develop noninvasive diagnostic assays for the assessment of liver fibrosis, it is urgently necessary to identify molecules that are robustly expressed in association with the disease. We analyzed biopsied tissue samples from 95 patients with HBV/HCV-associated hepatic fibrosis using three different quantification methods. We performed a label-free proteomics discovery study to identify novel disease-associated proteins using a subset of the cohort (n = 27). Subsequently, gene expression data from all available clinical samples were analyzed (n = 77). Finally, we performed a targeted proteomics approach, multiple reaction monitoring (MRM), to verify the disease-associated expression in samples independent from the discovery approach (n = 68). We identified fibulin-5 (FBLN5) as a novel protein expressed in relation to hepatic fibrosis. Furthermore, we confirmed the altered expression of microfibril-associated glycoprotein 4 (MFAP4), lumican (LUM), and collagen alpha-1(XIV) chain (COL14A1) in association to hepatic fibrosis. To our knowledge, no tissue-based quantitative proteomics study for hepatic fibrosis has been performed using a cohort of comparable size. By this means, we add substantial evidence for the disease-related expression of the proteins examined in this study.

  8. The use of transient elastography and non-invasive serum markers of fibrosis in pediatric liver transplant recipients.

    Science.gov (United States)

    Goldschmidt, Imeke; Stieghorst, Henrik; Munteanu, Mona; Poynard, Thierry; Schlue, Jerome; Streckenbach, Carolin; Baumann, Ulrich

    2013-09-01

    The use of non-invasive markers to diagnose liver allograft fibrosis is not well established in children after LTx. TE, FT, and ELF score were performed in 117 liver-transplanted children (60M, 8.9 [0.5-18.5] yr) and 336 healthy controls. Liver biopsy was available in 36 children. Results of histology and non-invasive markers were compared using correlation coefficient or Mann-Whitney U-test as appropriate. TE correlated best with histological degree of fibrosis (r = 0.85 vs. r = 0.04 [FT] or r = -0.38 [ELF]). Liver stiffness values for transplanted children without fibrosis were significantly higher than those of healthy controls (7.55 [5.4-20.4] kPa vs. 4.5 [2.5-8.9] kPa). Presence of rejection was a potent confounder for the performance of TE. Both TE and FT reflected clinical changes (acute rejection, cholestasis, increasing fibrosis) in a total of 16 patients who underwent serial measurements. TE correlates better with histological degree of fibrosis in liver-transplanted children than FT or ELF, but an individual baseline value needs to be determined for each patient. Normal or cutoff values for pathological degrees of fibrosis cannot be transferred from non-transplanted children. Follow-up studies, preferably with protocol biopsies, might help to improve the diagnostic quality of TE.

  9. Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia.

    Directory of Open Access Journals (Sweden)

    Valia Verrière

    Full Text Available Cystic Fibrosis (CF is a genetic disease characterised by a deficit in epithelial Cl(- secretion which in the lung leads to airway dehydration and a reduced Airway Surface Liquid (ASL height. The endogenous lipoxin LXA(4 is a member of the newly identified eicosanoids playing a key role in ending the inflammatory process. Levels of LXA(4 are reported to be decreased in the airways of patients with CF. We have previously shown that in normal human bronchial epithelial cells, LXA(4 produced a rapid and transient increase in intracellular Ca(2+. We have investigated, the effect of LXA(4 on Cl(- secretion and the functional consequences on ASL generation in bronchial epithelial cells obtained from CF and non-CF patient biopsies and in bronchial epithelial cell lines. We found that LXA(4 stimulated a rapid intracellular Ca(2+ increase in all of the different CF bronchial epithelial cells tested. In non-CF and CF bronchial epithelia, LXA(4 stimulated whole-cell Cl(- currents which were inhibited by NPPB (calcium-activated Cl(- channel inhibitor, BAPTA-AM (chelator of intracellular Ca(2+ but not by CFTRinh-172 (CFTR inhibitor. We found, using confocal imaging, that LXA(4 increased the ASL height in non-CF and in CF airway bronchial epithelia. The LXA(4 effect on ASL height was sensitive to bumetanide, an inhibitor of transepithelial Cl(- secretion. The LXA(4 stimulation of intracellular Ca(2+, whole-cell Cl(- currents, conductances and ASL height were inhibited by Boc-2, a specific antagonist of the ALX/FPR2 receptor. Our results provide, for the first time, evidence for a novel role of LXA(4 in the stimulation of intracellular Ca(2+ signalling leading to Ca(2+-activated Cl(- secretion and enhanced ASL height in non-CF and CF bronchial epithelia.

  10. Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia.

    LENUS (Irish Health Repository)

    2012-01-01

    Cystic Fibrosis (CF) is a genetic disease characterised by a deficit in epithelial Cl(-) secretion which in the lung leads to airway dehydration and a reduced Airway Surface Liquid (ASL) height. The endogenous lipoxin LXA(4) is a member of the newly identified eicosanoids playing a key role in ending the inflammatory process. Levels of LXA(4) are reported to be decreased in the airways of patients with CF. We have previously shown that in normal human bronchial epithelial cells, LXA(4) produced a rapid and transient increase in intracellular Ca(2+). We have investigated, the effect of LXA(4) on Cl(-) secretion and the functional consequences on ASL generation in bronchial epithelial cells obtained from CF and non-CF patient biopsies and in bronchial epithelial cell lines. We found that LXA(4) stimulated a rapid intracellular Ca(2+) increase in all of the different CF bronchial epithelial cells tested. In non-CF and CF bronchial epithelia, LXA(4) stimulated whole-cell Cl(-) currents which were inhibited by NPPB (calcium-activated Cl(-) channel inhibitor), BAPTA-AM (chelator of intracellular Ca(2+)) but not by CFTRinh-172 (CFTR inhibitor). We found, using confocal imaging, that LXA(4) increased the ASL height in non-CF and in CF airway bronchial epithelia. The LXA(4) effect on ASL height was sensitive to bumetanide, an inhibitor of transepithelial Cl(-) secretion. The LXA(4) stimulation of intracellular Ca(2+), whole-cell Cl(-) currents, conductances and ASL height were inhibited by Boc-2, a specific antagonist of the ALX\\/FPR2 receptor. Our results provide, for the first time, evidence for a novel role of LXA(4) in the stimulation of intracellular Ca(2+) signalling leading to Ca(2+)-activated Cl(-) secretion and enhanced ASL height in non-CF and CF bronchial epithelia.

  11. Exhaled breath analysis using electronic nose in cystic fibrosis and primary ciliary dyskinesia patients with chronic pulmonary infections

    DEFF Research Database (Denmark)

    Joensen, Odin; Paff, Tamara; Haarman, Eric G;

    2014-01-01

    The current diagnostic work-up and monitoring of pulmonary infections may be perceived as invasive, is time consuming and expensive. In this explorative study, we investigated whether or not a non-invasive exhaled breath analysis using an electronic nose would discriminate between cystic fibrosis...... (CF) and primary ciliary dyskinesia (PCD) with or without various well characterized chronic pulmonary infections. We recruited 64 patients with CF and 21 with PCD based on known chronic infection status. 21 healthy volunteers served as controls. An electronic nose was employed to analyze exhaled......, this method significantly discriminates CF patients suffering from a chronic pulmonary P. aeruginosa (PA) infection from CF patients without a chronic pulmonary infection. Further studies are needed for verification and to investigate the role of electronic nose technology in the very early diagnostic workup...

  12. Assessment of Myocardial Fibrosis in Mice Using a T2*-Weighted 3D Radial Magnetic Resonance Imaging Sequence.

    Directory of Open Access Journals (Sweden)

    Bastiaan J van Nierop

    Full Text Available Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI. Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis.To goal of this paper was to explore the use of a T2*-weighted radial sequence for the visualization of fibrosis in mouse heart.C57BL/6 mice were studied with MI (n = 20, replacement fibrosis, transverse aortic constriction (TAC (n = 18, diffuse fibrosis, and as control (n = 10. 3D center-out radial T2*-weighted images with varying TE were acquired in vivo and ex vivo (TE = 21 μs-4 ms. Ex vivo T2*-weighted signal decay with TE was analyzed using a 3-component model. Subtraction of short- and long-TE images was used to highlight fibrotic tissue with short T2*. The presence of fibrosis was validated using histology and correlated to MRI findings.Detailed ex vivo T2*-weighted signal analysis revealed a fast (T2*fast, slow (T2*slow and lipid (T2*lipid pool. T2*fast remained essentially constant. Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts. T2*slow correlated with the presence of diffuse fibrosis in TAC hearts (r = 0.82, P = 0.01. Ex vivo and in vivo subtraction images depicted a positive contrast in the infarct co-localizing with the scar. Infarct volumes from histology and subtraction images linearly correlated (r = 0.94, P<0.001. Region-of-interest analysis in the in vivo post-MI and TAC hearts revealed significant T2* shortening due to fibrosis, in agreement with the ex vivo results. However, in vivo contrast on subtraction images was rather poor

  13. Marijuana Use Is Not Associated With Progression to Advanced Liver Fibrosis in HIV/Hepatitis C Virus–coinfected Women

    Science.gov (United States)

    Kelly, Erin M.; Dodge, Jennifer L.; Sarkar, Monika; French, Audrey L.; Tien, Phyllis C.; Glesby, Marshall J.; Golub, Elizabeth T.; Augenbraun, Michael; Plankey, Michael; Peters, Marion G.

    2016-01-01

    Background. Marijuana (hereafter “tetrahydrocannabinol [THC]”) use has been associated with liver fibrosis progression in retrospective analyses of patients with chronic hepatitis C (HCV). We studied long-term effects of THC on fibrosis progression in women coinfected with human immunodeficiency virus (HIV)/HCV enrolled in the Women's Interagency HIV Study (WIHS). Methods. Liver fibrosis was categorized according to FIB-4 scores as none, moderate, or significant. THC and alcohol use were quantified as average exposure per week. Associations between THC use and progression to significant fibrosis were assessed using Cox proportional hazards regression. Results. Among 575 HIV/HCV-coinfected women followed for a median of 11 (interquartile range, 6–17) years, 324 (56%) reported no THC use, 141 (25%) less than weekly use, 70 (12%) weekly use, and 40 (7%) daily use at WIHS entry. In univariable analysis, entry FIB-4 score (hazard ratio [HR], 2.26 [95% confidence interval {CI}, 1.88–2.73], P < .001), log HCV RNA (HR, 1.19 [95% CI, 1.02–1.38], P = .02), tobacco use (HR, 1.37 [95% CI, 1.02–1.85], P = .04), CD4+ count (risk per 100-cell increase: HR, 0.90 [95% CI, .86–.95], P < .001), and log HIV RNA (HR, 1.18 [95% CI, 1.05–1.32], P = .005) were associated with progression to significant fibrosis, as was cumulative alcohol use in follow-up (HR, 1.03 [95% CI, 1.02–1.04], P < .001). In multivariable analysis, entry FIB-4, entry CD4+ count, and cumulative alcohol use remained significant. Cumulative THC use was not associated with fibrosis progression (HR, 1.01 [95% CI, .92–1.10], P = .83). Conclusions. In this large cohort of HIV/HCV-coinfected women, THC was not associated with progression to significant liver fibrosis. Alcohol use was independently associated with liver fibrosis, and may better predict fibrosis progression in HIV/HCV-coinfected women. PMID:27225241

  14. The potential of phage therapy in cystic fibrosis: Essential human-bacterial-phage interactions and delivery considerations for use in Pseudomonas aeruginosa-infected airways.

    Science.gov (United States)

    Trend, Stephanie; Fonceca, Angela M; Ditcham, William G; Kicic, Anthony; Cf, Arest

    2017-07-15

    As antimicrobial-resistant microbes become increasingly common and a significant global issue, novel approaches to treating these infections particularly in those at high risk are required. This is evident in people with cystic fibrosis (CF), who suffer from chronic airway infection caused by antibiotic resistant bacteria, typically Pseudomonas aeruginosa. One option is bacteriophage (phage) therapy, which utilises the natural predation of phage viruses upon their host bacteria. This review summarises the essential and unique aspects of the phage-microbe-human lung interactions in CF that must be addressed to successfully develop and deliver phage to CF airways. The current evidence regarding phage biology, phage-bacterial interactions, potential airway immune responses to phages, previous use of phages in humans and method of phage delivery to the lung are also summarised. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  15. Non-invasive molecular imaging of fibrosis using a collagen-targeted peptidomimetic of the platelet collagen receptor glycoprotein VI.

    Directory of Open Access Journals (Sweden)

    Julien Muzard

    Full Text Available BACKGROUND: Fibrosis, which is characterized by the pathological accumulation of collagen, is recognized as an important feature of many chronic diseases, and as such, constitutes an enormous health burden. We need non-invasive specific methods for the early diagnosis and follow-up of fibrosis in various disorders. Collagen targeting molecules are therefore of interest for potential in vivo imaging of fibrosis. In this study, we developed a collagen-specific probe using a new approach that takes advantage of the inherent specificity of Glycoprotein VI (GPVI, the main platelet receptor for collagens I and III. METHODOLOGY/PRINCIPAL FINDINGS: An anti-GPVI antibody that neutralizes collagen-binding was used to screen a bacterial random peptide library. A cyclic motif was identified, and the corresponding peptide (designated collagelin was synthesized. Solid-phase binding assays and histochemical analysis showed that collagelin specifically bound to collagen (Kd 10(-7 M in vitro, and labelled collagen fibers ex vivo on sections of rat aorta and rat tail. Collagelin is therefore a new specific probe for collagen. The suitability of collagelin as an in vivo probe was tested in a rat model of healed myocardial infarctions (MI. Injecting Tc-99m-labelled collagelin and scintigraphic imaging showed that uptake of the probe occurred in the cardiac area of rats with MI, but not in controls. Post mortem autoradiography and histological analysis of heart sections showed that the labeled areas coincided with fibrosis. Scintigraphic molecular imaging with collagelin provides high resolution, and good contrast between the fibrotic scars and healthy tissues. The capacity of collagelin to image fibrosis in vivo was confirmed in a mouse model of lung fibrosis. CONCLUSION/SIGNIFICANCE: Collagelin is a new collagen-targeting agent which may be useful for non-invasive detection of fibrosis in a broad spectrum of diseases.

  16. Endoscopic Ultrasound Elastography: Current Clinical Use in Pancreas.

    Science.gov (United States)

    Mondal, Utpal; Henkes, Nichole; Patel, Sandeep; Rosenkranz, Laura

    2016-08-01

    Elastography is a newer technique for the assessment of tissue elasticity using ultrasound. Cancerous tissue is known to be stiffer (hence, less elastic) than corresponding healthy tissue, and as a result, could be identified in an elasticity-based imaging. Ultrasound elastography has been used in the breast, thyroid, and cervix to differentiate malignant from benign neoplasms and to guide or avoid unnecessary biopsies. In the liver, elastography has enabled a noninvasive and reliable estimate of fibrosis. Endoscopic ultrasound has become a robust diagnostic and therapeutic tool for the management of pancreatic diseases. The addition of elastography to endoscopic ultrasound enabled further characterization of pancreas lesions, and several European and Asian studies have reported encouraging results. The current clinical role of endoscopic ultrasound elastography in the management of pancreas disorders and related literature are reviewed.

  17. Histopathological Examination may be Useful for Assessment of Fibrosis and Lipomatosis of Pancreas Allograft Prior to Solid Organ Transplantation.

    Science.gov (United States)

    Kajor, Maciej; Ziaja, Jacek; Liszka, Łukasz; Kostrząb-Zdebel, Anna; Właszczuk, Paweł; Karkoszka, Henryk; Sekta, Sylwia; Król, Robert; Cierpka, Lech

    2015-11-03

    The results of pancreas transplantation depend in a large degree on appropriate pancreas allograft donor selection. Several risk factors of early surgical complications or pancreas allograft loss following transplantation have been identified, but the final decision on pancreas harvesting for transplantation belongs to the surgeon. In the present study we aimed to assess whether histopathological examination may be utilized for detection of fibrosis and lipomatosis in tissue from a potential pancreas allograft. Additionally, we aimed to test whether presence of pancreatic fibrosis and lipomatosis may be explained solely by donor age and/or body mass index (BMI). Pancreata retrieved from 50 deceased organ donors referred to our institution and not transplanted between 2010 and 2013 were used for the present study. Tissue samples were excised from pancreata, fixed in formalin, and embedded in paraffin. Presence and intensity of pancreatic fibrosis and lipomatosis were assessed semi-quantitatively. Fibrosis was found in the majority of study samples (72%), but it was usually mild or moderate. Lipomatosis was present in 34% of the study cases. Presence of fibrosis was more frequent in older donors, but was still not rare in donors under 40 years old. Presence of lipomatosis did not seem to be significantly related to donor age. Neither pancreatic fibrosis nor lipomatosis was related to donor BMI. There is no clear relationship between histological parenchymal changes in potential pancreas allograft and donor age and BMI. Histopathological assessment of pancreatic fibrosis and/or lipomatosis can potentially facilitate decision making on pancreas allograft acceptance for solid organ transplantation.

  18. The Use of Buccal Fat Pad in the Treatment of Oral Submucous Fibrosis: A Newer Method

    Directory of Open Access Journals (Sweden)

    K. Saravanan

    2012-01-01

    Full Text Available Purpose of the study. This study was to evaluate the use of buccal fat pad as an interpositioning material in surgical management of oral sub mucous fibrosis. Materials and methods. A series of 8 cases with proven oral sub mucous fibrosis, with mouth opening less than 20 mm, involving the buccal mucosa were treated surgically in the Department of Oral and Maxillofacial Surgery, College of Dental Surgery, Saveetha University, Chennai. Pedicled buccal fat pad was used as an interpositioning material to cover the raw areas in the oral cavity after incision and release of fibrous bands. Results. In 8 patients, the range of pre operative mouth opening was 3–18 mm (mean 14 mm. As the result of the successful surgical procedure, the size of the intra operative mouth opening was ranged from 25–38 mm (mean 33.25 mm. The patients were discharged 5–7 days after the operation. The range of the mouth opening at this time was 25–36 mm (mean 30.63 mm. The results were evaluated using student’s t test and found to be statistically significant. The pedicled grafts took up uneventfull.

  19. Determination of right ventricular ejection fraction in children with cystic fibrosis, using krypton-81m

    Energy Technology Data Exchange (ETDEWEB)

    Piepsz, A.; Ham, H.R.; Millet, E.; Dab, I.

    1984-01-01

    The diagnosis of cor pulmonale and incipient heart failure remains difficult to assess in cystic fibrosis (CF) on the basis of the clinical as well as the biological parameters. The measurement of the right ventricular ejection fraction has been facilitated these last years by the introduction of the radionuclide methods. Methodological difficulties are however encountered when Tc-99m RBC are used, and are mainly related to heart chambers superposition (equilibrium method) or the low count density (first pass method). Few papers have been published on RVEF in cystic fibrosis and the results are somewhat contradictory. The authors have recently introduced a new method for the determination of RVEF, using equilibrium study during continuous injection of Kr-81m in glucose solution. This method offers several advantages related to an increased accuracy and a favorable dosimetry. In 25 patients aged 2 to 23 years with CF, one or more RVEF studies were performed. The severity of the disease was evaluated on the basis of the clinical Schwachman score, the lung function tests, the ventilation scan and the pa02. RVEF tended to decrease with the progression of the lung disease, although, owing to the spread of the results, no RVEF could be predicted on the basis of the other parameters. The decrease of RVEF in patients with advanced lung disease was moderate and terminal lung disease was sometimes associated with normal right heart contractility.

  20. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis.

    Science.gov (United States)

    Dekkers, Johanna F; Berkers, Gitte; Kruisselbrink, Evelien; Vonk, Annelotte; de Jonge, Hugo R; Janssens, Hettie M; Bronsveld, Inez; van de Graaf, Eduard A; Nieuwenhuis, Edward E S; Houwen, Roderick H J; Vleggaar, Frank P; Escher, Johanna C; de Rijke, Yolanda B; Majoor, Christof J; Heijerman, Harry G M; de Winter-de Groot, Karin M; Clevers, Hans; van der Ent, Cornelis K; Beekman, Jeffrey M

    2016-06-22

    Identifying subjects with cystic fibrosis (CF) who may benefit from cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs is time-consuming, costly, and especially challenging for individuals with rare uncharacterized CFTR mutations. We studied CFTR function and responses to two drugs-the prototypical CFTR potentiator VX-770 (ivacaftor/KALYDECO) and the CFTR corrector VX-809 (lumacaftor)-in organoid cultures derived from the rectal epithelia of subjects with CF, who expressed a broad range of CFTR mutations. We observed that CFTR residual function and responses to drug therapy depended on both the CFTR mutation and the genetic background of the subjects. In vitro drug responses in rectal organoids positively correlated with published outcome data from clinical trials with VX-809 and VX-770, allowing us to predict from preclinical data the potential for CF patients carrying rare CFTR mutations to respond to drug therapy. We demonstrated proof of principle by selecting two subjects expressing an uncharacterized rare CFTR genotype (G1249R/F508del) who showed clinical responses to treatment with ivacaftor and one subject (F508del/R347P) who showed a limited response to drug therapy both in vitro and in vivo. These data suggest that in vitro measurements of CFTR function in patient-derived rectal organoids may be useful for identifying subjects who would benefit from CFTR-correcting treatment, independent of their CFTR mutation.

  1. Inhibition of hepatic fibrosis with artificial microRNA using ultrasound and cationic liposome-bearing microbubbles.

    Science.gov (United States)

    Yang, D; Gao, Y-H; Tan, K-B; Zuo, Z-X; Yang, W-X; Hua, X; Li, P-J; Zhang, Y; Wang, G

    2013-12-01

    We sought to investigate the antifibrotic effects of an artificial microRNA (miRNA) targeting connective tissue growth factor (CTGF) using the ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system. Cationic liposomes were conjugated with microbubbles using a biotin-avidin system. Plasmids carrying the most effective artificial miRNA sequences were delivered by ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system to rats with hepatic fibrosis. The results show that this method of gene delivery effectively transported the plasmids to the rat liver. The artificial miRNA reduced hepatic fibrosis pathological alterations as well as the protein and mRNA expressions of CTGF and transforming growth factor β1. Furthermore, the CTGF gene silencing decreased the levels of type I collagen and α-smooth muscle actin (Pliposome-bearing microbubble destruction may be an efficacious therapeutic method to ameliorate hepatic fibrosis.

  2. Use and sanctification of complementary and alternative medicine by parents of children with cystic fibrosis.

    Science.gov (United States)

    Grossoehme, Daniel H; Cotton, Sian; McPhail, Gary

    2013-01-01

    Complementary and alternative medicine (CAM) use, including spiritual modalities, is common in pediatric chronic diseases. However, few users discuss CAM treatments with their child's physician. Semi-structured interviews of 25 parents of children who have cystic fibrosis (CF) were completed. Primary themes were identified by thematic analyses. Most parents (19/25) used at least one CAM modality with their child. Only two reported discussing CAM use with their child's pulmonologist. Most reported prayer as helpful (81%) and multi-faceted, including individual and group prayer; using aromatherapy or scented candles as an adjunct for relaxation; and the child's sleeping with a blessed prayer. Parents ascribed sacred significance to natural oral supplements. CAM use is relevant to the majority of participating parents of children under age 13 with CF. Chaplains can play a significant role by reframing prayer's integration into chronic disease care, co-creating rituals with pediatric patients, and mediating conversations between parents and providers.

  3. Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach.

    Science.gov (United States)

    Zobell, Jeffery T; Epps, Kevin; Kittell, Frederick; Sema, Clarissa; McDade, Erin J; Peters, Stacy J; Duval, Mariela A; Pettit, Rebecca S

    2016-01-01

    Survey suggests that recommended doses and dosage regimens for antipseudomonal antibiotics for the treatment of acute pulmonary exacerbations in cystic fibrosis (CF) patients are not used, and one way to address these disparities is the involvement of pharmacists who are dedicated to CF. This is the first survey specifically designed for pharmacists at Cystic Fibrosis Foundation (CFF)-accredited centers to identify how tobramycin and antipseudomonal beta-lactams are being used. The purpose of this survey is to quantify this information and to promote future study to allow for implementation of tobramycin and beta-lactam dosage and monitoring standardization. An anonymous national cross-sectional survey of pharmacists that are affliated with CFF-accredited programs was performed using Qualtrics.com. The survey had a 48.5% response rate. Most pediatric pharmacists (78.6%) report using extended-interval tobramycin dosage. The most common reported starting dosage was 10 mg/kg every 24 hours; most centers aim for a maximum serum concentration (Cmax) between 20 and 40 mg/L (78.6%). A total of 26 adult pharmacists reported using extended-interval dosage (96%), using an initial dosage of 10 mg/kg/day. The most common parameters used to adjust dosage were Cmax and area under the curve (AUC; 31%); the Cmax goal was 20 to 40 mg/L (84.2%). Most respondents (79%) report using beta-lactams in combination with tobramycin. Extended-infusion and continuous-infusion beta-lactams were used more in adults than pediatric patients. Most CF pharmacists report using extended-interval tobramycin. With the information from this survey, the establishment of future consensus recommendations by pharmacists for optimal and consistent tobramycin and antipseudomonal beta-lactam dosage and monitoring strategies needs to be considered.

  4. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

    NARCIS (Netherlands)

    Dekkers, Johanna F; Berkers, Gitte; Kruisselbrink, Evelien; Vonk, Annelotte; de Jonge, Hugo R; Janssens, Hettie M; Bronsveld, Inez; van de Graaf, Eduard A; Nieuwenhuis, Edward E S; Houwen, Roderick H J; Vleggaar, Frank P; Escher, Johanna C; de Rijke, Yolanda B; Majoor, Christof J; Heijerman, Harry G M; de Winter-de Groot, Karin M; Clevers, Hans; van der Ent, Cornelis K; Beekman, Jeffrey M

    2016-01-01

    Identifying subjects with cystic fibrosis (CF) who may benefit from cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs is time-consuming, costly, and especially challenging for individuals with rare uncharacterized CFTR mutations. We studied CFTR function and responses to tw

  5. Clostridium difficile Infection and Proton Pump Inhibitor Use in Hospitalized Pediatric Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    John F. Pohl

    2011-01-01

    Full Text Available Children with cystic fibrosis (CF often take proton pump inhibitors (PPIs, which helps improve efficacy of fat absorption with pancreatic enzyme replacement therapy. However, PPI use is known to be associated with Clostridium difficile-(C. diff- associated diarrhea (CDAD. We retrospectively evaluated the incidence of C. diff infection from all pediatric hospital admissions over a 5-year period at a single tertiary children's hospital. We found significantly more C. diff-positive stool tests in hospitalized patients with CF compared to patients with no diagnosis of CF. However, use of a PPI was not associated with an increased risk of CDAD in hospitalized CF patients. In summary, C. diff infection is more common in hospitalized pediatric CF patients although PPI use may not be a risk factor for CDAD development in this patient population.

  6. Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Erin Shammel; Burnum-Johnson, Kristin E.; Jacobs, Jon M.; Diamond, Deborah L.; Brown, Roslyn N.; Ibrahim, Yehia M.; Orton, Daniel J.; Piehowski, Paul D.; Purdy, David E.; Moore, Ronald J.; Danielson, William F.; Monroe, Matthew E.; Crowell, Kevin L.; Slysz, Gordon W.; Gritsenko, Marina A.; Sandoval, John D.; Lamarche, Brian L.; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Simons, Brenna C.; McMahon, Brian J.; Bhattacharya, Renuka; Perkins, James D.; Carithers, Robert L.; Strom, Susan; Self, Steven; Katze, Michael G.; Anderson, Gordon A.; Smith, Richard D.

    2014-04-01

    Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is an imperative goal for the field of medicine. While mass spectrometry (MS)-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry (IMS) separations [1, 2] with liquid chromatography (LC) and MS to dramatically increase measurement sensitivity and throughput, further enabling future MS-based clinical applications. An initial application of the LC-IMS-MS platform for the analysis of blood serum samples from stratified post-liver transplant patients with recurrent fibrosis progression illustrates its potential utility for disease characterization and use in personalized medicine [3, 4].

  7. Clostridium difficile Infection and Proton Pump Inhibitor Use in Hospitalized Pediatric Cystic Fibrosis Patients.

    Science.gov (United States)

    Pohl, John F; Patel, Raza; Zobell, Jeffery T; Lin, Ellen; Korgenski, E Kent; Crowell, Kody; Mackay, Mark W; Richman, Aleesha; Larsen, Christian; Chatfield, Barbara A

    2011-01-01

    Children with cystic fibrosis (CF) often take proton pump inhibitors (PPIs), which helps improve efficacy of fat absorption with pancreatic enzyme replacement therapy. However, PPI use is known to be associated with Clostridium difficile-(C. diff-) associated diarrhea (CDAD). We retrospectively evaluated the incidence of C. diff infection from all pediatric hospital admissions over a 5-year period at a single tertiary children's hospital. We found significantly more C. diff-positive stool tests in hospitalized patients with CF compared to patients with no diagnosis of CF. However, use of a PPI was not associated with an increased risk of CDAD in hospitalized CF patients. In summary, C. diff infection is more common in hospitalized pediatric CF patients although PPI use may not be a risk factor for CDAD development in this patient population.

  8. The cost-effectiveness of neonatal screening for Cystic Fibrosis: an analysis of alternative scenarios using a decision model

    Directory of Open Access Journals (Sweden)

    Tu Karen

    2005-08-01

    Full Text Available Abstract Background The use of neonatal screening for cystic fibrosis is widely debated in the United Kingdom and elsewhere, but the evidence available to inform policy is limited. This paper explores the cost-effectiveness of adding screening for cystic fibrosis to an existing routine neonatal screening programme for congenital hypothyroidism and phenylketonuria, under alternative scenarios and assumptions. Methods The study is based on a decision model comparing screening to no screening in terms of a number of outcome measures, including diagnosis of cystic fibrosis, life-time treatment costs, life years and QALYs gained. The setting is a hypothetical UK health region without an existing neonatal screening programme for cystic fibrosis. Results Under initial assumptions, neonatal screening (using an immunoreactive trypsin/DNA two stage screening protocol costs £5,387 per infant diagnosed, or £1.83 per infant screened (1998 costs. Neonatal screening for cystic fibrosis produces an incremental cost-effectiveness of £6,864 per QALY gained, in our base case scenario (an assumed benefit of a 6 month delay in the emergence of symptoms. A difference of 11 months or more in the emergence of symptoms (and mean survival means neonatal screening is both less costly and produces better outcomes than no screening. Conclusion Neonatal screening is expensive as a method of diagnosis. Neonatal screening may be a cost-effective intervention if the hypothesised delays in the onset of symptoms are confirmed. Implementing both antenatal and neonatal screening would undermine potential economic benefits, since a reduction in the birth incidence of cystic fibrosis would reduce the cost-effectiveness of neonatal screening.

  9. Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry*

    Science.gov (United States)

    Baker, Erin Shammel; Burnum-Johnson, Kristin E.; Jacobs, Jon M.; Diamond, Deborah L.; Brown, Roslyn N.; Ibrahim, Yehia M.; Orton, Daniel J.; Piehowski, Paul D.; Purdy, David E.; Moore, Ronald J.; Danielson, William F.; Monroe, Matthew E.; Crowell, Kevin L.; Slysz, Gordon W.; Gritsenko, Marina A.; Sandoval, John D.; LaMarche, Brian L.; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Simons, Brenna C.; McMahon, Brian J.; Bhattacharya, Renuka; Perkins, James D.; Carithers, Robert L.; Strom, Susan; Self, Steven G.; Katze, Michael G.; Anderson, Gordon A.; Smith, Richard D.

    2014-01-01

    Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography - ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization. PMID:24403597

  10. Advancing the high throughput identification of liver fibrosis protein signatures using multiplexed ion mobility spectrometry.

    Science.gov (United States)

    Baker, Erin Shammel; Burnum-Johnson, Kristin E; Jacobs, Jon M; Diamond, Deborah L; Brown, Roslyn N; Ibrahim, Yehia M; Orton, Daniel J; Piehowski, Paul D; Purdy, David E; Moore, Ronald J; Danielson, William F; Monroe, Matthew E; Crowell, Kevin L; Slysz, Gordon W; Gritsenko, Marina A; Sandoval, John D; Lamarche, Brian L; Matzke, Melissa M; Webb-Robertson, Bobbie-Jo M; Simons, Brenna C; McMahon, Brian J; Bhattacharya, Renuka; Perkins, James D; Carithers, Robert L; Strom, Susan; Self, Steven G; Katze, Michael G; Anderson, Gordon A; Smith, Richard D

    2014-04-01

    Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography--ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization.

  11. Problem behaviours, caregiver mental health symptoms and health service use in Australian children with cystic fibrosis: a prospective cohort study

    OpenAIRE

    Sheehan, Jane

    2017-01-01

    Background: Cystic fibrosis (CF) is an inherited, recessive condition, primarily affecting the respiratory and digestive systems. The current median life expectancy for adults with CF is approximately 37 years. Children with CF endure an intensive daily treatment regimen including dietary requirements, pancreatic enzyme replacements, vitamin supplementation, regular antibiotics, and airway clearance, in order to maintain their health status and reduce CF symptoms. The treatment regimen is ...

  12. Using polarization-sensitive optical coherence tomography to identify tumor stromal fibrosis and increase tumor biopsy yield (Conference Presentation)

    Science.gov (United States)

    Hariri, Lida P.; Adams, David C.; Miller, Alyssa J.; Mino-Kenudson, Mari; Suter, Melissa J.

    2016-03-01

    Tissue biopsy is the principal method used to diagnose tumors in a variety of organ systems. It is essential to maximize tumor yield in biopsy specimens for both clinical diagnostic and research purposes. This is particularly important in tumors where additional tissue is needed for molecular analysis to identify patients who would benefit from mutation-specific targeted therapy, such as in lung carcinomas. Inadvertent sampling of fibrotic stroma within tumor nodules contaminates biopsies, decreases tumor yield, and can impede diagnosis. The ability to assess tumor composition and guide biopsy site selection in real time is likely to improve diagnostic yield. Polarization sensitive OCT (PS-OCT) measures birefringence in organized tissues, such as collagen, and could be used to distinguish tumor from fibrosis. In this study, PS-OCT was obtained in 65 lung nodule samples from surgical resection specimens containing varying ratios of tumor and fibrosis. PS-OCT was obtained with either a custom-built helical scanning catheter (0.8 or 1.6mm in diameter) or a dual-axis bench top scanner. Strong birefringence was observed in nodules containing dense fibrosis, with no birefringence in adjacent regions of tumor. Tumors admixed with early, loosely-organized collagen demonstrated mild-to-moderate birefringence, and tumors with little collagen content showed little to no birefringent signal. PS-OCT provides significant insights into tumor nodule composition, and has potential to differentiate tumor from stromal fibrosis during biopsy site selection to increase diagnostic tumor yield.

  13. Separation of advanced from mild fibrosis in diffuse liver disease using {sup 31}P magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Noren, Bengt [Department of Radiology, Linkoeping University, SE-581 85 Linkoeping (Sweden); Dahlqvist, Olof [Department of Radiation Physics, Linkoeping University, SE-581 85 Linkoeping (Sweden); Center for Medical Image Science and Visualization (CMIV), Linkoeping University, SE-581 85 Linkoeping (Sweden); Lundberg, Peter [Department of Radiology, Linkoeping University, SE-581 85 Linkoeping (Sweden); Department of Radiation Physics, Linkoeping University, SE-581 85 Linkoeping (Sweden); Center for Medical Image Science and Visualization (CMIV), Linkoeping University, SE-581 85 Linkoeping (Sweden)], E-mail: Peter.Lundberg@imv.liu.se; Almer, Sven [Department of Gastroenterology and Hepatology, Linkoeping University, SE-581 85 Linkoeping (Sweden); Kechagias, Stergios [Department of Internal Medicine, Linkoeping University, SE-581 85 Linkoeping (Sweden); Ekstedt, Mattias [Department of Gastroenterology and Hepatology, Linkoeping University, SE-581 85 Linkoeping (Sweden); Franzen, Lennart [Medilab, SE-183 53 Taeby Sweden (Sweden); Wirell, Staffan [Department of Radiology, Linkoeping University, SE-581 85 Linkoeping (Sweden); Smedby, Orjan [Department of Radiology, Linkoeping University, SE-581 85 Linkoeping (Sweden); Center for Medical Image Science and Visualization (CMIV), Linkoeping University, SE-581 85 Linkoeping (Sweden)

    2008-05-15

    {sup 31}P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, {gamma}ATP, {alpha}ATP, {beta}ATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation (n = 13), and one group with severe fibrosis or cirrhosis (n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n = 13) was also included. Absolute concentrations and the anabolic charge, AC = {l_brace}PME{r_brace}/({l_brace}PME{r_brace} + {l_brace}PDE{r_brace}), were calculated. Comparing the control and cirrhosis groups, lower concentrations of PDE (p = 0.025) and a higher AC (p < 0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE (p = 0.01) and a higher AC (p = 0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0-1 and stage F4 and in AC between stage F0-1 and stage F2-3. Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild, F0-2, and advanced, F3-4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%. In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.

  14. Assessment of Liver Fibrosis with Diffusion-Weighted Magnetic Resonance Imaging Using Different b-values in Chronic Viral Hepatitis.

    Science.gov (United States)

    Kocakoc, Ercan; Bakan, Ayse Ahsen; Poyrazoglu, Orhan Kursat; Dagli, Adile Ferda; Gul, Yeliz; Cicekci, Mehtap; Bahcecioglu, Ibrahim Halil

    2015-01-01

    To examine the effectiveness of apparent diffusion coefficient (ADC) values and to compare the reliability of different b-values in detecting and identifying significant liver fibrosis. There were 44 patients with chronic viral hepatitis (CVH) in the study group and 30 healthy participants in the control group. Diffusion-weighted magnetic resonance imaging (DWI) was performed before the liver biopsy in patients with CVH. The values of ADC were measured with 3 different b-values (100, 600, 1,000 s/mm2). In addition, liver fibrosis was classified using the modified Ishak scoring system. Liver fibrosis stages and ADC values were compared using areas under the receiver-operating characteristic (ROC) curve. The study group's mean ADC value was not statistically significantly different from the control group's mean ADC value at b = 100 s/mm2 (3.69 ± 0.5 × 10-3 vs. 3.7 ± 0.3 × 10-3 mm2/s) and b = 600 s/mm2 (2.40 ± 0.3 × 10-3 vs. 2.5 ± 0.5 × 10-3 mm2/s). However, the study group's mean ADC value (0.99 ± 0.3 × 10-3 mm2/s) was significantly lower than that of the control group (1.2 ± 0.1 × 10-3 mm2/s) at b = 1,000 s/mm2. With b = 1,000 s/mm2 and the cutoff ADC value of 0.0011 mm2/s for the diagnosis of liver fibrosis, the mean area under the ROC curve was 0.702 ± 0.07 (p = 0.0015). For b = 1,000 s/mm2 and the cutoff ADC value of 0.0011 mm2/s to diagnose significant liver fibrosis (Ishak score = 3), the mean area under the ROC curve was 0.759 ± 0.07 (p = 0.0001). Measurement of ADC values by DWI was effective in detecting liver fibrosis and accurately identifying significant liver fibrosis when a b-value of 1,000 s/mm2 was used. © 2015 S. Karger AG, Basel.

  15. Pathological assessment of liver fibrosis regression

    Directory of Open Access Journals (Sweden)

    WANG Bingqiong

    2017-03-01

    Full Text Available Hepatic fibrosis is the common pathological outcome of chronic hepatic diseases. An accurate assessment of fibrosis degree provides an important reference for a definite diagnosis of diseases, treatment decision-making, treatment outcome monitoring, and prognostic evaluation. At present, many clinical studies have proven that regression of hepatic fibrosis and early-stage liver cirrhosis can be achieved by effective treatment, and a correct evaluation of fibrosis regression has become a hot topic in clinical research. Liver biopsy has long been regarded as the gold standard for the assessment of hepatic fibrosis, and thus it plays an important role in the evaluation of fibrosis regression. This article reviews the clinical application of current pathological staging systems in the evaluation of fibrosis regression from the perspectives of semi-quantitative scoring system, quantitative approach, and qualitative approach, in order to propose a better pathological evaluation system for the assessment of fibrosis regression.

  16. Radioimmunotherapy Using Vascular Targeted 213Bi: The Role of TNF-Alpha in the Development of Pulmonary Fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Davis, I.A.; Kennel, S.J.

    1998-10-14

    A monoclonal antibody (201B) specific to murine thrombomodulin, covalently linked to CHX-b-DTPA, successfully delivers chelated 213Bi, an {alpha}-particle emitter, (213Bi-201B) rapidly to lungvascular endothelium. When injected at doses of l MBq/mouse, 213Bi-201B destroyed most of the 100 colonies of EMT-6 mammary carcinomas growing as lung tumors of up to 2000 cells/colony. Some mice were cured of lung tumors and others had extended life-spans compared to untreated control animals but eventually succumbed to tumor recurrence. At injected doses of 4-6 MBq/mouse, 100% of lung tumor colonies were eliminated; however, 3-4 months later these mice developed pulmonary fibrosis and died. The mechanisms leading to the fibrotic response in other pulmonary irradiation models strongly implicate tumor necrosis factor-alpha (TNF-{alpha}), released from damaged tissues, as the pivotal inflammatory cytokine in a cascade of events which culminate in fibrosis. Attempts to prevent the development of pulmonary fibrosis, by using antibodies or soluble receptor (Enbrel{trademark}) as inhibitors of TNF-{alpha}, were unsuccessful. Additionally, mice genetically deficient for TNF-{alpha} production developed pulmonary fibrosis following 213Bi-201B treatment. Interestingly, non-tumor bearing BALB/c mice receiving Enbrel{trademark} or mice genetically deficient in TNF-{alpha} production and treated with 213Bi-201B, had significantly reduced life spans compared to mice receiving no treatment or 213Bi-201B alone. We speculate that, in normal mice, while TNF-{alpha} may induce an inflammatory response following {alpha}-particle radiation mediated tumor clearance and pulmonary damage, its effects in the post-tumor clearance time period may actually retard the development of fibrosis.

  17. Noninvasive assessment of hepatic fibrosis in patients with chronic hepatic B viral Infection using magnetic resonance elastography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Eun [Dept. of Radiology, Chungnam National University Hospital, Daejeon (Korea, Republic of); Lee, Jeong Min; Yoon, Jeong Hee; Shin, Cheong Il; Han, Joon Koo; Choi, Byung Ihn [Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Kyung Bun [Dept. of Pathology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2014-04-15

    To evaluate the diagnostic performance of magnetic resonance elastography (MRE) for staging hepatic fibrosis in patients with chronic hepatitis B virus (HBV) infection. Patients with chronic HBV infection who were suspected of having focal or diffuse liver diseases (n = 195) and living donor candidates (n = 166) underwent MRE as part of the routine liver MRI examination. We measured liver stiffness (LS) values on quantitative shear stiffness maps. The technical success rate of MRE was then determined. Liver cell necroinflammatory activity and fibrosis were assessed using histopathologic examinations as the reference. Areas under the receiver operating characteristic curve (Az) were calculated in order to predict the liver fibrosis stage. The technical success rate of MRE was 92.5% (334/361). The causes of technical failure were poor wave propagation (n = 12), severe respiratory motion (n = 3), or the presence of iron deposits in the liver (n = 12). The mean LS values, as measured by MRE, increased significantly along with an increase in the fibrosis stage (r = 0.901, p < 0.001); however, the mean LS values did not increase significantly along with the degree of necroinflammatory activity. The cutoff values of LS for ≥ F1, ≥ F2, ≥ F3, and F4 were 2.45 kPa, 2.69 kPa, 3.0 kPa, and 3.94 kPa, respectively, and with Az values of 0.987-0.988. MRE has a high technical success rate and excellent diagnostic accuracy for staging hepatic fibrosis in patients with chronic HBV infection.

  18. Molecular Diagnosis of Cystic Fibrosis.

    Science.gov (United States)

    Deignan, Joshua L; Grody, Wayne W

    2016-01-01

    This unit describes a recommended approach to identifying causal genetic variants in an individual suspected of having cystic fibrosis. An introduction to the genetics and clinical presentation of cystic fibrosis is initially presented, followed by a description of the two main strategies used in the molecular diagnosis of cystic fibrosis: (1) an initial targeted variant panel used to detect only the most common cystic fibrosis-causing variants in the CFTR gene, and (2) sequencing of the entire coding region of the CFTR gene to detect additional rare causal CFTR variants. Finally, the unit concludes with a discussion regarding the analytic and clinical validity of these approaches.

  19. Aggrandizing oral submucous fibrosis grading using an adjunct special stain: A pilot study

    Directory of Open Access Journals (Sweden)

    V Reshma

    2016-01-01

    Full Text Available Introduction: Oral submucous fibrosis (OSMF is graded according to various histological factors which include the epithelial changes and the connective tissue changes. These features though could be identified in routine hematoxylin and eosin (H and E staining; they could be better appreciated in special stains. This pilot study is an attempt to identify a single special stain that can act as an adjunct to H and E stain to help grade this potentially malignant disease. Aims and Objectives: To assess if special stains can improvise on differentiating the various histological changes seen in OSMF and to accordingly grade OSMF cases. Materials and Methods: Formalin-fixed paraffin-embedded tissue sections of OSMF-10 cases of each grade (n = 30. Three special stains: Van-Gieson, Mallory′s trichrome and Masson trichrome. Statistical Analysis: The results obtained were tabulated and statistically analyzed using Chi-square test. Observations and Results: The thickness and degree of keratinization were best detected in Mallory′s stain (100% and were statistically significant; the subepithelial changes were better detected using special stains, especially Mallory′s stain (100%. The changes in collagen fibers were better visualized in all three special stains but were not statistically significant. The changes in blood vessels were better detected in Van-Gieson′s and Mallory′s stain; the obtained results were statistically significant. The degree of fibrosis between muscle bundles could be detected in all the three special stains, but when compared the results were not statistically significant. The questionable areas of muscle degeneration, especially in deeper connective tissue were better detected in Mallory′s (43% and Masson′s stain (43% as compared to Van-Gieson stain (14% and the results obtained were statistically significant. The inflammatory cells and dysplastic features are better visualized in routine H and E stains. Conclusion

  20. Establishment of a standardized mouse model of hepatic fibrosis for biomedical research

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    Hai Nhung Truong

    2014-02-01

    Full Text Available Liver injury causes nodule and scar tissue formation and diffuse fibrosis, which are characteristic of liver cirrhosis. Since there are currently no efficacious therapies to prevent fibrosis, the development of animal models of liver fibrosis is necessary to facilitate further in vivo studies of this pathology. In this study, a mouse model of liver fibrosis was generated using Swiss mice and carbon tetrachloride (CCl4 treatment. Induction of liver fibrosis was analyzed using 0.8, 1.0, or 1.2 mL/kg CCl4 to determine the effective dose. In this study, we aimed to develop a standardized hepatic fibrosis mouse model by using CCl4 induction to facilitate further studies in this field. In Swiss mice, we evaluated the dose of CCl4 and the criteria of fibrosis, such as serum markers, fibrosis marker genes, and histopathology. Mice were administered CCl4 three times per week for 8 consecutive weeks. Body weights, survival rates, levels of serum markers (aspartate aminotransferase/alanine aminotransferase [AST/ALT] and fibrosis markers (fibronectin, procollagen, nt5e, transforming growth factor-beta [TGF-beta], and integrin, and histopathology (using hematoxylin and eosin [H and E] staining were analyzed to determine the optimal dose of CCl4 for induction of liver fibrosis. Results showed that 1.0 mL/kg CCl4 was the most efficient dose for the establishment of a liver fibrosis mouse model. In a standardized liver fibrosis model, mice were treated with 1.0 mL/kg CCl4 three times per week for 11 consecutive weeks, and levels of serum markers (AST, ALT, bilirubin, and albumin, expression of fibrosis marker genes (using quantitative reverse transcription polymerase chain reaction [RT-PCR], histopathology (using Hematoxylin and eosin staining, and connective tissue formation (using Massive trichrome staining were analyzed. The outcomes showed that serum markers and the levels of fibrosis marker genes were significantly increased in the standardized liver

  1. Establishment of a standardized mouse model of hepatic fibrosis for biomedical research

    Directory of Open Access Journals (Sweden)

    Hai Nhung Truong

    2014-05-01

    Full Text Available Liver injury causes nodule and scar tissue formation and diffuse fibrosis, which are characteristic of liver cirrhosis. Since there are currently no efficacious therapies to prevent fibrosis, the development of animal models of liver fibrosis is necessary to facilitate further in vivo studies of this pathology. In this study, a mouse model of liver fibrosis was generated using Swiss mice and carbon tetrachloride (CCl4 treatment. Induction of liver fibrosis was analyzed using 0.8, 1.0, or 1.2 mL/kg CCl4 to determine the effective dose. In this study, we aimed to develop a standardized hepatic fibrosis mouse model by using CCl4 induction to facilitate further studies in this field. In Swiss mice, we evaluated the dose of CCl4 and the criteria of fibrosis, such as serum markers, fibrosis marker genes, and histopathology. Mice were administered CCl4 three times per week for 8 consecutive weeks. Body weights, survival rates, levels of serum markers (aspartate aminotransferase/alanine aminotransferase [AST/ALT] and fibrosis markers (fibronectin, procollagen, nt5e, transforming growth factor-beta [TGF-β], and integrin, and histopathology (using hematoxylin and eosin [H&E] staining were analyzed to determine the optimal dose of CCl4 for induction of liver fibrosis. Results showed that 1.0 mL/kg CCl4 was the most efficient dose for the establishment of a liver fibrosis mouse model. In a standardized liver fibrosis model, mice were treated with 1.0 mL/kg CCl4 three times per week for 11 consecutive weeks, and levels of serum markers (AST, ALT, bilirubin, and albumin, expression of fibrosis marker genes (using quantitative reverse transcription polymerase chain reaction [RT-PCR], histopathology (using Hematoxylin and eosin staining, and connective tissue formation (using Massive trichrome staining were analyzed. The outcomes showed that serum markers and the levels of fibrosis marker genes were significantly increased in the standardized liver fibrosis

  2. Using the internet to exchange information and experience on cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Ellen Dayane Cargnin Pimentel

    2013-12-01

    Full Text Available Objective. Describing the experience of patients with cystic fibrosis (CF and their families using the internet as a means for information, interaction and exchange of experiences with this disease. Methodology. A descriptive qualitative exploratory study was carried out in 2011. The subjects of the study were patients with CF and their parents or other family members contacted via e-mail on social networking websites. The requested information included the guiding question: ''Tell me about your experience on the internet as a means of information and exchange of experiences involving CF'', as well as demographic information and whether the respondent was the patient or a family member. Results. A total of 40 invitations were sent by email asking for information and 22 were accepted (55%. According to participants (15 patients and seven family members, the most widely used internet media were websites related to seeking information about CF. The use of internet was divided in three categories: 1 scientific and technical aspects, 2 emotional aspects, and c modes of disseminating information. Conclusion. The internet proved to be a medium of opinion formation which could eventually replace medical advice. It is necessary to establish criteria for constructing and monitoring information related to CF published on internet websites.

  3. In vitro prevention of Pseudomonas aeruginosa early biofilm formation with antibiotics used in cystic fibrosis patients.

    Science.gov (United States)

    Fernández-Olmos, Ana; García-Castillo, María; Maiz, Luis; Lamas, Adelaida; Baquero, Fernando; Cantón, Rafael

    2012-08-01

    The ability of antibiotics used in bronchopulmonary infections in cystic fibrosis (CF) patients to prevent Pseudomonas aeruginosa early biofilm formation was studied using a biofilm microtitre assay with 57 non-mucoid P. aeruginosa isolates (44 first colonisers and 13 recovered during the initial intermittent colonisation stage) obtained from 35 CF patients. Minimum biofilm inhibitory concentrations (BICs) of levofloxacin, ciprofloxacin, imipenem, ceftazidime, tobramycin, colistin and azithromycin were determined by placing a peg lid with a formed biofilm onto microplates containing antibiotics. A modification of this protocol consisting of antibiotic challenge during biofilm formation was implemented in order to determine the biofilm prevention concentration (BPC), i.e. the minimum concentration able to prevent biofilm formation. The lowest BPCs were for fluoroquinolones, tobramycin and colistin and the highest for ceftazidime and imipenem. The former antibiotics had BPCs identical to or only slightly higher than their minimum inhibitory concentrations (MICs) determined by standard Clinical and Laboratory Standards Institute (CLSI) microdilution and were also active on formed biofilms as reflected by their low BIC values. In contrast, ceftazidime and imipenem were less effective for prevention of biofilm formation and on formed biofilms. In conclusion, the new BPC parameter determined in non-mucoid P. aeruginosa isolates recovered during early colonisation stages in CF patients supports early aggressive antimicrobial treatment guidelines in first P. aeruginosa-colonised CF patients. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  4. Fibrosis retroperitoneal

    Directory of Open Access Journals (Sweden)

    Claudio Orlich-Castelán

    2005-07-01

    Full Text Available Se reporta el caso de una mujer de 61 años de edad, con antecedente de tuberculosis pélvica en la adolescencia, que se presentó con insuficiencia renal aguda y dolor lumbar y a quien se le diagnosticó fibrosis retroperitoneal. Se revisa la bibliografía reciente y los principales aspectos de esta enfermedadRetroperitoneal fibrosis. is an uncommon disease complicated by ureteral entrapment causing hydronephrosis and obstructive renal failure. We herein report a case recently diagnosed at our institution and review the literature on this topic

  5. Ultrasound Elastography Is Useful for Evaluation of Liver Fibrosis in Children-A Systematic Review

    DEFF Research Database (Denmark)

    Andersen, Sofie Bech; Ewertsen, Caroline; Carlsen, Jonathan Frederik;

    2016-01-01

    was investigated in 14 studies and were comparable to those existing for adults. Twelve studies compared elastography with liver biopsy in children with liver disease and found that cirrhosis was correctly diagnosed, whereas it was more difficult to assess severe fibrosis correctly. For the distinction between no......OBJECTIVES: Adult studies have proven ultrasound elastography as a validated measure of liver fibrosis. The present study aimed to review the available literature on ultrasound elastography in children to evaluate the ability of the method to distinguish healthy from fibrotic liver tissue...... and investigate whether cutoff values for liver fibrosis in children have been established. METHODS: A literature search was performed in MEDLINE, EMBASE, the Cochrane Library, and Web of Science to identify studies on ultrasound elastography of the liver in children. Only original research articles in English...

  6. Coefficient of Variance as Quality Criterion for Evaluation of Advanced Hepatic Fibrosis Using 2D Shear-Wave Elastography.

    Science.gov (United States)

    Lim, Sanghyeok; Kim, Seung Hyun; Kim, Yongsoo; Cho, Young Seo; Kim, Tae Yeob; Jeong, Woo Kyoung; Sohn, Joo Hyun

    2017-08-14

    To compare the diagnostic performance for advanced hepatic fibrosis measured by 2D shear-wave elastography (SWE), using either the coefficient of variance (CV) or the interquartile range divided by the median value (IQR/M) as quality criteria. In this retrospective study, from January 2011 to December 2013, 96 patients, who underwent both liver stiffness measurement by 2D SWE and liver biopsy for hepatic fibrosis grading, were enrolled. The diagnostic performances of the CV and the IQR/M were analyzed using receiver operating characteristic curves with areas under the curves (AUCs) and were compared by Fisher's Z test, based on matching the cutoff points in an interactive dot diagram. All P values less than 0.05 were considered significant. When using the cutoff value IQR/M of 0.21, the matched cutoff point of CV was 20%. When a cutoff value of CV of 20% was used, the diagnostic performance for advanced hepatic fibrosis ( ≥ F3 grade) with CV of less than 20% was better than that in the group with CV greater than or equal to 20% (AUC 0.967 versus 0.786, z statistic = 2.23, P = .025), whereas when the matched cutoff value IQR/M of 0.21 showed no difference (AUC 0.918 versus 0.927, z statistic = -0.178, P = .859). The validity of liver stiffness measurements made by 2D SWE for assessing advanced hepatic fibrosis may be judged using CVs, and when the CV is less than 20% it can be considered "more reliable" than using IQR/M of less than 0.21. © 2017 by the American Institute of Ultrasound in Medicine.

  7. Segmental Difference of the Hepatic Fibrosis from Chronic Viral Hepatitis due to Hepatitis B versus C Virus Infection: Comparison Using Dual Contrast Material-Enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jae Ho; Yu, Jeong Sik; Chung, Jae Joon; Kim, Joo Hee; Kim, Ki Whang [Gangnam Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of)

    2011-08-15

    We wanted to identify the geographic differences in hepatic fibrosis and their associations with the atrophy-hypertrophy complex in patients with chronic viral hepatitis using the dual-contrast material-enhanced MRI (DC-MRI) with gadopentetate dimeglumine and ferucarbotran. Patients with chronic C (n = 22) and B-viral hepatitis (n = 35) were enrolled for determining the subjective grade of fibrosis (the extent and thickness of fibrotic reticulations) in the right lobe (RL), the caudate lobe (CL), the medial segment (MS) and the lateral segment (LS) of the liver, with using a 5-grade scale, on the gradient echo T2-weighted images of DC-MRI. The fibrosis grades of different segments were compared using the Kruskal-Wallis test followed by post-hoc analysis to establish the segment-by-segment differences. The incidences of two pre-established morphologic signs of cirrhosis were also compared with each other between the two groups of patients. There were significant intersegmental differences in fibrosis grades of the C-viral group (p = 0.005), and the CL showed lower fibrosis grades as compared with the grades of the RL and MS, whereas all lobes were similarly affected in the B-viral group (p = 0.221). The presence of a right posterior hepatic notch was significantly higher in the patients with intersegmental differences of fibrosis between the RL and the CL (19 out of 25, 76%) than those without such differences (6 out of 32, 19%) (p < 0.001). An expanded gallbladder fossa showed no significant relationship (p = 0.327) with the segmental difference of the fibrosis grades between the LS and the MS. The relative lack of fibrosis in the CL with more advanced fibrosis in the RL can be a distinguishing feature to differentiate chronic C-viral hepatitis from chronic B-viral hepatitis and this is closely related to the presence of a right posterior hepatic notch.

  8. Genomic analysis of lung cell lines exposures to space radiation and the effect of lunar dust on selected fibrosis gene using RT2 PCR Array

    Science.gov (United States)

    Yeshitla, Samrawit

    In the United States (U.S.), lung cancer is the number one cause of cancer death among men and women. Previous studies on human and animal epithelial lung cells showed that ionizing radiation and certain environmental pollutants are carcinogens. The surface area of the lungs and the slow turnover rate of the epithelial cells are suggested to play a role in the vulnerability of the cells, which lead to increase in the progenitor cell of the lung. It has been proposed that these progenitor cells, when exposed to radiation undergo multiple alterations that cause the cells to become cancerous. The current thought is that the lungs contain several facultative progenitor cells that are situated throughout the lung epithelium and are regionally restricted in their regenerative capacity. In this study, normal Human Bronchial Epithelial Cells (HBECs) were immortalized through the expression of Cdk4 and hTERT and evaluated for the effects radiation using in vitro study. The HBECs retained its novel multipotent capacity in vitro and represented unrestricted progenitor cells of the adult lungs, which resemble an embryonic progenitor. Analysis of the transformed clones of human bronchial epithelial cell line, HEBC3KT exposed to Fe ions and gamma rays revealed chromosomal abnormality, which was detected with the Multi-color Fluorescent In Situ Hybridization (mFish). In Part two of this study the F344 rats exposed to lunar dust, for 4 weeks (6h/d; 5d/wk.) in nose-only inhalation chambers at concentrations of 0 (control air), 2.1, 6.8, 20.8, and 61 mg/m3 of lunar dust, were used to determine the lunar dust toxicity on the lung tissues and total RNA were prepared from the tissues and used for gene expression. Analysis of gene expression data using Ingenuity Pathway Analysis tool identified multiple pathways of which fibrosis was one of the pathways. The Rat Fibrosis RT 2 Profile PCR Array was used to profile the expression of 84 genes that are relevant to fibrosis in the lung

  9. Adeno-associated virus for cystic fibrosis gene therapy

    Directory of Open Access Journals (Sweden)

    S.V. Martini

    2011-11-01

    Full Text Available Gene therapy is an alternative treatment for genetic lung disease, especially monogenic disorders such as cystic fibrosis. Cystic fibrosis is a severe autosomal recessive disease affecting one in 2500 live births in the white population, caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR. The disease is classically characterized by pancreatic enzyme insufficiency, an increased concentration of chloride in sweat, and varying severity of chronic obstructive lung disease. Currently, the greatest challenge for gene therapy is finding an ideal vector to deliver the transgene (CFTR to the affected organ (lung. Adeno-associated virus is the most promising viral vector system for the treatment of respiratory disease because it has natural tropism for airway epithelial cells and does not cause any human disease. This review focuses on the basic properties of adeno-associated virus and its use as a vector for cystic fibrosis gene therapy.

  10. Enhancement of hidden structures of early skin fibrosis using polarization degree patterns and Pearson correlation analysis.

    Science.gov (United States)

    Sviridov, Alexander P; Chernomordik, Victor; Hassan, Moinuddin; Boccara, Albert C; Russo, Angelo; Smith, Paul; Gandjbakhche, Amir

    2005-01-01

    The skin of athymic nude mice is irradiated with a single dose of x-ray irradiation that initiated fibrosis. Digital photographs of the irradiated mice are taken by illuminating the mouse skin with linearly polarized probe light of 650 nm. The specific pattern of the surface distribution of the degree of polarization enables the detection of initial skin fibrosis structures that were not visually apparent. Data processing of the raw spatial distributions of the degree of polarization based on Fourier filtering of the high-frequency noise improves subjective perception of the revealed structure in the images. In addition, Pearson correlation analysis provides information about skin structural size and directionality.

  11. Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier-Transform Infrared Imaging Technique.

    Science.gov (United States)

    Vuiblet, Vincent; Fere, Michael; Gobinet, Cyril; Birembaut, Philippe; Piot, Olivier; Rieu, Philippe

    2016-08-01

    Renal interstitial fibrosis and interstitial active inflammation are the main histologic features of renal allograft biopsy specimens. Fibrosis is currently assessed by semiquantitative subjective analysis, and color image analysis has been developed to improve the reliability and repeatability of this evaluation. However, these techniques fail to distinguish fibrosis from constitutive collagen or active inflammation. We developed an automatic, reproducible Fourier-transform infrared (FTIR) imaging-based technique for simultaneous quantification of fibrosis and inflammation in renal allograft biopsy specimens. We generated and validated a classification model using 49 renal biopsy specimens and subsequently tested the robustness of this classification algorithm on 166 renal grafts. Finally, we explored the clinical relevance of fibrosis quantification using FTIR imaging by comparing results with renal function at 3 months after transplantation (M3) and the variation of renal function between M3 and M12. We showed excellent robustness for fibrosis and inflammation classification, with >90% of renal biopsy specimens adequately classified by FTIR imaging. Finally, fibrosis quantification by FTIR imaging correlated with renal function at M3, and the variation in fibrosis between M3 and M12 correlated well with the variation in renal function over the same period. This study shows that FTIR-based analysis of renal graft biopsy specimens is a reproducible and reliable label-free technique for quantifying fibrosis and active inflammation. This technique seems to be more relevant than digital image analysis and promising for both research studies and routine clinical practice.

  12. CURRENT AND FUTURE USE OF MANAGEMENT TOOLS

    National Research Council Canada - National Science Library

    Zlatko Nedelko; Vojko Pototcan; Marina Dabic

    2015-01-01

    .... The authors developed and tested a model for predicting the future use of management tools based on the current use of tools by employees in organizations, underlying assumptions of the theory...

  13. Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis.

    Science.gov (United States)

    Rifai, N; Sakamoto, M; Law, T; Galpchian, V; Harris, N; Colin, A A

    1996-11-01

    High doses of ibuprofen have been shown to delay the progression of lung disease without serious adverse effects in patients with cystic fibrosis. To be effective, peak ibuprofen concentration of 50 to 100 mg/L has to be achieved. We developed an HPLC assay to rapidly determine plasma ibuprofen concentration. We used this assay to determine the pharmacokinetics of ibuprofen in patients with cystic fibrosis. The assay possessed linearity up to 500 mg/L, sensitivity to 1 mg/L, average recovery of 98%, and run-to-run precision (n = 23) of 3%. Furthermore, the assay proved to be free of interference from 51 medications. Observed time to peak concentration varied significantly between those receiving ibuprofen tablets (mean + SD, 94 +/- 29 min, n = 16) and syrup (30 +/- 0 min, n = 4) (P < 0.0001). We conclude that the method described here is ideal for therapeutic monitoring of ibuprofen.

  14. Desensitization to inhaled aztreonam lysine in an allergic patient with cystic fibrosis using a novel approach.

    Science.gov (United States)

    Guglani, Lokesh; Abdulhamid, Ibrahim; Ditouras, Joanna; Montejo, Jenny

    2012-10-01

    To report the successful desensitization of a highly allergic patient with cystic fibrosis (CF) to inhaled aztreonam lysine using the novel approach of intravenous desensitization followed by full-dose inhaled therapy without any adverse reactions. A 19-year-old woman with CF had persistent Pseudomonas aeruginosa-positive cultures and a history of type I hypersensitivity reactions to multiple medications, including aztreonam and tobramycin (intravenous and inhaled). To start therapy with an inhaled antipseudomonal antibiotic on a chronic basis, she underwent rapid desensitization to intravenous aztreonam followed by initiation of inhaled aztreonam lysine. Following intravenous desensitization with aztreonam, there was no adverse reaction or decline in lung function noted with inhaled aztreonam lysine and the chronic therapy was continued at home, with a modified regimen to maintain desensitization. Aztreonam lysine has been used for treatment of patients with CF with chronic P. aeruginosa colonization. Previous allergic reaction to intravenous aztreonam is considered a contraindication for use of aztreonam lysine. Our patient had a history of hives and facial swelling following administration of intravenous aztreonam (type I hypersensitivity reaction) as well as hypersensitivity to tobramycin. Rapid desensitization can be done for drugs that mediate a type I hypersensitivity reaction, with mast cells and basophils being the cellular targets. There are a few case reports of desensitization to inhaled antibiotics such as tobramycin and colistin, but desensitization to aztreonam lysine has not previously been reported. Desensitization of a patient with CF who is allergic to intravenous aztreonam was successfully accomplished with the novel approach of rapid intravenous desensitization followed by inhaled therapy. As inhaled antibiotics are being increasingly used for patients with CF, this novel strategy can be used for desensitizing allergic patients with CF to

  15. Feasibility study of the diagnosis and monitoring of cystic fibrosis in pediatric patients using stationary digital chest tomosynthesis

    Science.gov (United States)

    Potuzko, Marci; Shan, Jing; Pearce, Caleb; Lee, Yueh Z.; Lu, Jianping; Zhou, Otto

    2015-03-01

    Digital chest tomosynthesis (DCT) is a 3D imaging modality which has been shown to approach the diagnostic capability of CT, but uses only one-tenth the radiation dose of CT. One limitation of current commercial DCT is the mechanical motion of the x-ray source which prolongs image acquisition time and introduces motion blurring in images. By using a carbon nanotube (CNT) x-ray source array, we have developed a stationary digital chest tomosynthesis (s- DCT) system which can acquire tomosynthesis images without mechanical motion, thus enhancing the image quality. The low dose and high quality 3D image makes the s-DCT system a viable imaging tool for monitoring cystic fibrosis (CF) patients. The low dose is especially important in pediatric patients who are both more radiosensitive and have a longer lifespan for radiation symptoms to develop. The purpose of this research is to evaluate the feasibility of using s-DCT as a faster, lower dose means for diagnosis and monitoring of CF in pediatric patients. We have created an imaging phantom by injecting a gelatinous mucus substitute into porcine lungs and imaging the lungs from within an anthropomorphic hollow chest phantom in order to mimic the human conditions of a CF patient in the laboratory setting. We have found that our s-DCT images show evidence of mucus plugging in the lungs and provide a clear picture of the airways in the lung, allowing for the possibility of using s- DCT to supplement or replace CT as the imaging modality for CF patients.

  16. Why is insulin pump treatment rarely used in adolescents and young adults with cystic fibrosis-related diabetes?

    Science.gov (United States)

    Scheuing, Nicole; Badenhoop, Klaus; Borkenstein, Martin; Konrad, Katja; Lilienthal, Eggert; Laubner, Katharina; Naeke, Andrea; Rami-Merhar, Birgit; Thon, Angelika; Wiemann, Dagobert; Holl, Reinhard W

    2015-02-01

    In type 1 diabetes (T1D), the use of continuous subcutaneous insulin infusion (CSII) has increased steadily in the last years. Compared with conventional insulin injection regimes, major advantages might be a nearly physiological insulin secretion, lower rates of hypoglycemia, higher flexibility in daily life, and increased quality of life. Data on CSII in cystic fibrosis-related diabetes (CFRD) are scarce. To analyze current use of insulin pumps in CFRD and compare demographics of pump-treated patients between CFRD and T1D. Data from the prospective German/Austrian diabetes patient registry on insulin-treated patients with either CFRD (n = 515) or T1D (n = 43 165) aged >10 yr at manifestation of diabetes were analyzed. A total of 4.1% (n = 21) of CFRD and 17.7% (n = 7647) of T1D patients received insulin pump treatment within the recent year of care (p Pump-treated patients with CFRD had a significantly shorter duration of diabetes [median (Q1 ; Q3 ): 5.8 (2.9; 9.5) vs. 7.8 (4.3; 20.4) yr, p = 0.026] and tended to be younger [22.0 (18.2; 30.1) vs. 24.9 (17.3; 45.9) yr] than pump-treated T1D patients. Age at initiation of CSII seemed to be lower in CFRD [19.2 (16.5; 29.2) vs. 23.3 (14.8; 43.5) yr]. Insulin pump therapy was used slightly more often in male CFRD patients than females (4.7 vs. 3.6%), whereas in T1D the opposite was observed (14.9 vs. 21.2%, p insulin pump therapy was rarely used among adolescent and young adult CFRD patients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Assessment of liver steatosis and fibrosis in rats using integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique

    Science.gov (United States)

    Lin, Jian; Lu, Fake; Zheng, Wei; Xu, Shuoyu; Tai, Dean; Yu, Hanry; Huang, Zhiwei

    2011-11-01

    We report the implementation of a unique integrated coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), and two-photon excitation fluorescence (TPEF) microscopy imaging technique developed for label-free monitoring of the progression of liver steatosis and fibrosis generated in a bile duct ligation (BDL) rat model. Among the 21 adult rats used in this study, 18 rats were performed with BDL surgery and sacrificed each week from weeks 1 to 6 (n = 3 per week), respectively; whereas 3 rats as control were sacrificed at week 0. Colocalized imaging of the aggregated hepatic fats, collagen fibrils, and hepatocyte morphologies in liver tissue is realized by using the integrated CARS, SHG, and TPEF technique. The results show that there are significant accumulations of hepatic lipid droplets and collagen fibrils associated with severe hepatocyte necrosis in BDL rat liver as compared to a normal liver tissue. The volume of normal hepatocytes keeps decreasing and the fiber collagen content in BDL rat liver follows a growing trend until week 6; whereas the hepatic fat content reaches a maximum in week 4 and then appears to stop growing in week 6, indicating that liver steatosis and fibrosis induced in a BDL rat liver model may develop at different rates. This work demonstrates that the integrated CARS and multiphoton microscopy imaging technique has the potential to provide an effective means for early diagnosis and detection of liver steatosis and fibrosis without labeling.

  18. Exercise Intensity Self-Regulation using the OMNI Scale in Children with Cystic Fibrosis

    Science.gov (United States)

    Higgins, Linda W.; Robertson, Robert J.; Kelsey, Sheryl F.; Olson, Marian B.; Hoffman, Leslie A.; Rebovich, Paul J.; Haile, Luke; Orenstein, David M.

    2012-01-01

    Summary Prescribing exercise at intensities that improve fitness is difficult in children with cystic fibrosis (CF) due to ventilatory limitations and fluctuating health status. Our aim was to determine if children with CF could regulate the intensity of cycle ergometer and treadmill exercise using target ratings of perceived exertion (RPE) derived from the Children’s OMNI Scale. We examined prescription congruence [similar oxygen consumption (VO2) and heart rate (HR) for target RPE] and intensity discrimination (different VO2 and HR for different RPEs), from cycle to cycle and cycle to treadmill. Subjects were 24 children (12 male, 12 female), aged 10–17 years with varying disease severity. Each child participated in one orientation, one estimation trial (graded maximal exercise test), and two production trials (cycle and treadmill, alternating between RPE 4 and 7). At RPE 4, congruence was evident for both VO2 and HR on the treadmill. On the cycle at RPE 4, VO2 was significantly higher only in the first production trial, although HRs tended to be higher in the production trials than the estimation trial. Prescription congruence was also supported at RPE 7, with no significant differences in VO2 or HR between estimation and production trials on cycle or treadmill. Results fully supported intensity discrimination, with significant differences between VO2 and HR at RPE 4 and 7 (p<0.0001). Children with CF appear capable of using the OMNI Scale to regulate cycle and treadmill exercise intensity. Training using this methodology has the potential to promote fitness in children with CF of varying severity. PMID:22997144

  19. Serum markers of liver fibrosis

    DEFF Research Database (Denmark)

    Veidal, Sanne Skovgård; Bay-Jensen, Anne-Christine; Tougas, Gervais

    2010-01-01

    BACKGROUND: Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable......-epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers. METHODS: Pubmed was search for keywords; Liver fibrosis, neo......, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis....

  20. Cost of care for cystic fibrosis: an investigation of cost determinants using national registry data.

    Science.gov (United States)

    Gu, Yuanyuan; García-Pérez, Sonia; Massie, John; van Gool, Kees

    2015-09-01

    Cystic fibrosis (CF) is a progressive disease with treatments intensifying as patients get older and severity worsens. To inform policy makers about the cost burden in CF, it is crucial to understand what factors influence the costs and how they affect the costs. Based on 1,060 observations (from 731 patients) obtained from the Australian Data Registry, individual annual health care costs were calculated and a regression analysis was carried out to examine the impact of multiple variables on the costs. A method of retransformation and a hypothetical patient were used for cost analysis. We show that an additional one unit improvement of FEV1pp (i.e., forced expiratory volume in 1 s as a percentage of predicted volume) reduces the costs by 1.4%, or for a hypothetical patient whose FEV1pp is 73 the cost reduction is A$252. The presence of chronic infections increases the costs by 69.9-163.5% (A$12,852-A$30,047 for the hypothetical patient) depending on the type of infection. The type of CF genetic mutation and the patient's age both have significant effects on the costs. In particular, being homozygous for p.F508del increases the costs by 26.8% compared to all the other gene mutations. We conclude that bacterial infections have a very strong influence on the costs, so reducing both the infection rates and the severity of the condition may lead to substantial cost savings. We also suggest that the patient's genetic profile should be considered as an important cost determinant.

  1. Fibrosis retroperitoneal

    Directory of Open Access Journals (Sweden)

    Claudio Orlich-Castelán

    2005-07-01

    Full Text Available Se reporta el caso de una mujer de 61 años de edad, con antecedente de tuberculosis pélvica en la adolescencia, que se presentó con insuficiencia renal aguda y dolor lumbar y a quien se le diagnosticó fibrosis retroperitoneal. Se revisa la bibliografía reciente y los principales aspectos de esta enfermedad

  2. [Retroperitoneal fibrosis].

    Science.gov (United States)

    Babski, Paweł; Wojtuń, Stanisław; Gil, Jerzy

    2007-05-01

    Retroperitoneal fibrosis is a rare clinical entity characterised by the presence of patologic collagen tissue in a retroperitoneal space. The fibrous mass covers abdominal organs causing their disfunctions. RPF was described at the begining of XX century but its etiology is not clear yet. Usually it causes an ureter obstuction and hydronephrosis, that is why most commonly is diagnosed by urologists and nephrologists. However, retroperitoneal fibrosis can be multifacial disease. In some patients localisation of fibrosis is atypical and manifestationns can be varied. Gastrological symptoms like jaundice, bowel obstuction, ascites can occure. Besides, some early signs of RPF are nonspecific and can imitate alarming symptoms of neoplasma, e.g.: weight loss, anemia, malaise, anorexia, fever. This force us to initiate gastrological investigation. The awareness of this disease is important. The early diagnosis and treatment improves prognosis and alows to avoid heavy complications. In typical cases radiology is often enough for diagnosis. However, histological examination is needed in many cases, especialy when patological mass is located atypical. A treatment is made up of farmacology and surgery. The first one is based on steroids, immunossuppressant and tamoxifen. Surgery is needed to eliminate organs obstruction.

  3. Logarithmic current electrometer using light emitting diodes

    Science.gov (United States)

    Acharya, Y. B.; Aggarwal, A. K.

    1996-02-01

    The limit of low current measurement using logarithmic current to voltage converter is improved by 6 - 7 orders of magnitude with the use of diodes of large band gap as compared with silicon diodes. Low cost commercially available light emitting diodes (LEDs) have been used for this purpose. A theoretical study and experimental measurement of device constant and reverse saturation currents of the whole class of commercially available LEDs has been carried out. A circuit has been developed which makes use of a new technique for temperature compensation and its performance is compared with the technique in common use. The performance of the amplifier is found to be stable in the temperature range 5 - 600957-0233/7/2/005/img5 for both polarity of signals from 0957-0233/7/2/005/img6 to 0957-0233/7/2/005/img7 A.

  4. Results of the 4th scientific workshop of the ECCO (I): pathophysiology of intestinal fibrosis in IBD.

    Science.gov (United States)

    Latella, Giovanni; Rogler, Gerhard; Bamias, Giorgos; Breynaert, Christine; Florholmen, Jon; Pellino, Gianluca; Reif, Shimon; Speca, Silvia; Lawrance, Ian C

    2014-10-01

    The fourth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of intestinal fibrosis in the disease course of inflammatory bowel disease (IBD). The objective was to better understand the pathophysiological mechanisms of intestinal fibrosis, to identify useful markers and imaging modalities of fibrosis in order to assess its presence and progression, and, finally, to point out possible approaches for the prevention and the treatment of fibrosis. The results of this workshop are presented in three separate manuscripts. This first section describes the most important mechanisms that contribute to the initiation and progression of intestinal fibrosis in IBD including the cellular and molecular mediators, the extracellular matrix molecules and matrix metalloproteinases/tissue inhibitors of metalloproteinases-system, the microbiota products, the role of fat, genetic and epigenetic factors, as well as the currently available experimental models. Furthermore, it identifies unanswered questions in the field of intestinal fibrosis and provides a framework for future research.

  5. Pathophysiology of cystic fibrosis and drugs used in associated digestive tract diseases

    OpenAIRE

    Haack, Adriana; Aragão, Giselle Gonçalves; Novaes,Maria Rita Carvalho Garbi

    2013-01-01

    Cystic fibrosis (CF) causes chronic infections in the respiratory tract and alters the digestive tract. This paper reviews the most important aspects of drug treatment and changes in the digestive tract of patients with CF. This is a review of the literature, emphasizing the discoveries made within the last 15 years by analyzing scientific papers published in journals indexed in the Scientific Electronic Library Online, Sciences Information, United States National Library of Medicine and Medi...

  6. [Nephrogenic systemic fibrosis].

    Science.gov (United States)

    Artunc, F; Schanz, S; Metze, D; Heyne, N

    2008-01-01

    Nephrogenic systemic fibrosis (NSF) is a novel disease entity, increasingly diagnosed over the last years in patients with renal functional impairment and chronic kidney disease. Recently, gadolinium-containing MR contrast agents have been causally associated with the development NSF. Herein, we present the case of a dialysis-dependent young patient with systemic lupus erythematodes, who developed disabling cutaneous sclerosis of extremities, abdomen and mammae. Clinical and laboratory investigations revealed no signs of activity of the underlying disease. Histopathological examination of a skin biopsy was consistent with NSF showing profound thickening of tissue septae with mucine deposition and slight fibroblast proliferation without inflammatory reaction. Analysis of the patient's medical history revealed that she had undergone repeated contrast enhanced MR scans, including MR angiographies with high doses of gadopentetate. UV phototherapy was little effective, and not until kidney transplantation two years later with good allograft function, improvement of clinical symptoms was observed. Discussion of this case summarizes the current knowledge of clinical features and pathogeneses of NSF, including the role of gadolinium-containing contrast agents. Evolving clinical implications are summarized in the current Tübingen University Hospital guideline for the use of contrast-enhanced MR scans in patients with impaired renal function.

  7. Cystic Fibrosis Research

    Science.gov (United States)

    ... please turn Javascript on. Feature: Steady Advances Against Cystic Fibrosis Cystic Fibrosis Research Past Issues / Fall 2012 Table of Contents "Remarkable strides in cystic fibrosis research over the past two decades have culminated ...

  8. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, Peter; Skov, Lone; Rossen, Kristian

    2006-01-01

    Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases of ne...

  9. Staging of liver fibrosis or cirrhosis: The role of hepaticvenous pressure gradient measurement

    Institute of Scientific and Technical Information of China (English)

    Ki Tae Suk; Dong Joon Kim

    2015-01-01

    Liver fibrosis is a common histological change ofchronic liver injury and it is closely related with portalhypertension which is hemodynamic complication ofchronic liver disease. Currently, liver fibrosis has beenknown as a reversible dynamic process in previousliteratures. Although liver biopsy is a gold standardfor assessing the stage of liver fibrosis, it may notcompletely represent the stage of liver fibrosis becauseof sampling error or semi-quantative measurement.Recent evidences suggested that histologic, clinical,hemodynamic, and biologic features are closelyassociated in patients with chronic liver disease. Hepaticvenous pressure gradient (HVPG) measurement has beenknown as a modality to evaluate the portal pressure.The HVPG measurement has been used clinicallyfor fibrosis diagnosis, risk stratification, preoperativescreening for liver resection, monitoring the efficacy ofmedical treatments, and assessing the prognosis of liverfibrosis. Therefore, the HVPG measurement can be usedto monitor areas the chronic liver disease but also otherimportant areas of chronic liver disease.

  10. Adipose tissue fibrosis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The increasing prevalence of obesity causes a majorinterest in white adipose tissue biology. Adipose tissuecells are surrounded by extracellular matrix proteinswhose composition and remodeling is of crucial importancefor cell function. The expansion of adipose tissue inobesity is linked to an inappropriate supply with oxygenand hypoxia development. Subsequent activation ofhypoxia inducible factor 1 (HIF-1) inhibits preadipocytedifferentiation and initiates adipose tissue fibrosis. Therebyadipose tissue growth is limited and excess triglyceridesare stored in ectopic tissues. Stressed adipocytes andhypoxia contribute to immune cell immigration andactivation which further aggravates adipose tissuefibrosis. There is substantial evidence that adipose tissuefibrosis is linked to metabolic dysfunction,both in rodentmodels and in the clinical setting. Peroxisome proliferatoractivated receptor gamma agonists and adiponectin bothreduce adipose tissue fibrosis, inflammation and insulinresistance. Current knowledge suggests that antifibroticdrugs, increasing adipose tissue oxygen supply or HIF-1antagonists will improve adipose tissue function andthereby ameliorate metabolic diseases.

  11. [The usefulness of the Chrispin-Norman score in the evaluation of pulmonary status in patients with cystic fibrosis].

    Science.gov (United States)

    Harms, H K; Bertele, R M; Weidl, B; Fendel, H

    1983-01-01

    Its objectivity and reproducibility having been checked by for independent researchers, the Chrispin-Norman score has proved to be a useful yardstick for evaluating pulmonary changes in cystic fibrosis. The correlation to arterial pO2 was r = 0.68, and to the Schwachman-Kulczycki score, r = 0.75. Scores still consistent with a good general clinical condition were 10.5 in patients under 8 years of age; 13.4 in patients aged between 8 and 13; and 15.5 in the 13-20 age group. An average increase of more than 2 points a year indicates a particularly high danger level.

  12. [News in cystic fibrosis].

    Science.gov (United States)

    Delaisi, B

    2013-08-01

    The improvement over the last two decades in the treatment of cystic fibrosis led to an increase in life expectancy approaching 40 years at birth. Logically, the population of adult patients has been increasing and is currently 50% of patients followed in France. These therapeutic advances have justified the establishment in 2003 of a generalized neonatal screening for cystic fibrosis. The latest data of this screening show an incidence of CF of 1/5359 live births, far below the incidence of 1/2500 which was widely accepted twenty years ago. The performance of this screening is currently based on the dosage of trypsin immuno reactive, followed in case of exceeding the threshold of a search of the 30 most common mutations, can detect around 96% of 150 to 200 CF cases every year. Therefore, the possibility of a false negative of the screening cannot be excluded and evocative symptoms of cystic fibrosis, even for children born after 2003, will lead to prescribe a sweat test. While treatments available so far goal consequences of cystic fibrosis, a new therapeutic class to correct the functional defect of the mutated protein, called CFTR modulators, is emerging. Ivacaftor, leader of this new class, belonging to the category of "CFTR potentiator" got its access on the market in September 2012 for patients carrying the G551D mutation. New other molecules, named "CFTR correctors" which can have synergistic effect with ivacaftor and concern patients carrying the most common mutation--DF 508--are under development. Copyright © 2013. Published by Elsevier Masson SAS.

  13. Low prevalence of fibrosis in thalassemia major assessed by late gadolinium enhancement cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Tanner Mark A

    2011-01-01

    Full Text Available Abstract Background Heart failure remains a major cause of mortality in thalassaemia major. The possible role of cardiac fibrosis in thalassemia major in the genesis of heart failure is not clear. It is also unclear whether cardiac fibrosis might arise as a result of heart failure. Methods We studied 45 patients with thalassaemia major who had a wide range of current cardiac iron loading and included patients with prior and current heart failure. Myocardial iron was measured using T2* cardiovascular magnetic resonance (CMR, and following this, late gadolinium enhancement (LGE was used to determine the presence of macroscopic myocardial fibrosis. Results The median myocardial T2* in all patients was 22.6 ms (range 5.3-58.8 ms. Fibrosis was detected in only one patient, whose myocardial T2* was 20.1 ms and left ventricular ejection fraction 57%. No fibrosis was identified in 5 patients with a history of heart failure with full recovery, in 3 patients with current left ventricular dysfunction undergoing treatment, or in 18 patients with myocardial iron loading with cardiacT2* Conclusion This study shows that macroscopic myocardial fibrosis is uncommon in thalassemia major across a broad spectrum of myocardial iron loading. Importantly, there was no macroscopic fibrosis in patients with current or prior heart failure, or in patients with myocardial iron loading without heart failure. Therefore if myocardial fibrosis indeed contributes to myocardial dysfunction in thalassemia, our data combined with the knowledge that the myocardial dysfunction of iron overload can be reversed, indicates that any such fibrosis would need to be both microscopic and reversible.

  14. Therapeutic use of fisetin, curcumin, and mesoporous carbaon nanoparticle loaded fisetin in bleomycin-induced idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Srabani Kar

    2015-04-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a devastating disease of unknown etiology, for which there is no curative pharmacological therapy. Bleomycin, an anti-neoplastic agent that causes lung fibrosis in human patients has been used extensively in rodent models to mimic IPF. The conventional therapy has been steroids and immunosuppressive agents. But only a minority of patients responds to such a therapy. IPF is a progressive, ultimately fatal disorder for which substantive medical therapy is desperately needed. Fisetin is a flavonol which inhibits the activity of several pro-inflammatory cytokines. The polyphenol curcumin is used to treat inflammatory diseases, abdominal disorders, and a variety of other ailments. The aim of this study was to evaluate the beneficial effect of fistine, curcumin and mesoporous carbaon nanoparticle (MCN loaded fisetin as an anti-inflammatory agents against bleomycin-induced changes in mice with IPF. In our study, flavonoids showed their anti fibrotic action. The inflammatory cell count was greatly increased for bleo treated individuals and effectiveness of fisein was increased after addition of MCN particles with it, curcumin also showed anti- inflammatory effects. In another experiment, bleomycin effectively inhibits the cellular recruitment to the spleen and treatment with fisetin, and curcumin increases the cellular recruitment in spleen. Colony count was also increased in MCN+fisetin treated groups, and it was statistically significant. We also observed the increased level of cytokines with fisetin treatment, with curcumin treatment and with MCN +fisetin treatment as compared to the bleo treated sample. In conclusion, the present research suggests that fisetin and curcumin and MCN loaded fisetin may be a promising therapeutic agent for bleomycin-induced changes in mice with IPF. This will open up new perspectives for a potential role of these drugs as a molecular target in Idiopathic pulmonary fibrosis. [Biomed

  15. Vaccine strategies against bacterial pathogens in cystic fibrosis patients.

    Science.gov (United States)

    Le Moigne, V; Gaillard, J-L; Herrmann, J-L

    2016-02-01

    A large number of cystic fibrosis pathogens such as bacteria of the Burkholderia cepacia complex, Pseudomonas aeruginosa, or Mycobacterium abscessus are associated with complex therapeutic problems due to their inherent resistance to antibiotics. No vaccine is currently available against those pathogens. Vaccines are therefore crucial to combat these multidrug-resistant bacteria in specific clinical situations including cystic fibrosis. Various strategies may be considered to develop these vaccines. Similar virulence factors are expressed during the infection with various pathogens; they could thus be used as antigen to assess cross-protection. Many clinical trials are currently being conducted to try and develop a prophylactic treatment for patients presenting with cystic fibrosis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Ocean current mapping using networked distributed sensors

    Science.gov (United States)

    Huang, Chen-Fen; Yang, T. C.; Liu, Jin-Yuan; Burchfield, Tom; Schindall, Jeff

    2012-11-01

    Distributed underwater sensors are expected to provide environmental (oceanographic) monitoring over large areas. As fabrication technology advances, low cost sensors will be available for many applications. The sensors communicate to each other and are networked using acoustic communications. This paper proposes a method for ocean current tomography using distributed networked sensors and presents preliminary experimental results by this approach. Conventional acoustic tomography uses the acoustic sensors distributed on the periphery of an area of interest. Environmental reconstruction requires solving a challenging high dimensional inverse problem, typically requiring substantial computational effort. Given distributed sensors, currents can be constructed locally based on data from neighboring sensors. It is shown using simulated data that results obtained by the proposed method are similar to those obtained by a conventional tomographic method based on peripheral sensors. In addition, one finds that the distributed sensors consume much less energy than that by the conventional tomographic approach. An acoustic communication and networking experiment was conducted near the Sizihwan Bay in Kaohsiung, Taiwan, in May 2011. The communication signals are analyzed to measure currents as a function of space and time. The procedure is simple and can be implemented in real-time using in-buoy processing.

  17. Routine ventilation scans in children with cystic fibrosis: diagnostic usefulness and prognostic value

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, A.; Hamutcu, R.; Adler, B.; Rosenthal, M.; Bush, A. [Dept. of Respiratory Paediatrics, Royal Brompton and Harefield, London (United Kingdom); Dhawan, R.T. [Department of Nuclear Medicine, Royal Brompton and Harefield, London (United Kingdom)

    2001-09-01

    Krypton ventilation scans (VS) provide an index of peripheral lung function, and may be particularly useful in children unable to perform pulmonary function testing. This communication reports on three linked studies which investigated whether a routine VS in young children with cystic fibrosis (CF) is diagnostically or prognostically useful. Study 1: In a preliminary study in 1991, VS were compared with clinical examination and chest radiography (CXR) in 50 CF children (29 females, 21 males) aged 0.4-5.2 years (median 2.2 years). The chest was divided into six zones, and abnormalities scored from 0 (normal) to 2 (very abnormal). Clinical examination was unhelpful in predicting abnormalities on imaging. In five children (10%) with a normal CXR, VS was abnormal, and in a further eight children (16%), CXR markedly underestimated VS changes. Study 2: In order to determine the long-term prognostic significance of VS abnormalities, we followed up 27 (19 females, 8 males) of the children from study 1, who had had their first VS at presentation at median age 1.6 years (range 0.4-5.2), scoring the same six zones from 0 to 2. Follow-up was for a mean of 11.6 years (range 7.8-14.8). Spirometry at age 7 years showed a mean forced expiratory volume in 1 s (FEV{sub 1}) of 96% (range 46%-145%) and a mean forced vital capacity (FVC) of 96% (range 46%-145%). A poor VS score at presentation was correlated with percent predicted FEV{sub 1} at age 7 (r=0.4, P=0.042, 16% of variance explained). Those with a normal VS at presentation had a mean FEV{sub 1} at presentation of 99% (range 80%-129%). Whereas four patients had an abnormal VS, a normal CXR and a low FEV{sub 1} at age 7 years, no patient had a normal VS, an abnormal CXR and a low FEV{sub 1}at age 7 years. Study 3: Fifty children (29 females, 21 males) aged 0.5-6.0 years (median 3.8) were prospectively studied in 1998, to determine whether the findings in study 1 were stable over time, and to assess whether VS altered clinical

  18. An Official American Thoracic Society Workshop Report: Use of Animal Models for the Preclinical Assessment of Potential Therapies for Pulmonary Fibrosis.

    Science.gov (United States)

    Jenkins, R Gisli; Moore, Bethany B; Chambers, Rachel C; Eickelberg, Oliver; Königshoff, Melanie; Kolb, Martin; Laurent, Geoffrey J; Nanthakumar, Carmel B; Olman, Mitchell A; Pardo, Annie; Selman, Moises; Sheppard, Dean; Sime, Patricia J; Tager, Andrew M; Tatler, Amanda L; Thannickal, Victor J; White, Eric S

    2017-05-01

    Numerous compounds have shown efficacy in limiting development of pulmonary fibrosis using animal models, yet few of these compounds have replicated these beneficial effects in clinical trials. Given the challenges associated with performing clinical trials in patients with idiopathic pulmonary fibrosis (IPF), it is imperative that preclinical data packages be robust in their analyses and interpretations to have the best chance of selecting promising drug candidates to advance to clinical trials. The American Thoracic Society has convened a group of experts in lung fibrosis to discuss and formalize recommendations for preclinical assessment of antifibrotic compounds. The panel considered three major themes (choice of animal, practical considerations of fibrosis modeling, and fibrotic endpoints for evaluation). Recognizing the need for practical considerations, we have taken a pragmatic approach. The consensus view is that use of the murine intratracheal bleomycin model in animals of both genders, using hydroxyproline measurements for collagen accumulation along with histologic assessments, is the best-characterized animal model available for preclinical testing. Testing of antifibrotic compounds in this model is recommended to occur after the acute inflammatory phase has subsided (generally after Day 7). Robust analyses may also include confirmatory studies in human IPF specimens and validation of results in a second system using in vivo or in vitro approaches. The panel also strongly encourages the publication of negative results to inform the lung fibrosis community. These recommendations are for preclinical therapeutic evaluation only and are not intended to dissuade development of emerging technologies to better understand IPF pathogenesis.

  19. Cytomorphometric analysis of oral submucous fibrosis and leukoplakia using methyl green-pyronin Y, Feulgen staining and exfoliative brush cytology.

    Science.gov (United States)

    Metgud, R; Gupta, K; Prasad, U; Gupta, J

    2015-01-01

    The incidence of potentially malignant oral pathology such as leukoplakia, oral submucous fibrosis and squamous cell carcinoma has increased in India. We investigated whether cytoplasmic diameter, nuclear diameter and nucleus:cytoplasm ratio in exfoliative cytology are reliable indicators of potentially malignant lesions. We also investigated methyl green-pyronin Y and Feulgen staining as simple time saving and cost effective staining techniques for diagnostic exfoliative cytology. Cell and nuclear diameters of squamous cells of normal buccal mucosa, oral leukoplakia and oral submucous fibrosis were measured using an ocular micrometer disc. The nucleus:cytoplasm ratios in pathological cells were compared to age, sex and site matched controls. We found a significant reduction in the mean cytoplasmic and nuclear diameter in the experimental groups compared to normal controls. Methyl green-pyronin Y stained smears were clearer than Feulgen stained cells. We suggest that a decreased mean cytoplasmic diameter of exfoliated buccal mucosal cells could serve as an early indicator of dysplastic change in lesions that otherwise appear benign. Methyl green-pyronin Y may be useful for identifying premalignant and malignant transformations before a lesion is visible. The simplicity of the technique makes its routine use feasible.

  20. The use of fructosamine in cystic fibrosis-related diabetes (CFRD) screening.

    Science.gov (United States)

    Lam, Grace Y; Doll-Shankaruk, Michelle; Dayton, Jan; Rodriguez-Capote, Karina; Higgins, Trefor N; Thomas, Dylan; Mulchey, Kimberley; Smith, Maeve P; Brown, Neil E; Leung, Winnie M; Estey, Mathew P

    2017-06-22

    To determine whether serum fructosamine correlates with glycemic control and clinical outcomes in patients being screened for cystic fibrosis-related diabetes (CFRD). Fructosamine and percent predicted forced expiratory volume in 1s (FEV1) were measured in patients undergoing a 2h oral glucose tolerance test (OGTT) for CFRD screening. Fractional serum fructosamine (FSF) was calculated as fructosamine/total protein. FSF exhibited a positive correlation with 2h OGTT results (r(2)=0.3201, p=0.009), and ROC curve analysis suggested that FSF can identify patients with an abnormal OGTT (AUC=0.840, p=0.0002). FSF also exhibited a negative correlation with FEV1 (r(2)=0.3732, p=0.035). Patients with FSF≥3.70μmol/g had significantly lower FEV1 (median 47%) compared to those with FSF<3.70μmol/g (median 90%; p=0.015). FSF correlated with both OGTT results and FEV1, and reliably identified patients with abnormal OGTT results. This simple blood test shows potential as an effective tool in CFRD screening. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. ANFIS IN THE CHARACTERIZATION OF FIBROSIS AND CARCINOMA USING LUNG CT IMAGES

    Directory of Open Access Journals (Sweden)

    D. Lakshmi

    2013-08-01

    Full Text Available The diagnosis of tuberculosis and lung cancer is difficult, as symptoms of both diseases are similar. Due to high TB prevalence and radiological similarities, a large number of lung cancer patients initially get wrongly treated for tuberculosis based on radiological picture alone. However, treating TB leads to inflammatory fibrosisin some of the patients. In all these cases, the diagnosis is confirmed only with a biopsy which is an invasive technique that is usually performed via Bronchoscopy or CT – guided biopsy. There comes the need of an efficient Computer Aided Diagnosis(CAD of the fibrosis and adenocarcinoma diseases. The increased chance of characterizing tissues with the help of CAD and the achievable workload reduction for the radiologist demand the usage of these systems in CT screenings as well as daily hospital practice. Generally, the CAD is designed based on the Region of Interest(ROI given by the radiologist which makes the system semi-automatic.Our work presents a fully automated method of characterization of carcinoma from other lung abnormalities namely fibrosis and suspicious of tuberculosis. A comparison study is also done by evaluating the performance of Adaptive Neuro-Fuzzy Inference System(ANFIS as a Classifier with three set of features. These feature set include entropy and parameters extracted by Gray Level Co-Occurrence Matrix(GLCM and Gray Level Run Length Matrix(GLRLM.

  2. Biomarkers for liver fibrosis

    Science.gov (United States)

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2015-09-15

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  3. Biomarkers for liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2017-05-16

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  4. Computation of current distributions using FEMLAB

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, M.S.; Pullabhotla, S.R. [Vellore Institute of Technology, Tamilnadu (India); Vijayasekaran, B. [Central Electrochemical Research Institute, Tamilnadu (India); Chemical Engineering, Tennessee Technological University, Tennessee (United States); Basha, C.A.

    2009-04-15

    An efficient method for the computation of current density and surface concentration distributions in electrochemical processes is analyzed using the commercial mathematical software FEMLAB. To illustrate the utility of the software, the procedure is applied to some realistic problems encountered in electrochemical engineering, such as current distribution in a continuous moving electrode, parallel plate electrode, hull cell, curvilinear hull cell, thin layer galvanic cell, through-hole plating, and a recessed disc electrode. The model equations of the above cases are considered and their implementations into the software, FEMLAB, are analyzed. The technique is attractive because it involves a systematic way of coupling equations to perform case studies. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

  5. Cell death biomarker M65 is a useful indicator of liver inflammation and fibrosis in chronic hepatitis B: A cross-sectional study of diagnostic accuracy.

    Science.gov (United States)

    Wei, Xinhuan; Wei, Hongshan; Lin, Wei; Hu, Zhongjie; Zhang, Jing

    2017-05-01

    Cell death markers, M65 and M30, have been suggested to be sensitive markers of liver inflammation and fibrosis in nonalcoholic fatty liver disease and chronic hepatitis C. Our aim was to investigate whether these markers were useful in diagnosing liver inflammation and fibrosis in chronic hepatitis B (CHB).We examined 186 patients with CHB; 18 sex- and age-matched healthy subjects were controls. The blood samples were collected from CHB patients within 1 week before or after liver biopsy. According to METAVIR score system, liver inflammation was graded from A0 to A3, and fibrosis from F0 to F4.Serum M65 and M30 levels were in parallel with the grades of liver inflammation. M65, not M30, increased significantly in patients with severe inflammation and normal alanine aminotransferase. M65 is one of the independent predictors of severe liver inflammation (≥A2). The levels of M65 and M30 levels significantly increased in parallel with the degree of inflammation in F1 patients, whereas they showed no statistical difference between different stages of fibrosis in A1 patients.Serum M65 is a useful indicator of liver inflammation in CHB patients. Serum M65, not M30, is valuable in the grading of liver fibrosis.

  6. Two cystic fibrosis transmembrane conductance regulator mutations have different effects on both pulmonary phenotype and regulation of outwardly rectified chloride currents.

    OpenAIRE

    Fulmer, S B; Schwiebert, E M; M.M. Morales; Guggino, W B; Cutting, G R

    1995-01-01

    Cystic fibrosis (CF), a disorder of electrolyte transport manifest in the lungs, pancreas, sweat duct, and vas deferens, is caused by mutations in the CF transmembrane conductance regulator (CFTR). The CFTR protein has been shown to function as a cAMP-activated chloride channel and also regulates a separate protein, the outwardly rectifying chloride channel (ORCC). To determine the consequence of disease-producing mutations upon these functions, mutant CFTR was transiently expressed in Xenopu...

  7. Global identification and analysis of isozyme-specific possible substrates crosslinked by transglutaminases using substrate peptides in mouse liver fibrosis

    Science.gov (United States)

    Tatsukawa, Hideki; Tani, Yuji; Otsu, Risa; Nakagawa, Haruka; Hitomi, Kiyotaka

    2017-01-01

    The transglutaminase (TG) family comprises eight isozymes that form the isopeptide bonds between glutamine and lysine residues and contribute to the fibrotic diseases via crosslinking-mediated stabilization of ECM and the activation of TGF-β in several tissues. However, despite a growing body of evidence implicating TG2 as a key enzyme in fibrosis, the causative role of TG2 and the involvement of the other isozymes have not yet been fully elucidated. Therefore, here we clarified the distributions of TG isozymes and their in situ activities and identified the isozyme-specific possible substrates for both TG1 and TG2 using their substrate peptides in mouse fibrotic liver. We found that TG1 activity was markedly enhanced intracellularly over a widespread area, whereas TG2 activity increased in the extracellular space. In total, 43 and 42 possible substrates were identified for TG1 and TG2, respectively, as involved in chromatin organization and cellular component morphogenesis. These included keratin 18, a biomarker for hepatic injury, which was accumulated in the fibrotic liver and showed the partly similar distribution with TG1 activity. These findings suggest that TG1 activity may be involved in the functional modification of intracellular proteins, whereas TG2 activity contributes to the stabilization of extracellular proteins during liver fibrosis. PMID:28327670

  8. 特发性肺纤维化急性加重的研究进展%Current progress in acute exacerbations of idiopathic pulmonary fibrosis

    Institute of Scientific and Technical Information of China (English)

    马兆娟

    2012-01-01

    Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) is a sudden, unpredictable clinical deterioration, which emerges in the course of idiopathic pulmonary fibrosis. It is a serious disease with high mortality and not uncommon in clinical practice. So far, the etiology and pathogenesis of AE-IPF is unclear. The existing diagnostic criteria of AE-IPF are controversial and there is still lack of effective Methods for treatment of AE-IPF.%特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)患者病程中出现的突然的、不可预测的临床急剧恶化称为特发性肺纤维化急性加重(acute exacerbations of idiopathic pulmonary fibrosis以下称为AE-IPF).其病情凶险,病死率高,且临床并非少见.目前AE-IPF病因、机制未明,现有的诊断标准尚有争议,缺乏有效的治疗措施,是临床医生面临的诊治难点之一.

  9. Impact of gene patents and licensing practices on access to genetic testing for cystic fibrosis.

    Science.gov (United States)

    Chandrasekharan, Subhashini; Heaney, Christopher; James, Tamara; Conover, Chris; Cook-Deegan, Robert

    2010-04-01

    Cystic fibrosis is one of the most commonly tested autosomal recessive disorders in the United States. Clinical cystic fibrosis is associated with mutations in the CFTR gene, of which the most common mutation among Caucasians, DeltaF508, was identified in 1989. The University of Michigan, Johns Hopkins University, and the Hospital for Sick Children, where much of the initial research occurred, hold key patents on cystic fibrosis genetic sequences, mutations, and methods for detecting them. Several patents, including the one that covers detection of the DeltaF508 mutation, are jointly held by the University of Michigan and the Hospital for Sick Children in Toronto, with Michigan administering patent licensing in the United States. The University of Michigan broadly licenses the DeltaF508 patent for genetic testing with >60 providers of genetic testing to date. Genetic testing is now used in newborn screening, diagnosis, and for carrier screening. Interviews with key researchers and intellectual property managers, a survey of laboratories' prices for cystic fibrosis genetic testing, a review of literature on cystic fibrosis tests' cost-effectiveness, and a review of the developing market for cystic fibrosis testing provide no evidence that patents have significantly hindered access to genetic tests for cystic fibrosis or prevented financially cost-effective screening. Current licensing practices for cystic fibrosis genetic testing seem to facilitate both academic research and commercial testing. More than 1000 different CFTR mutations have been identified, and research continues to determine their clinical significance. Patents have been nonexclusively licensed for diagnostic use and have been variably licensed for gene transfer and other therapeutic applications. The Cystic Fibrosis Foundation has been engaged in licensing decisions, making cystic fibrosis a model of collaborative and cooperative patenting and licensing practice.

  10. Cystic fibrosis lung disease in adult patients.

    Science.gov (United States)

    Vender, Robert L

    2008-04-01

    As the longevity of all patients with cystic fibrosis (CF) continues to increase (median 2005 survival=36.8 years), more adult patients will be receiving their medical care from nonpediatric adult-care providers. Cystic fibrosis remains a fatal disease, with more than 80% of patients dying after the age of 18 years, and most deaths resulting from pulmonary disease. The changing epidemiology requires adult-care providers to become knowledgeable and competent in the clinical management of adults with CF. Physicians must understand the influence of specific genotype on phenotypic disease presentation and severity, the pathogenic factors determining lung disease onset and progression, the impact of comorbid disease factors such as CF-related diabetes and malnutrition upon lung disease severity, and the currently approved or standard accepted therapies used for chronic management of CF lung disease. This knowledge is critical to help alleviate morbidity and improve mortality for the rapidly expanding population of adults with CF.

  11. Gadolinium-Induced Fibrosis.

    Science.gov (United States)

    Todd, Derrick J; Kay, Jonathan

    2016-01-01

    Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.

  12. Assessing health status and quality of life in idiopathic pulmonary fibrosis: which measure should be used?

    Science.gov (United States)

    De Vries, J; Seebregts, A; Drent, M

    2000-03-01

    Many studies conducted on the health status and quality of life (QOL) of patients with certain chronic diseases have demonstrated that their disease had an impact on their lives. However, less is known about the QOL and health status of patients suffering from idiopathic pulmonary fibrosis (IPF). In the present study, three focus groups of IPF patients (n=10) were run to identify the aspects of QOL or health status that are relevant to this population and to establish which measure is preferable to assess these aspects. The patients completed and discussed the St. George's Respiratory Questionnaire (SGRQ) and the World Health Organization Quality of Life assessment instrument (WHOQOL-100). Results indicated that hobbies/leisure activities, mobility, transport, social relationships, working capacity, energy and doing things slower were aspects relevant to IPF patients' QOL. The WHOQOL-100, with an additional social support questionnaire, appeared to be preferable.

  13. CYSTIC FIBROSIS: MICROBIOLOGY AND HOST RESPONSE

    Science.gov (United States)

    Zemanick, Edith T.

    2016-01-01

    THE EARLIEST DESCRIPTIONS OF LUNG DISEASE IN PEOPLE WITH CYSTIC FIBROSIS (CF) DEMONSTRATED THE INVOLVEMENT OF THREE INTERACTING PATHOPHYSIOLOGICAL ELEMENTS IN CF AIRWAYS: MUCUS OBSTRUCTION, INFLAMMATION, AND INFECTION. OVER THE PAST 7 DECADES, OUR UNDERSTANDING OF CF RESPIRATORY MICROBIOLOGY AND INFLAMMATION HAS EVOLVED WITH THE INTRODUCTION OF NEW TREATMENTS, WITH INCREASED LONGEVITY, AND WITH INCREASINGLY SOPHISTICATED LABORATORY TECHNIQUES. IN THIS CHAPTER, WE WILL REVIEW THE CURRENT STATE OF UNDERSTANDING OF THE ROLES OF INFECTION AND INFLAMMATION AND THEIR ROLES IN DRIVING LUNG DISEASE. WE WILL ALSO DISCUSS HOW THIS CONSTANTLY EVOLVING INFORMATION IS USED TO INFORM CURRENT THERAPEUTIC STRATEGIES, MEASURES AND PREDICTORS OF DISEASE SEVERITY, AND RESEARCH PRIORITIES. PMID:27469179

  14. Continuous glucose monitoring: current clinical use.

    Science.gov (United States)

    Kim, Hun-Sung; Shin, Jeong-Ah; Chang, Jin-Sun; Cho, Jae-Hyoung; Son, Ho-Young; Yoon, Kun-Ho

    2012-12-01

    Four kinds of subcutaneous continuous glucose monitoring (CGM) machines have been currently introduced in clinical practice. These machines exhibit real-time glucose on the monitor every 5 minutes and have alarms to indicate hypoglycaemia and hyperglycaemia. However, thus far, there is no clear consensus about the clinical indications for CGM in actual clinical practice. CGM should be an ideal and powerful tool for monitoring glucose variability. Glycaemic variability has become a major concern over the years with growing evidence on its detrimental impact with respect to the risk of diabetic complications. Although the HbA1c level is ubiquitously measures in clinical practice, this level does not adequately represent glycaemic variability. Currently available evidence indicates that CGM aids in lowering the HbA1c level without increasing the incidence of severe hypoglycaemic episodes in patients with type 1 diabetes. Thus far, CGM has not been indicated for preventing severe hypoglycaemia or for treating type 2 diabetes because sufficient supporting evidence has not been obtained. Promising results have been obtained for the use of CGM for pregnant women with diabetes and for patients with hospital hyperglycaemia. Predictions regarding the feasibility of the closed-loop system have proven to be optimistic. CGM-integrated communication systems using information technology such as smart phone help controlling blood glucose more easily and effectively.

  15. We can handle this: parents' use of religion in the first year following their child's diagnosis with cystic fibrosis.

    Science.gov (United States)

    Grossoehme, Daniel H; Ragsdale, Judy; Wooldridge, Jamie L; Cotton, Sian; Seid, Michael

    2010-01-01

    The diagnosis of a child's life-shortening disease leads many American parents to utilize religious beliefs. Models relating religious constructs to health have been proposed. Still lacking are inductive models based on parent experience. The specific aims of this study were: 1. develop a grounded theory of parental use of religion in the year after diagnosis; 2. describe whether parents understand a relationship between their religious beliefs and their follow-through with their child's at-home treatment regimen. Fifteen parent interviews were analyzed using grounded theory method. Parents used religion to make meaning of their child's cystic fibrosis (CF) diagnosis. Parents imagined God as active, benevolent, and interventionist; found hope in their beliefs; felt supported by God; and related religion to their motivation to adhere to their child's treatment plan. Religious beliefs are clinically significant in working with many parents of children recently diagnosed with CF. Interventions that improve adherence to treatment may be enhanced by including religious aspects.

  16. Visible Red Light Emitting Diode Photobiomodulation for Skin Fibrosis: Key Molecular Pathways.

    Science.gov (United States)

    Mamalis, Andrew; Siegel, Daniel; Jagdeo, Jared

    Skin fibrosis, also known as skin scarring, is an important global health problem that affects an estimated 100 million persons per year worldwide. Current therapies are associated with significant side effects and even with combination therapy, progression, and recurrence is common. Our goal is to review the available published data available on light-emitting diode-generated (LED) red light phototherapy for treatment of skin fibrosis. A search of the published literature from 1 January 2000 to present on the effects of visible red light on skin fibrosis, and related pathways was performed in January 2016. A search of PubMed and EMBASE was completed using specific keywords and MeSH terms. "Fibrosis" OR "skin fibrosis" OR "collagen" was combined with ("light emitting diode," "LED," "laser," or "red light"). The articles that were original research studies investigating the use of visible red light to treat skin fibrosis or related pathways were selected for inclusion. Our systematic search returned a total of 1376 articles. Duplicate articles were removed resulting in 1189 unique articles, and 133 non-English articles were excluded. From these articles, we identified six articles related to LED effects on skin fibrosis and dermal fibroblasts. We augmented our discussion with additional in vitro data on related pathways. LED phototherapy is an emerging therapeutic modality for treatment of skin fibrosis. There is a growing body of evidence demonstrating that visible LED light, especially in the red spectrum, is capable of modulating key cellular characteristic associated with skin fibrosis. We anticipate that as the understanding of LED-RL's biochemical mechanisms and clinical effects continue to advance, additional therapeutic targets in related pathways may emerge. We believe that the use of LED-RL, in combination with existing and new therapies, has the potential to alter the current treatment paradigm of skin fibrosis. There is a current lack of clinical trials

  17. Cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Radlović Nedeljko

    2012-01-01

    Full Text Available Cystic fibrosis (CF is a multisystemic autosomal recessive disease caused by a defect in the expression of CFTR protein, i.e. chloride channel present in the apical membrane of respiratory, digestive, reproductive and sweat glands epithelium. It primarily occurs in the Caucasians, while being considerably or exceptionally rare in persons of other races. Absence, deficit or structural and functional abnormalities of CFTR protein lead to mucosal hyperconcentration in the respiratory, digestive and reproductive systems and malabsorption of chloride and sodium in the sweat glands. Thus, the clinical features of patients’ with CF are predominated by respiratory, digestive and reproductive disorders, as well as the tendency to dehydration in the condition of increased sweating. Beside genotype variations, the degree of disease manifestation is also essentially influenced by various exogenous factors, such as the frequency and severity of respiratory infections, the level of aero-pollution, quality of immunoprophylaxis, patients’ nutritional condition and other. Chloride concentration of over 60 mmol/L in sweat, a high level of immunoreactive chymotrypsinogen in blood and the verification of homozygous mutation of CFTR gene are the basic methods in the diagnostics of the disease. CF belongs to the group of severe and complex chronic diseases, and therefore requires multidisciplinary therapeutic approach. Owing to the improvement of healthcare provision, most patients with CF now survive into adulthood. In addition, their quality of life is also considerably improved.

  18. The improving of ventilometric indices using Airway Clearance Techniques Asociated with Inhalation Therapy applied to adolescents with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Bogdan Almăjan-Guţă

    2010-12-01

    Full Text Available Introduction: this study gave particular attention to respiratory damage, lung disease being the main target for developingtherapies in MV. The purpose of this study was to demonstrate the efficiency of Classical Respiratory clearance techniquescombined with Inhalation Therapy and to compare the results of using acetylcysteine with those of using Pulmozyme Therapy.Aerosol (inhalation therapy is, along with exercise and respiratory clearance techniques, the third component in thephysiotherapy of patients with CF. Material and method: the study was developed during a period of six months, in TheNational Center of Cystic Fibrosis, Clinic II of Pediatrics in the Emergency County Hospital, Timisoara. The study group consistedof 12 children with MV . This group was divided into two groups of 6 patients (group 1 and group 2. Group 1 followedinhalation treatment with acetylcysteine, and group 2 with Pulmozyme. Results: The evaluation of the results was done after 2months and 6 months since the study started, by measuring the FEV, and FVC. For the first group, that used acetylcysteine inthe inhalation therapy, we observed, after 6 months, an increase of FEV with an average of 2.08% and of FVC with 2.13%.Thegrowth of ventilometric indices were relatively accelerated in the first two months and later there was a slower growth,achieving final value. For the second group, that used Pulmozyme, the growth of ventilometric indices was significantly higher.Discussion: considering the two relatively homogeneous groups, in what concerns the values of ventilometric indices andsuperimposed infection, we believe that inhaled Pulmozyme therapy proved to be superior to acetylcysteine. Conclusions:inhalation therapy is an important part of physiotherapy for patients with cystic fibrosis. A consistent physiotherapy is probablythe most important element in preventing chronic pulmonary infection and, along with antibiotherapy, improves significantlythe prognosis and helps

  19. Fault current limiter using bulk oxides superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Belmont, O.; Ferracci, P.; Porcar, L.; Barbut, J.M. [Schneider Electric, Grenoble (France). Usine A3; Tixador, P.; Noudem, J.G.; Bourgault, D.; Tournier, R

    1998-08-01

    We study the limitation possibilities of bulk Bi high T{sub c} materials. For this we test these materials with AC or DC currents above their critical currents. We study particularly the evolution of the voltage with time or with current. The material, the value of the current and the time duration play important parts. For sintered Bi samples the voltage depends only on the current even for values much larger than the critical current. With textured samples the V(I) curves shows an hysteretic behaviour due to a warming up. The textured materials are more interesting than sintered ones in terms of required volume for the current limitation. In both cases the superconductors are in a dissipative state but not in the normal state. This state is nevertheless reached if the dissipated energy inside the sample is sufficient. We have tried to apply a magnetic field on the samples in order to trigger a more effective limitation. The voltage increases but with a limited effect for currents much higher (3-4 times) than the critical zero field current. We think that the dissipative state is due mainly to the grain boundaries which become resistive above the critical current. (orig.) 11 refs.

  20. Usefulness of an index score as a predictor of hepatic fibrosis in obese patients undergoing bariatric surgery Utilidad de un índice de puntuación como predictor de fibrosis hepática en pacientes obesos sometidos a cirugía bariátrica

    Directory of Open Access Journals (Sweden)

    R. Díez Rodríguez

    2009-08-01

    Full Text Available Objective: to evaluate the usefulness of a non-invasive clinical score to predict liver fibrosis in the steatosis associated with morbid obesity. Patients and methods: we included 88 patients, who underwent bariatric surgery in the Sanitary Area of León, Spain, and who showed a liver biopsy with steatosis greater than 5%. This is a retrospective study in which the rate of fibrosis is calculated from tests performed during the preoperative period, and is then compared to data from intraoperative hepatic biopsies. The analysis population was grouped according to the presence of advanced fibrosis in the liver biopsy (grade 3-4 or its absence (grade 0-2. The cutoff used for diagnosing advanced fibrosis was 0.676 (high cutoff point, and the cutoff point to exclude advanced fibrosis was -1.455 (low cutoff. Results: the prevalence of advanced fibrosis in the histological samples was 5.5%, and 65.9% of patients had no fibrosis. The cutoff for a low negative predictive value was 100%, and sensitivity was 100%. The cutoff point for a high positive predictive value was 1.7%, and specificity was 31.3%. Conclusions: this scoring system for morbidly obese patients eligible for bariatric surgery allows to identify those without advanced fibrosis, but cannot predict who may have advanced fibrosis.Objetivo: evaluar la utilidad de un índice de puntuación clínica no invasivo para predecir fibrosis hepática en la esteatosis asociada a la obesidad mórbida. Pacientes y métodos: se incluyeron 88 pacientes, intervenidos de cirugía bariátrica en el área sanitaria de León, que presentaron en la biopsia hepática una esteatosis mayor del 5%. Se trata de un estudio retrospectivo en el que se calculó el índice de fibrosis a partir de los datos analíticos del preoperatorio, y se comparó su resultado con los datos de la biopsia hepática intraoperatoria realizada. Para el análisis los pacientes fueron agrupados según presentaban en la biopsia hep

  1. An American Thoracic Society Official Research Statement: Future Directions in Lung Fibrosis Research.

    Science.gov (United States)

    White, Eric S; Borok, Zea; Brown, Kevin K; Eickelberg, Oliver; Guenther, Andreas; Jenkins, R Gisli; Kolb, Martin; Martinez, Fernando J; Roman, Jesse; Sime, Patricia

    2016-04-01

    Pulmonary fibrosis encompasses a group of lung-scarring disorders that occur owing to known or unknown insults and accounts for significant morbidity and mortality. Despite intense investigation spanning decades, much remains to be learned about the natural history, pathophysiology, and biologic mechanisms of disease. To identify the most pressing research needs in the lung fibrosis community and to provide a roadmap of priorities to investigators, funding agencies, patient advocacy groups, and other interested stakeholders. An ad hoc international working group of the American Thoracic Society with experience in clinical, translational, and bench-based research in fibrotic lung diseases was convened. The group used an iterative consensus process to identify successes and challenges in pulmonary fibrosis research. The group identified five main priority areas in which substantial resources should be invested to advance our understanding and to develop novel therapies for patients with pulmonary fibrosis. These priorities include develop newer models of human lung fibrosis, engage current and new stakeholders to provide sustained funding for the initiatives, create a global infrastructure for storing patient-derived materials, establish collaborative preclinical and clinical research networks in fibrotic lung disease, and create a global lung fibrosis initiative that unites these multifaceted efforts into a single virtual umbrella structure. Despite recent advances in the treatment of some forms of lung fibrosis, many gaps in knowledge about natural history, pathophysiology, and treatment remain. Investment in the research priorities enumerated above will help address these shortcomings and enhance patient care worldwide.

  2. Plasma biomarker screening for liver fibrosis with the N-terminal isotope tagging strategy.

    Science.gov (United States)

    Li, ShuLong; Liu, Xin; Wei, Lai; Wang, HuiFen; Zhang, JiYang; Wei, HanDong; Qian, XiaoHong; Jiang, Ying; He, FuChu

    2011-05-01

    A non-invasive diagnostic approach is crucial for the evaluation of severity of liver disease, treatment decisions, and assessing drug efficacy. This study evaluated plasma proteomic profiling via an N-terminal isotope tagging strategy coupled with liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry measurement to detect liver fibrosis staging. Pooled plasma from different liver fibrosis stages, which were assessed in advance by the current gold-standard of liver biopsy, was quantitatively analyzed. A total of 72 plasma proteins were found to be dysregulated during the fibrogenesis process, and this finding constituted a valuable candidate plasma biomarker bank for follow-up analysis. Validation results of fibronectin by Western blotting reconfirmed the mass-based data. Ingenuity Pathways Analysis showed four types of metabolic networks for the functional effect of liver fibrosis disease in chronic hepatitis B patients. Consequently, quantitative proteomics via the N-terminal acetyl isotope labeling technique provides an effective and useful tool for screening plasma candidate biomarkers for liver fibrosis. We quantitatively monitored the fibrogenesis process in CHB patients. We discovered many new valuable candidate biomarkers for the diagnosis of liver fibrosis and also partly identified the mechanism involved in liver fibrosis disease. These results provide a clearer understanding of liver fibrosis pathophysiology and will also hopefully lead to improvement of clinical diagnosis and treatment.

  3. Self-reported use of vitamins and other nutritional supplements in adult patients with cystic fibrosis. Is daily practice in concordance with recommendations?

    NARCIS (Netherlands)

    Hollander, F.M.; Roos, de N.M.; Dopheide, J.

    2010-01-01

    Background: In cystic fibrosis (CF), prophylactic supplementation of the fat-soluble vitamins A, D, E, and K is recommended. Limited data is available describing vitamin prescription adherence by adult patients. The aim of this study was to assess the use of prescribed vitamins and other nutritional

  4. What Causes Cystic Fibrosis?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Cystic Fibrosis? A defect in the CFTR gene causes cystic ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  5. Learning about Cystic Fibrosis

    Science.gov (United States)

    ... Testing for Cystic Fibrosis Consensus Development Conference Statement Learning About Cystic Fibrosis What do we know about ... and treatment information. Hosted by the Dolan DNA Learning Center at Cold Spring Harbor Laboratory. What is ...

  6. Cystic fibrosis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui [Gachon Medical School, Inchon (Korea, Republic of)

    2002-12-01

    Cystic fibrosis is an autosomal recessive genetic disease. Among Caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among Caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis.

  7. Simulation of Gravity Currents Using VOF Model

    Institute of Scientific and Technical Information of China (English)

    邹建锋; 黄钰期; 应新亚; 任安禄

    2002-01-01

    By the Volume of Fluid (VOF) multiphase flow model two-dimensional gravity currents with three phases including air are numerically simulated in this article. The necessity of consideration of turbulence effect for high Reynolds numbers is demonstrated quantitatively by LES (the Large Eddy Simulation) turbulence model. The gravity currents are simulated for h ≠ H as well as h = H, where h is the depth of the gravity current before the release and H is the depth of the intruded fluid. Uprising of swell occurs when a current flows horizontally into another lighter one for h ≠ H. The problems under what condition the uprising of swell occurs and how long it takes are considered in this article. All the simulated results are in reasonable agreement with the experimental results available.

  8. Cardiovascular magnetic resonance imaging to assess myocardial fibrosis in valvular heart disease.

    Science.gov (United States)

    Podlesnikar, Tomaz; Delgado, Victoria; Bax, Jeroen J

    2017-06-22

    The left ventricular (LV) remodeling process associated with significant valvular heart disease (VHD) is characterized by an increase of myocardial interstitial space with deposition of collagen and loss of myofibers. These changes occur before LV systolic function deteriorates or the patient develops symptoms. Cardiovascular magnetic resonance (CMR) permits assessment of reactive fibrosis, with the use of T1 mapping techniques, and replacement fibrosis, with the use of late gadolinium contrast enhancement. In addition, functional consequences of these structural changes can be evaluated with myocardial tagging and feature tracking CMR, which assess the active deformation (strain) of the LV myocardium. Several studies have demonstrated that CMR techniques may be more sensitive than the conventional measures (LV ejection fraction or LV dimensions) to detect these structural and functional changes in patients with severe left-sided VHD and have shown that myocardial fibrosis may not be reversible after valve surgery. More important, the presence of myocardial fibrosis has been associated with lesser improvement in clinical symptoms and recovery of LV systolic function. Whether assessment of myocardial fibrosis may better select the patients with severe left-sided VHD who may benefit from surgery in terms of LV function and clinical symptoms improvement needs to be demonstrated in prospective studies. The present review article summarizes the current status of CMR techniques to assess myocardial fibrosis and appraises the current evidence on the use of these techniques for risk stratification of patients with severe aortic stenosis or regurgitation and mitral regurgitation.

  9. Serum hyaluronic acid as a noninvasive marker of hepatic fibrosis in chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    Geramizadeh Bita

    2008-01-01

    Full Text Available Background/Aims: Chronic hepatitis B is a serious global health problem. Liver biopsy is currently recommended as the gold standard for the evaluation of the degree of fibrosis in patients with chronic hepatitis B. This procedure, however, is invasive and has potential complications. In this study, we attempted to validate the level of hyaluronic acid as a simple laboratory test to discriminate between patients with and without significant fibrosis in chronic hepatitis B. Methods: This study included 93 patients with chronic hepatitis B who had undergone percutaneous liver biopsy from 2003 to 2006. At the time of biopsy, a sample of serum was taken for the hyaluronic acid (HA assay. Histological assessment consisted of the semiquantitative analysis of the degree of fibrosis according to the criteria proposed by the Ishak system. These findings were then compared by using statistical analysis. Results: HA levels and stage groups of fibrosis were well correlated (Spearman r = 0.945, P < 0.005. There was a significant increase in HA levels when considering S0 to S6. The mean values of HA concentrations were 59.7 ± 10.5 ng/mL for stages 0-2, 149.4 ± 15.9 ng/mL for stages 3-4 , and 284.5 ± 14.5 ng/mL for the last group (stages 5-6. There were significant differences between the three groups. Serum HA levels of cases with extensive fibrosis were significantly higher than in those with mild and moderate fibrosis ( P = 0.0001, P = 0.0005, and P = 0.0001, respectively. Conclusion: Serum HA level is a precise predictor of extensive liver fibrosis in chronic hepatitis B. HA is well correlated with the stage of fibrosis and can reflect the severity of fibrosis. Thus, it can be used as a noninvasive test to monitor these patients.

  10. Enteral tube feeding for individuals with cystic fibrosis: Cystic Fibrosis Foundation evidence-informed guidelines.

    Science.gov (United States)

    Schwarzenberg, Sarah Jane; Hempstead, Sarah E; McDonald, Catherine M; Powers, Scott W; Wooldridge, Jamie; Blair, Shaina; Freedman, Steven; Harrington, Elaine; Murphy, Peter J; Palmer, Lena; Schrader, Amy E; Shiel, Kyle; Sullivan, Jillian; Wallentine, Melissa; Marshall, Bruce C; Leonard, Amanda Radmer

    2016-11-01

    Nutrition is integral to the care of individuals with cystic fibrosis (CF). Better nutritional status is associated with improved pulmonary function. In some individuals with CF, enteral tube feeding can be useful in achieving optimal nutritional status. Current nutrition guidelines do not include detailed recommendations for enteral tube feeding. The Cystic Fibrosis Foundation convened an expert panel to develop enteral tube feeding recommendations based on a systematic review of the evidence and expert opinion. These guidelines address when to consider enteral tube feeding, assessment of confounding causes of poor nutrition in CF, preparation of the patient for placement of the enteral feeding tube, management of the tube after placement and education about enteral feeding. These recommendations are intended to guide the CF care team, individuals with CF, and their families through the enteral tube feeding process.

  11. Cost-Effectiveness Analysis: Risk Stratification of Nonalcoholic Fatty Liver Disease (NAFLD by the Primary Care Physician Using the NAFLD Fibrosis Score.

    Directory of Open Access Journals (Sweden)

    Elliot B Tapper

    Full Text Available The complications of Nonalcoholic Fatty Liver Disease (NAFLD are dependent on the presence of advanced fibrosis. Given the high prevalence of NAFLD in the US, the optimal evaluation of NAFLD likely involves triage by a primary care physician (PCP with advanced disease managed by gastroenterologists.We compared the cost-effectiveness of fibrosis risk-assessment strategies in a cohort of 10,000 simulated American patients with NAFLD performed in either PCP or referral clinics using a decision analytical microsimulation state-transition model. The strategies included use of vibration-controlled transient elastography (VCTE, the NAFLD fibrosis score (NFS, combination testing with NFS and VCTE, and liver biopsy (usual care by a specialist only. NFS and VCTE performance was obtained from a prospective cohort of 164 patients with NAFLD. Outcomes included cost per quality adjusted life year (QALY and correct classification of fibrosis.Risk-stratification by the PCP using the NFS alone costs $5,985 per QALY while usual care costs $7,229/QALY. In the microsimulation, at a willingness-to-pay threshold of $100,000, the NFS alone in PCP clinic was the most cost-effective strategy in 94.2% of samples, followed by combination NFS/VCTE in the PCP clinic (5.6% and usual care in 0.2%. The NFS based strategies yield the best biopsy-correct classification ratios (3.5 while the NFS/VCTE and usual care strategies yield more correct-classifications of advanced fibrosis at the cost of 3 and 37 additional biopsies per classification.Risk-stratification of patients with NAFLD primary care clinic is a cost-effective strategy that should be formally explored in clinical practice.

  12. Temperature compensated and self-calibrated current sensor using reference current

    Science.gov (United States)

    Yakymyshyn, Christopher Paul; Brubaker, Michael Allen; Yakymyshyn, Pamela Jane

    2008-01-22

    A method is described to provide temperature compensation and self-calibration of a current sensor based on a plurality of magnetic field sensors positioned around a current carrying conductor. A reference electrical current carried by a conductor positioned within the sensing window of the current sensor is used to correct variations in the output signal due to temperature variations and aging.

  13. The reticular network contributes to the staging of idiopathic lung fibrosis

    Directory of Open Access Journals (Sweden)

    Djeska Irina Stoia

    2013-01-01

    Full Text Available The aspect of reticular fibers is not considered in the current classifications of lung fibrosis. The aim of our study was to evaluate the distribution and the architecture of the reticular fibers for potential use as a tissue marker of fibrosis severity. We included in our study 25 pulmonary samples obtained by video-assisted thoracoscopy surgery (VATS from a number of 20 cases. The cases were subdivided according to four criteria into: degree II, III and IV. We noticed no significant changes in the reticular network from interalveolar septa to the cases scored with 0, an accumulation of reticular fibers in the interalveolar septa (stage II, the condensation and thick bundles with network disorganization in all areas affected by fibrosis (stage III, partial to full depletion of reticular fibers (stage IV. Depletion of reticular fibers was constantly associated with advanced fibrosis stages.

  14. Floating RC Networks Using Current Conveyors

    OpenAIRE

    Zeman, V; J. Cajka; Vrba, K.

    1996-01-01

    The paper deals with the design of floating one- and/or two-port high-order networks. The current conveyor CCII+ seems to be a suitable active building block for this purpose. Some examples of the above mentioned networks are shown .

  15. Floating RC Networks Using Current Conveyors

    Directory of Open Access Journals (Sweden)

    V. Zeman

    1996-06-01

    Full Text Available The paper deals with the design of floating one- and/or two-port high-order networks. The current conveyor CCII+ seems to be a suitable active building block for this purpose. Some examples of the above mentioned networks are shown .

  16. The effect of caffeine and alcohol consumption on liver fibrosis - a study of 1045 Asian hepatitis B patients using transient elastography.

    Science.gov (United States)

    Ong, Arlinking; Wong, Vincent Wai-Sun; Wong, Grace Lai-Hung; Chan, Henry Lik-Yuen

    2011-08-01

    Role of caffeine consumption in chronic hepatitis B virus (HBV)-infected patients and the interaction with alcohol consumption is unclear. This study aimed to investigate the relationship between caffeine and alcohol consumption and liver stiffness in chronic HBV-infected patients. Chronic HBV-infected patients who underwent transient elastography examination in 2006-2008 were studied. Advanced fibrosis was defined as liver stiffness > 9 kPa for patients with normal alanine aminotransferase (ALT) or > 12 kPa for those with elevated ALT according to previous validation study. Caffeine and alcohol consumption was recorded using a standardized questionnaire. Excessive alcohol intake was defined as 30 g/day in men and 20 g/day in women. The liver stiffness of 1045 patients who completed the questionnaire was 8.3 ± 6.2 kPa. Two hundred and sixteen (20.7%) patients had advanced fibrosis. Ninety-five (19.0%) patients who drank ≥ 1 cup of coffee had advanced fibrosis, compared with 121 (22.2%) patients who drank caffeine intake had positive correlation with the amount of alcohol intake (r(s) = 0.167, P consumption, only 11 (1%) had excessive alcohol intake. The prevalence of advanced fibrosis among patients with mild to moderate alcohol intake (26, 18.8%) was comparable to that among non-drinkers (190, 21.0%) (P = 0.57). Caffeine intake does not affect liver stiffness in chronic HBV-infected patients. Patients who drink coffee regularly tend to drink alcohol. Most chronic HBV-infected patients do not have excessive alcohol consumption. The prevalence of advanced fibrosis among mild to moderate alcohol drinkers was low in this population. © 2011 John Wiley & Sons A/S.

  17. Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Jun Tashiro

    2017-07-01

    Full Text Available Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF; yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM-induced pulmonary fibrosis—though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent. Additional studies that profile these examples of spontaneous fibroses in animals for similarities to human IPF should prove useful for both human and animal investigators. In the meantime, studies of BLM-induced fibrosis in aged male mice remain the most clinically relevant model for preclinical study for human IPF. Addressing issues such as time course of treatment, animal size and characteristics, clinically irrelevant treatment endpoints, and reproducibility of therapeutic outcomes will improve the current status of preclinical studies. Elucidating the mechanisms responsible for the development of fibrosis and disrepair associated with aging through a collaborative approach between researchers will promote the development of models that more accurately represent the realm of interstitial lung diseases in humans.

  18. Electronic health records: current and future use.

    Science.gov (United States)

    Peters, Steve G; Khan, Munawwar A

    2014-09-01

    This paper provides an overview of the current state of the electronic medical record, including benefits and shortcomings, and presents key factors likely to drive development in the next decade and beyond. The current electronic medical record to a large extent represents a digital version of the traditional paper legal record, owned and maintained by the practitioner. The future electronic health record is expected to be a shared tool, engaging patients in decision making, wellness and disease management and providing data for individual decision support, population management and analytics. Many drivers will determine this path, including payment model reform, proliferation of mobile platforms, telemedicine, genomics and individualized medicine and advances in 'big data' technologies.

  19. HOME CARE IN CYSTIC-FIBROSIS PATIENTS

    NARCIS (Netherlands)

    VANAALDEREN, WMC; MANNES, GPM; BOSMA, ES; ROORDA, RJ; HEYMANS, HSA

    1995-01-01

    Intravenous antibiotics and enteral tube feeding at home for the treatment of pulmonary exacerbations and underweight condition in cystic fibrosis (CF) patients have become tools that are used in many cystic fibrosis centres, The experience with home care programmes from different countries is quite

  20. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, Peter

    2008-01-01

    that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. One particular agent, gadodiamide, caused the majority of cases, but gadopentetate dimeglumine has also been implicated in several cases....... Increasingly poor renal function, aberrations in calcium-phosphate metabolism and erythropoietin treatment seem to increase the risk of the disease and its severity. Up to 25-30% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. The figure...

  1. [Nephrogenic systemic fibrosis].

    Science.gov (United States)

    Cavallini, L; Abaterusso, C; Bedogna, V; Pertica, N; Loschiavo, C; Lupo, A

    2008-01-01

    Nephrogenic systemic fibrosis (NSF) is a new, rare, and severe disease occurring in patients with renal failure who have been exposed to gadolinium. The pathogenesis of NSF is not completely known. In fact, the first warning about a significant relationship between NSF and gadolinium (a contrast medium used in magnetic resonance imaging) was only issued in 2006. No cases of NSF have been reported in Italy to date. A nationwide investigation should therefore be carried out to assess the real prevalence of NSF within the Italian uremic population. Furthermore, we need guidelines to reduce the risk of NSF in renal patients undergoing MRI with contrast medium.

  2. Quantitative analysis of regional airways obstruction using dynamic hyperpolarized 3He MRI-preliminary results in children with cystic fibrosis.

    Science.gov (United States)

    Koumellis, Panos; van Beek, Edwin J R; Woodhouse, Neil; Fichele, Stan; Swift, Andrew J; Paley, Martyn N J; Hill, Catherine; Taylor, Chris J; Wild, Jim M

    2005-09-01

    To investigate regional airways obstruction in patients with cystic fibrosis (CF) with quantitative analysis of dynamic hyperpolarized (HP) (3)He MRI. Dynamic radial projection MRI of HP (3)He gas was used to study respiratory dynamics in a group of eight children with CF. Signal kinetics in a total of seven regions of interest (ROIs; three in each lung, and one in the trachea) were compared with the results of spirometric pulmonary function tests (PFTs). The tracheal signal intensity was used as a form of "input function" to normalize for input flow effects. A pattern of low flow rate in the upper lobes was observed. When the flow measurements from the peripheral ROIs were averaged to obtain an index of flow in the peripheral lung, a good correlation was found (P = 3.74 x 10(-5)) with the forced expired volume in one second (FEV1). These results suggest that a quantitative measurement of localized airways obstruction in the early stages of CF may be obtained from dynamic (3)He MRI by using the slope of the signal rise as a measure of air flow into the peripheral lung. This study also demonstrates that children can cooperate well with the (3)He MRI technique. (c) 2005 Wiley-Liss, Inc.

  3. Doxycycline Attenuated Pulmonary Fibrosis Induced by Bleomycin in Mice

    OpenAIRE

    Fujita, Masaki; Ye, Qing; Ouchi, Hiroshi; Harada, Eiji; Inoshima, Ichiro; Kuwano, Kazuyoshi; Nakanishi, Yoichi

    2006-01-01

    The administration of doxycycline prior to bleomycin in mice attenuated pulmonary fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not caseinolytic activity, were attenuated by doxycycline. Established fibrosis was not affected by doxycycline. Thus, doxycycline might be useful for slowing down pulmonary fibrosis by biological activity other than antibacterial activity.

  4. [Laparoscopic treatment of retroperitoneal fibrosis].

    Science.gov (United States)

    Joual, Abdenbi; Rabii, Redouane; El Mejjad, Amine; Fekak, Hamid; Debbagh, Adil; El Mrini, Mohamed

    2004-04-01

    The authors report a case of idiopathic retroperitoneal fibrosis (RPF) in a 38-year-old man presenting with obstructive acute renal failure. The initial management consisted of urinary diversion by bilateral double-J ureteric stenting. After restoration of normal renal function, CT urography demonstrated retroperitoneal fibrosis surrounding the two ureters. Surgical treatment was performed by laparoscopy using four trocars. The operation consisted of detachment of the ascending and descending colon followed by release of the ureters from the lumbar segment to the pelvic segment and finally intraperitonealization of the ureters. The operating time was six hours, the postoperative course was uneventful and the double-J stents were removed at the third week. Laparoscopic treatment of RPF is a treatment option providing all of the benefits of minimally invasive surgery. In the light of this case and a review of the literature, the authors describe the laparoscopic treatment of idiopathic retroperitoneal fibrosis.

  5. The current research of the male cystic fibrosis with infertility%男性囊性纤维化伴不育的研究现状

    Institute of Scientific and Technical Information of China (English)

    李永伟

    2010-01-01

    囊性纤维化(cystic fibrosis,CF)是一种可以累及全身多个系统的常染色体隐性遗传病,是白种人最常见的致死性遗传性疾病,而在亚洲黄种人中较少见.由于50%的该疾病患者为成年人,并且这其中很多男性患者伴有不育等生殖方面的问题,通常表现为先天性双侧输精管缺如.但由于目前该疾病的诊治比较棘手,因此规范与CF相关的生殖健康方面的指南对这部分患者显得尤为重要.虽然国内该病发病率很低,但基于我国庞大的人口基数我们不能对该病掉以轻心.本文就目前男性囊性纤维化伴不育的研究现状作一综述.

  6. Improved In vivo Assessment of Pulmonary Fibrosis in Mice using X-Ray Dark-Field Radiography

    Science.gov (United States)

    Yaroshenko, Andre; Hellbach, Katharina; Yildirim, Ali Önder; Conlon, Thomas M.; Fernandez, Isis Enlil; Bech, Martin; Velroyen, Astrid; Meinel, Felix G.; Auweter, Sigrid; Reiser, Maximilian; Eickelberg, Oliver; Pfeiffer, Franz

    2015-12-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with a median life expectancy of 4-5 years after initial diagnosis. Early diagnosis and accurate monitoring of IPF are limited by a lack of sensitive imaging techniques that are able to visualize early fibrotic changes at the epithelial-mesenchymal interface. Here, we report a new x-ray imaging approach that directly visualizes the air-tissue interfaces in mice in vivo. This imaging method is based on the detection of small-angle x-ray scattering that occurs at the air-tissue interfaces in the lung. Small-angle scattering is detected with a Talbot-Lau interferometer, which provides the so-called x-ray dark-field signal. Using this imaging modality, we demonstrate-for the first time-the quantification of early pathogenic changes and their correlation with histological changes, as assessed by stereological morphometry. The presented radiography method is significantly more sensitive in detecting morphological changes compared with conventional x-ray imaging, and exhibits a significantly lower radiation dose than conventional x-ray CT. As a result of the improved imaging sensitivity, this new imaging modality could be used in future to reduce the number of animals required for pulmonary research studies.

  7. Roger S. Mitchell lecture. Uses of expression microarrays in studies of pulmonary fibrosis, asthma, acute lung injury, and emphysema.

    Science.gov (United States)

    Sheppard, Dean

    2002-03-01

    Expression microarrays are a powerful tool that could provide new information about the molecular pathways regulating common lung diseases. To exemplify how this tool can be useful, selected examples of informative experiments are reviewed. In studies relevant to asthma, the cytokine interleukin-13 has been shown to produce many of the phenotypic features of this disease, but the cellular targets in the airways and the molecular pathways activated are largely unknown. We have used microarrays to begin to dissect the different transcriptional responses of primary lung cells to this cytokine. In experiments designed to identify global transcriptional programs responsible for regulating lung inflammation and pulmonary fibrosis, we performed microarray experiments on lung tissue from wild-type mice and mice lacking a member of the integrin family know to be involved in activation of latent transforming growth factor (TGF)-beta. In addition to identifying distinct cluster of genes involved in each of these processes, these studies led to the identification of novel pathways by which TGF-beta can regulate acute lung injury and emphysema. Together, these examples demonstrate how careful application and thorough analysis of expression microarrays can facilitate the discovery of novel molecular targets for intervening in common lung diseases.

  8. Use of Selective Fungal Culture Media Increases Rates of Detection of Fungi in the Respiratory Tract of Cystic Fibrosis Patients.

    Science.gov (United States)

    Hong, Gina; Miller, Heather B; Allgood, Sarah; Lee, Richard; Lechtzin, Noah; Zhang, Sean X

    2017-04-01

    The prevalence of fungi in the respiratory tracts of cystic fibrosis (CF) patients has risen. However, fungal surveillance is not routinely performed in most clinical centers in the United States, which may lead to an underestimation of the true prevalence of the problem. We conducted a prospective study comparing the rates of detection for clinically important fungi (CIF), defined as Aspergillus, Scedosporium, and Trichosporon species and Exophiala dermatitidis, in CF sputa using standard bacterial and selective fungal culture media, including Sabouraud dextrose agar with gentamicin (SDA), inhibitory mold agar (IMA), and brain heart infusion (BHI) agar with chloramphenicol and gentamicin. We described the prevalence of these fungi in an adult CF population. A total of 487 CF respiratory samples were collected from 211 unique participants. CIF were detected in 184 (37.8%) samples. Only 26.1% of CIF-positive samples were detected in bacterial culture medium, whereas greater rates of detection for fungi were found in IMA (65.8%; P fungi by bacterial culture alone. The prevalence of fungi in CF may be better estimated by using selective fungal culture media, and this may translate to important clinical decisions. Copyright © 2017 American Society for Microbiology.

  9. Molecular analysis using DHPLC of cystic fibrosis: increase of the mutation detection rate among the affected population in Central Italy

    Directory of Open Access Journals (Sweden)

    Nardone Anna

    2004-04-01

    Full Text Available Abstract Background Cystic fibrosis (CF is a multisystem disorder characterised by mutations of the CFTR gene, which encodes for an important component in the coordination of electrolyte movement across of epithelial cell membranes. Symptoms are pulmonary disease, pancreatic exocrine insufficiency, male infertility and elevated sweat concentrations. The CFTR gene has numerous mutations (>1000 and functionally important polymorphisms (>200. Early identification is important to provide appropriate therapeutic interventions, prognostic and genetic counselling and to ensure access to specialised medical services. However, molecular diagnosis by direct mutation screening has proved difficult in certain ethnic groups due to allelic heterogeneity and variable frequency of causative mutations. Methods We applied a gene scanning approach using DHPLC system for analysing specifically all CFTR exons and characterise sequence variations in a subgroup of CF Italian patients from the Lazio region (Central Italy characterised by an extensive allelic heterogeneity. Results We have identified a total of 36 different mutations representing 88% of the CF chromosomes. Among these are two novel CFTR mutations, including one missense (H199R and one microdeletion (4167delCTAAGCC. Conclusion Using this approach, we were able to increase our standard power rate of mutation detection of about 11% (77% vs. 88%.

  10. Statistics used in current nursing research.

    Science.gov (United States)

    Zellner, Kathleen; Boerst, Connie J; Tabb, Wil

    2007-02-01

    Undergraduate nursing research courses should emphasize the statistics most commonly used in the nursing literature to strengthen students' and beginning researchers' understanding of them. To determine the most commonly used statistics, we reviewed all quantitative research articles published in 13 nursing journals in 2000. The findings supported Beitz's categorization of kinds of statistics. Ten primary statistics used in 80% of nursing research published in 2000 were identified. We recommend that the appropriate use of those top 10 statistics be emphasized in undergraduate nursing education and that the nursing profession continue to advocate for the use of methods (e.g., power analysis, odds ratio) that may contribute to the advancement of nursing research.

  11. End-use taxes: Current EIA practices

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-17

    There are inconsistencies in the EIA published end-use price data with respect to Federal, state, and local government sales and excise taxes; some publications include end-use taxes and others do not. The reason for including these taxes in end-use energy prices is to provide consistent and accurate information on the total cost of energy purchased by the final consumer. Preliminary estimates are made of the effect on prices (bias) reported in SEPER (State Energy Price and Expenditure Report) resulting from the inconsistent treatment of taxes. EIA has undertaken several actions to enhance the reporting of end-use energy prices.

  12. Autophagy in Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Yang Song

    2014-01-01

    Full Text Available Hepatic fibrosis is a leading cause of morbidity and mortality worldwide. Hepatic fibrosis is usually associated with chronic liver diseases caused by infection, drugs, metabolic disorders, or autoimmune imbalances. Effective clinical therapies are still lacking. Autophagy is a cellular process that degrades damaged organelles or protein aggregation, which participates in many pathological processes including liver diseases. Autophagy participates in hepatic fibrosis by activating hepatic stellate cells and may participate as well through influencing other fibrogenic cells. Besides that, autophagy can induce some liver diseases to develop while it may play a protective role in hepatocellular abnormal aggregates related liver diseases and reduces fibrosis. With a better understanding of the potential effects of autophagy on hepatic fibrosis, targeting autophagy might be a novel therapeutic strategy for hepatic fibrosis in the near future.

  13. Left ventricular diastolic function in patients with advanced cystic fibrosis.

    Science.gov (United States)

    Koelling, Todd M; Dec, G William; Ginns, Leo C; Semigran, Marc J

    2003-05-01

    To assess left ventricular systolic and diastolic function in adult patients with cystic fibrosis using radionuclide ventriculography. Although myocardial fibrosis has been described in autopsy specimens of patients with cystic fibrosis, the possibility that myocardial dysfunction may occur during life in adult patients with cystic fibrosis has not been explored. To assess the possibility of cardiac dysfunction occurring in cystic fibrosis, we studied 40 patients with advanced cystic fibrosis with first-pass radionuclide ventriculography and compared them to 9 patients with advanced bronchiectasis and 18 normal control subjects. Indexes of right ventricular systolic function were similarly impaired in patients with cystic fibrosis and patients with bronchiectasis. Left ventricular ejection fraction of patients with cystic fibrosis, patients with bronchiectasis, and normal control subjects did not differ. Fractional left ventricular filling at 50% of diastole, an index of diastolic function, was significantly lower in patients with cystic fibrosis (54 +/- 13%, mean +/- SD) in comparison to patients with bronchiectasis (66 +/- 4%, p = 0.009) or normal control subjects (69 +/- 14, p = 0.0002). The contribution of atrial systole to total diastolic left ventricular filling was greater in patients with cystic fibrosis (38 +/- 18%) than in patients with bronchiectasis (21 +/- 4%, p = 0.01) or normal control subjects (25 +/- 12%, p = 0.01). Patients with advanced cystic fibrosis demonstrate impaired left ventricular distensibility when compared to normal control subjects and patients with bronchiectasis. Patients with cystic fibrosis may be at risk of heart failure due to right ventricular dysfunction or left ventricular diastolic dysfunction.

  14. Performance of 2-Dimensional Ultrasound Shear Wave Elastography in Liver Fibrosis Detection Using Magnetic Resonance Elastography as the Reference Standard: A Pilot Study.

    Science.gov (United States)

    Song, Pengfei; Mellema, Daniel C; Sheedy, Shannon P; Meixner, Duane D; Karshen, Ryan M; Urban, Matthew W; Manduca, Armando; Sanchez, William; Callstrom, Matthew R; Greenleaf, James F; Chen, Shigao

    2016-02-01

    To investigate the correlation between 2-dimensional (2D) ultrasound shear wave elastography (SWE) and magnetic resonance elastography (MRE) in liver stiffness measurement and the diagnostic performance of 2D SWE for liver fibrosis when imaging from different intercostal spaces and using MRE as the reference standard. Two-dimensional SWE was performed on 47 patients. One patient was excluded from the study. Each of the remaining 46 patients underwent same-day MRE for clinical purposes. The study was compliant with the Health Insurance Portability and Accountability Act and approved by the Institutional Review Board. Informed consent was obtained from each patient. Two-dimensional SWE measurements were acquired from the ninth, eighth, and seventh intercostal spaces. The correlation with MRE was calculated at each intercostal space and multiple intercostal spaces combined. The performance of 2D SWE in diagnosing liver fibrosis was evaluated by receiver operating characteristic curve analysis using MRE as the standard. The 47 patients who initially underwent 2D SWE included 22 female and 25 male patients (age range, 19-77 years). The highest correlation between 2D SWE and MRE was from the eighth and seventh intercostal spaces (r = 0.68-0.76). The ranges of the areas under the receiver operating characteristic curves for separating normal or inflamed livers from fibrotic livers using MRE as the clinical reference were 0.84 to 0.92 when using the eighth and seventh intercostal spaces individually and 0.89 to 0.90 when combined. The results suggest that 2D SWE and MRE are well correlated when SWE is performed at the eighth and seventh intercostal spaces. The ninth intercostal space is less reliable for diagnosing fibrosis with 2D SWE. Combining measurements from multiple intercostal spaces does not significantly improve the performance of 2D SWE for detection of fibrosis. © 2016 by the American Institute of Ultrasound in Medicine.

  15. Noninvasive diagnosis of hepatic fibrosis in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Assessment of hepatic fibrosis is important for determining prognosis, guiding management decisions,and monitoring disease. Histological evaluation of liver biopsy specimens is currently considered the reference test for staging hepatic fibrosis. Since liver biopsy carries a small but significant risk, noninvasive tests to assess hepatic fibrosis are desirable. This editorial gives an overview on noninvasive methods currently available to determine hepatic fibrosis and their diagnostic accuracy for predicting significant fibrosis and cirrhosis in chronic hepatitis C. Based on available data, the performance of simple tests derived from routine laboratory parameters appears to be similar to that of more complex and expensive fibrosis panels. Transient elastography seems more accurate than blood tests for diagnosing cirrhosis.

  16. How Is Cystic Fibrosis Treated?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. How Is Cystic Fibrosis Treated? Cystic fibrosis (CF) has no cure. However, ... help oral pancreatic enzymes work better. Treatments for Cystic Fibrosis Complications A common complication of CF is diabetes . ...

  17. Genetics Home Reference: cystic fibrosis

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions cystic fibrosis cystic fibrosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Cystic fibrosis is an inherited disease characterized by the buildup ...

  18. Use of Amplified Ribosomal DNA Restriction Analysis for Identification of Ralstonia and Pandoraea Species: Interest in Determination of the Respiratory Bacterial Flora in Patients with Cystic Fibrosis

    Science.gov (United States)

    Segonds, Christine; Paute, Sandrine; Chabanon, Gérard

    2003-01-01

    The recovery of Ralstonia and Pandoraea species from respiratory tract cultures of patients with cystic fibrosis has recently been reported. These species are difficult to identify, and especially to differentiate from Burkholderia cepacia complex organisms, with classical methods. The discriminatory power of amplified ribosomal DNA restriction analysis (ARDRA) within the two genera was assessed by comparing the restriction profiles of reference strains of each species by using a panel of six enzymes already proven suitable for the identification of Burkholderia species. ARDRA provided differentiation of all the Ralstonia species tested and of Pandoraea norimbergensis. Pandoraea species P. pnomenusa, P. sputorum, P. pulmonicola, and P. apista were not discriminated to the species level. This method allowed the identification of five clinical isolates recovered from French cystic fibrosis patients as Ralstonia mannitolilytica. PMID:12843108

  19. Lung morphology assessment of cystic fibrosis using MRI with ultra-short echo time at submillimeter spatial resolution

    Energy Technology Data Exchange (ETDEWEB)

    Dournes, Gael [University of Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); CHU de Bordeaux, Service d' Imagerie Thoracique et Cardiovasculaire, Service des Maladies Respiratoires, Service d' Exploration Fonctionnelle Respiratoire, Pessac (France); Centre de Recherche Cardio-thoracique de Bordeaux, INSERM, U1045, Universite de Bordeaux, Bordeaux (France); Menut, Fanny [CHU de Bordeaux, Service d' Imagerie de la Femme et de l' Enfant, Unite de Pneumologie pediatrique, Bordeaux (France); Macey, Julie; Montaudon, Michel; Berger, Patrick; Laurent, Francois [University of Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); CHU de Bordeaux, Service d' Imagerie Thoracique et Cardiovasculaire, Service des Maladies Respiratoires, Service d' Exploration Fonctionnelle Respiratoire, Pessac (France); Fayon, Michael [University of Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); CHU de Bordeaux, Service d' Imagerie de la Femme et de l' Enfant, Unite de Pneumologie pediatrique, Bordeaux (France); Chateil, Jean-Francois [CHU de Bordeaux, Service d' Imagerie de la Femme et de l' Enfant, Unite de Pneumologie pediatrique, Bordeaux (France); University of Bordeaux, Centre de Resonance Magnetique des Systemes Biologiques, Bordeaux (France); Salel, Marjorie; Corneloup, Olivier [University of Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); CHU de Bordeaux, Service d' Imagerie Thoracique et Cardiovasculaire, Service des Maladies Respiratoires, Service d' Exploration Fonctionnelle Respiratoire, Pessac (France)

    2016-11-15

    We hypothesized that non-contrast-enhanced PETRA (pointwise encoding time reduction with radial acquisition) MR (magnetic resonance) sequencing could be an alternative to unenhanced computed tomography (CT) in assessing cystic fibrosis (CF) lung structural alterations, as well as compared agreements and concordances with those of conventional T1-weighted and T2-weighted sequences. Thirty consecutive CF patients completed both CT and MRI the same day. No contrast injection was used. Agreement in identifying structural alterations was evaluated at the segmental level using a kappa test. Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to assess concordances and reproducibility in Helbich-Bhalla disease severity scoring. Agreement between PETRA and CT was higher than that of T1- or T2-weighted sequences, notably in assessing the segmental presence of bronchiectasis (Kappa = 0.83; 0.51; 0.49, respectively). The concordance in Helbich-Bhalla scores was very good using PETRA (ICC = 0.97), independently from its magnitude (mean difference (MD) = -0.3 [-2.8; 2.2]), whereas scoring was underestimated using both conventional T1 and T2 sequences (MD = -3.6 [-7.4; 0.1]) and MD = -4.6 [-8.2; -1.0], respectively. Intra- and interobserver reproducibility were very good for all imaging modalities (ICC = 0.86-0.98). PETRA showed higher agreement in describing CF lung morphological changes than that of conventional sequences, whereas the Helbich-Bhalla scoring matched closely with that of CT. (orig.)

  20. Update on nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, P.; Logager, V.B.; Thomsen, Henrik S.

    2008-01-01

    Gadolinium-based contrast agents were for many years considered safe, but this is no longer the case. The least stable agents may trigger the development of nephrogenic systemic fibrosis (NSF), a generalized fibrotic disorder, in renal failure patients. The use of gadodiamide and gadopentetate di...

  1. Retroperitoneal fibrosis - the state-of-the-art.

    Science.gov (United States)

    Runowska, Marta; Majewski, Dominik; Puszczewicz, Mariusz

    2016-01-01

    Retroperitoneal fibrosis (RPF) is a rare disease, hallmarked by inflammation and deposition of fibrous tissue around the abdominal aorta. This process may spread contiguously and involve adjacent structures, leading to many complications, among which the most frequent and most severe is ureteral obstruction. The condition usually has idiopathic origin (idiopathic retroperitoneal fibrosis - IRF), but can also develop secondarily to a number of factors. The etiology of the disease remains unclear. Current research suggests that about half of the cases of IRF may be a symptom of a recently discovered, clinically heterogeneous immunoglobulin G4-related disease (IgG4-RD). Corticosteroids are the first-line treatment for IRF, but effective attempts to use immunosuppressants are also made. This paper presents the current state of knowledge on the etiopathogenesis, clinical presentation, diagnosis and therapeutic possibilities in different forms of RPF. Based on the latest research, an analysis of the relationship between IRF and IgG4-RD was performed.

  2. Quantitative computed tomography analysis of the airways in patients with cystic fibrosis using automated software: correlation with spirometry in the evaluation of severity*

    Science.gov (United States)

    Santos, Marcel Koenigkam; Cruvinel, Danilo Lemos; de Menezes, Marcelo Bezerra; Teixeira, Sara Reis; Vianna, Elcio de Oliveira; Elias Júnior, Jorge; Martinez, José Antonio Baddini

    2016-01-01

    Objective To perform a quantitative analysis of the airways using automated software, in computed tomography images of patients with cystic fibrosis, correlating the results with spirometric findings. Materials and Methods Thirty-four patients with cystic fibrosis were studied-20 males and 14 females; mean age 18 ± 9 years-divided into two groups according to the spirometry findings: group I (n = 21), without severe airflow obstruction (forced expiratory volume in first second [FEV1] > 50% predicted), and group II (n = 13), with severe obstruction (FEV1 ≤ 50% predicted). The following tracheobronchial tree parameters were obtained automatically: bronchial diameter, area, thickness, and wall attenuation. Results On average, 52 bronchi per patient were studied. The number of bronchi analyzed was higher in group II. The correlation with spirometry findings, especially between the relative wall thickness of third to eighth bronchial generation and predicted FEV1, was better in group I. Conclusion Quantitative analysis of the airways by computed tomography can be useful for assessing disease severity in cystic fibrosis patients. In patients with severe airflow obstruction, the number of bronchi studied by the method is higher, indicating more bronchiectasis. In patients without severe obstruction, the relative bronchial wall thickness showed a good correlation with the predicted FEV1. PMID:28100929

  3. Quantitative computed tomography analysis of the airways in patients with cystic fibrosis using automated software: correlation with spirometry in the evaluation of severity

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Marcel Koenigkam; Cruvinel, Danilo Lemos; Menezes, Marcelo Bezerra de; Teixeira, Sara Reis; Vianna, Elcio de Oliveira; Elias Junior, Jorge; Martinez, Jose Antonio Baddini, E-mail: marcelk46@yahoo.com.br [Universidade de Sao Paulo (HC/FMRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina

    2016-11-15

    Objective: To perform a quantitative analysis of the airways using automated software, in computed tomography images of patients with cystic fibrosis, correlating the results with spirometric findings. Materials and methods: Thirty-four patients with cystic fibrosis were studied-20 males and 14 females; mean age 18 ± 9 years - divided into two groups according to the spirometry findings: group I (n = 21), without severe airflow obstruction (forced expiratory volume in first second [FEV1] > 50% predicted), and group II (n = 13), with severe obstruction (FEV1 ≤ 50% predicted). The following tracheobronchial tree parameters were obtained automatically: bronchial diameter, area, thickness, and wall attenuation. Results: On average, 52 bronchi per patient were studied. The number of bronchi analyzed was higher in group II. The correlation with spirometry findings, especially between the relative wall thickness of third to eighth bronchial generation and predicted FEV1, was better in group I. Conclusion: Quantitative analysis of the airways by computed tomography can be useful for assessing disease severity in cystic fibrosis patients. In patients with severe airflow obstruction, the number of bronchi studied by the method is higher, indicating more bronchiectasis. In patients without severe obstruction, the relative bronchial wall thickness showed a good correlation with the predicted FEV1. (author)

  4. Relationship between Fibrosis and Ventricular Arrhythmias in Chagas Heart Disease Without Ventricular Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Tassi, Eduardo Marinho, E-mail: etassi@ibest.com.br [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Continentino, Marcelo Abramoff [Hospital Frei Galvão, Guaratinguetá, SP (Brazil); Nascimento, Emília Matos do; Pereira, Basílio de Bragança [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Coppe - Instituto Alberto Luiz Coimbra de Pós-Graduação e Pesquisa de Engenharia - UFRJ, Rio de Janeiro, RJ (Brazil); Pedrosa, Roberto Coury [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)

    2014-05-15

    Patients with Chagas disease and segmental wall motion abnormality (SWMA) have worse prognosis independent of left ventricular ejection fraction (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect SWMA and to assess fibrosis. To quantify fibrosis by using late gadolinium enhancement CMR in patients with Chagas disease and preserved or minimally impaired ventricular function (> 45%), and to detect patterns of dependence between fibrosis, SWMA and LVEF in the presence of ventricular arrhythmia. Electrocardiogram, treadmill exercise test, Holter and CMR were carried out in 61 patients, who were divided into three groups as follows: (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram. The number of patients with ventricular arrhythmia in relation to the total of patients, the percentage of fibrosis, and the LVEF were, respectively: Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3, 11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87% and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%, respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the latter was significant for the presence of ventricular arrhythmia, with a cutoff point of 11.78% for fibrosis mass (p < 0.001). Even in patients with Chagas disease and preserved or minimally impaired ventricular function, electrical instability can be present. Regarding the presence of ventricular arrhythmia, fibrosis is the most important variable, its amount being proportional to the complexity of the groups.

  5. Neonatal cystic fibrosis screening test

    Science.gov (United States)

    Cystic fibrosis screening - neonatal; Immunoreactive trypsinogen; IRT test; CF - screening ... Cystic fibrosis is a disease passed down through families. CF causes thick, sticky mucus to build up in ...

  6. New Universal Current-Mode Filter Using Non-Inverting Second-Generation Current-Conveyors

    OpenAIRE

    Muhammad Taher Abuelma'atti; Aamir Alam Farooqui

    1995-01-01

    A new universal active current-mode filter with single input and five outputs is presented. The proposed filter avoids the use of feedback in any part of the circuit and uses only one type of second-generation current-conveyors, grounded resistors, and grounded capacitors. The proposed circuit can simultaneously realize lowpass, highpass, bandpass, allpass, and notch biquadratic filter functions.

  7. Uso de vitamina C en la solución tumescente de liposucción como inductor de lipolisis y fibrosis: Trabajo experimental Use of vitamine C in liposuction tumescent solution as lipolisis and fibrosis inductor: Experimental study

    National Research Council Canada - National Science Library

    N. Antoniadis Petrakis; T.C. González Romero

    2007-01-01

    ... lipólisis y aumenta la fibrosis. El presente es un estudio descriptivo, prospectivo, experimental y comparativo de una muestra de 30 ratas Sprague-Dawley de ambos sexos, a las cuales se les infiltró...

  8. Content validity of CASA-Q cough domains and UCSD-SOBQ for use in patients with Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Gries, Katharine Suzanne; Esser, Dirk; Wiklund, Ingela

    2013-09-16

    The study objective was to assess the content validity of the Cough and Sputum Assessment Questionnaire (CASA-Q) cough domains and the UCSD Shortness of Breath Questionnaire (SOBQ) for use in patients with Idiopathic Pulmonary Fibrosis (IPF). Cross-sectional, qualitative study with cognitive interviews in patients with IPF. Study outcomes included relevance, comprehension of item meaning, understanding of the instructions, recall period, response options, and concept saturation. Interviews were conducted with 18 IPF patients. The mean age was 68.9 years (SD 11.9), 77.8% were male, and 88.9% were Caucasian. The intended meaning of the CASA-Q cough domain items was clearly understood by most of the participants (89-100%). All participants understood the CASA-Q instructions; the correct recall period was reported by 89% of the patients, and the response options were understood by 76%. The intended meaning of the UCSD-SOBQ items was relevant and clearly understood by all participants. Participants understood the instructions (83%) and all patients understood the response options (100%). The reported recall period varied based on the type of activity performed. No concepts were missing, suggesting that saturation was demonstrated for both measures. This study provides evidence for content validity for the CASA-Q cough domains and the UCSD-SOBQ for patients with IPF. Items of both questionnaires were understood and perceived as relevant to measure the key symptoms of IPF. The results of this study support the use of these instruments in IPF clinical trials as well as further studies of their psychometric properties.

  9. [Biomarkers for liver fibrosis: advances, advantages and disadvantages].

    Science.gov (United States)

    Cequera, A; García de León Méndez, M C

    2014-01-01

    Liver cirrhosis in Mexico is one of the most important causes of death in persons between the ages of 25 and 50 years. One of the reasons for therapeutic failure is the lack of knowledge about the molecular mechanisms that cause liver disorder and make it irreversible. One of its prevalent anatomical characteristics is an excessive deposition of fibrous tissue that takes different forms depending on etiology and disease stage. Liver biopsy, traditionally regarded as the gold standard of fibrosis staging, has been brought into question over the past decade, resulting in the proposal for developing non-invasive technologies based on different, but complementary, approaches: a biological one that takes the serum levels of products arising from the fibrosis into account, and a more physical one that evaluates scarring of the liver by methods such as ultrasound and magnetic resonance elastography; some of the methods were originally studied and validated in patients with hepatitis C. There is great interest in determining non-invasive markers for the diagnosis of liver fibrosis, since at present there is no panel or parameter efficient and reliable enough for diagnostic use. In this paper, we describe the biomarkers that are currently being used for studying liver fibrosis in humans, their advantages and disadvantages, as well as the implementation of new-generation technologies and the evaluation of their possible use in the diagnosis of fibrosis. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  10. Fibrosis and Cancer

    DEFF Research Database (Denmark)

    Cox, Thomas R.; Erler, Janine T.

    2016-01-01

    The relation between fibrosis and cancer has long been debated, specifically whether desmoplasia precedes, accompanies, or succeeds tumourigenesis, progression, and metastasis. Recent reports have published opposing data, adding to the perplexity. However, what is emerging is that it is likely...... the specific properties of the extracellular matrix (ECM) that determine the paradoxical nature of cancer-associated fibrosis....

  11. Fibrosis and Cardiac Arrhythmias

    NARCIS (Netherlands)

    de Jong, Sanne; van Veen, Toon A. B.; van Rijen, Harold V. M.; de Bakker, Jacques M. T.

    2011-01-01

    In this review article about fibrosis and arrhythmias, we show that the amount of collagen, a normal element of the heart muscle, increases with age and in heart disease. The relation between fibrosis and electrophysiological parameters such as conduction, fractionation of electrograms, abnormal imp

  12. Detection of inrush current in distribution transformer using wavelet transform

    Energy Technology Data Exchange (ETDEWEB)

    Sedighi, A.-R.; Haghifam, M.-R. [Tarbiat Modarres Univ., Dept. of Electrical Engineering, Tehran (Iran)

    2005-07-01

    Inrush currents in transformers are non-sinusoidal, high magnitude currents generated due to flux saturation in the core during energization. For protection purpose, in this paper an efficient method for detection of inrush current in distribution transformer based on wavelet transform is presented. Using this method inrush current can be discriminated from the other switching transients such as: load switching, capacitor switching and single phase to ground fault. Inrush current and other events for feature extraction and discrimination are simulated using Electro Magnetic Transient Program (EMTP). Results in all cases show the effectiveness of proposed procedure in identifying inrush current from other transients. (Author)

  13. Atmospheric point discharge current measurements using a\\ud temperature-compensated logarithmic current amplifier

    OpenAIRE

    Marlton, Graeme; Harrison, R. Giles; Nicoll, Keri A.

    2013-01-01

    Measurements of atmospheric corona currents have been made for over 100 years to indicate the atmospheric electric field. Corona currents vary substantially, in polarity and in magnitude. The instrument described here uses a sharp point sensor connected to a temperature compensated bi-polar\\ud logarithmic current amplifier. Calibrations over a range of currents from ±10 fA to ±3 μA and across ±20 ◦C show it has an excellent logarithmic response over six orders of magnitude from 1 pA to 1 μA i...

  14. Simulation of the Cystic Fibrosis patient airway habitats using microfluidic devices

    DEFF Research Database (Denmark)

    Skolimowski, Maciej

    2013-01-01

    , and their growth is then monitored using confocal microscopy. However, this is not either a suitable CF model as the human airways are subdivided into aerobic and anaerobic compartments. To investigate the different compartments of the human airways system it is crucial importance to construct a microfluidic model...

  15. Viral infection drives tissue fibrosis in vitro

    Directory of Open Access Journals (Sweden)

    Andrea P. Malizia

    2008-04-01

    Full Text Available Idiopathic Pulmonary Fibrosis (IPF is a refractory and lethal interstitial lung disease characterized by loss of alveolar epithelial cells, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. In this study we utilised a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV associated with lung fibrosis. A549 cells and an alveolar epithelial cell line infected with EBV (VAAK were used to identify genes whose expression was altered by EBV reactivation. EBV reactivation by TGFbeta1 drives alterations in expression of non-canonical Wnt pathway mediators, implicating it in epithelial mesenchymal transition (EMT, the molecular event underpinning scar production in tissue fibrosis. Cell invasion, EMT correlated transcripts expression, GSK-3b and c-Jun activation were altered in response to non-canonical Wnt pathway regulation. The role of EBV in promoting fibrosis can be attenuated by antiviral strategies and inhibition of Wnt signalling. Activation of non-canonical Wnt signalling pathway by EBV in epithelial cells suggests a novel mechanism of tissue fibrosis. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  16. Research advances in immune cellular pathogenesis in liver fibrosis

    Directory of Open Access Journals (Sweden)

    XIAO Chunyang

    2015-09-01

    Full Text Available Liver fibrosis is the common pathological consequence of all chronic liver diseases with various etiologies. The mechanism of liver fibrosis is associated with the activation and proliferation of hepatic stellate cells (HSCs. The interaction between immune cells and HSCs can regulate the production of extracellular matrix (ECM and lead to the excessive deposition of ECM and subsequent liver fibrosis and cirrhosis. This article reviews the current understanding of the effects and action mechanisms of immune cells in the development of liver fibrosis and summarizes the regulatory functions of the innate and adaptive immune systems in liver fibrosis. Further study of the interactions between immune cells, cytokines, and HSCs and the regulatory mechanisms of the immune system will provide novel opportunity for the treatment of liver fibrosis.

  17. Noninvasive Biomarkers of Liver Fibrosis: An Overview

    Directory of Open Access Journals (Sweden)

    Hind I. Fallatah

    2014-01-01

    Full Text Available Chronic liver diseases of differing etiologies are among the leading causes of mortality and morbidity worldwide. Establishing accurate staging of liver disease is very important for enabling both therapeutic decisions and prognostic evaluations. A liver biopsy is considered the gold standard for assessing the stage of hepatic fibrosis, but it has many limitations. During the last decade, several noninvasive markers for assessing the stage of hepatic fibrosis have been developed. Some have been well validated and are comparable to liver biopsy. This paper will focus on the various noninvasive biochemical markers used to stage liver fibrosis.

  18. Vitamin K supplementation for cystic fibrosis.

    Science.gov (United States)

    Jagannath, Vanitha A; Thaker, Vidhu; Chang, Anne B; Price, Amy I

    2017-08-22

    Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. This is an updated version of the review. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 30 January 2017. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin

  19. Discrimination of Inrush Currents from Faults Current in Power Transformers using Gravitational Search Algorithm (GSA

    Directory of Open Access Journals (Sweden)

    Mohamad Kazem Daryabari

    2011-01-01

    Full Text Available The magnetizing inrush current phenomenon is a large transient condition, which occurs when a transformer is energized. The inrush current magnitude may be as high as ten times of transformer rated current that causes mal-operation of protection systems. Indeed, the similarity between signatures of Inrush current and internal fault condition make this failure. So, for safe running of a transformer, it is necessary to distinguish inrush current from fault currents. In this project, an Artificial Neural Network (ANN which is trained by two different swarm based algorithms; Gravitational Search Algorithm (GSA and Particle Swarm Optimization (PSO have been used to discriminate inrush current from fault currents in power transformers. GSA works based on gravity laws and in opposite of other swarm based algorithms, particles have identity and PSO is based on behaviors of bird flocking. Proposed approach has two general stages, in first step, obtained data from simulation have been processed and applied to ANN, and then in step two, using training data considered ANN has been trained by GSA & PSO. Proposed method has been compared with one of the common training approach which is called Back Propagation (BP and Results show that proposed method is so quick and can do discrimination very accurate.

  20. Electronically Tunable Current-Mode Quadrature Oscillator Using Single MCDTA

    Directory of Open Access Journals (Sweden)

    Y. Li

    2010-12-01

    Full Text Available This paper presents a modified current differencing transconductance amlpifier (MCDTA and the MCDTA based quadrature oscillator. The oscillator is current-mode and provides current output from high output impedance terminals. The circuit uses only one MCDTA and two grounded capacitors, and is easy to be integrated. Its oscillation frequency can be tuned electronically by tuning bias currents of MCDTA. Finally, frequency error is analyzed. The results of circuit simulations are in agreement with theory.

  1. Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis

    Institute of Scientific and Technical Information of China (English)

    Rodrigo Goulart Pacheco; Christiano Costa Esposito; Lucas CM Müller; Morgana TL Castelo-Branco; Leonardo Pereira Quintella; Vera Lucia A Chagas; Heitor Siffert P de Souza

    2012-01-01

    AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine,butyrate,or saline.Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure.Follow-up colonoscopy was performed every 4 wk for 12 wk.The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β,tumor necrosis factor-alpha,and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.RESULTS:Colonoscopies of the diverted segment showed mucosa with hyperemia,increased number of vessels,bleeding and mucus discharge.Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic (P < 0.02) and histological scores (P < 0.01) and restored the densities of collagen fibers in tissue (P =0.015; P =0.001),the number of goblet cells (P =0.021; P =0.029),and the rate of apoptosis within the epithelium (P =0.043; P =0.011) to normal values.The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.CONCLUSION:The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.

  2. Profile of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Mona M. El-Falaki

    2014-09-01

    Full Text Available It was generally believed that Cystic fibrosis (CF is rare among Arabs; however, the few studies available from Egypt and other Arabic countries suggested the presence of many undiagnosed patients. The aim of the present study was to determine the frequency of CF patients out of the referred cases in a single referral hospital in Egypt. A total of 100 patients clinically suspected of having CF were recruited from the CF clinic of the Allergy and Pulmonology Unit, Children’s Hospital, Cairo University, Egypt, throughout a 2 year period. Sweat chloride testing was done for all patients using the Wescor macroduct system for collection of sweat. Quantitative analysis for chloride was then done by the thiocyanate colorimetric method. Patients positive for sweat chloride (⩾60 mmol/L were tested for the ΔF508 mutation using primer specific PCR for cystic fibrosis transmembrane conductance regulator (CFTR gene. Thirty-six patients (36% had a positive sweat chloride test. The main clinical presentations in patients were chronic cough in 32 (88.9%, failure to thrive in 27 (75%, steatorrhea in 24 (66.7%, and hepatobiliary involvement in 5 (13.9%. Positive consanguinity was reported in 50% of CF patients. Thirty-two patients were screened for ΔF508 mutation. Positive ΔF508 mutation was detected in 22 (68.8% patients, 8 (25% were homozygous, 14 (43.8% were heterozygous, and 10 (31.3% tested were negative. CF was diagnosed in more than third of patients suspected of having the disease on clinical grounds. This high frequency of CF among referred patients indicates that a high index of suspicion and an increasing availability of diagnostic tests lead to the identification of a higher number of affected individuals.

  3. Pirfenidone treatment of idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Ye Gan

    2011-02-01

    Full Text Available Ye Gan1,2, Erica L Herzog2, Richard H Gomer31Department of Medicine, Central South University, Changsha, Hunan, China; 2Department of Medicine, Yale University School of Medicine, New Haven, CT, USA; 3Department of Biology, Texas A&M University, College Station, TX, USAAbstract: Idiopathic pulmonary fibrosis (IPF is a discrete clinicopathologic entity defined by the presence of usual interstitial pneumonia on high-resolution CT scan and/or open lung biopsy and the absence of an alternate diagnosis or exposure explaining these findings. There are currently no FDA-approved therapies available to treat this disease, and the 5-year mortality is ~80%. The pyridone derivative pirfenidone has been studied extensively as a possible therapeutic agent for use in this deadly disease. This review will present the unique clinical features and management issues encountered by physicians caring for IPF patients, including the poor response to conventional therapy. The biochemistry and preclinical efficacy of pirfenidone will be discussed along with a comprehensive review of the clinical efficacy, safety, and side effects and patient-centered foci such as quality of life and tolerability. It is hoped that this information will lend insight into the complex issues surrounding the use of pirfenidone in IPF and lead to further investigation of this agent as a possible therapy in this devastating disease.Keywords: pirfenidone, fibrosis, clinical trials 

  4. Uso de vitamina C en la solución tumescente de liposucción como inductor de lipolisis y fibrosis: Trabajo experimental Use of vitamine C in liposuction tumescent solution as lipolisis and fibrosis inductor: Experimental study

    Directory of Open Access Journals (Sweden)

    N. Antoniadis Petrakis

    2007-06-01

    Full Text Available La Liposucción no permite siempre extraer todo el tejido adiposo causante de la lipodistrofia, por lo cual se plantea la necesidad de perfeccionar esta técnica. Nuestro objetivo es el demostrar que el uso de la vitamina C en la solución tumescente induce lipólisis y aumenta la fibrosis. El presente es un estudio descriptivo, prospectivo, experimental y comparativo de una muestra de 30 ratas Sprague-Dawley de ambos sexos, a las cuales se les infiltró solución tumescente en el tejido subdérmico de la región inguinal, con vitamina C al grupo experimental y con solución tumescente sin vitamina C al grupo control, para su posterior estudio histológico macroscópico y microscópico. El 100% de las muestras con vitamina C evidenciaron cambios a nivel del tejido adiposo sugerentes de lipólisis y en el 82% se evidenciaron cambios en el tejido conectivo sugerentes de formación de colágeno joven. Concluimos que la vitamina C favorece la lipolisis y promueve la síntesis de colágeno cuando se utiliza como parte de la solución tumescente en animales de experimentaciónLiposuction does not always let to remove all the amount of adipose tissue which causes lipodistrophy, for that reason, it is recommended the necessity to improve that technique. We try to demonstrate that the use of vitamin C in the tumescence solution induces lipolysis and raises fibrosis. This article is a descriptive, prospective, experimental and comparative research of a sample of 30 mice of Sprague- Dawley type of both sexes, which were infiltrated with a tumescence solution in the subdermic inguinal region with vitamin C to the experimental group and with tumescence solution without vitamin C to the control group, for a further histological macroscopic as well as microscopic study. The results showed that 100% of the samples with vitamin C presented changes in the adipose tissue which suggested lipolysis, whereas 82% were evidence for the formation of young collagen. As a

  5. Pharmacoeconomic review of recombinant human DNase in the management of cystic fibrosis

    NARCIS (Netherlands)

    Zijlstra, Gerrit; Boersma, Cornelis; Frijlink, Henderik W.; Postma, Maarten J.

    2004-01-01

    For the treatment of patients with cystic fibrosis, recombinant human deoxyribonuclease I is widely used. Deoxyribonuclease I has a positive effect on lung function and the number of hospitalizations. Deoxyribonuclease I is currently administered by nebulization, which is an inefficient administrati

  6. Note: Atmospheric point discharge current measurements using a temperature-compensated logarithmic current amplifier

    Science.gov (United States)

    Marlton, G. J.; Harrison, R. G.; Nicoll, K. A.

    2013-06-01

    Measurements of atmospheric corona currents have been made for over 100 years to indicate the atmospheric electric field. Corona currents vary substantially, in polarity and in magnitude. The instrument described here uses a sharp point sensor connected to a temperature compensated bi-polar logarithmic current amplifier. Calibrations over a range of currents from ±10 fA to ±3 μA and across ±20 °C show it has an excellent logarithmic response over six orders of magnitude from 1 pA to 1 μA in both polarities for the range of atmospheric temperatures likely to be encountered in the southern UK. Comparison with atmospheric electric field measurements during disturbed weather confirms that bipolar electric fields induce corona currents of corresponding sign, with magnitudes ˜0.5 μA.

  7. Note: atmospheric point discharge current measurements using a temperature-compensated logarithmic current amplifier.

    Science.gov (United States)

    Marlton, G J; Harrison, R G; Nicoll, K A

    2013-06-01

    Measurements of atmospheric corona currents have been made for over 100 years to indicate the atmospheric electric field. Corona currents vary substantially, in polarity and in magnitude. The instrument described here uses a sharp point sensor connected to a temperature compensated bi-polar logarithmic current amplifier. Calibrations over a range of currents from ±10 fA to ±3 μA and across ±20 °C show it has an excellent logarithmic response over six orders of magnitude from 1 pA to 1 μA in both polarities for the range of atmospheric temperatures likely to be encountered in the southern UK. Comparison with atmospheric electric field measurements during disturbed weather confirms that bipolar electric fields induce corona currents of corresponding sign, with magnitudes ~0.5 μA.

  8. qFibrosis: A fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients

    Science.gov (United States)

    Tai, Dean C.S.; Wang, Shi; Cheng, Chee Leong; Peng, Qiwen; Yan, Jie; Chen, Yongpeng; Sun, Jian; Liang, Xieer; Zhu, Youfu; Rajapakse, Jagath C.; Welsch, Roy E.; So, Peter T.C.; Wee, Aileen; Hou, Jinlin; Yu, Hanry

    2014-01-01

    Background & Aims There is increasing need for accurate assessment of liver fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment method combining quantification of histopathological architectural features, to address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B (CHB) patients. Methods qFibrosis was established as a combined index based on 87 parameters of architectural features. Images acquired from 25 Thioacetamide-treated rat samples and 162 CHB core biopsies were used to train and test qFibrosis and to demonstrate its reproducibility. qFibrosis scoring was analyzed employing Metavir and Ishak fibrosis staging as standard references, and collagen proportionate area (CPA) measurement for comparison. Results qFibrosis faithfully and reliably recapitulates Metavir fibrosis scores, as it can identify differences between all stages in both animal samples (p biopsies (p biopsies: 10–44 mm in length). qFibrosis can significantly predict staging underestimation in suboptimal biopsies (<15 mm) and under- and over-scoring by different pathologists (p <0.001). qFibrosis can also differentiate between Ishak stages 5 and 6 (AUC: 0.73, p = 0.008), suggesting the possibility of monitoring intra-stage cirrhosis changes. Best of all, qFibrosis demonstrates superior performance to CPA on all counts. Conclusions qFibrosis can improve fibrosis scoring accuracy and throughput, thus allowing for reproducible and reliable analysis of efficacies of anti-fibrotic therapies in clinical research and practice. PMID:24583249

  9. PROFILEing idiopathic pulmonary fibrosis: rethinking biomarker discovery

    Directory of Open Access Journals (Sweden)

    Toby M. Maher

    2013-06-01

    Full Text Available Despite major advances in the understanding of the pathogenesis of idiopathic pulmonary fibrosis (IPF, diagnosis and management of the condition continue to pose significant challenges. Clinical management of IPF remains unsatisfactory due to limited availability of effective drug therapies, a lack of accurate indicators of disease progression, and an absence of simple short-term measures of therapeutic response. The identification of more accurate predictors of prognosis and survival in IPF would facilitate counseling of patients and their families, aid communication among clinicians, and would guide optimal timing of referral for transplantation. Improvements in molecular techniques have led to the identification of new disease pathways and a more targeted approach to the development of novel anti-fibrotic agents. However, despite an increased interest in biomarkers of IPF disease progression there are a lack of measures that can be used in early phase clinical trials. Careful longitudinal phenotyping of individuals with IPF together with the application of novel omics-based technology should provide important insights into disease pathogenesis and should address some of the major issues holding back drug development in IPF. The PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints study is a currently enrolling, prospective cohort study designed to tackle these issues.

  10. Visual vs Fully Automatic Histogram-Based Assessment of Idiopathic Pulmonary Fibrosis (IPF Progression Using Sequential Multidetector Computed Tomography (MDCT.

    Directory of Open Access Journals (Sweden)

    Davide Colombi

    Full Text Available To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF at multidetector computed tomography (MDCT assessed by semi-quantitative visual scores (VSs and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification.Forty IPF patients (median age: 70 y, interquartile: 62-75 years; M:F, 33:7 that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10th-90th percentile in 5th percentile steps. Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles.In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE increased in median by 5%/year (interquartile: 0%/y; +11%/y. Substantial difference was found between treated and untreated patients in HU changes of the 40th and of the 80th percentiles of density histogram. Correlation analysis between VSs and selected percentiles showed higher correlation between the changes (Δ in OE and Δ 40th percentile (r=0.69; p<0.001 as compared to Δ 80th percentile (r=0.58; p<0.001; closer correlation was found between Δ ground-glass extent and Δ 40th percentile (r=0.66, p<0.001 as compared to Δ 80th percentile (r=0.47, p=0.002, while the Δ reticulations correlated better with the Δ 80th percentile (r=0.56, p<0.001 in comparison to Δ 40th percentile (r=0.43, p=0.003.There is a relevant and fully automatically measurable difference at MDCT in VSs and in histogram analysis at one year follow-up of IPF patients, whether treated or untreated: Δ 40th percentile might reflect the change in overall extent of lung abnormalities, notably of ground-glass pattern

  11. Gastroesophageal Reflux and Idiopathic Pulmonary Fibrosis: A Review

    Directory of Open Access Journals (Sweden)

    Ahmed Fahim

    2011-01-01

    Full Text Available The histological counterpart of idiopathic pulmonary fibrosis is usual interstitial pneumonia, in which areas of fibrosis of various ages are interspersed with normal lung. This pattern could be explained by repeated episodes of lung injury followed by abnormal wound healing responses. The cause of the initiating alveolar epithelial injury is unknown, but postulated mechanisms include immunological, microbial, or chemical injury, including aspirated gastric refluxate. Reflux is promoted by low basal pressure in the lower oesophageal sphincter and frequent relaxations, potentiated by hiatus hernia or oesophageal dysmotility. In susceptible individuals, repeated microaspiration of gastric refluxate may contribute to the pathogenesis of IPF. Microaspiration of nonacid or gaseous refluxate is poorly detected by current tests for gastroesophageal reflux which were developed for investigating oesophageal symptoms. Further studies using pharyngeal pH probes, high-resolution impedance manometry, and measurement of pepsin in the lung should clarify the impact of reflux and microaspiration in the pathogenesis of IPF.

  12. Growth factors in idiopathic pulmonary fibrosis: relative roles

    Directory of Open Access Journals (Sweden)

    Allen Jeremy T

    2001-11-01

    Full Text Available Abstract Treatment of idiopathic pulmonary fibrosis patients has evolved very slowly; the fundamental approach of corticosteroids alone or in combination with other immunosuppressive agents has had little impact on long-term survival. The continued use of corticosteroids is justified because of the lack of a more effective alternative. Current research indicates that the mechanisms driving idiopathic pulmonary fibrosis reflect abnormal, dysregulated wound healing within the lung, involving increased activity and possibly exaggerated responses by a spectrum of profibrogenic growth factors. An understanding of the roles of these growth factors, and the way in which they modulate events at cellular level, could lead to more targeted therapeutic strategies, improving patients' quality of life and survival.

  13. Learn About Pulmonary Fibrosis

    Science.gov (United States)

    ... Fibrosis Month - Hope of a Better Future Blog: Yoga, Tai Chi and Your Lungs: The Benefits of ... number of items"); $("#local_list_xml").quickPagination(); }, error: function() { console.log("An error occurred while processing XML ...

  14. Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

    Science.gov (United States)

    Zahr, Abdallah Abou; Salama, Mohamed E.; Carreau, Nicole; Tremblay, Douglas; Verstovsek, Srdan; Mesa, Ruben; Hoffman, Ronald; Mascarenhas, John

    2016-01-01

    Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk-adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment. PMID:27252511

  15. Detection of magnetising inrush current using real time integration method

    Science.gov (United States)

    Ling, P. C. Y.; Basak, A.

    1990-01-01

    A technique of predicting magnetising inrush currents in transformers is described. Computed results show an inconsistency in second harmonic decay resulting detection failure while using conventional second harmonic techniques. A new detection scheme using real time integration values of the inrush current is proposed to provide reliable relay operation.

  16. Simulation of leakage current measurement on medical devices using helmholtz coil configuration with different current flow

    Science.gov (United States)

    Sutanto, E.; Chandra, F.; Dinata, R.

    2017-05-01

    Leakage current measurement which can follow IEC standard for medical device is one of many challenges to be answered. The IEC 60601-1 has defined that the limit for a leakage current for Medical Device can be as low as 10 µA and as high as 500 µA, depending on which type of contact (applied part) connected to the patient. Most people are using ELCB (Earth-leakage circuit breaker) for safety purpose as this is the most common and available safety device in market. One type of ELCB devices is RCD (Residual Current Device) and this RCD type can measure the leakage current directly. This work will show the possibility on how Helmholtz Coil Configuration can be made to be like the RCD. The possibility is explored by comparing the magnetic field formula from each device, then it proceeds with a simulation using software EJS (Easy Java Simulation). The simulation will make sure the concept of magnetic field current cancellation follows the RCD concept. Finally, the possibility of increasing the measurement’s sensitivity is also analyzed. The sensitivity is needed to see the possibility on reaching the minimum leakage current limit defined by IEC, 0.01mA.

  17. Angiogenesis and liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Gülsüm ?zlem Elpek

    2015-01-01

    Recent data indicate that hepatic angiogenesis,regardless of the etiology, takes place in chronic liverdiseases (CLDs) that are characterized by inflammationand progressive fibrosis. Because antiangiogenictherapy has been found to be efficient inthe prevention of fibrosis in experimental models ofCLDs, it is suggested that blocking angiogenesis couldbe a promising therapeutic option in patients withadvanced fibrosis. Consequently, efforts are beingdirected to revealing the mechanisms involved inangiogenesis during the progression of liver fibrosis.Literature evidences indicate that hepatic angiogenesisand fibrosis are closely related in both clinical andexperimental conditions. Hypoxia is a major inducer ofangiogenesis together with inflammation and hepaticstellate cells. These profibrogenic cells stand at theintersection between inflammation, angiogenesis andfibrosis and play also a pivotal role in angiogenesis.This review mainly focuses to give a clear view on therelevant features that communicate angiogenesis withprogression of fibrosis in CLDs towards the-end point ofcirrhosis that may be translated into future therapies.The pathogenesis of hepatic angiogenesis associatedwith portal hypertension, viral hepatitis, non-alcoholicfatty liver disease and alcoholic liver disease are alsodiscussed to emphasize the various mechanisms involvedin angiogenesis during liver fibrogenesis.

  18. Three Microwave Frequency Dividers Using Current Source/Sink and Modified Current Source Inverters

    Directory of Open Access Journals (Sweden)

    Gautham S. Harinarayan

    2013-01-01

    Full Text Available In a preceding paper Carlos E. Saavedra, 2005, established that frequency division can be achieved with the use of inverter rings and transmission gates. In this paper, we suggest three modified circuits which obtain the similar function, namely, using Current Sink Inverter, Current Source Inverter, and Modified Current Source Inverter. The performances of the proposed circuits are examined using Cadence and the model parameters of a 45 nm CMOS process. The simulation results of the three circuits are presented and are compared. We also present the results of a simple but effective novel technique to reduce clock skew between real and complementary clock signals and the corresponding improvement achieved in maximum frequency of operation. One of the proposed circuits can operate at up to 8.2 GHz input while performing a divide-by-4 operation.

  19. Liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfection: Diagnostic methods and clinical impact

    Institute of Scientific and Technical Information of China (English)

    Caterina; Sagnelli; Salvatore; Martini; Mariantonietta; Pisaturo; Giuseppe; Pasquale; Margherita; Macera; Rosa; Zampino; Nicola; Coppola; Evangelista; Sagnelli

    2015-01-01

    Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus(HCV)-monoinfected and human immunodeficiency virus(HIV)/HCV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HCV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of noninvasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HCVcoinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice.

  20. Non-invasive ventilation used as an adjunct to airway clearance treatments improves lung function during an acute exacerbation of cystic fibrosis: a randomised trial

    Directory of Open Access Journals (Sweden)

    Tiffany J Dwyer

    2015-07-01

    Full Text Available Question: During an acute exacerbation of cystic fibrosis, is non-invasive ventilation beneficial as an adjunct to the airway clearance regimen? Design: Randomised controlled trial with concealed allocation and intention-to-treat analysis. Participants: Forty adults with moderate to severe cystic fibrosis lung disease and who were admitted to hospital for an acute exacerbation. Intervention: Comprehensive inpatient care (control group compared to the same care with the addition of non-invasive ventilation during airway clearance treatments from Day 2 of admission until discharge (experimental group. Outcome measures: Lung function and subjective symptom severity were measured daily. Fatigue was measured at admission and discharge on the Schwartz Fatigue Scale from 7 (no fatigue to 63 (worst fatigue points. Quality of life and exercise capacity were also measured at admission and discharge. Length of admission and time to next hospital admission were recorded. Results: Analysed as the primary outcome, the experimental group had a greater rate of improvement in forced expiratory volume in 1 second (FEV1 than the control group, but this was not statistically significant (MD 0.13% predicted per day, 95% CI –0.03 to 0.28. However, the experimental group had a significantly higher FEV1 at discharge than the control group (MD 4.2% predicted, 95% CI 0.1 to 8.3. The experimental group reported significantly lower levels of fatigue on the Schwartz fatigue scale at discharge than the control group (MD 6 points, 95% CI 1 to 11. There was no significant difference between the experimental and control groups in subjective symptom severity, quality of life, exercise capacity, length of hospital admission or time to next hospital admission. Conclusion: Among people hospitalised for an acute exacerbation of cystic fibrosis, the use of non-invasive ventilation as an adjunct to the airway clearance regimen significantly improves FEV1 and fatigue. Trial

  1. Detection of collagen by second harmonic microscopy as a diagnostic tool for liver fibrosis

    Science.gov (United States)

    Banavar, Maruth; Kable, Eleanor P. W.; Braet, Filip; Wang, X. M.; Gorrell, M. D.; Cox, Guy

    2006-02-01

    Liver fibrosis has many causes, including hepatitis C, alcohol abuse, and non-alcoholic steatohepatitis. It is characterized by abnormal deposition of extracellular matrix proteins, mainly collagen. The deposition of these proteins results in impaired liver function caused by distortion of the hepatic architecture by fibrous scar tissue. The unique triple helix structure of collagen and high level of crystallinity make it very efficient for generating second harmonic signals. In this study we have set out to see if second harmonic imaging of collagen can be used as a non-biased quantitative tool for classification of fibrosis levels in liver biopsies and if it can detect early fibrosis formation not detected by current methods.

  2. A comparison of four fibrosis indexes in chronic HCV: Development of new fibrosis-cirrhosis index (FCI

    Directory of Open Access Journals (Sweden)

    Khaliq Saba

    2011-04-01

    Full Text Available Abstract Background Hepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers. Methods We studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin / (Albumin × Platelet count]. Results Already established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p Conclusions The fibrosis-cirrhosis index (FCI accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.

  3. Using electric current to surpass the microstructure breakup limit

    Science.gov (United States)

    Qin, Rongshan

    2017-01-01

    The elongated droplets and grains can break up into smaller ones. This process is driven by the interfacial free energy minimization, which gives rise to a breakup limit. We demonstrated in this work that the breakup limit can be overpassed drastically by using electric current to interfere. Electric current free energy is dependent on the microstructure configuration. The breakup causes the electric current free energy to reduce in some cases. This compensates the increment of interfacial free energy during breaking up and enables the processing to achieve finer microstructure. With engineering practical electric current parameters, our calculation revealed a significant increment of the obtainable number of particles, showing electric current a powerful microstructure refinement technology. The calculation is validated by our experiments on the breakup of Fe3C-plates in Fe matrix. Furthermore, there is a parameter range that electric current can drive spherical particles to split into smaller ones.

  4. Induction Motor Speed Estimation by Using Spectral Current Analysis

    OpenAIRE

    2009-01-01

    An interesting application for the FFT analysis is related to the induction motor speed estimation based on spectral current analysis. The paper presents the possibility of induction motor speed estimation by using the current harmonics generated because of the rotor slots and of the eccentricity.

  5. Inhibition of SIRT2 suppresses hepatic fibrosis.

    Science.gov (United States)

    Arteaga, Maribel; Shang, Na; Ding, Xianzhong; Yong, Sherri; Cotler, Scott J; Denning, Mitchell F; Shimamura, Takashi; Breslin, Peter; Lüscher, Bernhard; Qiu, Wei

    2016-06-01

    Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis.

  6. The Role of PPARs in Lung Fibrosis

    Directory of Open Access Journals (Sweden)

    Heather F. Lakatos

    2007-01-01

    wound healing. PPARβ/δ agonists inhibit lung fibroblast proliferation and enhance the antifibrotic properties of PPARγ agonists. PPARγ ligands oppose the profibrotic effect of TGF-β, which induces differentiation of fibroblasts to myofibroblasts, a critical effector cell in fibrosis. PPARγ ligands, including the thiazolidinedione class of antidiabetic drugs, effectively inhibit lung fibrosis in vitro and in animal models. The clinical availability of potent and selective PPARα and PPARγ agonists should facilitate rapid development of successful treatment strategies based on current and ongoing research.

  7. Experimental systems to study the origin of the myofibroblast in peritoneal fibrosis.

    Science.gov (United States)

    Padwal, Manreet; Margetts, Peter J

    2016-09-01

    Peritoneal fibrosis is one of the major complications occurring in long-term peritoneal dialysis patients as a result of injury. Peritoneal fibrosis is characterized by submesothelial thickening and fibrosis which is associated with a decline in peritoneal membrane function. The myofibroblast has been identified as the key player involved in the development and progression of peritoneal fibrosis. Activation of the myofibroblast is correlated with expansion of the extracellular matrix and changes in peritoneal membrane integrity. Over the years, epithelial to mesenchymal transition (EMT) has been accepted as the predominant source of the myofibroblast. Peritoneal mesothelial cells have been described to undergo EMT in response to injury. Several animal and in vitro studies support the role of EMT in peritoneal fibrosis; however, emerging evidence from genetic fate-mapping studies has demonstrated that myofibroblasts may be arising from resident fibroblasts and pericytes/perivascular fibroblasts. In this review, we will discuss hypotheses currently surrounding the origin of the myofibroblast and highlight the experimental systems predominantly being used to investigate this.

  8. IDENTIFICATION OF SPONTANEOUS FELINE IDIOPATHIC PULMONARY FIBROSIS: MORPHOLOGY AND ULTRASTRUCTURAL EVIDENCE FOR A TYPE II PNEUMOCYTE DEFECT

    Science.gov (United States)

    AbstractIdiopathic pulmonary fibrosis currently lacks an animal model that develops the persistent, progressive lung fibrosis characteristic of the disease. Sixteen domestic cats developed dyspnea that was not responsive to therapy and which rapidly progressed until death/eu...

  9. Floating Inductance and FDNR Using Positive Polarity Current Conveyors

    OpenAIRE

    Pal, K.

    2004-01-01

    A generalized circuit based on five positive polarity second-generation current conveyors is introduced. The circuit simulates a floating inductance, capacitor floatation circuit and floating fdnr. All these circuits use grounded capacitors.

  10. Current Cigarette Use Among Adults (BRFSS) PDF Slides

    Data.gov (United States)

    U.S. Department of Health & Human Services — Download the current cigarette use among adults slides. These slides are available in PDF and PowerPoint formats. The PowerPoint version can be found at:...

  11. Floating Inductance and FDNR Using Positive Polarity Current Conveyors

    Directory of Open Access Journals (Sweden)

    K. Pal

    2004-01-01

    Full Text Available A generalized circuit based on five positive polarity second-generation current conveyors is introduced. The circuit simulates a floating inductance, capacitor floatation circuit and floating fdnr. All these circuits use grounded capacitors.

  12. Medicinal Use of Cannabis: History and Current Status

    Directory of Open Access Journals (Sweden)

    Harold Kalant

    2001-01-01

    Full Text Available OBJECTIVE: To provide an overview of the history and pharmacology of cannabis in relation to current scientific knowledge concerning actual and potential therapeutic uses of cannabis preparations and pure cannabinoids.

  13. Current Research Status of Repair Mechanism of Epithelial-to-Mesenchymal Transition of Idiopathic Pulmonary Fibrosis%肺纤维化及其上皮细胞转分化修复机制研究现状

    Institute of Scientific and Technical Information of China (English)

    彭彩钰; 赵荣光; 李戎

    2013-01-01

    特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种严重的难愈的肺间质疾病,由于其发病原因不明,治疗效果不良,对于寻找该病发病机制迫在眉睫.该文通过整理和分析相关肺纤维化机制,并综述相关研究概况,从EMT这个新的角度找寻肺纤维化的机制,以期为肺纤维化提供新的研究方向.%Idiopathic pulmonary fibrosis (IPF) is a kind of interstitial diseases which is hard to be cured.Because the etiology of pulmonary fibrosis is generally unknown and there is bad effective cure rate,to find the pathogenesis of this disease seems to be very important.The paper summarizes the present state of IPF through classifying and analyzing the relevant lung fibrosis mechanism.Overall,we propose the concept of Epithelial-to-Mesenchymal Transition about pulmonary fibrosis to dig out its mechanism which is the new perspective.

  14. The Processes and Mechanisms of Cardiac and Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Lucy A. Murtha

    2017-10-01

    Full Text Available Fibrosis is the formation of fibrous connective tissue in response to injury. It is characterized by the accumulation of extracellular matrix components, particularly collagen, at the site of injury. Fibrosis is an adaptive response that is a vital component of wound healing and tissue repair. However, its continued activation is highly detrimental and a common final pathway of numerous disease states including cardiovascular and respiratory disease. Worldwide, fibrotic diseases cause over 800,000 deaths per year, accounting for ~45% of total deaths. With an aging population, the incidence of fibrotic disease and subsequently the number of fibrosis-related deaths will rise further. Although, fibrosis is a well-recognized cause of morbidity and mortality in a range of disease states, there are currently no viable therapies to reverse the effects of chronic fibrosis. Numerous predisposing factors contribute to the development of fibrosis. Biological aging in particular, interferes with repair of damaged tissue, accelerating the transition to pathological remodeling, rather than a process of resolution and regeneration. When fibrosis progresses in an uncontrolled manner, it results in the irreversible stiffening of the affected tissue, which can lead to organ malfunction and death. Further investigation into the mechanisms of fibrosis is necessary to elucidate novel, much needed, therapeutic targets. Fibrosis of the heart and lung make up a significant proportion of fibrosis-related deaths. It has long been established that the heart and lung are functionally and geographically linked when it comes to health and disease, and thus exploring the processes and mechanisms that contribute to fibrosis of each organ, the focus of this review, may help to highlight potential avenues of therapeutic investigation.

  15. Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis.

    Science.gov (United States)

    Schierwagen, Robert; Maybüchen, Lara; Zimmer, Sebastian; Hittatiya, Kanishka; Bäck, Christer; Klein, Sabine; Uschner, Frank E; Reul, Winfried; Boor, Peter; Nickenig, Georg; Strassburg, Christian P; Trautwein, Christian; Plat, Jogchum; Lütjohann, Dieter; Sauerbruch, Tilman; Tacke, Frank; Trebicka, Jonel

    2015-08-11

    Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis, inflammation and fibrosis, which might progress to cirrhosis. Human NASH is associated with metabolic syndrome (MS). Currently, rodent NASH models either lack significant fibrosis or MS. ApoE(-/-) mice are a MS model used in cardiovascular research. The aim of this work was to establish and characterise a novel mouse NASH model with significant fibrosis and MS. ApoE(-/-) and wild-type mice (wt) were fed either a western-diet (WD), methionine-choline-deficient-diet (MCD) or normal chow. Liver histology, RT-PCR, hepatic hydroxyproline content, triglycerides and cholesterol levels, and fasting glucose levels assessed hepatic steatosis, inflammation and fibrosis. Further, portal pressure was measured invasively, and kidney pathology was assessed by histology. ApoE(-/-) mice receiving WD showed abnormal glucose tolerance, hepatomegaly, weight gain and full spectrum of NASH including hepatic steatosis, fibrosis and inflammation, with no sign of renal damage. MCD-animals showed less severe liver fibrosis, but detectable renal pathological changes, besides weight loss and unchanged glucose tolerance. This study describes a murine NASH model with distinct hepatic steatosis, inflammation and fibrosis, without renal pathology. ApoE(-/-) mice receiving WD represent a novel and fast model with all characteristic features of NASH and MS well suitable for NASH research.

  16. Reversal of liver fibrosis: From fiction to reality.

    Science.gov (United States)

    Zoubek, Miguel Eugenio; Trautwein, Christian; Strnad, Pavel

    2017-04-01

    In chronic liver diseases, an ongoing hepatocellular injury together with inflammatory reaction results in activation of hepatic stellate cells (HSCs) and increased deposition of extracellular matrix (ECM) termed as liver fibrosis. It can progress to cirrhosis that is characterized by parenchymal and vascular architectural changes together with the presence of regenerative nodules. Even at late stage, liver fibrosis is reversible and the underlying mechanisms include a switch in the inflammatory environment, elimination or regression of activated HSCs and degradation of ECM. While animal models have been indispensable for our understanding of liver fibrosis, they possess several important limitations and need to be further refined. A better insight into the liver fibrogenesis resulted in a large number of clinical trials aiming at reversing liver fibrosis, particularly in patients with non-alcoholic steatohepatitis. Collectively, the current developments demonstrate that reversal of liver fibrosis is turning from fiction to reality. Copyright © 2017. Published by Elsevier Ltd.

  17. Cystic Fibrosis Gene Therapy in the UK and Elsewhere.

    Science.gov (United States)

    Griesenbach, Uta; Pytel, Kamila M; Alton, Eric W F W

    2015-05-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) gene was identified in 1989. This opened the door for the development of cystic fibrosis (CF) gene therapy, which has been actively pursued for the last 20 years. Although 26 clinical trials involving approximately 450 patients have been carried out, the vast majority of these trials were short and included small numbers of patients; they were not designed to assess clinical benefit, but to establish safety and proof-of-concept for gene transfer using molecular end points such as the detection of recombinant mRNA or correction of the ion transport defect. The only currently published trial designed and powered to assess clinical efficacy (defined as improvement in lung function) administered AAV2-CFTR to the lungs of patients with CF. The U.K. Cystic Fibrosis Gene Therapy Consortium completed, in the autumn of 2014, the first nonviral gene therapy trial designed to answer whether repeated nonviral gene transfer (12 doses over 12 months) can lead to clinical benefit. The demonstration that the molecular defect in CFTR can be corrected with small-molecule drugs, and the success of gene therapy in other monogenic diseases, is boosting interest in CF gene therapy. Developments are discussed here.

  18. Endomyocardial fibrosis in infancy

    Directory of Open Access Journals (Sweden)

    Jatene Marcelo Biscegli

    2003-01-01

    Full Text Available The patient was a 4-month-old infant, who underwent persistent ductus arteriosus interruption with titanium clips at the age of 13 days and, since the age of 2 months, had crises of hypoxia and hypertonicity. After clinical investigation, the presence of pulmonary hypertension was confirmed and left ventricular inflow tract obstruction was suspected. The patient underwent surgical treatment at the age of 4 months, during which right and left ventricular endocardial fibrosis was identified. The fibrosis was resected, but the infant had an unfavorable clinical evolution with significant diastolic restriction and died on the sixth postoperative day. Anatomicopathological and surgical findings suggested endomyocardial fibrosis, although that pathology is very rare at the patient's age.

  19. Dual core quantum dots for highly quantitative ratiometric detection of trypsin activity in cystic fibrosis patients

    Science.gov (United States)

    Castelló Serrano, Iván; Stoica, Georgiana; Matas Adams, Alba; Palomares, Emilio

    2014-10-01

    We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. Current detection methods for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a highly sensitive, fast (minutes), and single-step approach nanosensor for the screening and diagnosis of cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range relevant for clinical applications (25-350 μg L-1). Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human genotypes, i.e. CF homozygotic, CF heterozygotic, and unaffected, respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescent biomarkers for recessive genetic diseases like human cystic fibrosis. In a screening program in which the goal is to detect disease and also the carrier status, early diagnosis could be of great help.We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. Current detection methods for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a highly sensitive, fast (minutes), and single-step approach nanosensor for the screening and diagnosis of cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range relevant for clinical applications (25-350 μg L-1). Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human genotypes, i.e. CF homozygotic, CF heterozygotic, and unaffected, respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescent biomarkers for

  20. Plasma heating and current drive using intense, pulsed microwaves

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, B.I.; Cohen, R.H.; Nevins, W.M.; Rognlien, T.D.; Bonoli, P.T.; Porkolab, M.

    1988-01-01

    The use of powerful new microwave sources, e.g., free-electron lasers and relativistic gyrotrons, provide unique opportunities for novel heating and current-drive schemes in the electron-cyclotron and lower-hybrid ranges of frequencies. These high-power, pulsed sources have a number of technical advantages over conventional, low-intensity sources; and their use can lead to improved current-drive efficiencies and better penetration into a reactor-grade plasma in specific cases. The Microwave Tokamak Experiment at Lawrence Livermore National Laboratory will provide a test for some of these new heating and current-drive schemes. This paper reports theoretical progress both in modeling absorption and current drive for intense pulses and in analyzing some of the possible complications that may arise, e.g., parametric instabilities and nonlinear self-focusing. 22 refs., 9 figs., 1 tab.

  1. Fibrosis: a structural modulator of Sinoatrial Node physiology and dysfunction

    Directory of Open Access Journals (Sweden)

    Thomas A Csepe

    2015-02-01

    Full Text Available Heart rhythm is initialized and controlled by the Sinoatrial Node (SAN, the primary pacemaker of the heart. The SAN is a heterogeneous multi-compartment structure characterized by clusters of specialized cardiomyocytes, enmeshed within strands of connective tissue or fibrosis. Intranodal fibrosis is emerging as an important modulator of structural and functional integrity of the SAN pacemaker complex. In adult human hearts, fatty tissue and fibrosis insulate the SAN from the hyperpolarizing effect of the surrounding atria while electrical communication between the SAN and right atrium is restricted to discrete SAN conduction pathways. The amount of fibrosis within the SAN is inversely correlated with heart rate, while age and heart size are positively correlated with fibrosis. Pathological upregulation of fibrosis within the SAN may lead to tachycardia-bradycardia arrhythmias and cardiac arrest, possibly due to SAN reentry and exit block, and is associated with atrial fibrillation, ventricular arrhythmias, heart failure and myocardial infarction. In this review, we will discuss current literature on the role of fibrosis in normal SAN structure and function, as well as the causes and consequences of SAN fibrosis upregulation in disease conditions.

  2. A Simple Current-Mode Quadrature Oscillator Using Single CDTA

    Directory of Open Access Journals (Sweden)

    D. Biolek

    2008-12-01

    Full Text Available This article presents a simple current-mode quadrature oscillator using a single Current Differencing Transconductance Amplifier (CDTA as the active element. The oscillation condition and oscillation frequency can be electronically controlled. The circuit structure is very simple, consisting of merely one CDTA, one resistor and two capacitors. The proposed circuit is suitable for IC architecture. The PSpice simulation and experimental results are shown, and the results agree well with the theoretical assumptions.

  3. Pergolide-induced pleuropulmonary fibrosis

    NARCIS (Netherlands)

    Bleumink, G S; van der Molen-Eijgenraam, M; Strijbos, J H; Sanwikarja, S; van Puijenbroek, E P; Stricker, B H Ch

    2002-01-01

    Pleuropulmonary fibrosis is a rare, but well-recognized adverse effect of ergot alkaloids. We report on four patients who developed pleural and/or pulmonary fibrosis during treatment with pergolide and give characteristics of 87 cases with one or more symptoms of serosal fibrosis. Retroperitoneal an

  4. Effect of Pistacia lentiscus oil on experimental pulmonary fibrosis.

    Science.gov (United States)

    Abidi, Anouar; Serairi Beji, Raja; Kourda, Nadia; Ennigrou, Samir; Ksouri, Riadh; Jameleddine, Saloua

    2016-07-01

    Background - Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by histopathological lesions in lung tissue. This is the most common and most severe idiopathic interstitial pneumonias. Current treatments are based on the combination of corticosteroids and immunosuppressants, but their effectiveness is still debated. Purpose of work - Testing the preventive effect of Pistacia Lentiscus oil, known for its antioxidant, anti-mutagenic and anti-proliferative effects, on a model of experimental lung fibrosis. Methods - Two groups of rats received an intratracheal injection of bleomycin (4.5 mg / kg). The first group, control (n = 20 rats), has received no treatment. The second group was treated with Pistacia Lentiscus oil (n = 20 rats) for 30 days before fibrosis induction, by daily gavage oil Pistacia Lentiscus oil (3,33ml / kg). This treatment was continued for 10 days. At the end of the experimental period, all rats were sacrificed and the lung tissue was examined histopathologically and immunostained for TGFβ. Results - The chromatographic profile oil Pistacia Lentiscus oil shows the dominance of two fatty acids that are linoleic acid and palmitic acid representing respectively 70.57 and 24.67%. Our results also show a decrease in the distribution of TGFβ both at the level of the inflammatory infiltrate and at the level of the pulmonary parenchyma histiocytes of rats treated with Pistacia Lentiscus oil compared with control rats. However, these changes are not accompanied by statistically significant changes of fibrosis score and inflammatory index. Conclusion - Our results are interesting to consider. Further studies using higher doses of Pistacia Lentiscus oil are important to conduct.

  5. Decoding of covert vowel articulation using electroencephalography cortical currents

    Directory of Open Access Journals (Sweden)

    Natsue eYoshimura

    2016-05-01

    Full Text Available With the goal of providing assistive technology for the communication impaired, we proposed electroencephalography (EEG cortical currents as a new approach for EEG-based brain-computer interface spellers. EEG cortical currents were estimated with a variational Bayesian method that uses functional magnetic resonance imaging (fMRI data as a hierarchical prior. EEG and fMRI data were recorded from ten healthy participants during covert articulation of Japanese vowels /a/ and /i/, as well as during a no-imagery control task. Applying a sparse logistic regression (SLR method to classify the three tasks, mean classification accuracy using EEG cortical currents was significantly higher than that using EEG sensor signals and was also comparable to accuracies in previous studies using electrocorticography. SLR weight analysis revealed vertices of EEG cortical currents that were highly contributive to classification for each participant, and the vertices showed discriminative time series signals according to the three tasks. Furthermore, functional connectivity analysis focusing on the highly contributive vertices revealed positive and negative correlations among areas related to speech processing. As the same findings were not observed using EEG sensor signals, our results demonstrate the potential utility of EEG cortical currents not only for engineering purposes such as brain-computer interfaces but also for neuroscientific purposes such as the identification of neural signaling related to language processing.

  6. Decoding of Covert Vowel Articulation Using Electroencephalography Cortical Currents

    Science.gov (United States)

    Yoshimura, Natsue; Nishimoto, Atsushi; Belkacem, Abdelkader Nasreddine; Shin, Duk; Kambara, Hiroyuki; Hanakawa, Takashi; Koike, Yasuharu

    2016-01-01

    With the goal of providing assistive technology for the communication impaired, we proposed electroencephalography (EEG) cortical currents as a new approach for EEG-based brain-computer interface spellers. EEG cortical currents were estimated with a variational Bayesian method that uses functional magnetic resonance imaging (fMRI) data as a hierarchical prior. EEG and fMRI data were recorded from ten healthy participants during covert articulation of Japanese vowels /a/ and /i/, as well as during a no-imagery control task. Applying a sparse logistic regression (SLR) method to classify the three tasks, mean classification accuracy using EEG cortical currents was significantly higher than that using EEG sensor signals and was also comparable to accuracies in previous studies using electrocorticography. SLR weight analysis revealed vertices of EEG cortical currents that were highly contributive to classification for each participant, and the vertices showed discriminative time series signals according to the three tasks. Furthermore, functional connectivity analysis focusing on the highly contributive vertices revealed positive and negative correlations among areas related to speech processing. As the same findings were not observed using EEG sensor signals, our results demonstrate the potential utility of EEG cortical currents not only for engineering purposes such as brain-computer interfaces but also for neuroscientific purposes such as the identification of neural signaling related to language processing. PMID:27199638

  7. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

    Science.gov (United States)

    Kaminski, Naftali; Allard, John D.; Pittet, Jean F.; Zuo, Fengrong; Griffiths, Mark J. D.; Morris, David; Huang, Xiaozhu; Sheppard, Dean; Heller, Renu A.

    2000-02-01

    The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin 6 subunit (6/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.

  8. Detecting surface geostrophic currents using wavelet filter from satellite geodesy

    Institute of Scientific and Technical Information of China (English)

    HSU; HouTse

    2007-01-01

    According to the features of spatial spectrum of the dynamic ocean topography (DOT),wavelet filter is proposed to reduce short-wavelength and noise signals in DOT. The surface geostrophic currents calculated from the DOT models filtered by wavelet filter in global and Kuroshio regions show more detailed information than those from the DOT models filtered by Gaussian filter. Based on a satellite gravity field model (CG01C) and a gravity field model (EGM96),combining an altimetry-derived mean sea surface height model (KMSS04),two mean DOT models are estimated. The short-wavelength and noise signals of these two DOT models are removed by using wavelet filter,and the DOT models asso-ciated global mean surface geostrophic current fields are calculated separately. Comparison of the surface geostrophic currents from CG01C and EGM96 model in global,Kuroshio and equatorial Pacific regions with that from oceanography,and comparison of influences of the two gravity models errors on the precision of the surface geostrophic currents velocity show that the accuracy of CG01C model has been greatly improved over pre-existing models at long wavelengths. At large and middle scale,the surface geostrophic current from satellite gravity and satellite altimetry agrees well with that from oceanography,which indicates that ocean currents detected by satellite measurement have reached relatively high precision.

  9. Detecting surface geostrophic currents using wavelet filter from satellite geodesy

    Institute of Scientific and Technical Information of China (English)

    ZHANG ZiZhan; LU Yang; HSU HouTse

    2007-01-01

    According to the features of spatial spectrum of the dynamic ocean topography (DOT), wavelet filter is proposed to reduce short-wavelength and noise signals in DOT. The surface geostrophic currents calculated from the DOT models filtered by wavelet filter in global and Kuroshio regions show more detailed information than those from the DOT models filtered by Gaussian filter. Based on a satellite gravity field model (CG01C) and a gravity field model (EGM96), combining an altimetry-derived mean sea surface height model (KMSS04), two mean DOT models are estimated. The short-wavelength and noise signals of these two DOT models are removed by using wavelet filter, and the DOT models associated global mean surface geostrophic current fields are calculated separately. Comparison of the surface geostrophic currents from CG01C and EGM96 model in global, Kuroshio and equatorial Pacific regions with that from oceanography, and comparison of influences of the two gravity models errors on the precision of the surface geostrophic currents velocity show that the accuracy of CG01C model has been greatly improved over pre-existing models at long wavelengths. At large and middle scale, the surface geostrophic current from satellite gravity and satellite altimetry agrees well with that from oceanography, which indicates that ocean currents detected by satellite measurement have reached relatively high precision.

  10. Prevention of Staphylococcus epidermidis biofilm formation using electrical current.

    Science.gov (United States)

    Del Pozo, Jose L; Rouse, Mark S; Euba, Gorane; Greenwood-Quaintance, Kerryl E; Mandrekar, Jayawant N; Steckelberg, James M; Patel, Robin

    2014-09-05

    A technique for the prevention of staphylococcal adhesion by electrical current exposure was investigated. Teflon coupons were exposed to a continuous flow of 103 cfu/ml Staphylococcus epidermidis with or without 2000 microA DC electrical current delivered by electrodes on opposite sides of a coupon, touching neither each other nor the coupon. A mean 3.46 (SD, 0.20) and 5.70 (SD, 1.03) log10 cfu/cm2 were adhered to the non-electrical current exposed coupons after 4 h and 24 h, respectively. A mean 2.46 (SD, 0.31) and 1.47 (SD, 0.73) log10 cfu/cm2 were adhered after 4 h and 24 h with exposure to 2000 microA electrical current delivered by graphite electrodes. A mean 2.21 (SD, 0.14) and 0.55 (SD, 0.00) log10 cfu/cm2 were adhered after 4 h and 24 h with exposure to 2000 microA electrical current delivered by stainless steel electrodes. Electrical current may be useful in the prevention of staphylococcal adhesion to biomaterials.

  11. A transmission-loss monitor using current transformers

    Energy Technology Data Exchange (ETDEWEB)

    Power, J.F.; Gilpatrick, J.D.; Jason, A.J.

    1993-12-01

    A system for measuring the amount of beam-charge loss in a linear-accelerator structure has been developed that uses a pair of beam-current transformers, otherwise used to monitor the linac beam current. This system is necessary to enable the Ground Test Accelerator (GTA) fast-protect system to shut off the accelerated beam in the event of a beam loss that would deposit sufficient energy to damage the accelerator structure. The present GTA accelerator consists of a 2.5-MeV, H{sup {minus}} RFQ, an intermediate matching section (IMS) and a single DTL cavity with an output energy of 3.2-MeV and transmitted current of 35 mA. Based on the RFQ output beam, melting of the copper structures will occur when about 40 nC of beam is deposited in a point loss. For a grazing angle of 30 mrad, up to 640 nC may be tolerated. The beam-current-transmission-loss monitor (BCTLM) system in conjunction with the fast-protect system measures the amount of beam loss between two toroidal beam-current monitors and automatically terminates the macropulse when the integrated loss reaches a predetermined set point. The design and operation of the BCTLM system used in the IMS and DTL section of the accelerator is described.

  12. Eddy current NDE performance demonstrations using simulation tools

    Energy Technology Data Exchange (ETDEWEB)

    Maurice, L. [EDF - CEIDRE, 2 rue Ampere, 93206 Saint-Denis Cedex 1 (France); Costan, V.; Guillot, E.; Thomas, P. [EDF - R and D, THEMIS, 1, avenue du General de Gaulle, 92141 Clamart (France)

    2013-01-25

    To carry out performance demonstrations of the Eddy-Current NDE processes applied on French nuclear power plants, EDF studies the possibility of using simulation tools as an alternative to measurements on steam generator tube mocks-up. This paper focuses on the strategy led by EDF to assess and use code{sub C}armel3D and Civa, on the case of Eddy-Current NDE on wears problem which may appear in the U-shape region of steam generator tubes due to the rubbing of anti-vibration bars.

  13. Understanding Nephrogenic Systemic Fibrosis

    Directory of Open Access Journals (Sweden)

    Tushar Chopra

    2012-01-01

    Full Text Available Nephrogenic systemic fibrosis (NSF is a rare and a debilitating disease noted uncommonly in patients with impaired renal function when exposed to low-stability gadolinium-based contrast agents (Gd-CAs. According to experimental studies, cytokines released by the stimulation of effector cells such as skin macrophages and peripheral blood monocytes activate circulating fibroblasts which play a major role in the development of NSF lesions. The presence of permissive factors, presumably, provides an environment conducive to facilitate the process of fibrosis. Multiple treatment modalities have been tried with variable success rates. More research is necessary to elucidate the underlying pathophysiological mechanisms which could potentially target the initial steps of fibrosis in these patients. This paper attempts to collate the inferences from the in vivo and in vitro experiments to the clinical observations to understand the pathogenesis of NSF. Schematic representations of receptor-mediated molecular pathways of activation of macrophages and fibroblasts by gadolinium and the final pathway to fibrosis are incorporated in the discussion.

  14. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Khurram, Misbah; Skov, Lone; Rossen, Kristian

    2007-01-01

    Nephrogenic systemic fibrosis (NSF) is a fibrotic disease seen in renal failure patients that may lead to severe physical disability. It has been demonstrated in recent studies that NSF can be caused by some gadolinium-containing MRI contrast agents. In this report we present one of a total of 26...

  15. Direct-current-like Phase Space Manipulation Using Chirped Alternating Current Fields

    Energy Technology Data Exchange (ETDEWEB)

    P.F. Schmit and N.J. Fisch

    2010-02-01

    Waves in plasmas can accelerate particles that are resonant with the wave. A dc electric field also accelerates particles, but without a resonance discrimination, which makes the acceleration mechanism profoundly different. Whereas wave-particle acceleration mechanisms have been widely discussed in the literature, this work discusses the direct analogy between wave acceleration and dc field acceleration in a particular parameter regime explored in previous works. Apart from the academic interest of this correspondence, there may be practical advantages in using waves to mimic dc electric fields, for example, in driving plasma current with high efficiency.

  16. The association between indirect bilirubin levels and liver fibrosis due to chronic hepatitis C virus infection.

    Science.gov (United States)

    Cengiz, Mustafa; Yılmaz, Guldal; Ozenirler, Seren

    2014-08-01

    We proposed to evaluate the association between serum indirect bilirubin levels and liver fibrosis in patients with chronic hepatitis C (CHC) genotype 1b. Biopsy proven CHC genotype 1b patients' demographics, clinical and histopathological characteristics were evaluated. Logistic regression analysis was done to evaluate the clinical, laboratory and demographic features of the histologically proven liver fibrosis in CHC patients. A total of 112 biopsy proven CHC genotype 1b patients were enrolled into the study. Liver fibrosis scores were measured by using Ishak fibrosis scores and were divided into two groups; fibrosis scores ≤ 2 were categorized as mild fibrosis, 82 patients (73.2%), whereas fibrosis scores >2 were categorized as advanced fibrosis group, 30 patients (26.8%). Patients with advanced fibrosis had lower indirect bilirubin levels than the mild fibrosis group (0.28 ± 0.02 mg/dl vs. 0.44 ± 0.032 mg/dl, pbilirubin level was negatively correlated with advanced fibrosis scores (r=-0.416 and pbilirubin level was an independent predicting factor of advanced liver fibrosis (OR: 0.001, 95% CI: 0.0-0.005, pbilirubin levels and advanced liver fibrosis caused by CHC genotype 1b.

  17. Schmitt Trigger with Controllable Hysteresis Using Current Conveyors

    Directory of Open Access Journals (Sweden)

    Jiri Misurec

    2012-07-01

    Full Text Available Active elements working in the current or mixed mode are still attractive for the design of analog functional blocks. The current conveyor (CC was defined already in 1968. This paper deals with hysteresis comparators using second generation current conveyor. The comparator is basically a pulse circuit. In these circuits, the maximum rate of change in the output voltage is required during switching from one state to another. In comparators with operational amplifiers the switching time is given by the slew rate of the operational amplifier used, which is not too high. If a current conveyor is used, the time of switching the comparator gets shorter. The comparator is capable to operate at a higher frequency bands and if it is used, for example, in converters, a higher operating frequency can be reached. The connection of an inverting and a non-inverting comparator with adjustable hysteresis is shown as a practical implementation. Using the AD844, results of experimental measurements are presented that confirm the theoretical  assumptions and the results of computer simulation.

  18. Improved air trapping evaluation in chest computed tomography in children with cystic fibrosis using real-time spirometric monitoring and biofeedback

    DEFF Research Database (Denmark)

    Kongstad, Thomas; Buchvald, Frederik F; Green, Kent

    2013-01-01

    BACKGROUND: The quality of chest Computed Tomography (CT) images in children is dependent upon a sufficient breath hold during CT scanning. This study evaluates the influence of spirometric breath hold monitoring with biofeedback software on inspiratory and expiratory chest CT lung density measures......, and on trapped air (TA) scoring in children with cystic fibrosis (CF). This is important because TA is an important component of early and progressive CF lung disease. METHODS: A cross sectional comparison study was completed for chest CT imaging in two cohorts of CF children with comparable disease severity......, using spirometric breath hold monitoring and biofeedback software (Copenhagen (COP)) or unmonitored breath hold manoeuvres (Gothenburg (GOT)). Inspiratory-expiratory lung density differences were calculated, and TA was scored to assess the difference between the two cohorts. RESULTS: Eighty-four chest...

  19. Retrospective observational study of trends in hospital admissions for idiopathic pulmonary fibrosis in Spain (2004–2013) using administrative data

    Science.gov (United States)

    Pedraza-Serrano, Fernando; López de Andrés, Ana; Jiménez-García, Rodrigo; Jiménez-Trujillo, Isabel; Hernández-Barrera, Valentín; Sánchez-Muñoz, Gema; Puente-Maestu, Luis; de Miguel-Díez, Javier

    2017-01-01

    Objective To assess changes in incidence, diagnostic procedures, comorbidity profiles, length of hospital stay (LOHS), economic costs and in-hospital mortality (IHM) associated with idiopathic pulmonary fibrosis (IPF). Methods We identified patients hospitalised with IPF in Spain from 2004 to 2013. Data were collected from the National Hospital Discharge Database. Results The study population comprised 22 214 patients. Overall crude incidence increased from 3.82 to 6.98 admissions per 100 000 inhabitants from 2004 to 2013 (p<0.05). The percentage of lung biopsies decreased significantly from 10.68% in 2004 to 9.04% in 2013 (p<0.05). The percentage of patients with a Charlson comorbidity index ≥2 was 15.14% in 2004, increasing to 26.95% in 2013 (p<0.05). IHM decreased from 14.77% in 2004 to 13.72% in 2013 (adjusted OR 0.98; 95% CI 0.97 to 0.99). Mean LOHS was 11.87±11.18 days in 2004, decreasing to 10.20±11.12 days in 2013 (p<0.05). The mean cost per patient increased from €4838.51 in 2004 to €5410.90 in 2013 (p<0.05). Conclusions The frequency of hospital admissions for IPF increased during the study period, as did healthcare costs. However, IHM and LOHS decreased. PMID:28193850

  20. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Uses its C-Terminus to Regulate the A2B Adenosine Receptor.

    Science.gov (United States)

    Watson, Michael J; Lee, Shernita L; Marklew, Abigail J; Gilmore, Rodney C; Gentzsch, Martina; Sassano, Maria F; Gray, Michael A; Tarran, Robert

    2016-06-09

    CFTR is an apical membrane anion channel that regulates fluid homeostasis in many organs including the airways, colon, pancreas and sweat glands. In cystic fibrosis, CFTR dysfunction causes significant morbidity/mortality. Whilst CFTR's function as an ion channel has been well described, its ability to regulate other proteins is less understood. We have previously shown that plasma membrane CFTR increases the surface density of the adenosine 2B receptor (A2BR), but not of the β2 adrenergic receptor (β2AR), leading to an enhanced, adenosine-induced cAMP response in the presence of CFTR. In this study, we have found that the C-terminal PDZ-domain of both A2BR and CFTR were crucial for this interaction, and that replacing the C-terminus of A2BR with that of β2AR removed this CFTR-dependency. This observation extended to intact epithelia and disruption of the actin cytoskeleton prevented A2BR-induced but not β2AR-induced airway surface liquid (ASL) secretion. We also found that CFTR expression altered the organization of the actin cytoskeleton and PDZ-binding proteins in both HEK293T cells and in well-differentiated human bronchial epithelia. Furthermore, removal of CFTR's PDZ binding motif (ΔTRL) prevented actin rearrangement, suggesting that CFTR insertion in the plasma membrane results in local reorganization of actin, PDZ binding proteins and certain GPCRs.

  1. Using Current Resources to Implement Wellness Programming for Preschoolers

    Science.gov (United States)

    Cirignano, Sherri M.

    2013-01-01

    Currently, there is a nationwide effort to include preschool-aged children in wellness efforts for the prevention of obesity. National resources include guidelines, best practices, and tip sheets to assist in the implementation of these interventions. The Let's Move! Child Care Checklist is a resource that can be used to assess the level at…

  2. California Current Monitoring Using the NPS Ocean Acoustic Observatory

    Science.gov (United States)

    2016-06-07

    acoustic measurements generated by this project can be used to validate and calibrate ocean forecast model for the region. The data can also be... Innovative Coastal Observing Network (ICON). ICON studies the ocean processes in the Monterey Bay area which is influenced by the California Current

  3. Merits and Pitfalls of Currently Used Diagnostic Tools in Mycetoma

    NARCIS (Netherlands)

    W.W.J. van de Sande (Wendy); A.H. Fahal (Ahmed); H. Goodfellow (Henry); E.S. Mahgoub (El Sheikh); O. Welsh (Oliverio); E. Zijlstra (Ed)

    2014-01-01

    textabstractTreatment of mycetoma depends on the causative organism and since many organisms, both actinomycetes (actinomycetoma) and fungi (eumycetoma), are capable of producing mycetoma, an accurate diagnosis is crucial. Currently, multiple diagnostic tools are used to determine the extent of infe

  4. How to Use Current Medical Literature and APA Format Style.

    Science.gov (United States)

    Peek, Robin

    Directives and guidance in obtaining current medical literature are provided in this publication with special emphasis given to locating material in the Portland, Oregon area. The uses and types of periodical indexes are identified and periodical index citation examples are indicated. Explanations are offered on: (1) how to conduct an effective…

  5. How to Use Current Medical Literature and APA Format Style.

    Science.gov (United States)

    Peek, Robin

    Directives and guidance in obtaining current medical literature are provided in this publication with special emphasis given to locating material in the Portland, Oregon area. The uses and types of periodical indexes are identified and periodical index citation examples are indicated. Explanations are offered on: (1) how to conduct an effective…

  6. Assessment of lung disease in children with cystic fibrosis using hyperpolarized 3-Helium MRI: comparison with Shwachman score, Chrispin-Norman score and spirometry

    Energy Technology Data Exchange (ETDEWEB)

    Beek, Edwin J.R. van [University of Sheffield, Unit of Academic Radiology, Sheffield (United Kingdom); University of Iowa, Department of Radiology, Carver College of Medicine, Iowa City (United States); University of Iowa, Department of Radiology, Iowa City, IA (United States); Hill, Catherine; Woodhouse, Neil; Fichele, Stanislao; Fleming, Sally; Wild, Jim M. [University of Sheffield, Unit of Academic Radiology, Sheffield (United Kingdom); Howe, Bridget; Bott, Sandra; Taylor, Christopher J. [University of Sheffield, Academic Unit of Child Health, Sheffield (United Kingdom)

    2007-04-15

    This study assesses the feasibility of hyperpolarized 3-Helium MRI in children with cystic fibrosis (CF) and correlates the findings with standard clinical parameters based on chest radiograph (CXR) and pulmonary function tests (PFT). An uncontrolled, observational study in eighteen children with cystic fibrosis aged 5 - 17 years (median 12.1 years), with different severity of disease was carried out. All subjects underwent routine clinical assessment including PFT and standard auxology; CXR was obtained and Shwachman and Chrispin-Norman scores calculated. Hyperpolarized 3-He magnetic resonance imaging (MRI) was carried out using a spin-exchange polarizer and a whole body 1.5 T scanner. Ventilation distribution images were obtained during a 21-second breath-hold and scored according to previously defined criteria. Spearman's non-parametric correlations test was performed to assess for statistical significance at the p<0.05 level. The children tolerated the procedure well. No desaturation events were observed during 3-He MRI. A significant, albeit moderate, correlation was found between MRI score and FEV1% predicted (r=-0.41; p=0.047) and FVC% predicted (r=-0.42; p=0.04), while there were trends of correlations between Shwachman score and MRI score (r=-0.38; p=0.06) and Shwachman score and FEV1% predicted (r=0.39; p=0.055). The feasibility of hyperpolarized 3-He MRI in children with CF was demonstrated. MRI appears to be able to demonstrate functional lung changes, although correlations with routine clinical tests are only moderate to poor. This non-ionising radiation technique could be useful for monitoring lung disease and assessing therapy in this patient population. (orig.)

  7. The current relevance and use of prednisone in rheumatoid arthritis.

    Science.gov (United States)

    Krasselt, Marco; Baerwald, Christoph

    2014-05-01

    Prednisone is an old and very valuable drug in clinical use for over 60 years by now. It is well known by physicians and widely used for different kinds of inflammatory states including rheumatoid arthritis (RA). Clinical trials during the last 20 years have changed its clinical use, particularly with regards to dosage. Today, rheumatologists are treating their patients much more likely over a long period of time using a low-dose scheme. The effectiveness and safety of this low-dose use is the objective of the current clinical research and shall be enlightened in this drug profile. It is also featuring current knowledge about the value of modified-release prednisone with regards to the just published results of the 2nd Circadian Administration of Prednisone in Rheumatoid Arthritis trial. Moreover, the mechanisms of action of prednisone and its relatives will be summed up.

  8. Defect detection in conducting materials using eddy current testing techniques

    Directory of Open Access Journals (Sweden)

    Brauer Hartmut

    2014-01-01

    Full Text Available Lorentz force eddy current testing (LET is a novel nondestructive testing technique which can be applied preferably to the identification of internal defects in nonmagnetic moving conductors. The LET is compared (similar testing conditions with the classical eddy current testing (ECT. Numerical FEM simulations have been performed to analyze the measurements as well as the identification of internal defects in nonmagnetic conductors. The results are compared with measurements to test the feasibility of defect identification. Finally, the use of LET measurements to estimate of the electrical conductors under test are described as well.

  9. Using silver nanoparticle to enhance current response of biosensor.

    Science.gov (United States)

    Ren, Xiangling; Meng, Xianwei; Chen, Dong; Tang, Fangqiong; Jiao, Jun

    2005-09-15

    In this paper, we present a simple procedure to increase the sensitivity of a glucose biosensor. The feasibility of an amperometric glucose biosensor based on immobilization of glucose oxidase (GOx) in silver (Ag) sol was investigated for the first time. GOx was simply mixed with Ag nanoparticles and cross-linked with a polyvinyl butyral (PVB) medium by glutaraldehyde. Then a platinum electrode was coated with the mixed solution. The effects of the amount of the Ag particles used, with respect to the current response for enzyme electrodes, were studied. A set of experimental results indicate that the current response for the enzyme electrode containing hydrophobic Ag sol increased from 0.531 to 31.17 microA in the solution of 10 mmol/L beta-D glucose. The time reaching the steady-state current response reduced from 60 to 20s, three times less than those without Ag particles involved.

  10. Collagen immunostains can distinguish capsular fibrous tissue from septal fibrosis and may help stage liver fibrosis.

    Science.gov (United States)

    Chen, Wei; Rock, Jonathan B; Yearsley, Martha M; Hanje, A James; Frankel, Wendy L

    2014-01-01

    Core-needle biopsy remains essential for diagnosis of cirrhosis; however, evaluation of fibrosis in such biopsies is often challenging due to the fragmented nature of cirrhotic liver specimens. It is also common to see portions of liver capsules present in the biopsy which adds to the diagnostic challenge. The distinction between capsular/subcapsular fibrous tissue and septal fibrosis is critical to avoid potential overstaging of liver fibrosis. We compared the differential immunostaining in liver capsular and septal areas for collagens III, IV, V, VI, vitronectin, laminin, Orcein, and Trichrome in 15 whole sections of explanted cirrhotic livers and 5 simulated liver biopsies. Collagens III, IV, V, VI, Trichrome, and Orcein show distinct staining patterns in capsular fibrous tissue and septal fibrosis. Collagen IV shows strong diffuse septal staining and consistently weak to negative capsular staining. Collagens III and VI stain similar to IV for septal fibrosis, whereas collagen V, Trichrome, and Orcein show strong staining in both areas. Collagen IV, possibly with III or VI in addition to the routine Trichrome and hematoxylin and eosin stain, is useful in differentiating capsular fibrous tissue from septal fibrosis on challenging and fragmented liver biopsies.

  11. Non-invasive diagnosis of liver fibrosis by FibroScan imaging

    Directory of Open Access Journals (Sweden)

    WANG Chunyan

    2013-03-01

    Full Text Available Liver fibrosis is a common etiology of chronic liver diseases. Treatment in the early stage, by anti-inflammatories or other drugs targeting the specific fibrosis-promoting factor/pathogen, can reverse the liver fibrosis; treatments in the later stages can effectively reduce the extent of fibrosis. Therefore, sensitive and accurate methods to predict and/or diagnose liver fibrosis are crucial for identifying the condition at the earliest possible stage to initiate timely therapy and inhibit disease progression. Liver biopsy is currently the gold standard for diagnosing and staging fibrosis. However, the procedure is invasive and presents surgery-related risks, such as infection and bleeding. The FibroScan imaging system represents a new, non-invasive approach to diagnose and stage liver fibrosis. This review discusses the FibroScan technology and its clinical application and efficacy.

  12. Endocrine Disorders in Cystic Fibrosis.

    Science.gov (United States)

    Blackman, Scott M; Tangpricha, Vin

    2016-08-01

    Cystic fibrosis is frequently complicated by endocrine disorders. Diabetes can be expected to affect most with CF and pancreatic insufficiency and varies widely in age of onset, but early identification and treatment improve morbidity and mortality. Short stature can be exacerbated by relative delay of puberty and by use of inhaled corticosteroids. Bone disease in CF causes fragility fractures and should be assessed by monitoring bone mineral density and optimizing vitamin D status. Detecting and managing endocrine complications in CF can reduce morbidity and mortality in CF. These complications can be expected to become more common as the CF population ages. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The use of DWI to assess spleen and liver quantitative ADC changes in the detection of liver fibrosis stages in chronic viral hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Cece, Hasan, E-mail: hasan_cece@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Ercan, Abdulbasit, E-mail: abdulbasitercan@hotmail.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Yıldız, Sema, E-mail: drsemayildiz@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Karakas, Ekrem, E-mail: karakasekrem@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Karakas, Omer, E-mail: dromerkarakas@hotmail.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Boyacı, Fatıma Nurefsan, E-mail: drnurefsan@yahoo.com [Harran University, Faculty of Medicine, Department of Radiology, Sanliurfa (Turkey); Aydogan, Timucin, E-mail: drtaydogan@yahoo.com.tr [Harran University, Faculty of Medicine, Department of Gastroenterology, Sanliurfa (Turkey); Karakas, Emel Yigit, E-mail: e.ygtkarakas@yahoo.com.tr [Sanliurfa Training and Research Hospital, Department of İnternal Medicine, Sanliurfa (Turkey); Cullu, Nesat, E-mail: nesatcullu77@gmail.com [Muğla Sıtkı Koçman University, Faculty of Medicine, Department of Radiology, Mugla (Turkey); Ulas, Turgay, E-mail: turgayulas@yahoo.com [Harran University, Faculty of Medicine, Department of İnternal Medicine, Sanliurfa (Turkey)

    2013-08-15

    This study aimed to evaluate the changes in spleen and liver diffusion-weighted magnetic resonance imaging (DWI) in chronic viral hepatitis patients. The study comprised 47 patients and 30 healthy volunteers. DWIs were obtained. Apparent Diffusion Coefficient (ADC) measurements were made by transferring the images to the workstation. The measurements of value b 1000 were made from a total of five points of the liver and three points of the spleen. Liver biopsy was performed on the 47 patients. The fibrosis stages of the patients were defined according to the METAVIR scoring system. Student's t-test was used in the comparison of mean ages, liver and spleen ADC values between the patient and the control group. Kruskal–Wallis followed by Mann–Whitney U Test with Bonferroni adjustment was performed in the comparison of mean ADC values of the patients at different stages and the control group. A statistically significant difference was determined between the patient and control group in respect of liver and spleen mean ADC values (P < 0.05). F3 group showed a significant difference compared to control and F1 and F4 group showed a significant difference compared to control, F1, F2 and F3 group in terms of the mean liver ADC value (P < 0.01). F3 and F4 group showed a significant difference compared to control and F1 group in terms of the mean spleen ADC value (P < 0.01). As a result we believe that the measurement of liver and spleen ADC values may be an indicator in the determination of the level of fibrosis.

  14. Eddy current testing probe optimization using a parallel genetic algorithm

    Directory of Open Access Journals (Sweden)

    Dolapchiev Ivaylo

    2008-01-01

    Full Text Available This paper uses the developed parallel version of Michalewicz's Genocop III Genetic Algorithm (GA searching technique to optimize the coil geometry of an eddy current non-destructive testing probe (ECTP. The electromagnetic field is computed using FEMM 2D finite element code. The aim of this optimization was to determine coil dimensions and positions that improve ECTP sensitivity to physical properties of the tested devices.

  15. DEATH BY VOLUNTARY CESSATION OF THERAPY BY NON-TERMINALLY ILL CYSTIC FIBROSIS PATIENTS - INTERNATIONAL SURVEY OF CLINICIANS

    OpenAIRE

    PISATURO, M.

    2014-01-01

    Background: Little is known about non-terminally ill cystic fibrosis (CF) patients who die by voluntary cessation of therapy. The current study was undertaken to provide an international snapshot of this problem. Methods: An online survey was distributed to the medical directors of the CF Centres affiliated with the US Cystic Fibrosis Foundation and Cystic Fibrosis Australia (with the inclusion of New Zealand); the same letter was sent to every clinician member of the European Cystic Fibrosis...

  16. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

    DEFF Research Database (Denmark)

    Johansen, H.K.; Gøtzsche, Peter C.; Johansen, Helle Krogh

    2008-01-01

    BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. OBJECTIVES......: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search May 2008) and PubMed using the terms vaccin* AND cystic...... fibrosis (last search May 2008). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently selected trials...

  17. Evaluación de la fibrosis hepática en la hepatitis crónica por virus C mediante la aplicación prospectiva del Sabadell's NIHCED score: Sabadell's Non Invasive, Hepatitis C Related-Cirrhosis Early Detection Score Prospective evaluation of liver fibrosis in chronic viral hepatitis C infection using the Sabadell NIHCED: non-invasive hepatitis C related cirrhosis early detection index

    Directory of Open Access Journals (Sweden)

    G. Bejarano

    2009-05-01

    of fibrosis grade is liver biopsy. Our group validated a predictive index - NIHCED - based on demographic, laboratory parameters, and echoghraphic data to determine the presence of cirrhosis. Objective: our objective is to evaluate whether the NIHCED score predicts the presence of advanced fibrosis in patients with chronic HCV infection. Material and methods: this prospective study included patients with chronic HCV infection who underwent liver biopsy and were administered the NIHCED score. Fibrosis grade correlated with the NIHCED score using the ROC curve analysis and Spearman's correlation coefficient. Results: in total 321 patients were included (male/female ratio 1.27 with a mean age of 48 ± 14 years. Liver biopsy showed that 131 (30.5% had no fibrosis or had portal expansion while 190 (69.5% had advanced fibrosis or cirrhosis. At a cut-off point of 6, sensitivity was 72%, specificity was 76.3%, positive predictive value (PPV was 81%, negative predictive value (NPV was 63.7%, and diagnostic accuracy was 72.5%, with an area under the curve (AUC of 0.787, and a Spearman's correlation coefficient of r = 0.65. Conclusions: the NIHCED score predicts the presence of advanced fibrosis in an elevated percentage of patients with a need of liver biopsy.

  18. Current use pesticides in Arctic media; 2000-2007.

    Science.gov (United States)

    Hoferkamp, Lisa; Hermanson, Mark H; Muir, Derek C G

    2010-07-01

    This review will summarize the levels of selected current use pesticides (CUPs) that have been identified and reported in Arctic media (i.e. air, water, sediment, and biota) since the year 2000. Almost all of the 10 CUPs (chlorothalonil, chlorpyrifos, dacthal, diazinon, dicofol, lindane, methoxychlor, pentachloronitrobenzene (PCNB), pentachlorophenol, and trifluralin) examined in the review currently are, or have been, high production volume chemicals i.e. >1M lbs/y in USA or >1000 t/y globally. Characteristic travel distances for the 10 chemicals range from 55 km (methoxychlor) to 12,100 km (PCNB). Surveys and long-term monitoring studies have demonstrated the presence of 9 of the 10 CUPs included in this review in the Arctic environment. Only dicofol has not been reported. The presence of these chemicals has mainly been reported in high volume air samples and in snow from Arctic ice caps and lake catchments. There are many other CUPs registered for use which have not been determined in Arctic environments. The discovery of the CUPs currently measured in the Arctic has been mainly serendipitous, a result of analyzing some samples using the same suite of analytes as used for studies in mid-latitude locations. A more systematic approach is needed to assess whether other CUPs might be accumulating in the arctic and ultimately to assess whether their presence has any significance biologically or results in risks for human consumers.

  19. Programmable Input Mode Instrumentation Amplifier Using Multiple Output Current Conveyors

    Directory of Open Access Journals (Sweden)

    Pankiewicz Bogdan

    2017-03-01

    Full Text Available In this paper a programmable input mode instrumentation amplifier (IA utilising second generation, multiple output current conveyors and transmission gates is presented. Its main advantage is the ability to choose a voltage or current mode of inputs by setting the voltage of two configuration nodes. The presented IA is prepared as an integrated circuit block to be used alone or as a sub-block in a microcontroller or in a field programmable gate array (FPGA, which shall condition analogue signals to be next converted by an analogue-to-digital converter (ADC. IA is designed in AMS 0.35 µm CMOS technology and the power supply is 3.3 V; the power consumption is approximately 9.1 mW. A linear input range in the voltage mode reaches ± 1.68 V or ± 250 µA in current mode. A passband of the IA is above 11 MHz. The amplifier works in class A, so its current supply is almost constant and does not cause noise disturbing nearby working precision analogue circuits.

  20. Gefitinib attenuates murine pulmonary fibrosis induced by bleomycin

    Institute of Scientific and Technical Information of China (English)

    WANG Ping; TIAN Qing; LIANG Zhi-xin; YANG Zhen; XU Shu-feng; SUN Ji-ping; CHEN Liang-an

    2010-01-01

    Background Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer (NSCLC), and is generally well tolerated.However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction.This study investigated the effect of gefitinib on lung fibrosis in mice.Methods We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib.C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline.Lung tissues were harvested on day 14 or 21 for histology and genetic analysis.Results The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells.In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR (p-EGFR).Furthermore, quantitative real-time PCR (qRT-PCR) demonstrated that gefitinib inhibited the accumulation of collagens Ⅰ and Ⅲ.Conclusions These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.

  1. Cystic fibrosis. Diagnosis.

    Directory of Open Access Journals (Sweden)

    Luis Ortigosa

    2009-11-01

    Full Text Available Cystic fibrosis (CF is one of the most frequent inherited mortal diseases in Caucasian population. Dysfunction in exocrine glands is described in CF patients, with severe pancreatic insufficiency and chronic lung disease. CF is inherited as an autosomal recessive disorder. More than 1000 disease-associated mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene have been described. DF508 mutation is the most common mutation in the CF gen. Diagnosis in CF is based on clinical and laboratory tests findings. Meconial ileus, CF in other relatives, chronic lung disease, congenital absence of the vas deferens with azoospermia are among other clinical findings, main criteria in CF patients. Two positive results in sweat chloride test , or demonstration in nasal epithelial ionic transport alteration (nasal potential difference and identification of two CF mutations in the patient are laboratory findings in CF.

  2. Current uses of virtual reality for children with disabilities.

    Science.gov (United States)

    McComas, J; Pivik, J; Laflamme, M

    1998-01-01

    Technological advances, including the use of virtual reality, have contributed enormously to improving the treatment, training, and quality of life of children with disabilities. This paper describes the advantages of VR for children with disabilities, how VR can minimize the effects of a disability, the role of VR in training and skills enhancement, and how social participation and the child's quality of life may be improved through the use of VR. Examples from published literature and Internet sites are given of current and completed projects which focus on improving the lives of children with disabilities. The research describing the efficacy of knowledge and skills transfer from a virtual environment to the real world are examined in relation to children with disabilities. Finally, the current limitations and future directions of VR for children with disabilities are considered.

  3. Gene therapy for the treatment of cystic fibrosis.

    Science.gov (United States)

    Burney, Tabinda J; Davies, Jane C

    2012-01-01

    Gene therapy is being developed as a novel treatment for cystic fibrosis (CF), a condition that has hitherto been widely-researched yet for which no treatment exists that halts the progression of lung disease. Gene therapy involves the transfer of correct copies of cystic fibrosis transmembrane conductance regulator (CFTR) DNA to the epithelial cells in the airways. The cloning of the CFTR gene in 1989 led to proof-of-principle studies of CFTR gene transfer in vitro and in animal models. The earliest clinical trials in CF patients were conducted in 1993 and used viral and non-viral gene transfer agents in both the nasal and bronchial airway epithelium. To date, studies have focused largely on molecular or bioelectric (chloride secretion) outcome measures, many demonstrating evidence of CFTR expression, but few have attempted to achieve clinical efficacy. As CF is a lifelong disease, turnover of the airway epithelium necessitates repeat administration. To date, this has been difficult to achieve with viral gene transfer agents due to host recognition leading to loss of expression. The UK Cystic Fibrosis Gene Therapy Consortium (Imperial College London, University of Edinburgh and University of Oxford) is currently working on a large and ambitious program to establish the clinical benefits of CF gene therapy. Wave 1, which has reached the clinic, uses a non-viral vector. A single-dose safety trial is nearing completion and a multi-dose clinical trial is shortly due to start; this will be powered for clinically-relevant changes. Wave 2, more futuristically, will look at the potential of lentiviruses, which have long-lasting expression. This review will summarize the current status of translational research in CF gene therapy.

  4. Nondestructive examination of PHWR pressure tube using eddy current technique

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hee Jong; Choi, Sung Nam; Cho, Chan Hee; Yoo, Hyun Joo; Moon, Gyoon Young [KHNP Central Research Institute, Daejeon (Korea, Republic of)

    2014-06-15

    A pressurized heavy water reactor (PHWR) core has 380 fuel channels contained and supported by a horizontal cylindrical vessel known as the calandria, whereas a pressurized water reactor (PWR) has only a single reactor vessel. The pressure tube, which is a pressure-retaining component, has a 103.4 mm inside diameter x 4.19 mm wall thickness, and is 6.36 m long, made of a zirconium alloy (Zr-2.5 wt% Nb). This provides support for the fuel while transporting the D2O heat-transfer fluid. The simple tubular geometry invites highly automated inspection, and good approach for all inspection. Similar to all nuclear heat-transfer pressure boundaries, the PHWR pressure tube requires a rigorous, periodic inspection to assess the reactor integrity in accordance with the Korea Nuclear Safety Committee law. Volumetric-based nondestructive evaluation (NDE) techniques utilizing ultrasonic and eddy current testing have been adopted for use in the periodic inspection of the fuel channel. The eddy current testing, as a supplemental NDE method to ultrasonic testing, is used to confirm the flaws primarily detected through ultrasonic testing, however, eddy current testing offers a significant advantage in that its ability to detect surface flaws is superior to that of ultrasonic testing. In this paper, effectiveness of flaw detection and the depth sizing capability by eddy current testing for the inside surface of a pressure tube, will be introduced. As a result of this examination, the ET technique is found to be useful only as a detection technique for defects because it can detect fine defects on the surface with high resolution. However, the ET technique is not recommended for use as a depth sizing method because it has a large degree of error for depth sizing.

  5. Thickness Evaluation of Aluminium Plate Using Pulsed Eddy Current Technique

    Science.gov (United States)

    Singh, Gurpartap; Bapat, Harsh Madhukar; Singh, Bhanu Pratap; Bandyopadhyay, Manojit; Puri, Rakesh Kumar; Badodkar, Deepak Narayanrao

    2013-10-01

    This paper describes a pulsed eddy current (PEC) based non-destructive testing system used for detection of thickness variation in aluminium plate. A giant magneto-resistive sensor has been used instead of pick up coil for detecting resultant magnetic field. The PEC response signals obtained from 1 to 5 mm thickness change in aluminium plate were investigated. Two time domain features, namely peak value and time to peak, of PEC response were used for extracting information about thickness variation in aluminium plate. The variation of peak value and time to peak with thickness was compared. A program was developed to display the thickness variation of the tested sample.

  6. Comparison of analytical eddy current models using principal components analysis

    Science.gov (United States)

    Contant, S.; Luloff, M.; Morelli, J.; Krause, T. W.

    2017-02-01

    Monitoring the gap between the pressure tube (PT) and the calandria tube (CT) in CANDU® fuel channels is essential, as contact between the two tubes can lead to delayed hydride cracking of the pressure tube. Multifrequency transmit-receive eddy current non-destructive evaluation is used to determine this gap, as this method has different depths of penetration and variable sensitivity to noise, unlike single frequency eddy current non-destructive evaluation. An Analytical model based on the Dodd and Deeds solutions, and a second model that accounts for normal and lossy self-inductances, and a non-coaxial pickup coil, are examined for representing the response of an eddy current transmit-receive probe when considering factors that affect the gap response, such as pressure tube wall thickness and pressure tube resistivity. The multifrequency model data was analyzed using principal components analysis (PCA), a statistical method used to reduce the data set into a data set of fewer variables. The results of the PCA of the analytical models were then compared to PCA performed on a previously obtained experimental data set. The models gave similar results under variable PT wall thickness conditions, but the non-coaxial coil model, which accounts for self-inductive losses, performed significantly better than the Dodd and Deeds model under variable resistivity conditions.

  7. Effects of 4% Icodextrin on Experimental Spinal Epidural Fibrosis.

    Science.gov (United States)

    Karanci, Turker; Kelten, Bilal; Karaoglan, Alper; Cinar, Nilgun; Midi, Ahmet; Antar, Veysel; Akdemir, Hidayet; Kara, Zeynep

    2017-01-01

    The aim of this experimental study was to investigate whether spinal epidural 4% glucose polymer solution is effective in the prevention of postoperative fibrosis. Twenty eight adult Wistar albino rats were randomly divided into two equal groups, including treatment and control. Both groups underwent L1 vertebral total laminectomy to expose the dura. Topical treatment group received 4% icodextrin. Four weeks later, epidural fibrosis was examined in both groups histologically, biochemically and macroscopically. Topical use of 4% icodextrin prevented significantly epidural fibrosis following the laminectomy operation. Topical 4% icodextrin application inhibits postoperative epidural fibrosis with various mechanisms and prevents adhesions by playing barrier role between tissue surfaces through flotation. Our study is first to present evidence of experimental epidural fibrosis prevention with 4% icodextrin.

  8. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

    Science.gov (United States)

    2013-01-01

    Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research. PMID:24274743

  9. Reactor coolant pump testing using motor current signatures analysis

    Energy Technology Data Exchange (ETDEWEB)

    Burstein, N.; Bellamy, J.

    1996-12-01

    This paper describes reactor coolant pump motor testing carried out at Florida Power Corporation`s Crystal River plant using Framatome Technologies` new EMPATH (Electric Motor Performance Analysis and Trending Hardware) system. EMPATH{trademark} uses an improved form of Motor Current Signature Analysis (MCSA), technology, originally developed at Oak Ridge National Laboratories, for detecting deterioration in the rotors of AC induction motors. Motor Current Signature Analysis (MCSA) is a monitoring tool for motor driven equipment that provides a non-intrusive means for detecting the presence of mechanical and electrical abnormalities in the motor and the driven equipment. The base technology was developed at the Oak Ridge National Laboratory as a means for determining the affects of aging and service wear specifically on motor-operated valves used in nuclear power plant safety systems, but it is applicable to a broad range of electric machinery. MCSA is based on the recognition that an electric motor (ac or dc) driving a mechanical load acts as an efficient and permanently available transducer by sensing mechanical load variations, large and small, long-term and rapid, and converting them into variations in the induced current generated in the motor windings. The motor current variations, resulting from changes in load caused by gears, pulleys, friction, bearings, and other conditions that may change over the life of the motor, are carried by the electrical cables powering the motor and are extracted at any convenient location along the motor lead. These variations modulate the 60 Hz carrier frequency and appear as sidebands in the spectral plot.

  10. Design of Current steering DAC using 250nm CMOS Technology

    Directory of Open Access Journals (Sweden)

    Vineet Tiwari

    2012-06-01

    Full Text Available To build a digital to analog converter, that only receives digital signal that can only receives digital signal and produces only analog signal. A converter in which digital input signals are changed to essentially proportional analog signals. Abbreviated DAC a device for converting information in the forms of combination of discrete(usually binary states or signal to information in the form of combinations of discrete(usually binary states or signal to information in the form of value or magnitude of some characteristics of signal, in relation to standard or reference signal. Digital-toanalog (D/A converters (sometimes called DACs are used to present the results of digital computation, storage, or transmission, typically for graphical display or for the control of devices that operate with continuously varying quantities. D/A converter circuits are also used in the design of analog-to-digital converters that employ feedback techniques, such as successive-approximation and counter-comparator types. In such applications, the D/A converter may not necessarily appear as a separately identifiable entity. The fundamental circuit of most D/A converters involves a voltage or current reference; a resistive “ladder network” that derives weighted currents or voltages, usually as discrete fractions of the reference; and a set of switches, operated by the digital input, that determines which currents or voltages will be summed to constitute the output. The output of the D/A converter is proportional to the product of the digital input value and the reference. In many applications, the reference is fixed, and the output bears a fixed proportion to the digital input. In other applications, the reference, as well as the digital input, can vary; a D/A converter that is used in these applications is thus called a multiplying D/A converter. It is principally used for imparting a digitally controlled scale factor, or “gain,” to an analog input signal

  11. Neutron detection using a current biased kinetic inductance detector

    Energy Technology Data Exchange (ETDEWEB)

    Shishido, Hiroaki, E-mail: shishido@pe.osakafu-u.ac.jp; Miyajima, Shigeyuki; Ishida, Takekazu [Department of Physics and Electronics, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka 599-8531 (Japan); Institute for Nanofabrication Research, Osaka Prefecture University, Sakai, Osaka 599-8531 (Japan); Narukami, Yoshito [Department of Physics and Electronics, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka 599-8531 (Japan); Oikawa, Kenichi; Harada, Masahide; Oku, Takayuki; Arai, Masatoshi [Materials and Life Science Division, J-PARC Center, Japan Atomic Energy Agency, Tokai, Ibaraki 319-1195 (Japan); Hidaka, Mutsuo [National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8568 (Japan); Fujimaki, Akira [Department of Quantum Engineering, Nagoya University, Nagoya, Aichi 464-8603 (Japan)

    2015-12-07

    We demonstrate neutron detection using a solid state superconducting current biased kinetic inductance detector (CB-KID), which consists of a superconducting Nb meander line of 1 μm width and 40 nm thickness. {sup 10}B-enriched neutron absorber layer of 150 nm thickness is placed on top of the CB-KID. Our neutron detectors are able to operate in a wide superconducting region in the bias current–temperature diagram. This is in sharp contrast with our preceding current-biased transition edge detector, which can operate only in a narrow range just below the superconducting critical temperature. The full width at half maximum of the signals remains of the order of a few tens of ns, which confirms the high speed operation of our detectors.

  12. Current and Future Uses of Aluminum in the Automotive Industry

    Science.gov (United States)

    Long, R. S.; Boettcher, E.; Crawford, D.

    2017-08-01

    Aluminum use is growing in automotive closures and body in white applications to improve vehicle performance and fuel economy. The auto industry is looking for higher-strength aluminum materials needed for strength-driven safety-critical parts. Through cooperation with industrial partners and support from the Department of Energy (DOE), multiple experimental 7xxx alloys were developed for automotive applications. The objective is to enable complex shapes to be formed at temperatures below 225°C. A demonstration part has been developed that is representative of the forming challenges within a current hot-stamped door ring component. This part tooling has been built and installed into a press line which includes blank heating and robotic transfer. Forming trials of these alloys are currently underway and the formability, strength and corrosion performance of these materials are being evaluated.

  13. A brief review on molecular, genetic and imaging techniques for HCV fibrosis evaluation

    Directory of Open Access Journals (Sweden)

    Sumrin Aleena

    2011-02-01

    Full Text Available Abstract Background Chronic HCV is one of the major causes of morbidity and mortality in the present day world. The assessment of disease progression not only provides useful information for diagnosis and therapeutic supervision judgment but also for monitoring disease. Different invasive and non invasive methods are applied to diagnose the disease from initial to end stage (mild fibrosis to cirrhosis. Although, liver biopsy is still considered as gold standard to identify liver histological stages, an assessment of the disease development based on non-invasive clinical findings is also emerging and this may replace the need of biopsy in near future. This review gives brief insight on non-invasive methods currently available for predicting liver fibrosis in HCV with their current pros and cons to make easier for a clinician to choose better marker to assess liver fibrosis in HCV infected patients. Methods More than 200 studies regarding invasive and noninvasive markers available for HCV liver disease diagnosis were thoroughly reviewed. We examined year wise results of these markers based on their sensitivity, specificity, PPV, NPV and AUROCs. Results We found that in all non-invasive serum markers for HCV, FibroTest, Forn's Index, Fibrometer and HepaScore have high five-year predictive value but with low AUROCs (0.60~0.85 and are not comparable to liver biopsy (AUROC = 0.97. Even though from its beginning, Fibroscan is proved to be best with high AUROCs (> 0.90 in all studies, no single noninvasive marker is able to differentiate all fibrosis stages from end stage cirrhosis. Meanwhile, specific genetic markers may not only discriminate fibrotic and cirrhotic liver but also differentiate individual fibrosis stages. Conclusions There is a need of marker which accurately determines the stage based on simplest routine laboratory test. Genetic marker in combination of imaging technique may be the better non invasive diagnostic method in future.

  14. Protease-activated receptor-2 induces myofibroblast differentiation and tissue factor up-regulation during bleomycin-induced lung injury: Potential role in pulmonary fibrosis

    NARCIS (Netherlands)

    K. Borensztajn (Keren); P. Bresser (Paul); C.M. van der Loos (Chris); I. Bot (Ilze); B. van den Blink (Bernt); M.A. den Bakker (Michael); J. Daalhuisen (Joost); A.P. Groot (Angelique); M.P. Peppelenbosch (Maikel); J. von der Thusen (Jan); C.A. Spek (Arnold)

    2010-01-01

    textabstractIdiopathic pulmonary fibrosis constitutes the most devastating form of fibrotic lung disorders and remains refractory to current therapies. The coagulation cascade is frequently activated during pulmonary fibrosis, but this observation has so far resisted a mechanistic explanation. Recen

  15. The development of the pediatric NAFLD fibrosis score (PNFS to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Naim Alkhouri

    Full Text Available BACKGROUND: Noninvasive hepatic fibrosis scores that predict the presence of advanced fibrosis have been developed and validated in adult patients with NAFLD. The aims of our study were to assess the utility of commonly used adult fibrosis scores in pediatric NAFLD and to develop a pediatric specific fibrosis score that can predict advanced fibrosis. METHODS: Consecutive children with biopsy-proven NAFLD were included. Fibrosis was determined by an experienced pathologist (F0-4. Advanced fibrosis was defined as fibrosis stage ≥ 3. The following adult fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI, NAFLD fibrosis score (NFS, and FIB-4 Index. Multivariable logistic regression analysis was performed to build a new pediatric model for predicting advanced fibrosis. RESULTS: Our cohort consisted of 242 children with a mean age of 12.4 ± 3.1 years and 63% were female. 36 (15% subjects had advanced fibrosis. APRI and FIB-4 were higher in patients with advanced fibrosis compared to those with fibrosis stage 0-2; however, AST/ALT ratio and NFS were not different between the two groups. We used our data to develop a new model to predict advanced fibrosis which included: ALT, alkaline phosphatase, platelet counts and GGT. The multivariable logistic regression model (z was defined as follows: z = 1.1+(0.34*sqrt(ALT+(0.002*alkaline phosphatase - (1.1*log(platelets - (0.02*GGT. This value was then converted into a probability distribution (p with a value between 0 to 100 by the following formula: p = 100 × exp(z/[1+exp(z]. The AUCROC for this model was 0.74 (95% CI: 0.66, 0.82. This was found to be significantly better than APRI, NAFLD Fibrosis Score and FIB-4 Index. CONCLUSION: Noninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing advanced fibrosis in children with NAFLD. We developed a new pediatric NAFLD fibrosis score with improved performance characteristics.

  16. Simulation of vibration-induced effect on plasma current measurement using a fiber optic current sensor.

    Science.gov (United States)

    Descamps, Frédéric; Aerssens, Matthieu; Gusarov, Andrei; Mégret, Patrice; Massaut, Vincent; Wuilpart, Marc

    2014-06-16

    An accurate measurement of the plasma current is of paramount importance for controlling the plasma magnetic equilibrium in tokamaks. Fiber optic current sensor (FOCS) technology is expected to be implemented to perform this task in ITER. However, during ITER operation, the vessel and the sensing fiber will be subject to vibrations and thus to time-dependent parasitic birefringence, which may significantly compromise the FOCS performance. In this paper we investigate the effects of vibrations on the plasma current measurement accuracy under ITER-relevant conditions. The simulation results show that in the case of a FOCS reflection scheme including a spun fiber and a Faraday mirror, the error induced by the vibrations is acceptable regarding the ITER current diagnostics requirements.

  17. Pharmacotherapy in idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Gaurav Acharya

    2014-10-01

    Full Text Available Idiopathic pulmonary fibrosis or cryptogenic fibrosing alveolitis is a form of chronic, progressive interstitial lung disease causing scarring of lung tissue and usually affect adults. Treatment is usually aimed at controlling inflammation and thus slowing the process of fibrosis. With only few patients responding to treatment and the disease being ultimately fatal with poor progression, the underlying lesion was considered to be fibrotic rather than inflammatory. Fibrotic foci, deposition of collagen, and lack of inflammatory cells are a predominant finding. Pirfenidone and N-acetyl cysteine are the only effective pharmacotherapy available till date. Interim results of PANTHER Trial clearly indicate more risk with triple therapy. However, in Indian patients, trial of steroid therapy may be tried when there is doubt of chronic hypersensitivity pneumonitis. BIBF 1120 has also shown positive results in Phase II clinical trial and shows a positive response in deteriorating lung function. Supplemental oxygen, education of patient, pulmonary rehabilitation, and Streptococcus pneumoniae and influenza vaccine are the most important supportive care. Pulmonary rehabilitation should be used as a treatment in the majority of patients. [Int J Basic Clin Pharmacol 2014; 3(5.000: 761-763

  18. Cystic Fibrosis: Brazilian ENT Experience

    Directory of Open Access Journals (Sweden)

    Tania Sih

    2012-01-01

    Full Text Available Most published studies about Cystic Fibrosis (CF are European or North American. There are still few publications about the characteristics of fibrocystic populations in developing countries. The incidence of cystic fibrosis (CF in Brazil varies among different regions (1 : 10,000 in Minas Gerais, 1 : 9,500 in Paraná, 1 : 8,700 in Santa Catarina, and 1 : 1600 in Rio Grande do Sul. The prevalence of the DF508 mutation also varies according to population: 33% in Sao Paulo, 49% in Rio Grande do Sul, 27% in Santa Catarina, and 52% in Minas Gerais. Cough and nasal obstruction are the most common symptoms. The variation in nasal polyposis prevalence may be explained by population genotypic characteristics in a country that spans a continent. Findings on nasal endoscopy and computed tomography (CT have better correlation than do this information compared with surgical and clinical history. Microbiologic studies suggest a high level of early contamination of the airways. Sensorineural hearing loss (SNHL occurs in these patients as a result of ototoxic antibiotics. The data compiled in this paper is useful, but also lead to the general agreement that more research would be welcome due to the unique characteristics of this country.

  19. Highly Selective Targeting of Hepatic Stellate Cells for Liver Fibrosis Treatment Using a d-Enantiomeric Peptide Ligand of Fn14 Identified by Mirror-Image mRNA Display.

    Science.gov (United States)

    Huang, Luying; Xie, Jing; Bi, Qiuyan; Li, Zhuoxuan; Liu, Sha; Shen, Qing; Li, Chong

    2017-05-01

    Although liver fibrosis is a major public health issue, there is still no effective drug therapy in the clinic. Fibroblast growth factor-inducible 14 (Fn14), a membrane receptor highly specifically expressed in activated hepatic stellate cells (HSCs), is the key driver of liver fibrosis, and thus, it has a great potential as a novel target for the development of effective treatment. Here, we identified a d-enantiomeric peptide ligand of Fn14 through mirror-image mRNA display. This included the chemical synthesis of a d-enantiomer of the target protein (extracellular domain of Fn14), identification of an l-peptide ligand of d-Fn14 using a constructed mRNA peptide library, and identification of a d-enantiomer of the l-peptide, which is a ligand of the natural Fn14 for reasons of symmetry. The obtained d-peptide ligand showed strong binding to Fn14 while maintaining high proteolytic resistance. As a targeting moiety, this d-peptide successfully mediated high selectivity of activated HSCs for liposomal vehicles compared to that of other major cell types in the liver and significantly enhanced the accumulation of liposomes in the liver fibrosis region of a carbon tetrachloride-induced mouse model. Moreover, in combination with curcumin as an encapsulated load, a liposomal formulation conjugated with this d-peptide showed powerful inhibition of the proliferation of activated HSCs and reduced the liver fibrosis to a significant extent in vivo. This Fn14-targeting strategy may represent a promising approach to targeted drug delivery for liver fibrosis treatment. Meanwhile, the mirror-image mRNA display can provide a new arsenal for the development of d-peptide-based therapeutics against a variety of human diseases.

  20. Cardiac activation mapping using ultrasound current source density imaging (UCSDI).

    Science.gov (United States)

    Olafsson, Ragnar; Witte, Russell S; Jia, Congxian; Huang, Sheng-Wen; Kim, Kang; O'Donnell, Matthew

    2009-03-01

    We describe the first mapping of biological current in a live heart using ultrasound current source density imaging (UCSDI). Ablation procedures that treat severe heart arrhythmias require detailed maps of the cardiac activation wave. The conventional procedure is time-consuming and limited by its poor spatial resolution (5-10 mm). UCSDI can potentially improve on existing mapping procedures. It is based on a pressure-induced change in resistivity known as the acousto-electric (AE) effect, which is spatially confined to the ultrasound focus. Data from 2 experiments are presented. A 540 kHz ultrasonic transducer (f/# = 1, focal length = 90 mm, pulse repetition frequency = 1600 Hz) was scanned over an isolated rabbit heart perfused with an excitation-contraction decoupler to reduce motion significantly while retaining electric function. Tungsten electrodes inserted in the left ventricle recorded simultaneously the AE signal and the low-frequency electrocardiogram (ECG). UCSDI displayed spatial and temporal patterns consistent with the spreading activation wave. The propagation velocity estimated from UCSDI was 0.25 +/- 0.05 mm/ms, comparable to the values obtained with the ECG signals. The maximum AE signal-to-noise ratio after filtering was 18 dB, with an equivalent detection threshold of 0.1 mA/ cm(2). This study demonstrates that UCSDI is a potentially powerful technique for mapping current flow and biopotentials in the heart.

  1. Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis

    Directory of Open Access Journals (Sweden)

    Cuiyuan Huang

    2017-07-01

    Full Text Available Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble–mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

  2. [Bacterial prostatitis and prostatic fibrosis: modern view on the treatment and prophylaxis].

    Science.gov (United States)

    Zaitsev, A V; Pushkar, D Yu; Khodyreva, L A; Dudareva, A A

    2016-08-01

    Treatments of chronic bacterial prostatitis (CP) remain difficult problem. Bacterial prostatitis is a disease entity diagnosed clinically and by evidence of inflammation and infection localized to the prostate. Risk factors for UTI in men include urological interventions, such as transrectal prostate biopsy. Ensuing infections after prostate biopsy, such as UTI and bacterial prostatitis, are increasing due to increasing rates of fluoroquinolone resistance. The increasing global antibiotic resistance also significantly affects management of UTI in men, and therefore calls for alternative strategies. Prostatic inflammation has been suggested to contribute to the etiology of lower urinary tract symptoms (LUTS) by inducing fibrosis. Several studies have shown that prostatic fibrosis is strongly associated with impaired urethral function and LUTS severity. Fibrosis resulting from excessive deposition of collagen is traditionally recognized as a progressive irreversible condition and an end stage of inflammatory diseases; however, there is compelling evidence in both animal and human studies to support that the development of fibrosis could potentially be a reversible process. Prostate inflammation may induce fibrotic changes in periurethral prostatic tissues, promote urethral stiffness and LUTS. Patients experiencing CP and prostate-related LUTS could benefit from anti-inflammatory therapies, especially used in combination with the currently prescribed enzyme treatment with Longidase. Treatment results showed that longidase is highly effective in bacterial and abacterial CP. Longidase addition to standard therapeutic methods significantly reduced the disease symptoms and regression of inflammatory-proliferative alterations in the prostate.

  3. Cystic fibrosis-related diabetes: a distinct condition.

    Science.gov (United States)

    Cano Megías, Marta; González Albarrán, Olga

    2015-01-01

    Cystic fibrosis is the most common fatal inherited autosomal recessive disease in Caucasians, affecting approximately one out of every 2,000 births. Survival of patients with cystic fibrosis has significantly improved due to advances in respiratory and nutritional care, and their current average life expectancy is 30-40 years. Development of cystic fibrosis-related diabetes is a comorbidity that increases with age and may reach a prevalence up to 50% in adults. Its development is associated to impaired lung function and nutritional status, and early diagnosis and treatment are therefore essential to improve quality of life and performance status. Insulin therapy for diabetes and other early carbohydrate metabolism disorders may improve lung function and nutritional status of patients with cystic fibrosis. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

  4. Nephrogenic systemic fibrosis: history and epidemiology

    DEFF Research Database (Denmark)

    Thomsen, Henrik S

    2009-01-01

    Nephrogenic systemic fibrosis (NSF) is a new disease; the first case was diagnosed in 1997. It took 9 years before an association between NSF and gadolinium-based contrast agents (Gd-CAs) was identified. Gadolinium has several advantages for use in relation to enhanced MRI, but it is also a toxic...

  5. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J; Brimicombe, R W; Hodson, M E; Heijerman, H G; Bakker, W

    Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of

  6. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J; Brimicombe, R W; Hodson, M E; Heijerman, H G; Bakker, W

    1995-01-01

    Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of antibi

  7. Psychosocial problems in children with cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, V; Thastum, M; Schiøtz, P O

    2007-01-01

    AIM: To compare the well-being of children (7-14 years) with cystic fibrosis (CF) (n = 43) with the well-being of healthy controls (n = 1121). METHODS: The self-report questionnaire Beck Youth Inventories (BYI) was used to study depression, anxiety, anger, disruptive behaviour and self...

  8. Intestinal organoids as model for cystic fibrosis

    NARCIS (Netherlands)

    Dekkers, J.F.

    2015-01-01

    Recent advances in adult stem cell culture technology have enabled long-term in vitro expansion of intestinal organoids or ‘mini-guts’. In this thesis, we used the organoid model to develop a novel assay to measure function of CFTR, the protein mutated in subjects with cystic fibrosis (CF). This met

  9. Investigating the biochemical progression of liver disease through fibrosis, cirrhosis, dysplasia, and hepatocellular carcinoma using Fourier transform infrared spectroscopic imaging

    Science.gov (United States)

    Sreedhar, Hari; Pant, Mamta; Ronquillo, Nemencio R.; Davidson, Bennett; Nguyen, Peter; Chennuri, Rohini; Choi, Jacqueline; Herrera, Joaquin A.; Hinojosa, Ana C.; Jin, Ming; Kajdacsy-Balla, Andre; Guzman, Grace; Walsh, Michael J.

    2014-03-01

    Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma. HCC ranks the fourth most prevalent malignant tumor and the third leading cause of cancer related death in the world. Hepatocellular carcinoma develops in the context of chronic liver disease and its evolution is characterized by progression through intermediate stages to advanced disease and possibly even death. The primary sequence of hepatocarcinogenesis includes the development of cirrhosis, followed by dysplasia, and hepatocellular carcinoma.1 We addressed the utility of Fourier Transform Infrared (FT-IR) spectroscopic imaging, both as a diagnostic tool of the different stages of the disease and to gain insight into the biochemical process associated with disease progression. Tissue microarrays were obtained from the University of Illinois at Chicago tissue bank consisting of liver explants from 12 transplant patients. Tissue core biopsies were obtained from each explant targeting regions of normal, liver cell dysplasia including large cell change and small cell change, and hepatocellular carcinoma. We obtained FT-IR images of these tissues using a modified FT-IR system with high definition capabilities. Firstly, a supervised spectral classifier was built to discriminate between normal and cancerous hepatocytes. Secondly, an expanded classifier was built to discriminate small cell and large cell changes in liver disease. With the emerging advances in FT-IR instrumentation and computation there is a strong drive to develop this technology as a powerful adjunct to current histopathology approaches to improve disease diagnosis and prognosis.

  10. Safety and efficacy of photodynamic therapy using BCECF-AM compared to mitomycin C in controlling post-operative fibrosis in a rabbit model of subscleral trabeculectomy

    Directory of Open Access Journals (Sweden)

    Azza Mohamed Ahmed Said

    2016-03-01

    Full Text Available AIM: To evaluate the safety and efficacy of cellular photoablation using BCECF-AM [2’, 7’-bis-(2-carboxyethyl-5-(and-6-carboxyfluorescein, acetoxymethyl ester mixed isomers] as a method to control postoperative fibrosis in subscleral trabeculectomy (SST compared to mitomycin C (MMC in a rabbit model. METHODS: A comparative prospective case-control animal study was conducted. Fourteen rabbits were subjected to SST with intraoperative use of wound modulating agents (MMC or BCECF-AM of the right eye (study groups I and II respectively and SST without use of intraoperative wound modulating agents for the left eye (control group II. Two rabbits 4 eyes were considered as control group I with no surgical intervention. BCECF-AM was injected subconjunctivally 30min before surgery followed by intraoperative illumination with diffuse blue light for 10min. Antifibrotic efficacy was established by clinical response and histological examination. Clinical response was assessed by measuring intraocular pressure (IOP at day 1, 3, 5, 7, 14, 21 postoperatively. Success was defined by >20.0% reduction in IOP from the preoperative values without anti-glaucoma medications. RESULTS: The mean percentage of reduction was 35.0% in the study group I with only one eye (14.3% had 12.5% reduction. The mean percentage of reduction was 28.0 % in the study group II with two eyes (28.6% in study group II had 14.2% reduction each. Regarding the control group II, the mean percentage of reduction was 14.3 % with 64.3% eyes had <20.0% reduction. There was a highly statistically significant difference between each of the study groups (right eyes and the corresponding control group II (left eyes as regards the mean postoperative IOP values started from day 5 in both study groups and this highly significant difference remained so till the end of the follow up period. Histologically, MMC treated blebs showed thinning of conjunctival epithelium with marked reduction of the goblet

  11. Childhood obesity: current definitions and recommendations for their use.

    Science.gov (United States)

    Rolland-Cachera, Marie Françoise

    2011-10-01

    Childhood obesity is considered a major issue because of its high prevalence and because of its severe consequences on adult health. Prevalence studies are carried out in numerous countries. Analysis of time trends and geographic comparisons are particularly useful, as they may help to identify factors promoting obesity. These studies require adequate definitions of nutritional status and standardized protocols, but in practice, the references, cut-offs and the terminology used vary considerably, and consequently ambiguous information may be found in the literature. Recommendations for the definition of childhood obesity were previously published in 1995 by the European Childhood Obesity Group (ECOG), but new references appeared later. A clarification of the different definitions was needed. Currently used classifications of nutritional status in children are summarized, and recommendations for the references, cut-offs and terms to be used in different contexts are provided. These new ECOG recommendations should help harmonize the various protocols and improve comparisons between studies.

  12. Bacterial protein toxins: current and potential clinical use.

    Science.gov (United States)

    Fabbri, A; Travaglione, S; Falzano, L; Fiorentini, C

    2008-01-01

    Natural toxins are the product of a long-term evolution, and act on essential mechanisms in the most crucial and vital processes of living organisms. They can attack components of the protein synthesis machinery, actin polymerization, signal transduction pathways, intracellular trafficking of vesicles as well as immune and inflammatory responses. For this reason, toxins have increasingly being used as valuable tools for analysis of cellular physiology, and in the recent years, some of them are used medicinally for the treatment of human diseases. This review is devoted to protein toxins of bacterial origin, specifically those toxins that are currently used in therapy or those under study for their potential clinical applications. Bacterial protein toxins are all characterized by a specific mechanism of action that involves the central molecular pathways in the eukaryotic cell. Knowledge of their properties could be used for medical purposes.

  13. Systems Level Analysis and Identification of Pathways and Networks Associated with Liver Fibrosis

    Science.gov (United States)

    2014-11-07

    liver cholestasis, liver steatosis, and myocardial infarction . More recently, the concept of adverse outcome pathways (AOPs) has been proposed as a novel...and control of fibrosis is accurate diagnosis or early indicators of damage. The gold standard for diagnosing fibrosis is currently via liver biopsy...identify sensitive, specific, and non-invasive biomarkers of liver fibrosis. Identification of such biomarkers will improve diagnosis and allow better

  14. Use of denaturing high-performance liquid chromatography (DHPLC) to characterize the bacterial and fungal airway microbiota of cystic fibrosis patients.

    Science.gov (United States)

    Mounier, Jérôme; Gouëllo, Audrey; Keravec, Marlène; Le Gal, Solène; Pacini, Grégory; Debaets, Stella; Nevez, Gilles; Rault, Gilles; Barbier, Georges; Héry-Arnaud, Geneviève

    2014-04-01

    The aim of this study was to evaluate the use of denaturing high-performance liquid chromatography (DHPLC) to characterize cystic fibrosis (CF) airway microbiota including both bacteria and fungi. DHPLC conditions were first optimized using a mixture of V6, V7 and V8 region 16S rRNA gene PCR amplicons from 18 bacterial species commonly found in CF patients. Then, the microbial diversity of 4 sputum samples from 4 CF patients was analyzed using cultural methods, cloning/sequencing (for bacteria only) and DHPLC peak fraction collection/sequencing. DHPLC analysis allowed identifying more bacterial and fungal species than the classical culture methods, including well-recognized pathogens such as Pseudomonas aeruginosa. Even if a lower number of bacterial Operational Taxonomic Units (OTUs) was identified by DHPLC, it allowed to find OTUs unidentified by cloning/sequencing. The combination of both techniques permitted to correlate the majority of DHPLC peaks to defined OTUs. Finally, although Aspergillus fumigatus detection using DHPLC can still be improved, this technique clearly allowed to identify a higher number of fungal species versus classical culture-based methods. To conclude, DHPLC provided meaningful additional data concerning pathogenic bacteria and fungi as well as fastidious microorganisms present within the CF respiratory tract. DHPLC can be considered as a complementary technique to culture-dependent analyses in routine microbiological laboratories.

  15. Retroperitoneal fibrosis – the state-of-the-art

    Science.gov (United States)

    Majewski, Dominik; Puszczewicz, Mariusz

    2016-01-01

    Retroperitoneal fibrosis (RPF) is a rare disease, hallmarked by inflammation and deposition of fibrous tissue around the abdominal aorta. This process may spread contiguously and involve adjacent structures, leading to many complications, among which the most frequent and most severe is ureteral obstruction. The condition usually has idiopathic origin (idiopathic retroperitoneal fibrosis – IRF), but can also develop secondarily to a number of factors. The etiology of the disease remains unclear. Current research suggests that about half of the cases of IRF may be a symptom of a recently discovered, clinically heterogeneous immunoglobulin G4-related disease (IgG4-RD). Corticosteroids are the first-line treatment for IRF, but effective attempts to use immunosuppressants are also made. This paper presents the current state of knowledge on the etiopathogenesis, clinical presentation, diagnosis and therapeutic possibilities in different forms of RPF. Based on the latest research, an analysis of the relationship between IRF and IgG4-RD was performed. PMID:27994271

  16. Current Trends in Heparin Use During Arterial Vascular Interventional Radiology

    Energy Technology Data Exchange (ETDEWEB)

    Durran, Alexandra C., E-mail: durranjobs@hotmail.com [Peninsula Radiology Academy, Plymouth International Business Park (United Kingdom); Watts, Christopher, E-mail: Christopher.watts@salisbury.nhs.uk [Salisbury District Hospital (United Kingdom)

    2012-12-15

    Purpose: This study was designed to assess the current use of heparinized saline and bolus doses of heparin in non-neurological interventional radiology and to determine whether consensus could be reached to produce guidance for heparin use during arterial vascular intervention. Methods: An interactive electronic questionnaire was distributed to members of the British Society of Interventional Radiology regarding their current practice in the use, dosage, and timing of heparin boluses and heparinized flushing solutions.ResultsA total of 108 completed questionnaires were received. More than 80% of respondents used heparinized saline with varying concentrations; the most prevalent was 1,000 IU/l (international units of heparin per liter) and 5,000 IU/l. Fifty-one percent of interventionalists use 3,000 IU as their standard bolus dose; however, the respondents were split regarding the timing of bolus dose with {approx}60% administering it after arterial access is obtained and 40% after crossing the lesion. There was no consensus on altering dose according to body weight, and only 4% monitored clotting parameters. Conclusions: There seems to be some coherence among practicing interventionalists regarding heparin administration. We hypothesize that heparinized saline should be used at a recognized standard concentration of 1,000 IU/l as a flushing concentration in all arterial vascular interventions and that 3,000 IU bolus is considered the standard dose for straightforward therapeutic procedures and 5000 IU for complex, crural, and endovascular aneurysm repair work. The bolus should be given after arterial access is obtained to allow time for optimal anticoagulation to be achieved by the time of active intervention and stenting. Further research into clotting abnormalities following such interventional procedures would be an interesting quantifiable follow-up to this initial survey of opinions and practice.

  17. Gene therapy for the treatment of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Burney TJ

    2012-05-01

    Full Text Available Tabinda J Burney1,2, Jane C Davies1,2,31Department of Gene therapy, Imperial College London, 2UK CF Gene Therapy Consortium London, 3Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, UKAbstract: Gene therapy is being developed as a novel treatment for cystic fibrosis (CF, a condition that has hitherto been widely-researched yet for which no treatment exists that halts the progression of lung disease. Gene therapy involves the transfer of correct copies of cystic fibrosis transmembrane conductance regulator (CFTR DNA to the epithelial cells in the airways. The cloning of the CFTR gene in 1989 led to proof-of-principle studies of CFTR gene transfer in vitro and in animal models. The earliest clinical trials in CF patients were conducted in 1993 and used viral and non-viral gene transfer agents in both the nasal and bronchial airway epithelium. To date, studies have focused largely on molecular or bioelectric (chloride secretion outcome measures, many demonstrating evidence of CFTR expression, but few have attempted to achieve clinical efficacy. As CF is a lifelong disease, turnover of the airway epithelium necessitates repeat administration. To date, this has been difficult to achieve with viral gene transfer agents due to host recognition leading to loss of expression. The UK Cystic Fibrosis Gene Therapy Consortium (Imperial College London, University of Edinburgh and University of Oxford is currently working on a large and ambitious program to establish the clinical benefits of CF gene therapy. Wave 1, which has reached the clinic, uses a non-viral vector. A single-dose safety trial is nearing completion and a multi-dose clinical trial is shortly due to start; this will be powered for clinically-relevant changes. Wave 2, more futuristically, will look at the potential of lentiviruses, which have long-lasting expression. This review will summarize the current status of translational

  18. Analysis of Sqp current systems by using corrected geomagneticcoordinates

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The Spq equivalent current system of the quiet day geomagnetic variation in the polar region is very complicated. It is composed of several currents, such as the ionospheric dynamo current and the auroral electrojet caused by the field-aligned current. Spq is unsymmetrical in both polar regions. In this paper, the Spq current systems are analyzed in the corrected geomagnetic coordinates (CGM) instead of the conventional geomagnetic coordinates (GM), and the symmetries of the Spq current indifferent systems are compared. Then the causes of Spq asymmetry in the GM coordinates are discussed; the effects of each component in Spq are determined.

  19. Respiratory medicines for children: current evidence, unlicensed use and research priorities

    DEFF Research Database (Denmark)

    Smyth, A R; Barbato, A; Beydon, N;

    2010-01-01

    and potentially harmful. Research areas in asthma include novel formulations and regimens, and individualised prescribing. In cystic fibrosis, future studies will focus on screened infants and robust outcome measures are needed. Other areas include new enzyme and antibiotic formulations and the basic defect...... disorders, drugs indicated for other conditions (e.g. dornase alfa) are commonly used and trials are needed. In neuromuscular disorders, the beta-agonists may enhance muscle strength and are in need of evaluation. Studies of antibiotic prophylaxis, immunoglobulin and antifungal drugs are needed in immune...

  20. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials.

    Science.gov (United States)

    Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

    2014-05-01

    Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

  1. [Cystic fibrosis in 2008].

    Science.gov (United States)

    Durieu, I; Josserand, R Nove

    2008-11-01

    To describe the epidemiological, physiopathological, clinical and therapeutic knowledge concerning cystic fibrosis (CF). Important modifications in the health organization of the care concerning this orphan disease have been implemented in France. The life expectancy has dramatically increased, as well as the knowledge concerning the pathological structure and function of the CFTR gene and protein. This will lead to the development of emerging drug treatments for this lethal disease. The life expectancy is predicted to exceed 40 years for children born in the 2000s. As a result, there has been a tremendous growth of the adult population that reached 40% of the overall approximately 5000 patients included in the CF French registry (Observatoire National de la Mucoviscidose). Lung disease remains the primary cause of morbidity and mortality. The characteristic phenotypic presentation associates bronchial and rhinosinusal symptoms, pancreatic insufficiency and liver disease. Bronchial damage leads to progressive chronic respiratory insufficiency. Diabetes mellitus and osteoporosis frequently appears in adulthood. Neonatal screening has been implemented in France since 2002. It will prevent delayed diagnosis and its deleterious consequences. Some atypical cases of CF presenting only with one or two organ system involvement can be diagnosed in adulthood. Isolated chronic rhinosinusitis, bronchiectasis, congenital bilateral absence of vas deferens, recurrent pancreatitis, allergic bronchopulmonary aspergillosis, and some case of cholangitis may so revealed late form of cystic fibrosis. The health care is organized in cystic fibrosis centres. Despite gene discovery, treatment still remains symptomatic, based on intensive pulmonary and nutritional treatments. Challenges for new treatments are to correct the basic defect, either by gene therapy or by pharmacological modulation of the abnormal physiological processes.

  2. ROC curves in evaluation of serum fibrosis indices for hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Min Zheng; Wei-Min Cai; Hong-Lei Weng; Rong-Hua Liu

    2002-01-01

    AIM: Use Receiver operating characteristic (ROC) curves to find out the relationship between serum level of hyaluronic acid (HA), type Ⅲ procollagen (PCⅢ), N-terminal procollagen Ⅲ peptide (PⅢNP), laminin (LN), type Ⅳ collagen (C-Ⅳ) and hepatic fibrosis, as well as to determine their value in clinical practice.METHODS: 114 serum samples from chronic hepatitis patients were assayed for fibrosis indices including HA, PCⅢ, PⅢNP, LN and Ⅳ-C with radioimmunoassay (RIA). Liver biopsy was also performed in all these patients and the biopsy material was examined histopathologically.RESULTS: ROC curves analysis showed that area under the curve (AUC) of PⅢNP, HA, PCⅢ, C-Ⅳ and LN was 0.800,0.728, 0.727, 0.583 and 0.463, respectively. The analysis also showed that PⅢNP (r=0.452), HA (r=0.497) and PCⅢ (r=0.404) have greater diagnosis performances than C-Ⅳ (r=0.238) and LN (r=0.128) according to fibrosis staging. The sensitivity of HA plus PⅢNP was 55.1%, it was the most sensitive combination. Combined three or more than three indices that based on HA, the specificity was 100 %.Using combination assays can improve the specificity, but its sensitivity was not high. Serum fibrosis indices increased as the grade of inflammation aggravated. But only PⅢNP and PCⅢ had significant difference between G1 and G2 (PⅢNP: 13.16±8.07 VS8.32±5.09; PCⅢ: 164.22±65.69 VS 138.23±77.63). The coefficient correlation of the results of inflammation grade and fibrosis staging to HA was 0.525 and 0.553 respectively, that to PCⅢ, 0.446 and 0.412, that to LN, 0.234 and 0.194, and that to Ⅳ-C, 0.363 and 0.351, respectively.CONCLUSION: Serum fibrosis indices can indicate tendency of hepatic fibrosis, but it cannot replace liver biopsy. However, as diagnostic markers, more efficient serum fibrosis indices for the diagnosis of hepatic fibrosis need to be explored.

  3. Current Trends in Adolescent Substance Use in Jamaica

    Directory of Open Access Journals (Sweden)

    U Atkinson

    2015-03-01

    Full Text Available Objective: National secondary school-based drug surveys facilitate the identification and understanding of patterns of substance use among adolescents, associated risk and protective factors which exist and inform prevention and treatment interventions and policies which are appropriate for resource constrained settings. This paper analyses current trends as well as reviews trends from the last National School Survey conducted by the National Council on Drug Abuse in 2006. Method: The study utilized a survey design that included a representative sample of secondary school students. Data were collected from 3365 students from 38 schools across the island. The study made specific reference to the prevalence of alcohol, tobacco cigarette, marijuana and inhalant use among secondary school students. Results: The most widely used substances among the sample were alcohol, tobacco cigarettes, marijuana and solvents/inhalants. A large number of students (64% reported a lifetime prevalence of alcohol use. Alcohol use was also the highest for one-year (44% and one-month (33.6% use. While lifetime use of tobacco cigarette was higher than marijuana, one-year and one-month use of marijuana was higher than that of tobacco cigarette. There has been a slight increase in the age of initiation for alcohol, tobacco cigarette and marijuana use. There has also been a significant decrease (approximately 50% in lifetime, past year and past month prevalence of inhalant use since the 2006 secondary school survey. Conclusions: Alcohol continues to be the substance most widely used by Jamaican adolescents, followed by tobacco, marijuana and inhalants. Though the average age of first use has slightly increased for all substances, prevalence remains a concern. As such, innovative school-based interventions are required to assist in reducing substance use among Jamaican adolescents.

  4. Cystic fibrosis and sleep.

    Science.gov (United States)

    Katz, Eliot S

    2014-09-01

    Sleep disturbances are frequently observed in cystic fibrosis (CF). The resultant sleep fragmentation, short sleep duration, and gas-exchange abnormalities are postulated to contribute to the neurocognitive, cardiovascular, and metabolic abnormalities associated with CF. There are no outcomes data to establish the optimal procedure for screening and treating CF patients for sleep-related respiratory abnormalities. Therapy with supplemental oxygen and bilevel ventilation are widely considered to be effective in the short term, but there are few evidence-based data to support long-term improvements in morbidity and mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Evaluation of Hepatic Tissue Blood Flow Using Xenon Computed Tomography with Fibrosis Progression in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Ryuta Shigefuku

    2014-01-01

    Full Text Available Aims: The present study evaluated the utility of xenon computed tomography (Xe-CT as a noninvasive diagnostic procedure for the measurement of hepatic tissue blood flow (TBF in patients with nonalcoholic fatty liver disease (NAFLD or chronic hepatitis C (CH-C. Methods: Xe-CT was performed in 93 patients with NAFLD and in 109 patients with CH-C. Subjects were classified into one of three groups, based on fibrosis stage: group 1, no bridging fibrosis; group 2, bridging fibrosis; and group 3, liver cirrhosis. Correlations between hepatic TBFs in each fibrosis stage were examined. Results: In group 1, portal venous TBF (PVTBF, hepatic arterial (HATBF, and total hepatic TBF (THTBF were significantly lower in patients with in nonalcoholic steatohepatitis (NASH than in those with CH-C (p < 0.001, p < 0.05, p < 0.001, respectively. In group 2, PVTBF and THTBF were significantly lower in patients with in NASH than in those with CH-C (p < 0.001, p < 0.05, respectively. In group 3, hepatic TBFs were not significantly different when comparing patients with NASH and those with CH-C. Conclusions: PVTBF decreased due to fat infiltration. Therefore, hemodynamic changes occur relatively earlier in NAFLD than in CH-C. Patients with NASH should be monitored carefully for portal hypertensive complications in the early fibrosis stage.

  6. Fast isolation of faults in transmission systems using current transients

    Energy Technology Data Exchange (ETDEWEB)

    Perera, N.; Rajapakse, A.D. [University of Manitoba, Department of Electrical and Computer Engineering, Engineering Building, 15 Gillson Street, Winnipeg, Manitoba (Canada)

    2008-09-15

    This paper presents a protection scheme that is capable of very fast isolation of faults in high voltage transmission systems. Proposed scheme comprises set of relays connected through a telecommunication network, located at different nodes of the system. Relays use wavelet coefficients of current signals to identify the fault directions relative to their location. Fault directions identified at different locations in the system can be combined to determine the faulted line (or busbar) and isolate it. A robust single ended traveling wave based fault distance estimation approach is proposed as a backup in case of communication failure. Investigations were carried out using time domain simulations in PSCAD/EMTDC for a high voltage transmission system. (author)

  7. Asthma and cystic fibrosis: A tangled web.

    LENUS (Irish Health Repository)

    Kent, Brian D

    2014-03-01

    Successfully diagnosing concomitant asthma in people with cystic fibrosis (CF) is a challenging proposition, and the utility of conventional diagnostic criteria of asthma in CF populations remains uncertain. Nonetheless, the accurate identification of individuals with CF and asthma allows appropriate tailoring of therapy, and should reduce the unnecessary use of asthma medication in broader CF cohorts. In this review, we discuss the diagnostic challenge posed by asthma in CF, both in terms of clinical evaluation, and of interpretation of pulmonary function testing and non-invasive markers of airway inflammation. We also examine how the role of cross-sectional thoracic imaging in CF and asthma can assist in the diagnosis of asthma in these patients. Finally, we critically appraise the evidence base behind the use of asthma medications in CF populations, with a particular focus on the use of inhaled corticosteroids and bronchodilators. As shall be discussed, the gaps in the current literature make further high-quality research in this field imperative. Pediatr Pulmonol. 2014; 49:205-213. © 2014 Wiley Periodicals, Inc.

  8. Management strategies for liver fibrosis.

    Science.gov (United States)

    Altamirano-Barrera, Alejandra; Barranco-Fragoso, Beatriz; Méndez-Sánchez, Nahum

    2017-01-01

    Liver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibrosis, viral infection is most common (hepatitis B and C). In addition, obesity rates worldwide have accelerated the risk of liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Also liver fibrosis is associated with the consumption of alcohol, or autoimmune hepatitis and chronic cholangiophaties. The response of hepatocytes to inflammation plays a decisive role in the physiopathology of hepatic fibrosis, which involves the recruitment of both pro- and anti-inflammatory cells such as monocytes and macrophages. As well as the production of other cytokines and chemokines, which increase the stimulus of hepatic stellate cells by activating proinflammatory cells. The aim of this review is to identify the therapeutic options available for the treatment of the liver fibrosis, enabling the prevention of progression when is detected in time.

  9. A low-power current self-adjusted VCO using a bottom PMOS current source

    Science.gov (United States)

    Zhixiong, Sheng; Fengqi, Yu

    2014-09-01

    This paper presents the design and implementation of a current self-adjusted VCO with low power consumption. In the proposed VCO, a bottom PMOS current source instead of a top one is adopted to decrease the tail noise. A current self-adjusted technique without additional external control signals is taken to ensure the VCO starts up in the whole band while keeping the power consumption relatively low. Meanwhile, the phase noise of the VCO at the low frequency (high Cvar) can be reduced by the technique. The circuit is implemented in 0.18 μm CMOS technology. The proposed VCO exhibits low power consumption of < 1.6 mW at a 1.5 V supply voltage and a tuning range from 11.79 to 12.53 GHz. The measured phase noise at 1 MHz offset from the frequency 11.79 GHz is -104.7 dBc/Hz, and the corresponding FOM is -184.2 dBc/Hz.

  10. Idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María

    2017-02-23

    Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  11. Current Mathematical Methods Used in QSAR/QSPR Studies

    Directory of Open Access Journals (Sweden)

    Peixun Liu

    2009-04-01

    Full Text Available This paper gives an overview of the mathematical methods currently used in quantitative structure-activity/property relationship (QASR/QSPR studies. Recently, the mathematical methods applied to the regression of QASR/QSPR models are developing very fast, and new methods, such as Gene Expression Programming (GEP, Project Pursuit Regression (PPR and Local Lazy Regression (LLR have appeared on the QASR/QSPR stage. At the same time, the earlier methods, including Multiple Linear Regression (MLR, Partial Least Squares (PLS, Neural Networks (NN, Support Vector Machine (SVM and so on, are being upgraded to improve their performance in QASR/QSPR studies. These new and upgraded methods and algorithms are described in detail, and their advantages and disadvantages are evaluated and discussed, to show their application potential in QASR/QSPR studies in the future.

  12. Asthma-related emergency department use: current perspectives.

    Science.gov (United States)

    Johnson, Laurie H; Chambers, Patricia; Dexheimer, Judith W

    2016-01-01

    Asthma is one of the most common chronic pediatric diseases. Patients with asthma often present to the emergency department for treatment for acute exacerbations. These patients may not have a primary care physician or primary care home, and thus are seeking care in the emergency department. Asthma care in the emergency department is multifaceted to treat asthma patients appropriately and provide quality care. National and international guidelines exist to help drive clinical care. Electronic and paper-based tools exist for both physicians and patients to help improve emergency, home, and preventive care. Treatment of patients with asthma should include the acute exacerbation, long-term management of controller medications, and controlling triggers in the home environment. We will address the current state of asthma research in emergency medicine in the US, and discuss some of the resources being used to help provide a medical home and improve care for patients who suffer from acute asthma exacerbations.

  13. Merits and pitfalls of currently used diagnostic tools in mycetoma.

    Directory of Open Access Journals (Sweden)

    Wendy W J van de Sande

    2014-07-01

    Full Text Available Treatment of mycetoma depends on the causative organism and since many organisms, both actinomycetes (actinomycetoma and fungi (eumycetoma, are capable of producing mycetoma, an accurate diagnosis is crucial. Currently, multiple diagnostic tools are used to determine the extent of infections and to identify the causative agents of mycetoma. These include various imaging, cytological, histopathological, serological, and culture techniques; phenotypic characterisation; and molecular diagnostics. In this review, we summarize these techniques and identify their merits and pitfalls in the identification of the causative agents of mycetoma and the extent of the disease. We also emphasize the fact that there is no ideal diagnostic tool available to identify the causative agents and that future research should focus on the development of new and reliable diagnostic tools.

  14. Merits and pitfalls of currently used diagnostic tools in mycetoma.

    Science.gov (United States)

    van de Sande, Wendy W J; Fahal, Ahmed H; Goodfellow, Michael; Mahgoub, El Sheikh; Welsh, Oliverio; Zijlstra, Ed E

    2014-07-01

    Treatment of mycetoma depends on the causative organism and since many organisms, both actinomycetes (actinomycetoma) and fungi (eumycetoma), are capable of producing mycetoma, an accurate diagnosis is crucial. Currently, multiple diagnostic tools are used to determine the extent of infections and to identify the causative agents of mycetoma. These include various imaging, cytological, histopathological, serological, and culture techniques; phenotypic characterisation; and molecular diagnostics. In this review, we summarize these techniques and identify their merits and pitfalls in the identification of the causative agents of mycetoma and the extent of the disease. We also emphasize the fact that there is no ideal diagnostic tool available to identify the causative agents and that future research should focus on the development of new and reliable diagnostic tools.

  15. Nutrient Status of Adults with Cystic Fibrosis

    Science.gov (United States)

    GORDON, CATHERINE M.; ANDERSON, ELLEN J.; HERLYN, KAREN; HUBBARD, JANE L.; PIZZO, ANGELA; GELBARD, RONDI; LAPEY, ALLEN; MERKEL, PETER A.

    2011-01-01

    Nutrition is thought to influence disease status in patients with cystic fibrosis (CF). This cross-sectional study sought to evaluate nutrient intake and anthropometric data from 64 adult outpatients with cystic fibrosis. Nutrient intake from food and supplements was compared with the Dietary Reference Intakes for 16 nutrients and outcomes influenced by nutritional status. Attention was given to vitamin D and calcium given potential skeletal implications due to cystic fibrosis. Measurements included weight, height, body composition, pulmonary function, and serum metabolic parameters. Participants were interviewed about dietary intake, supplement use, pulmonary function, sunlight exposure, and pain. The participants’ mean body mass index (±standard deviation) was 21.8±4.9 and pulmonary function tests were normal. Seventy-eight percent used pancreatic enzyme replacement for malabsorption. Vitamin D deficiency [25-hydroxyvitamin D (25OHD)<37.5 nmol/L] was common: 25 (39%) were deficient despite adequate vitamin D intake. Lipid profiles were normal in the majority, even though total and saturated fat consumption represented 33.0% and 16.8% of energy intake, respectively. Reported protein intake represented 16.9% of total energy intake (range 10%–25%). For several nutrients, including vitamin D and calcium, intake from food and supplements in many participants exceeded recommended Tolerable Upper Intake Levels. Among adults with cystic fibrosis, vitamin D deficiency was common despite reported adequate intake, and lipid profiles were normal despite a relatively high fat intake. Mean protein consumption was adequate, but the range of intake was concerning, as both inadequate or excessive intake may have deleterious skeletal effects. These findings call into question the applicability of established nutrient thresholds for patients with cystic fibrosis. PMID:18060897

  16. Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Jamille Souza Fernandes

    2014-01-01

    Full Text Available A major issue with Schistosoma mansoni infection is the development of periportal fibrosis, which is predominantly caused by the host immune response to egg antigens. Experimental studies have pointed to the participation of monocytes in the pathogenesis of liver fibrosis. The aim of this study was to characterize the subsets of monocytes in individuals with different degrees of periportal fibrosis secondary to schistosomiasis. Monocytes were classified into classical (CD14++CD16−, intermediate (CD14++CD16+, and nonclassical (CD14+CD16++. The expressions of monocyte markers and cytokines were assessed using flow cytometry. The frequency of classical monocytes was higher than the other subsets. The expression of HLA-DR, IL-6, TNF-α, and TGF-β was higher in monocytes from individuals with moderate to severe fibrosis as compared to other groups. Although no differences were observed in receptors expression (IL-4R and IL-10R between groups of patients, the expression of IL-12 was lower in monocytes from individuals with moderate to severe fibrosis, suggesting a protective role of this cytokine in the development of fibrosis. Our data support the hypothesis that the three different monocyte populations participate in the immunopathogenesis of periportal fibrosis, since they express high levels of proinflammatory and profibrotic cytokines and low levels of regulatory markers.

  17. Simvastatin attenuates bleomycin-induced pulmonary fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    OU Xue-mei; FENG Yu-lin; WEN Fu-qiang; HUANG Xiang-yang; XIAO Jun; WANG Ke; WANG Tao

    2008-01-01

    Background Bleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice.Methods Bleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days.We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis.Results Simvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (Ⅰand Ⅲ) mRNA expression induced by bleomycin. Moreover,simvastatin down-regulated the increased expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-(] (TNF-a) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore,the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration.Conclusions Simvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-βI and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.

  18. PECULIARITIES OF ENT-DAMAGE IN CHILDREN WITH CYSTIC FIBROSIS

    Directory of Open Access Journals (Sweden)

    I.V. Martynova

    2011-01-01

    Full Text Available Traditional approach to cystic fibrosis patients treatment doesn’t involve upper respiratory tract assessment, though abnormal changes — consequences of the cystic fibrosis transmembrane conductivity regulator gene mutation- do affect nasal and paranasal mucosa to the same extent. Approximately half of cystic fibrosis patients suffer from chronic rhinosinusitis and/or nasal polyposis that worsens the clinical course of already severe disease. Chronic hyperplasia in paranasal cavities can be quite extensive, recurrent and can lead to destruction of osseous walls of the cavity and of nasal septum. Thus increasing the amount of hospital admissions and and their duration. Low awareness of ENT-specialists working in polyclinics and in hospitals of ENT-pathology in cystic fibrosis patients leads to belated diagnostics, excessive manipulations, ineffective treatment, including surgery. All these lays grounds to implication of the early screening diagnostic program and development of proper treatment methods of ENT-complications of cystic fibrosis — therapeutic as well as surgical, with strict specification of indications and contraindications. Key words: cystic fibrosis, chronic rhino sinusitis, nasal polyposis. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 49–53.

  19. Minimizing Risk of Nephrogenic systemic fibrosis in Cardiovascular Magnetic Resonance

    Directory of Open Access Journals (Sweden)

    Reiter Theresa

    2012-05-01

    Full Text Available Abstract Nephrogenic Systemic Fibrosis is a rare condition appearing only in patients with severe renal impairment or failure and presents with dermal lesions and involvement of internal organs. Although many cases are mild, an estimated 5 % have a progressive debilitating course. To date, there is no known effective treatment thus stressing the necessity of ample prevention measures. An association with the use of Gadolinium based contrast agents (GBCA makes Nephrogenic Systemic Fibrosis a potential side effect of contrast enhanced magnetic resonance imaging and offers the opportunity for prevention by limiting use of gadolinium based contrast agents in renal failure patients. In itself toxic, Gadolinium is embedded into chelates that allow its safe use as a contrast agent. One NSF theory is that Gadolinium chelates distribute into the extracellular fluid compartment and set Gadolinium ions free, depending on multiple factors among which the duration of chelates exposure is directly related to the renal function. Major medical societies both in Europe and in North America have developed guidelines for the usage of GBCA. Since the establishment of these guidelines and the increased general awareness of this condition, the occurrence of NSF has been nearly eliminated. Giving an overview over the current knowledge of NSF pathobiochemistry, pathogenesis and treatment options this review focuses on the guidelines of the European Medicines Agency, the European Society of Urogenital Radiology, the FDA and the American College of Radiology from 2008 up to 2011 and the transfer of this knowledge into every day practice.

  20. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Pietrobattista Andrea

    2009-05-01

    Full Text Available Abstract Background Liver fibrosis is a stage of non-alcoholic fatty liver disease (NAFLD which is responsible for liver-related morbidity and mortality in adults. Accordingly, the search for non-invasive markers of liver fibrosis has been the subject of intensive efforts in adults with NAFLD. Here, we developed a simple algorithm for the prediction of liver fibrosis in children with NAFLD followed at a tertiary care center. Methods The study included 136 male and 67 female children with NAFLD aged 3.3 to 18.0 years; 141 (69% of them had fibrosis at liver biopsy. On the basis of biological plausibility, readily availability and evidence from adult studies, we evaluated the following potential predictors of liver fibrosis at bootstrapped stepwise logistic regression: gender, age, body mass index, waist circumference, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase, albumin, prothrombin time, glucose, insulin, triglycerides and cholesterol. A final model was developed using bootstrapped logistic regression with bias-correction. We used this model to develop the 'pediatric NAFLD fibrosis index' (PNFI, which varies between 0 and 10. Results The final model was based on age, waist circumference and triglycerides and had a area under the receiver operating characteristic curve of 0.85 (95% bootstrapped confidence interval (CI with bias correction 0.80 to 0.90 for the prediction of liver fibrosis. A PNFI ≥ 9 (positive likelihood ratio = 28.6, 95% CI 4.0 to 201.0; positive predictive value = 98.5, 95% CI 91.8 to 100.0 could be used to rule in liver fibrosis without performing liver biopsy. Conclusion PNFI may help clinicians to predict liver fibrosis in children with NAFLD, but external validation is needed before it can be employed for this purpose.

  1. Evaluation of recently validated non- invasive formula using basic lung functions as new screening tool for pulmonary hypertension in idiopathic pulmonary fibrosis patients

    Directory of Open Access Journals (Sweden)

    Ghanem Maha

    2009-01-01

    Full Text Available Background: A prediction formula for mean pulmonary artery pressure (MPAP using standard lung function measurement has been recently validated to screen for pulmonary hypertension (PH in idiopathic pulmonary fibrosis (IPF patients. Objective: To test the usefulness of this formula as a new non invasive screening tool for PH in IPF patients. Also, to study its correlation with patients′ clinical data, pulmonary function tests, arterial blood gases (ABGs and other commonly used screening methods for PH including electrocardiogram (ECG, chest X ray (CXR, trans-thoracic echocardiography (TTE and computerized tomography pulmonary angiography (CTPA. Materials and Methods: Cross-sectional study of 37 IPF patients from tertiary hospital. The accuracy of MPAP estimation was assessed by examining the correlation between the predicted MPAP using the formula and PH diagnosed by other screening tools and patients′ clinical signs of PH. Results: There was no statistically significant difference in the prediction of PH using cut off point of 21 or 25 mm Hg (p0 = 0.24. The formula-predicted MPAP greater than 25 mm Hg strongly correlated in the expected direction with O2 saturation (r = −0.95, P < 0.000, partial arterial O2 tension (r = −0.71, P < 0.000, right ventricular systolic pressure measured by TTE (r = 0.6, P < 0.000 and hilar width on CXR (r = 0.31, P = 0.03. Chest symptoms, ECG and CTPA signs of PH poorly correlated with the same formula (P > 0.05. Conclusions: The prediction formula for MPAP using standard lung function measurements is a simple non invasive tool that can be used as TTE to screen for PH in IPF patients and select those who need right heart catheterization.

  2. Current and anticipated uses of thermal hydraulic codes in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung-Doo; Chang, Won-Pyo [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1997-07-01

    In Korea, the current uses of thermal hydraulic codes are categorized into 3 areas. The first application is in designing both nuclear fuel and NSSS. The codes have usually been introduced based on the technology transfer programs agreed between KAERI and the foreign vendors. Another area is in the supporting of the plant operations and licensing by the utility. The third category is research purposes. In this area assessments and some applications to the safety issue resolutions are major activities using the best estimate thermal hydraulic codes such as RELAP5/MOD3 and CATHARE2. Recently KEPCO plans to couple thermal hydraulic codes with a neutronics code for the design of the evolutionary type reactor by 2004. KAERI also plans to develop its own best estimate thermal hydraulic code, however, application range is different from KEPCO developing code. Considering these activities, it is anticipated that use of the best estimate hydraulic analysis code developed in Korea may be possible in the area of safety evaluation within 10 years.

  3. Current state and use of biological adhesives in orthopedic surgery.

    Science.gov (United States)

    Shah, Neil V; Meislin, Robert

    2013-12-01

    Bone and tissue adhesives are common and beneficial supplements to standard methods of musculoskeletal tissue suture repair. Knowledge and development of biologically derived or inspired adhesives useful in orthopedic surgery are rapidly advancing. Recent literature demonstrates the increased adjunct or primary use of biological adhesives in the repair of musculoskeletal soft tissues, chondral fractures, and osteochondral fractures. Adhesives offer more benefits and enhancements to tissue healing than current fixation methods afford, including improved biocompatibility, resorbability, and non-immunogenicity. Further investigation is required to determine the extent of the role that these bioadhesives can play in orthopedic surgery. The largest group of biologically derived adhesives and sealants is fibrin sealants, which include first- and second-generation commercially available fibrin sealants, autologous fibrin sealants, and variants. Other groups include gelatin-resorcin aldehydes, protein-aldehyde systems, collagen-based adhesives, polysaccharide- based adhesives, mussel adhesive proteins, and various biologically inspired or biomimetic glues. Potential uses include applications in orthopedic-related blood conservation, arthroplasty, articular cartilage disorders, sports medicine, spine surgery, trauma, and tumors. The development of an adhesive with universal application is likely unfeasible, given the unique characteristics of various musculoskeletal tissues. However, the literature demonstrates the overall underuse of adhesives and indicates the rising probability of the development of a successful variety of bioadhesives for use in orthopedic surgery. As a result of reading this article, physicians should be able to: 1. Describe the difference between adhesives and sealants. 2. Recognize fibrin adhesives commonly used in practice today and identify other biological adhesives with rising potential. 3. Analyze how fibrin sealants work relative to fibrin and

  4. Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

    Science.gov (United States)

    Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

    2015-08-12

    Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 25 June 2015.Date of latest search of all other sources: 10 December 2014. Any randomised or quasi-randomised control trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease

  5. Update on diagnosis and treatment of idiopathic pulmonary fibrosis

    Science.gov (United States)

    Baddini-Martinez, José; Baldi, Bruno Guedes; da Costa, Cláudia Henrique; Jezler, Sérgio; Lima, Mariana Silva; Rufino, Rogério

    2015-01-01

    Idiopathic pulmonary fibrosis is a type of chronic fibrosing interstitial pneumonia, of unknown etiology, which is associated with a progressive decrease in pulmonary function and with high mortality rates. Interest in and knowledge of this disorder have grown substantially in recent years. In this review article, we broadly discuss distinct aspects related to the diagnosis and treatment of idiopathic pulmonary fibrosis. We list the current diagnostic criteria and describe the therapeutic approaches currently available, symptomatic treatments, the action of new drugs that are effective in slowing the decline in pulmonary function, and indications for lung transplantation. PMID:26578138

  6. Review of drug treatment of oral submucous fibrosis.

    Science.gov (United States)

    Chole, Revant H; Gondivkar, Shailesh M; Gadbail, Amol R; Balsaraf, Swati; Chaudhary, Sudesh; Dhore, Snehal V; Ghonmode, Sumeet; Balwani, Satish; Mankar, Mugdha; Tiwari, Manish; Parikh, Rima V

    2012-05-01

    This study undertook a review of the literature on drug treatment of oral submucous fibrosis. An electronic search was carried out for articles published between January 1960 to November 2011. Studies with high level of evidence were included. The levels of evidence of the articles were classified after the guidelines of the Oxford Centre for Evidence-Based Medicine. The main outcome measures used were improvement in oral ulceration, burning sensation, blanching and trismus. Only 13 publications showed a high level of evidence (3 randomized controlled trials and 10 clinical trials/controlled clinical trials), with a total of 1157 patients. Drugs like steroids, hyaluronidase, human placenta extracts, chymotrypsin and collagenase, pentoxifylline, nylidrin hydrochloride, iron and multivitamin supplements including lycopene, have been used. Only systemic agents were associated with few adverse effects like gastritis, gastric irritation and peripheral flushing with pentoxifylline, and flushingly warm skin with nylidrin hydrochloride; all other side-effects were mild and mainly local. Few studies with high levels of evidence were found. The drug treatment that is currently available for oral submucous fibrosis is clearly inadequate. There is a need for high-quality randomized controlled trials with carefully selected and standardized outcome measures.

  7. Emulation of floating memcapacitors and meminductors using current conveyors

    OpenAIRE

    Pershin, Yuriy V.; Di Ventra, Massimiliano

    2010-01-01

    We suggest circuit realizations of emulators transforming memristive devices into effective floating memcapacitive and meminductive systems. The emulator's circuits are based on second generation current conveyors and involve either four single-output or two dual-output current conveyors. The equations governing the resulting memcapactive and meminductive systems are presented.

  8. Emulation of floating memcapacitors and meminductors using current conveyors

    CERN Document Server

    Pershin, Yuriy V

    2010-01-01

    We suggest circuit realizations of emulators transforming memristive devices into effective floating memcapacitive and meminductive systems. The emulator's circuits are based on second generation current conveyors and involve either four single-output or two dual-output current conveyors. The equations governing the resulting memcapactive and meminductive systems are presented.

  9. CURRENT WAYS TO HARVEST ENERGY USING A COMPUTER MOUSE

    Directory of Open Access Journals (Sweden)

    Frantisek Horvat

    2014-02-01

    Full Text Available This paper deals with the idea of an energy harvesting (EH system that uses the mechanical energy from finger presses on the buttons of a computer mouse by means of a piezomaterial (PVF2. The piezomaterial is placed in the mouse at the interface between the button and the body. This paper reviews the parameters of the PVF2 piezomaterial and tests their possible implementation into EH systems utilizing these types of mechanical interactions. The paper tests the viability of two EH concepts: a battery management system, and a semi-autonomous system. A statistical estimate of the button operations is performed for various computer activities, showing that an average of up to 3300 mouse clicks per hour was produced for gaming applications, representing a tip frequency of 0.91 Hz on the PVF2 member. This frequency is tested on the PVF2 system, and an assessment of the two EH systems is reviewed. The results show that fully autonomous systems are not suitable for capturing low-frequency mechanical interactions, due to the parameters of current piezomaterials, and the resulting very long startup phase. However, a hybrid EH system which uses available power to initiate the circuit and eliminate the startup phase may be explored for future studies.

  10. Role of vitamin A in liver fibrosis

    NARCIS (Netherlands)

    Knook, D.L.; Bosma, A.; Seifert, W.F.

    1995-01-01

    The relationship between vitamin A and liver fibrosis was studied with a CCl4-induced fibrosis model in rats. Depending on the time of administration, vitamin A can potentiate or reduce fibrosis: when present during CCl4-treatment parenchymal cell damage and fibrosis were enhanced, whereas vitamin A

  11. Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis.

    Science.gov (United States)

    Aslam, Aisha A; Higgins, Colin; Sinha, Ian P; Southern, Kevin W

    2017-01-19

    selective outcome reporting, especially when reporting on the trial's post hoc subgroup of participants by chronic inhaled antibiotic use.The trial was sponsored by PTC Therapeutics Incorporated with grant support by the Cystic Fibrosis Foundation, the Food and Drug Administration's Office of Orphan Products Development and the National Institutes of Health (NIH).The trial reported no significant difference between treatment groups in quality of life, assessed by the Cystic Fibrosis Questionnaire-Revised respiratory domain score and no improvement in respiratory function measures (mean difference of relative change in forced expiratory volume at one second 2.97% (95% confidence interval -0.58 to 6.52)). Ataluren was associated with a significantly higher rate of episodes of renal impairment, risk ratio 17.70 (99% confidence interval 1.28 to 244.40). The trial reported no significant treatment effect for ataluren for the review's secondary outcomes: pulmonary exacerbation; computerised tomography score; weight; body mass index; and sweat chloride. No deaths were reported in the trial.A post hoc subgroup analysis of participants not receiving chronic inhaled tobramycin (n = 146) demonstrated favourable results for ataluren (n = 72) for relative change in % predicted forced expiratory volume at one second and pulmonary exacerbation rate. Participants receiving chronic inhaled tobramycin appeared to have a reduced rate of pulmonary exacerbation compared to those not receiving chronic inhaled tobramycin. This drug interaction was not anticipated and may affect the interpretation of the trial results. There is currently insufficient evidence to determine the effect of ataluren as a therapy for people with cystic fibrosis with class I mutations. Future trials should carefully assess for adverse events, notably renal impairment and consider the possibility of drug interactions. Cross-over trials should be avoided given the potential for the treatment to change the natural history

  12. Validation of Fourier decomposition MRI with dynamic contrast-enhanced MRI using visual and automated scoring of pulmonary perfusion in young cystic fibrosis patients

    Energy Technology Data Exchange (ETDEWEB)

    Bauman, Grzegorz, E-mail: g.bauman@dkfz.de [German Cancer Research Center, Division of Medical Physics in Radiology, Im Neuenheimer Feld 223, 69120 Heidelberg (Germany); Puderbach, Michael, E-mail: m.puderbach@dkfz.de [Chest Clinics at the University of Heidelberg, Clinics for Interventional and Diagnostic Radiology, Amalienstr. 5, 69126 Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (Germany); Heimann, Tobias, E-mail: t.heimann@dkfz.de [German Cancer Research Center, Division of Medical and Biological Informatics, Im Neuenheimer Feld 223, 69120 Heidelberg (Germany); Kopp-Schneider, Annette, E-mail: kopp@dkfz.de [German Cancer Research Center, Division of Biostatistics, Im Neuenheimer Feld 223, 69120 Heidelberg (Germany); Fritzsching, Eva, E-mail: eva.fritzsching@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Translational Pulmonology and Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Im Neuenheimer Feld 430, Heidelberg (Germany); Mall, Marcus A., E-mail: marcus.mall@med.uni-heidelberg.de [Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (Germany); University Hospital Heidelberg, Department of Translational Pulmonology and Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Im Neuenheimer Feld 430, Heidelberg (Germany); Eichinger, Monika, E-mail: m.eichinger@dkfz.de [Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (Germany); German Cancer Research Center, Division of Radiology, Im Neuenheimer Feld 223, 69120 Heidelberg (Germany)

    2013-12-01

    Purpose: To validate Fourier decomposition (FD) magnetic resonance (MR) imaging in cystic fibrosis (CF) patients with dynamic contrast-enhanced (DCE) MR imaging. Materials and methods: Thirty-four CF patients (median age 4.08 years; range 0.16–30) were examined on a 1.5-T MR imager. For FD MR imaging, sets of lung images were acquired using an untriggered two-dimensional balanced steady-state free precession sequence. Perfusion-weighted images were obtained after correction of the breathing displacement and Fourier analysis of the cardiac frequency from the time-resolved data sets. DCE data sets were acquired with a three-dimensional gradient echo sequence. The FD and DCE images were visually assessed for perfusion defects by two readers independently (R1, R2) using a field based scoring system (0–12). Software was used for perfusion impairment evaluation (R3) of segmented lung images using an automated threshold. Both imaging and evaluation methods were compared for agreement and tested for concordance between FD and DCE imaging. Results: Good or acceptable intra-reader agreement was found between FD and DCE for visual and automated scoring: R1 upper and lower limits of agreement (ULA, LLA): 2.72, −2.5; R2: ULA, LLA: ±2.5; R3: ULA: 1.5, LLA: −2. A high concordance was found between visual and automated scoring (FD: 70–80%, DCE: 73–84%). Conclusions: FD MR imaging provides equivalent diagnostic information to DCE MR imaging in CF patients. Automated assessment of regional perfusion defects using FD and DCE MR imaging is comparable to visual scoring but allows for percentage-based analysis.

  13. Promising Therapy Candidates for Liver Fibrosis

    Directory of Open Access Journals (Sweden)

    Ping eWang

    2016-02-01

    Full Text Available Liver fibrosis is a wound-healing process in response to repeated and chronic injury to hepatocytes and/or cholangiocytes. Ongoing hepatocyte apoptosis or necrosis lead to increase in ROS production and decrease in antioxidant activity, which recruits inflammatory cells from the blood and activate hepatic stellate cells changing to myofibroblasts. Injury to cholangiocytes also recruits inflammatory cells to the liver and activates portal fibroblasts in the portal area, which release molecules to activate and amplify cholangiocytes. No matter what origin of myofibroblasts, either hepatic stellate cells or portal fibroblasts, they share similar characteristics, including being positive for -smooth muscle actin and sproducing extra cellular matrix. Based on the extensive pathogenesis knowledge of liver fibrosis, therapeutic strategies have been designed to target each step of this process, including hepatocyte apoptosis, cholangiocyte proliferation, inflammation, and activation of myofibroblasts to deposit extracellular matrix, yet the current therapies are still in early-phase clinical development. There is an urgent need to translate the molecular mechanism of liver fibrosis to effective and potent reagents or therapies in human.

  14. Smoking and Pulmonary Fibrosis: Novel Insights

    Directory of Open Access Journals (Sweden)

    Katerina D. Samara

    2011-01-01

    Full Text Available The relationship between smoking and pulmonary fibrosis is under debate and intense investigation. The aim of this paper is to review the existing literature and identify further areas of research interest. Recently the negative influence of cigarette smoking on IPF outcome was highlighted, as non-smokers exhibit a better survival than ex-smokers and combined current- and ex-smokers. In patients with non-specific interstitial pneumonia (NSIP, a high prevalence of emphysema was recently demonstrated, providing an indirect support for a smoking pathogenetic hypothesis in NSIP. The coexistence of pulmonary fibrosis and emphysema has been extensively described in a syndrome termed combined pulmonary fibrosis and emphysema (CPFE. Connective tissue disorders (CTDs are a group of autoimmune diseases which affect the lung, as one of the most common and severe manifestations. However, the relationship between smoking and autoimmune disorders is still conflicting. Rheumatoid arthritis results from the interaction between genetic and environmental factors, while the best established environmental factor is tobacco smoking. Smoking has also a negative impact on the response of the RA patients to treatment. The aforementioned smoking-related implications give rise to further research questions and certainly provide one more important reason for physicians to advocate smoking cessation and smoke-free environment.

  15. Gastrointestinal manifestations in cystic fibrosis.

    Science.gov (United States)

    Eggermont, E

    1996-08-01

    CFTR, or cystic fibrosis transmembrane conductance regulator, the gene product that is defective in cystic fibrosis, is present in the apical membrane of the epithelial cells from the stomach to the colon. In the foregut, the clinical manifestations are not directly related to the primary defect of the CFTR chloride channel. The most troublesome complaints and symptoms originate from the oesophagus as peptic oesophagitis or oesophageal varices. In the small intestinal wall, the clinical expression of CF depends largely on the decreased secretion of fluid and chloride ions, the increased permeability of the paracellular space between adjacent enterocytes and the sticky mucous cover over the enterocytes. As a rule, the brush border enzyme activities are normal and there is some enhanced active transport as shown for glucose and alanine. The results of continuous enteral feeding of CF patients clearly show that the small intestinal mucosa, in the daily situation, is not functioning at maximal capacity. Although CFTR expression in the colon is lower, the large intestine may be the site of several serious complications such as rectal prolapse, meconium ileus equivalent, intussusception, volvulus and silent appendicitis. In recent years colonic strictures, after the use of high-dose pancreatic enzymes, are being increasingly reported; the condition has recently been called CF fibrosing colonopathy. The CF gastrointestinal content itself differs mainly from the normal condition by the lower acidity in the foregut and the accretion of mucins and proteins, eventually resulting in intestinal obstruction, in the ileum and colon. Better understanding of the CF gastrointestinal phenotype may contribute to improvement of the overall wellbeing of these patients.

  16. A Correlation Based Method for Discriminating Inrush Current from Short Circuit Current Using Wavelet Transform in Power Transformer Differential Protection

    Directory of Open Access Journals (Sweden)

    M. Rasoulpoor

    2013-09-01

    Full Text Available This paper presents a new approach for power transformer differential protection. The Wavelet Transform is applied to discriminate between inrush currents and internal fault currents in power transformers. Discrete wavelet transform decomposes the current signal into sub-bands that give more information about the properties of the signals in different frequency bands. Also, this transform is used to investigate the energy distribution of the signal on the different time and frequency scales. Recognition method is based on the correlation factors between energy percentage vectors of the Wavelet coefficients. Discrete Wavelet transform is used for decomposing the current signals to different frequency coefficients. After that, by constituting the energy percentage vectors of wavelet transform coefficients and calculating the correlation factors between these vectors, it is possible to form a recognition criterion to distinguish between inrush and internal fault current in the proposed method. The proposed algorithm is tested for several conditions by simulated inrush and internal fault currents. Simulation of current signals is performed using electromagnetic transient program PSCAD/EMTDC software that is a powerful program for the investigation of transient signals. Simulation results show that the proposed scheme accurately identifies inrush and fault currents in the distance of the power transformer protection in less than quarter of power frequency cycle. Also, beside the sensitivity and high reliability, the proposed method has low computation content and unlike the common methods does not require to determine the threshold for each new power system.

  17. Nutritional Issues in Cystic Fibrosis.

    Science.gov (United States)

    Solomon, Missale; Bozic, Molly; Mascarenhas, Maria R

    2016-03-01

    The importance of maintaining adequate nutrition in patients with cystic fibrosis has been well known for the past 3 decades. Achieving normal growth and maintaining optimal nutrition is associated with improved lung function. Comprehensive and consistent nutritional assessments at regular intervals can identify those at risk of nutritional failure and uncover micronutrient deficiencies contributing to malnutrition. Management of malnutrition in cystic fibrosis should follow a stepwise approach to determine the causes and comorbidities and to develop a nutritional plan. Nutritional management is crucial at every stage in a person's life with cystic fibrosis and remains a cornerstone of management.

  18. Epigenetic regulation in cardiac fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li-Ming; Yu; Yong; Xu

    2015-01-01

    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.

  19. Nephrogenic systemic fibrosis.

    LENUS (Irish Health Repository)

    Kennedy, C

    2010-11-05

    Nephroaenic systemic fibrosis (NSF) is a potentiallv fatal dermatiological condition found exclusively in patients with advanced renal I failure. There is minimal literature regarding the epidemiology and outcomes of patients with NSF in Ireland. A retrospective chart review was performed for all patients with NSF in Ireland. Ireland\\'s experience with the disease was examined in light of international reports. There have been three cases of NSF in Ireland; an area which serves 1915 dialysis patients--giving a point prevalence among Irish end-stage kidney disease patients of 0.002. There was a large variation in disease severity between the three patients. All three patients had significant exposure to gadolinium chelate. Caution with gadolinium administration must be exercised in patients with advanced renal failure.

  20. Anti-Influenza Treatment: Drugs Currently Used and Under Development.

    Science.gov (United States)

    Amarelle, Luciano; Lecuona, Emilia; Sznajder, Jacob I

    2017-01-01

    Influenza is a very common contagious disease that carries significant morbidity and mortality. Treatment with antiviral drugs is available, which if administered early, can reduce the risk of severe complications. However, many virus types develop resistance to those drugs, leading to a notable loss of efficacy. There has been great interest in the development of new drugs to combat this disease. A wide range of drugs has shown anti-influenza activity, but they are not yet available for use in the clinic. Many of these target viral components, which others are aimed at elements in the host cell which participate in the viral cycle. Modulating host components is a strategy which minimizes the development of resistance, since host components are not subject to the genetic variability of the virus. The main disadvantage is the risk of treatment-related side effects. The aim of this review is to describe the main pharmacological agents currently available and new drugs in the pipeline with potential benefit in the treatment of influenza. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Current and Potential Uses of Immunocytokines as Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Paul M. Sondel

    2012-07-01

    Full Text Available Immunocytokines (ICs are a class of molecules created by linking tumor-reactive monoclonal antibodies to cytokines that are able to activate immune cells. Tumor selective localization is provided by the ability of the mAb component to bind to molecules found on the tumor cell surface or molecules found selectively in the tumor microenvronment. In this way the cytokine component of the immunocytokine is selectively localized to sites of tumor and can activate immune cells with appropriate receptors for the cytokine. Immunocytokines have been made and tested by us, and others, using a variety of tumor-reactive mAbs linked to distinct cytokines. To date, the majority of clinical progress has been made with ICs that have linked human interleukin-2 (IL2 to a select number of tumor reactive mAbs that had already been in prior clinical testing as non-modified mAbs. Here we briefly review the background for the creation of ICs, summarize current clinical progress, emphasize mechanisms of action for ICs that are distinct from those of their constituent components, and present some directions for future development and testing.

  2. Asthma-related emergency department use: current perspectives

    Directory of Open Access Journals (Sweden)

    Johnson LH

    2016-07-01

    Full Text Available Laurie H Johnson,1 Patricia Chambers,1 Judith W Dexheimer1,2 1Division of Emergency Medicine, 2Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Abstract: Asthma is one of the most common chronic pediatric diseases. Patients with asthma often present to the emergency department for treatment for acute exacerbations. These patients may not have a primary care physician or primary care home, and thus are seeking care in the emergency department. Asthma care in the emergency department is multifaceted to treat asthma patients appropriately and provide quality care. National and international guidelines exist to help drive clinical care. Electronic and paper-based tools exist for both physicians and patients to help improve emergency, home, and preventive care. Treatment of patients with asthma should include the acute exacerbation, long-term management of controller medications, and controlling triggers in the home environment. We will address the current state of asthma research in emergency medicine in the US, and discuss some of the resources being used to help provide a medical home and improve care for patients who suffer from acute asthma exacerbations. Keywords: asthma, pediatric, emergency department

  3. Bioresorbable vascular scaffolds technology: current use and future developments

    Directory of Open Access Journals (Sweden)

    Giacchi G

    2016-07-01

    Full Text Available Giuseppe Giacchi, Luis Ortega-Paz, Salvatore Brugaletta, Kohki Ishida, Manel Sabaté Cardiology Department, Clinic Cardiovascular Institute, Hospital Clinic, August Pi and Sunyer Biomedical Research Institute (IDIBAPS, University of Barcelona, Barcelona, Spain Abstract: Coronary bioresorbable vascular scaffolds are a new appealing therapeutic option in interventional cardiology. The most used and studied is currently the Absorb BVS™. Its backbone is made of poly-l-lactide and coated by a thin layer of poly-d,l-lactide, it releases everolimus and is fully degraded to H2O and CO2 in 2–3 years. Absorb BVS™ seems to offer several theoretical advantages over metallic stent, as it gives temporary mechanical support to vessel wall without permanently caging it. Therefore, long-term endothelial function and structure are not affected. A possible future surgical revascularization is not compromised. Natural vasomotion in response to external stimuli is also recovered. Several observational and randomized trials have been published about BVS clinical outcomes. The main aim of this review is to carry out a systematic analysis about Absorb BVS™ studies, evaluating also the technical improvements of the Absorb GT1 BVS™. Keywords: Absorb GT1, Absorb BVS™, bioresorbable vascular scaffold, BRS, coronary scaffold

  4. Combined pulmonary fibrosis and emphysema: an increasingly recognized condition

    Directory of Open Access Journals (Sweden)

    Olívia Meira Dias

    2014-06-01

    Full Text Available Combined pulmonary fibrosis and emphysema (CPFE has been increasingly recognized in the literature. Patients with CPFE are usually heavy smokers or former smokers with concomitant lower lobe fibrosis and upper lobe emphysema on chest HRCT scans. They commonly present with severe breathlessness and low DLCO, despite spirometry showing relatively preserved lung volumes. Moderate to severe pulmonary arterial hypertension is common in such patients, who are also at an increased risk of developing lung cancer. Unfortunately, there is currently no effective treatment for CPFE. In this review, we discuss the current knowledge of the pathogenesis, clinical characteristics, and prognostic factors of CPFE. Given that most of the published data on CPFE are based on retrospective analysis, more studies are needed in order to address the role of emphysema and its subtypes; the progression of fibrosis/emphysema and its correlation with inflammation; treatment options; and prognosis.

  5. ARRAY PULSED EDDY CURRENT IMAGING SYSTEM USED TO DETECT CORROSION

    Institute of Scientific and Technical Information of China (English)

    Yang Binfeng; Luo Feilu; Cao Xiongheng; Xu Xiaojie

    2005-01-01

    A theory model is established to describe the voltage-current response function. The peak amplitude and the zero-crossing time of the transient signal is extracted as the imaging features, array pulsed eddy current (PEC) imaging is proposed to detect corrosion. The test results show that this system has the advantage of fast scanning speed, different imaging mode and quantitative detection, it has a broad application in the aviation nondestructive testing.

  6. Air Quality Study Using Satellites - Current Capability and Future Plans

    Science.gov (United States)

    Bhartia, Pawan K.; Joiner, Joanna; Gleason, James; Liu, Xiong; Torres, Omar; Krotkov, Nickolay; Ziemke, Jerry; Chandra, Sushil

    2008-01-01

    Satellite instruments have had great success in monitoring the stratospheric ozone and in understanding the processes that control its daily to decadal scale variations. This field is now reaching its zenith with a number of satellite instruments from the US, Europe and Canada capping several decades of active research in this field. The primary public policy imperative of this research was to make reliable prediction of increases in biologically active surface UV radiation due to human activity. By contrast retrieval from satellite data of atmospheric constituents and photo-chemically active radiation that affect air quality is a new and growing field that is presenting us with unique challenges in measurement and data interpretation. A key distinction compared to stratospheric sensors is the greatly enhanced role of clouds, aerosols, and surfaces (CAS) in determining the quality and quantity of useful data that is available for air quality research. In our presentation we will use data from several sensors that are currently flying on the A-train satellite constellation, including OMI, MODIS, CLOUDSAT, and CALIPSO, to highlight that CAS can have both positive and negative effects on the information content of satellite measurements. This is in sharp contrast to other fields of remote sensing where CAS are usually considered an interference except in those cases when they are the primary subject of study. Our analysis has revealed that in the reflected wavelengths one often sees much further down into the atmosphere, through most cirrus, than one does in the emitted wavelengths. The lower level clouds provide a nice background against which one can track long-range transport of trace gases and aerosols. In addition, differences in trace gas columns estimated over cloudy and adjacent clear pixels can be used to measure boundary layer trace gases. However, in order to take full advantage of these features it will be necessary to greatly advance our understanding of

  7. Directed Motivational Currents: Using vision to create effective motivational pathways

    Directory of Open Access Journals (Sweden)

    Christine Muir

    2013-10-01

    Full Text Available Vision, that is, the mental representation of the sensory experience of a future goal state (involving imagination and imagery, is currently at the forefront of motivational innovation, and in recent years it has been seen increasingly more often in the motivational tool kit of practicing language teachers. Theories such as Dörnyei’s L2 motivational self system have explored the power that creating effective visions can harness (see, e.g., Dörnyei & Kubanyiova, 2014 and when viewed in conjunction with other current research avenues, such as future time perspective and dynamic systems theory, vision offers exciting potential. A Directed Motivational Current is a new motivational construct that we suggest is capable of integrating many current theoretical strands with vision: It can be described as a motivational drive which energises long-term, sustained behaviour (such as language learning, and through placing vision and goals as critical central components within this construct, it offers real and practical motivational potential. In this conceptual paper, we first discuss current understandings of vision and of Directed Motivational Currents, and then analyse how they may be optimally integrated and employed to create effective motivational pathways in language learning environments.

  8. Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model

    Directory of Open Access Journals (Sweden)

    Hasegawa Yoshinori

    2009-09-01

    Full Text Available Abstract Background To determine whether oral administration of geranylgeranylacetone (GGA, a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP 70, protects against drug-induced lung injury/fibrosis in vivo. Methods We used a bleomycin (BLM-induced lung fibrosis model in which mice were treated with oral 600 mg/kg of GGA before and after BLM administration. Inflammation and fibrosis were evaluated by histological scoring, hydroxyproline content in the lung and inflammatory cell count, and quantification by ELISA of macrophage inflammatory protein-2 (MIP-2 in bronchoalveolar lavage fluid. Apoptosis was evaluated by the TUNEL method. The induction of HSP70 in the lung was examined with western blot analysis and its localization was determined by immunohistochemistry. Results We confirmed the presence of inflammation and fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral administration of GGA. GGA prevented apoptosis of cellular constituents of lung tissue, such as epithelial cells, most likely related to the de novo induction of HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs, associated with the findings of suppression of both production of MIP-2 and inflammatory cell accumulation in the injured lung, compared with vehicle-treated mice. Conclusion GGA had a protective effect on drug-induced lung injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate, which are indispensable for the treatment of rheumatoid arthritis, often cause interstitial lung diseases, an adverse event that currently cannot be prevented. Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in the future.

  9. Male fertility in cystic fibrosis.

    LENUS (Irish Health Repository)

    Chotirmall, S H

    2011-04-05

    Infertility rates among males with cystic fibrosis (CF) approximate 97%. No information is currently available within Ireland determining an understanding of fertility issues and the best methods of information provision to this specialized group. This study aimed to determine understanding and preferred approaches to information provision on fertility issues to Irish CF males. A Descriptive Study utilizing prospective coded questionnaires was mailed to a male CF cohort (n=50). Sections included demographics, fertility knowledge & investigation. Response rate was 16\\/50 (32%). All were aware that CF affected their fertility. More than two-thirds (n=11) were able to provide explanations whilst only one-third (n=5) provided the correct explanation. Significant numbers stated thoughts of marriage and a future family. Half have discussed fertility with a healthcare professional (HCP). Mean age of discussion was 21.9 years. One third preferred an earlier discussion. The commonest first source for information was written material which was also the preferred source. Three-quarters requested further information preferring again, written material. Significant gaps in sex education of Irish CF males exist. Discussion should be initiated by HCPs and centre-directed written material devised to address deficiencies.

  10. A practical new way to measure kidney fibrosis.

    Science.gov (United States)

    Peti-Peterdi, János

    2016-11-01

    Proper histological measurement of kidney fibrosis is essentially important in both clinical pathology and basic research using animal models of chronic kidney disease (CKD). However, standard histology techniques and their blind evaluation are cumbersome. Ranjit et al. applied an advanced optical microscopy technique for hassle-free, unbiased, and highly sensitive characterization of kidney fibrosis and tested it in a classic model of chronic kidney disease in mice. This commentary emphasizes the advantages and future promise of this new approach.

  11. Regulatory effect of miR-149 on interleukin-6 expression in silica-induced pulmonary fibrosis

    Institute of Scientific and Technical Information of China (English)

    范晶晶

    2014-01-01

    Objective To investigate the regulatory effect of miR-149 on interleukin-6(IL-6)expression in silica-induced pulmonary fibrosis.Methods A mouse model of pulmonary fibrosis was established using silica dust;the level of miR-149 in the lung tissues of mice with silicainduced pulmonary fibrosis was measured by quantitative

  12. [Lung physiotherapy in cystic fibrosis].

    Science.gov (United States)

    Gursli, S; Haanaes, O C

    1991-02-28

    This article is intended as a brief practical guide for physicians and physiotherapists concerned with the treatment of cystic fibrosis. Physiotherapeutic techniques for the treatment of chest diseases have been developed and modified as advances have taken place in the medical management of cystic fibrosis. The article describes forced expiratory technique, positive expiratory pressure, postural drainage, autogenic drainage and other techniques. Patients with cystic fibrosis live longer and have a better quality of life than ever before, but progressive deterioration of lung function will always be their most serious problem. Physical activity and chest physiotherapy are essential parts of all treatment regimens for cystic fibrosis. It is important to realize that the physiotherapist is a very important member of the team which includes nurses, physicians-and the patient.

  13. Pulmonary fibrosis associated with nabumetone.

    OpenAIRE

    Morice, A.; Atherton, A.; GLEESON, F; Stewart, S.

    1991-01-01

    A patient is described who developed a rapid onset of pulmonary fibrosis following treatment with a new non-steroidal anti-inflammatory drug, nabumetone. Resolution of symptoms, physical signs and radiographic changes followed drug withdrawal and steroid therapy.

  14. Gadolinium contrast agent-induced CD163+ ferroportin+ osteogenic cells in nephrogenic systemic fibrosis.

    Science.gov (United States)

    Swaminathan, Sundararaman; Bose, Chhanda; Shah, Sudhir V; Hall, Kimberly A; Hiatt, Kim M

    2013-09-01

    Gadolinium-based contrast agents are linked to nephrogenic systemic fibrosis in patients with renal insufficiency. The pathology of nephrogenic systemic fibrosis is characterized by abnormal tissue repair: fibrosis and ectopic ossification. The mechanisms by which gadolinium could induce fibrosis and ossification are not known. We examined in vitro the effect of a gadolinium-based contrast agent on human peripheral blood mononuclear cells for phenotype and function relevant to the pathology of nephrogenic systemic fibrosis using immunofluorescence, flow cytometry, real-time PCR, and osteogenic assays. We also examined tissues from patients with nephrogenic systemic fibrosis, using IHC to identify the presence of cells with phenotype induced by gadolinium. Gadolinium contrast induced differentiation of human peripheral blood mononuclear cells into a unique cellular phenotype--CD163(+) cells expressing proteins involved in fibrosis and bone formation. These cells express fibroblast growth factor (FGF)23, osteoblast transcription factors Runt-related transcription factor 2, and osterix, and show an osteogenic phenotype in in vitro assays. We show in vivo the presence of CD163(+)/procollagen-1(+)/osteocalcin(+) cells in the fibrotic and calcified tissues of nephrogenic systemic fibrosis patients. Gadolinium contrast-induced CD163(+)/ferroportin(+)/FGF23(+) cells with osteogenic potential may play a role in systemic fibrosis and ectopic ossification in nephrogenic systemic fibrosis.

  15. A Single-Phase Multilevel Current-Source Converter using H-Bridge and DC Current Modules

    Directory of Open Access Journals (Sweden)

    Suroso Suroso

    2014-03-01

    Full Text Available This paper presents a different topology of H-bridge based multilevel current-source inverter (CSI. In this new topology, an H-bridge CSI is connected with a single or more current modules to generate a multilevel output current waveform with lower di/dt, and less distortion. Using the proposed multilevel CSI, the number of the power switching devices, and isolated gate drive circuits can be reduced. Moreover, chopper based DC current sources are presented to reduce the inductor size effectively to be in micro-Henry order, and ensure the balance of the intermediate current levels. The proposed topology is inherently able to reduce the inductor conduction losses if compared with the conventional multilevel CSIs and the H-bridge CSI. Seven-level PWM inverter configurations with non-isolated DC current sources and with a single DC power source are verified through computer simulations. Furthermore, laboratory prototypes of seven-level CSI is setup and tested. The results show that the inverter circuit works properly to generate the multilevel output current waveform with low harmonics currents, small inductors and with less conduction losses which proves feasibility of the proposed multilevel CSI. Normal 0 false false false EN-US X-NONE X-NONE

  16. Guidelines for the medical treatment of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Xaubet, Antoni; Molina-Molina, María; Acosta, Orlando; Bollo, Elena; Castillo, Diego; Fernández-Fabrellas, Estrella; Rodríguez-Portal, José Antonio; Valenzuela, Claudia; Ancochea, Julio

    2017-05-01

    Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Assessment of hemodynamic changes in the systemic and pulmonary arterial circulation in patients with cystic fibrosis using phase-contrast MRI

    Energy Technology Data Exchange (ETDEWEB)

    Ley, Sebastian; Eichinger, Monika [DKFZ, Department of Radiology (E010), Heidelberg (Germany); Johannes Gutenberg University, Department of Radiology, University Hospital Mainz, Mainz (Germany); Puderbach, Michael; Fink, Christian; Plathow, Christian; Kauczor, Hans-Ulrich [DKFZ, Department of Radiology (E010), Heidelberg (Germany); Teiner, Susanne [University of Heidelberg, Department of Pediatric Radiology, Heidelberg (Germany); Wiebel, Matthias [Thoraxklinik am Universitaetsklinikum, Department of Pulmonology, Heidelberg (Germany); Mueller, Frank-Michael [University of Heidelberg, Department of Pediatric Pulmonology, Heidelberg (Germany)

    2005-08-01

    Cystic fibrosis (CF) leads to disabling lung disease and pulmonary hypertension (PH). The goal of this study was to assess the hemodynamics in the systemic and pulmonary arterial circulation of patients with CF using MRI. Ten patients with CF and 15 healthy volunteers were examined (1.5-T MRI). Phase-contrast flow measurements were assessed in the ascending aorta, pulmonary trunc, and the left and right pulmonary arteries (PA), resulting in the following parameters: peak velocity (PV) (centimeters per second) velocity rise gradient (VRG), time to PV (milliseconds), and the average area (centimeters squared). The blood flow ratio between the right and left lungs and the bronchosystemic shunt were calculated. For the ascending aorta and pulmonary trunc no parameter was significantly different between both populations. In the right PA a significantly lower PV (p=0.001) and VRG (p=0.02) was found. In the left PA there was a significantly (p=0.007) lower PV but no significant (p=0.07) difference between the VRG. The areas of the right (p=0.08) and left (p=0.5) PA were not significantly enlarged. For the volunteers a linear increase of PV in both PA was found with age, while it decreased in patients with CF. The blood flow distribution (right/left lung) showed no significant (p=0.7) difference between the groups. There was a significantly (p<0.001) higher bronchosystemic shunt volume in patients with CF (1.3 l/min) than in volunteers (0.1 l/min). Magnetic resonance based flow measurements in the right and left PA showed first indications for early development of PH. The significant increase in bronchosystemic shunt volume might be indicative fo the extent of parenchymal changes. (orig.)

  18. Signal Processing Strategies for Cochlear Implants Using Current Steering

    Directory of Open Access Journals (Sweden)

    Waldo Nogueira

    2009-01-01

    Full Text Available In contemporary cochlear implant systems, the audio signal is decomposed into different frequency bands, each assigned to one electrode. Thus, pitch perception is limited by the number of physical electrodes implanted into the cochlea and by the wide bandwidth assigned to each electrode. The Harmony HiResolution bionic ear (Advanced Bionics LLC, Valencia, CA, USA has the capability of creating virtual spectral channels through simultaneous delivery of current to pairs of adjacent electrodes. By steering the locus of stimulation to sites between the electrodes, additional pitch percepts can be generated. Two new sound processing strategies based on current steering have been designed, SpecRes and SineEx. In a chronic trial, speech intelligibility, pitch perception, and subjective appreciation of sound were compared between the two current steering strategies and standard HiRes strategy in 9 adult Harmony users. There was considerable variability in benefit, and the mean results show similar performance with all three strategies.

  19. Currents and sub-currents in innovation flows : Explaining innovativeness using new-product announcements

    NARCIS (Netherlands)

    Dolfsma, Wilfred; van der Panne, Gerben

    2008-01-01

    The creation of new knowledge is a haphazard process: not every sector in an economy is equally involved. The effect of industry structure on innovativeness has been a focus of attention for a long time by both academics and policymakers. in a much quoted article, using unique data - new-product

  20. Fibrosis quística

    OpenAIRE

    Arturo Solís-Moya; José Pablo Gutiérrez-S

    2003-01-01

    Enfermedades Raras en Asturias. Dirección General de Salud Pública y Participación. Informes breves 09 Cystic fibrosis is a multisystem disease generates the formation and accumulation of viscous mucus that affects everything lungs, digestive system including liver and pancreas. Formerly known as mucoviscidosis or cystic fibrosis pancreas. Este proyecto ha sido financiado a cargo de los fondos para la cohesión territorial 2010 del Ministerio de Sanidad y Política Socia...

  1. Fibrosis quística

    OpenAIRE

    Arturo Solís-Moya; José Pablo Gutiérrez-S

    2014-01-01

    Enfermedades Raras en Asturias. Dirección General de Salud Pública y Participación. Informes breves 09 Cystic fibrosis is a multisystem disease generates the formation and accumulation of viscous mucus that affects everything lungs, digestive system including liver and pancreas. Formerly known as mucoviscidosis or cystic fibrosis pancreas. Este proyecto ha sido financiado a cargo de los fondos para la cohesión territorial 2010 del Ministerio de Sanidad y Política Socia...

  2. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona

    2010-01-01

    BACKGROUND: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release...... accumulated in type II alveolar epithelial cells, lacking CFTR. P. aeruginosa organisms were rarely present in inflamed alveoli. CONCLUSIONS: Chronic inflammation and remodeling is present in alveolar tissues of the CF lung and needs to be addressed by anti-inflammatory therapies....

  3. Cytokines in human lung fibrosis.

    Science.gov (United States)

    Martinet, Y; Menard, O; Vaillant, P; Vignaud, J M; Martinet, N

    1996-01-01

    Fibrosis is a pathological process characterized by the replacement of normal tissue by mesenchymal cells and the extracellular matrix produced by these cells. The sequence of events leading to fibrosis of an organ involves the subsequent processes of injury with inflammation and disruption of the normal tissue architecture, followed by tissue repair with accumulation of mesenchymal cells in the area of derangement. The same sequence of events occurs in wound healing with normal granulation tissue and scar formation, but, while normal scar formation is very localized and transient, in contrast, in fibrosis, the repair process is exaggerated and usually widespread and can be chronic. Inflammatory cells (mainly mononuclear phagocytes), platelets, endothelial cells, and type II pneumocytes play a direct and indirect role in tissue injury and repair. The evaluation of three human fibrotic lung diseases, two diffuse [idiopathic pulmonary fibrosis (IPF), and the adult respiratory distress syndrome (ARDS)], and one focal (tumor stroma in lung cancer), has shown that several cytokines participate to the local injury and inflammatory reaction [interleukin-1 (IL-1), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha)], while other cytokines are involved in tissue repair and fibrosis [platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta), and basic-fibroblast growth factor (b-FGF)]. A better understanding of the cytokines and cytokine networks involved in lung fibrosis leads to the possibility of new therapeutic approaches.

  4. Computed tomography dose optimisation in cystic fibrosis: A review.

    LENUS (Irish Health Repository)

    Ferris, Helena

    2016-04-28

    Cystic fibrosis (CF) is the most common autosomal recessive disease of the Caucasian population worldwide, with respiratory disease remaining the most relevant source of morbidity and mortality. Computed tomography (CT) is frequently used for monitoring disease complications and progression. Over the last fifteen years there has been a six-fold increase in the use of CT, which has lead to a growing concern in relation to cumulative radiation exposure. The challenge to the medical profession is to identify dose reduction strategies that meet acceptable image quality, but fulfil the requirements of a diagnostic quality CT. Dose-optimisation, particularly in CT, is essential as it reduces the chances of patients receiving cumulative radiation doses in excess of 100 mSv, a dose deemed significant by the United Nations Scientific Committee on the Effects of Atomic Radiation. This review article explores the current trends in imaging in CF with particular emphasis on new developments in dose optimisation.

  5. Increased caffeine consumption is associated with reduced hepatic fibrosis.

    Science.gov (United States)

    Modi, Apurva A; Feld, Jordan J; Park, Yoon; Kleiner, David E; Everhart, James E; Liang, T Jake; Hoofnagle, Jay H

    2010-01-01

    Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. This study was undertaken to use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Patients undergoing liver biopsy completed a detailed caffeine questionnaire on three occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis. One hundred seventy-seven patients (99 male, 104 white, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions. Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75(th) percentile for the cohort (308 mg = approximately 2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.80; P = 0.015) and the protective association persisted after controlling for age, sex, race, liver disease, body mass index, and alcohol intake in all patients (OR, 0.25; 95% CI, 0.09-0.67; P = 0.006), as well as the subset with HCV infection (OR, 0.19; 95% CI, 0.05-0.66; P = 0.009). Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis. A reliable tool for measurement of caffeine consumption demonstrated that caffeine consumption, particularly from regular coffee, above a threshold of approximately 2 coffee-cup equivalents per day, was associated with less severe hepatic fibrosis.

  6. Increased caffeine consumption is associated with reduced hepatic fibrosis

    Science.gov (United States)

    Modi, Apurva A; Feld, Jordan J; Park, Yoon; Kleiner, David E; Everhart, James E.; Liang, T. Jake; Hoofnagle, Jay H.

    2009-01-01

    Background Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. Aim To use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Methods Patients undergoing liver biopsy completed a detailed caffeine questionnaire on 3 occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis. Results 177 patients (99 male, 104 Caucasian, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions. Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75th percentile for the cohort (308 mg ~2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (OR 0.33, 95% CI: 0.14-0.80, p=0.015) and the protective association persisted after controlling for age, sex, race, liver disease, body mass index and alcohol intake in all patients (OR 0.25, 95% CI: 0.09-0.67, p=0.006), as well as the subset with HCV infection (OR 0.19, 95% CI: 0.05-0.66, p=0.009). Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis. Conclusion A reliable tool for measurement of caffeine consumption demonstrated that caffeine consumption, particularly from regular coffee, above a threshold of approximately 2 coffee-cup equivalents per day, was associated with less severe hepatic fibrosis. PMID:20034049

  7. [Measurement of pulmonary inflammation in cystic fibrosis].

    Science.gov (United States)

    Fayon, M; Chiron, R; Abely, M

    2008-06-01

    Lung inflammation is a pivotal phenomenon in the pathogenesis of cystic fibrosis. Inflammation can be measured and quantified within a research perspective, as well as in daily clinical practice. In this review paper, the "Inflammation Task Force" of the "Société Française de Mucoviscidose" has reviewed the literature regarding the various techniques currently available (bronchoalveolar lavage, sputum analysis, nasal wash and brushing, exhaled breath condensates, carbon monoxide and nitric oxide, and systemic measurements (plasma and urine)). The interpretation of all these determinations in children and adults is also discussed.

  8. Online junction temperature measurement using peak gate current

    DEFF Research Database (Denmark)

    Baker, Nick; Munk-Nielsen, Stig; Iannuzzo, Francesco

    2015-01-01

    A new method for junction temperature measurement of MOS-gated power semiconductor switches is presented. The measurement method involves detecting the peak voltage over the external gate resistor of an IGBT or MOSFET during turn-on. This voltage is directly proportional to the peak gate current...

  9. Directed Motivational Currents: Using Vision to Create Effective Motivational Pathways

    Science.gov (United States)

    Muir, Christine; Dörnyei, Zoltán

    2013-01-01

    Vision, that is, the mental representation of the sensory experience of a future goal state (involving imagination and imagery), is currently at the forefront of motivational innovation, and in recent years it has been seen increasingly more often in the motivational tool kit of practicing language teachers. Theories such as Dörnyei's L2…

  10. Polyhydroxyalkanoates - what are the uses? Current challenges and perspectives.

    Science.gov (United States)

    Masood, Farha; Yasin, Tariq; Hameed, Abdul

    2015-01-01

    Over the past few decades, a considerable attention has been focused on the microbial polyhydroxyalkanoates (PHAs) owing to its multifaceted properties, i.e. biodegradability, biocompatibility, non-toxicity and thermo-plasticity. This article presents a critical review of the foregoing research, current trends and future perspectives on the value added applications of PHAs in the biomedical, environmental and industrial domains of life.

  11. Analysis of short-distance current correlators using OPE

    CERN Document Server

    Tomii, M; Fahy, B; Fukaya, H; Hashimoto, S; Noaki, J

    2015-01-01

    We investigate the correlators of flavor non-singlet bilinear operators calculated on the lattice at short distances. In the continuum theory, non-perturbative effects are encoded in the form of the operator product expansion (OPE). We test the prediction of OPE by comparing lattice results with those in the continuum theory. We also determine the renormalization factors of quark currents.

  12. Detection of late radiation damage on left atrial fibrosis using cardiac late gadolinium enhancement magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Y. Jessica Huang, PhD

    2016-04-01

    Conclusions: With LGE-MRI and 3-dimensional dose mapping on the treatment planning system, it is possible to define subclinical cardiac damage and distinguish intrinsic cardiac tissue change from radiation induced cardiac tissue damage. Imaging myocardial injury secondary to EBRT using MRI may be a useful modality to follow cardiac toxicity from EBRT and help identify individuals who are more susceptible to EBRT damage. LGE-MRI may provide essential information to identify early screening strategy for affected cancer survivors after EBRT treatment.

  13. Persistent lung inflammation and fibrosis in serum amyloid P component (APCs-/- knockout mice.

    Directory of Open Access Journals (Sweden)

    Darrell Pilling

    Full Text Available Fibrosing diseases, such as pulmonary fibrosis, cardiac fibrosis, myelofibrosis, liver fibrosis, and renal fibrosis are chronic and debilitating conditions and are an increasing burden for the healthcare system. Fibrosis involves the accumulation and differentiation of many immune cells, including macrophages and fibroblast-like cells called fibrocytes. The plasma protein serum amyloid P component (SAP; also known as pentraxin-2, PTX2 inhibits fibrocyte differentiation in vitro, and injections of SAP inhibit fibrosis in vivo. SAP also promotes the formation of immuno-regulatory Mreg macrophages. To elucidate the endogenous function of SAP, we used bleomycin aspiration to induce pulmonary inflammation and fibrosis in mice lacking SAP. Compared to wildtype C57BL/6 mice, we find that in Apcs-/- "SAP knock-out" mice, bleomycin induces a more persistent inflammatory response and increased fibrosis. In both C57BL/6 and Apcs-/- mice, injections of exogenous SAP reduce the accumulation of inflammatory macrophages and prevent fibrosis. The types of inflammatory cells present in the lungs following bleomycin-aspiration appear similar between C57BL/6 and Apcs-/- mice, suggesting that the initial immune response is normal in the Apcs-/- mice, and that a key endogenous function of SAP is to promote the resolution of inflammation and fibrosis.

  14. Alcohol use, viral hepatitis and liver fibrosis among HIV-positive persons in West Africa: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Antoine Jaque

    2017-01-01

    Conclusions: Considering the WHO recommendations to screen for HBV infection and treat co-infected patients with tenofovir-based ART, screening of alcohol use and brief interventions to prevent alcohol abuse should be implemented in West Africa, especially in HBV/HIV co-infected patients.

  15. Idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Noble Paul W

    2008-03-01

    Full Text Available Abstract Idiopathic pulmonary fibrosis (IPF is a non-neoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known provocation. IPF is a rare disease which affects approximately 5 million persons worldwide. The prevalence is estimated to be slightly greater in men (20.2/100,000 than in women (13.2/100,000. The mean age at presentation is 66 years. IPF initially manifests with symptoms of exercise-induced breathless and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones upon physical exam. Clubbing is found in approximately 50% of IPF patients. Cor pulmonale develops in association with end-stage disease. In that case, classic signs of right heart failure may be present. Etiology remains incompletely understood. Some environmental factors may be associated with IPF (cigarette smoking, exposure to silica and livestock. IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP. The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images and a lung biopsy. In the absence of lung biopsy, the diagnosis of IPF can be made by defined clinical criteria that were published in guidelines endorsed by several professional societies. Differential diagnosis includes other idiopathic interstitial pneumonia, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis, forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis and other environmental (sometimes occupational exposures. IPF is typically progressive and leads to significant

  16. Prevalence and progression of combined pulmonary fibrosis and emphysema in asymptomatic smokers: A case-control study

    Energy Technology Data Exchange (ETDEWEB)

    Chae, Kum Ju; Jin, Gong Yong; Han, Young Min; Kim, Yong Seek; Chon, Su Bin; Lee, Young Sun [Chonbuk National University Medical School and Hospital, Department of Radiology, Institute of Medical Science, Research Institute of Clinical Medicine, Jeonju, Jeonbuk (Korea, Republic of); Kwon, Keun Sang [Chonbuk National University Medical School, Department of Preventive Medicine, Research Institute of Clinical Medicine, Jeonju, Jeonbuk (Korea, Republic of); Choi, Hye Mi [Chonbuk National University, Department of Statistics and Institute of Applied Statistics, Jeonju, Jeonbuk (Korea, Republic of); Lynch, David [National Jewish Health, Department of Radiology, Denver, CO (United States)

    2015-08-15

    We aimed to estimate the prevalence of combined pulmonary fibrosis and emphysema (CPFE) and describe the follow-up CT results of CPFE in asymptomatic smokers. This study was retrospective, and approved by an institutional review board. CT images of 2,016 current or previous male smokers who underwent low-dose chest CT at our healthcare centre were reviewed. Quantitative CT analysis was used to assess the extent of emphysema, and two radiologists visually analyzed the extent of fibrosis. Changes in fibrosis (no change, improvement, or progression) were evaluated on follow-up CT imaging (n = 42). Kaplan-Meier survival analysis, multivariate logistic regression and its ROC curve were used for survival and progression analysis. The prevalence of CPFE among asymptomatic male smokers was 3.1 % (63/2,016). The median follow-up period was 50.4 months, and 72.7 % (16/22) of continued smoker had progressing fibrosis on follow-up CT. CPFE progressed more rapidly in continuous smokers than in former smokers (p = 0.002). The 3.5-year follow-up period after initial CPFE diagnosis maximized the sum of sensitivity and specificity of CPFE progression prediction in continuous smokers. The prevalence of CPFE turned out not to be inconsiderable in asymptomatic male smokers, but serial CT follow-up would be helpful in recognizing disease progression. (orig.)

  17. Immunological status does not influence hepatitis c virus or liver fibrosis in HIV-hepatitis C virus-coinfected patients.

    Science.gov (United States)

    Collazos, Julio; Cartón, José Antonio; Asensi, Víctor

    2011-04-01

    The possible effects on liver fibrosis and HCV viral load of the immunological status of HIV-HCV-coinfected patients are unclear. A cohort of HIV-HCV-coinfected patients was divided according to the current CD4 counts into poor (≤200/μl, n = 117) or good (≥500/μl, n = 441) immunological status. The groups were compared for diverse HCV- and fibrosis-related parameters. Fibrosis was evaluated by transient elastometry and other noninvasive indexes. Many variables were significantly associated with the immunological status in univariate analyses, including fibrosis parameters. However, in multivariate analyses current immunological status or nadir CD4 were not associated with HCV viral load (p = 0.8 and p = 0.3, respectively), liver fibrosis at the time of evaluation (p = 0.9 for both), or fibrosis progression over time (p = 0.98 and p = 0.8, respectively). The factors independently associated with significant fibrosis, advanced fibrosis, and cirrhosis, as compared with minimal or no fibrosis, were alcohol abuse [OR 3.57 (95% CI 1.43-8.85), p = 0.006; OR 10.10 (3.75-27.03), p Immunological status did not associate with any fibrosis stage (significant fibrosis, p = 0.7; advanced fibrosis, p = 0.4; and cirrhosis p = 0.9). The current or past immunological status of HIV-HCV-coinfected patients does not seem to have any significant influence on HCV viral load or on the development of liver fibrosis when adjusting for important covariates.

  18. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

    2011-10-15

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation

  19. Idiopathic Pulmonary Fibrosis: Treatment and Prognosis

    Science.gov (United States)

    Fujimoto, Hajime; Kobayashi, Tetsu; Azuma, Arata

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a prognosis that can be worse than for many cancers. The initial stages of the condition were thought to mainly involve chronic inflammation; therefore, corticosteroids and other drugs that have anti-inflammatory and immunosuppressive actions were used. However, recently, agents targeting persistent fibrosis resulting from aberrant repair of alveolar epithelial injury have been in the spotlight. There has also been an increase in the number of available antifibrotic treatment options, starting with pirfenidone and nintedanib. These drugs prevent deterioration but do not improve IPF. Therefore, nonpharmacologic approaches such as long-term oxygen therapy, pulmonary rehabilitation, and lung transplantation must be considered as additional treatment modalities. PMID:27980445

  20. Lymphoplasmacytic Sclerosing Pancreatitis and Retroperitoneal Fibrosis

    Directory of Open Access Journals (Sweden)

    Nigel K. F. Koo Ng

    2008-01-01

    Full Text Available Although cases of lymphoplasmacytic sclerosing pancreatitis (LSP associated with idiopathic retroperitoneal fibrosis have been reported, the association is rare. We describe a 74-year-old man who presented with obstructive jaundice and weight loss. Nineteen months earlier, he had been diagnosed with idiopathic retroperitoneal fibrosis and treated with bilateral ureteric stents. Initial investigations were suggestive of a diagnosis of LSP, however, a malignant cause could not be ruled out. He underwent an exploratory laparotomy and frozen sections confirmed the diagnosis of LSP. An internal biliary bypass was performed using a Roux loop of jejunum, and the patient made an uneventful recovery. This case illustrates the difficulty in distinguishing LSP from pancreatic carcinoma preoperatively.

  1. New RC-Active Networks Using Current Conveyors

    Directory of Open Access Journals (Sweden)

    V. Zeman

    1997-06-01

    Full Text Available Two novel autonomous networks containing current conveyors are presented. The design of second-order oscillators and frequency filters based on the above general networks is described. The Q-factor of the circuits designed is controllable through a grounded single resistor. Some examples illustrate the procedure described. Two new one-port elements for high-order immittance realization are shown.

  2. A double-stage start-up structure to limit the inrush current used in current mode charge pump

    Science.gov (United States)

    Cong, Liu; Xinquan, Lai; Hanxiao, Du; Yuan, Chi

    2016-06-01

    A double-stage start-up structure to limit the inrush current used in current-mode charge pump with wide input range, fixed output and multimode operation is presented in this paper. As a widely utilized power source implement, a Li-battery is always used as the power supply for chips. Due to the internal resistance, a potential drop will be generated at the input terminal of the chip with an input current. A false shut down with a low supply voltage will happen if the input current is too large, leading to the degradation of the Li-battery's service life. To solve this problem, the inrush current is limited by introducing a new start-up state. All of the circuits have been implemented with the NUVOTON 0.6 μm CMOS process. The measurement results show that the inrush current can be limited below 1 A within all input supply ranges, and the power efficiency is higher than the conventional structure. Project supported by the National Natural Science Foundation of China (No. 61106026).

  3. Transcellular sodium transport in cultured cystic fibrosis human nasal epithelium

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

    Cystic fibrosis (CF) airway epithelia exhibit raised transepithelial Na+ transport rates, as determined by open-circuit isotope fluxes and estimates of the amiloride-sensitive equivalent short-circuit current (Ieq). To study the contribution of apical and basolateral membrane paths to raised Na+ ...

  4. Shifting paradigms of nontuberculous mycobacteria in cystic fibrosis

    DEFF Research Database (Denmark)

    Qvist, Tavs; Pressler, Tania; Høiby, Niels;

    2014-01-01

    Important paradigms of pulmonary disease with nontuberculous mycobacteria (NTM) are currently shifting based on an increasing attention within the field of cystic fibrosis (CF). These shifts are likely to benefit the management of all patients with pulmonary NTM, regardless of underlying pathology...

  5. Transcellular sodium transport in cultured cystic fibrosis human nasal epithelium

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

    Cystic fibrosis (CF) airway epithelia exhibit raised transepithelial Na+ transport rates, as determined by open-circuit isotope fluxes and estimates of the amiloride-sensitive equivalent short-circuit current (Ieq). To study the contribution of apical and basolateral membrane paths to raised Na...

  6. Prediction of fibrosis progression in chronic viral hepatitis

    Directory of Open Access Journals (Sweden)

    Grace Lai-Hung Wong

    2014-09-01

    Full Text Available Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.

  7. 特发性肺纤维化急性加重的诊治进展%Acute exacerbation of idiopathic pulmonary fibrosis: a review of current diagnosis and treatment

    Institute of Scientific and Technical Information of China (English)

    苏瑾; 代华平

    2009-01-01

    通常认为特发性肺纤维化(1PF)为慢性进行性病程.近年来发现在没有明确诱因的情况下部分IPF患者在自然病程中可以出现急性恶化,称为IPF急性加重.其病死率很高.且临床并非少见.目前治疗IPF急性加重多采用大剂量糖皮质激素冲击治疗及强化氧疗.一些研究证实环抱素A、吡非尼酮、抗凝治疗在防治IPF急性加重方面町能有效.%Idiopathic pulmonary fibrosis(lPF) has been described as a chronic progressive disease. Recent evidences have suggested that some patients may experience acute deterioration in the course of disease,which is termed acute exacerbation of IPF. Acute exacerbation of IPF is increasingly recognized as high fatality and common clinical event. Stoss therapy of large dose glucocorticosteroid and strengthening oxygen therapy are adopted in the treatment of the disease. A few studies have shown beneficial effects of cyclosporin A, pirfenidone and anticoagulant therapy in the management and prevention of acute exacerbation of IPF.

  8. Protective effect of fucoidan from Fucus vesiculosus on liver fibrosis via the TGF-β1/Smad pathway-mediated inhibition of extracellular matrix and autophagy.

    Science.gov (United States)

    Li, Jingjing; Chen, Kan; Li, Sainan; Feng, Jiao; Liu, Tong; Wang, Fan; Zhang, Rong; Xu, Shizan; Zhou, Yuqing; Zhou, Shunfeng; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

    2016-01-01

    Liver fibrosis is a dynamic reversible pathological process in the development of chronic liver disease to cirrhosis. However, the current treatments are not administered for a long term due to their various side effects. Autophagy is initiated to decompose damaged or excess organelles, which had been found to alter the progression of liver fibrosis. In this article, we hypothesized that fucoidan from Fucus vesiculosus may attenuate liver fibrosis in mice by inhibition of the extracellular matrix and autophagy in carbon tetrachloride- and bile duct ligation-induced animal models of liver fibrosis. The results were determined using enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemical staining. Fucoidan from F. vesiculosus could inhibit the activation of hepatic stellate cells and the formation of extracellular matrix and autophagosomes, and its effect may be associated with the downregulation of transforming growth factor beta 1/Smads pathways. Fucoidan, as an autophagy and transforming growth factor beta 1 inhibitor, could be a promising potential therapeutic agent for liver fibrosis.

  9. Assessment of myocardial fibrosis and coronary arteries in hypertrophic cardiomyopathy using combined arterial and delayed enhanced CT: comparison with MR and coronary angiography

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lei; Ma, Xiaohai; Zhang, Chen; Liu, Yi; Zhang, Zhaoqi [Capital Medical University, Department of Radiology, Beijing Anzhen Hospital, Beijing (China); DeLano, Mark C. [Michigan State University, Division of Radiology and Biomedical Imaging, College of Human Medicine, Lancing, MI (United States); Jiang, Tengyong [Capital Medical University, Department of Cardiology, Beijing Anzhen Hospital, Beijing (China)

    2013-04-15

    We sought to determine the feasibility and accuracy of dual-source computed tomography (DSCT) in assessing coronary artery disease and myocardial fibrosis of hypertrophic cardiomyopathy (HCM) compared with cardiac magnetic resonance (CMR) imaging and coronary angiography (CA). Forty-seven consecutive patients with HCM were prospectively enrolled. DSCT images were acquired in the arterial and late phases following intravenous contrast medium. The CMR and CA were performed within 7 days. Independent blinded readers read each study. Patients were classified according to myocardial delayed enhanced (MDE) CMR, coronary artery stenosis by CA, and arterial and MDE-DSCT. The diagnostic accuracy of DSCT in detecting coronary stenosis and MDE was analysed. Wall thickness determined by DSCT was strongly correlated with MR results (r = 0.91). DSCT and CMR MDE showed substantial agreement for the detection of myocardial fibrosis on per-patient and per-segment levels. The CT classification of patients by arterial stenosis and delayed enhancement had excellent agreement with MR and CA methods. The comprehensive cardiac CT examination provides reliable coronary artery and myocardial assessments. MDE-DSCT is a robust alternative method to MDE-CMR in assessing myocardial fibrosis in HCM particularly in patients with pacemakers or other contraindications to CMR. (orig.)

  10. A rabbit model of lower eyelid fibrosis.

    Science.gov (United States)

    Griepentrog, Gregory J; Park, D J John; Zaldivar, Renzo A; Pulido, Jose S; Cameron, J Douglas; Woog, John J

    2010-01-01

    To create and validate a new model of lower eyelid fibrosis in Dutch-belted rabbits. Five Dutch-belted rabbits were injected with a transcutaneous 1-ml injection of standard 95% ethanol alcohol just inferior to the eyelid margin of one lower eyelid. A control injection of 1 ml of balanced saline solution was given to the opposite eyelid. A small tattoo was placed on the skin overlying the inferior orbital rim and used as a measuring point of reference in relation to the lower eyelid margin. Analysis was twofold: eyelid measurements were made over 8 weeks to determine the presence of eyelid shortening, and a histopathologic analysis was performed. Mean lower eyelid shortening was greater in the ethanol alcohol intervention eyelids than the control group (-3.4 mm +/- 1.67 mm vs. 0.5 mm +/- 0.71 mm, p = 0.01). Histopathologic analysis revealed extensive fibrosis in the ethanol alcohol invention eyelids compared with the control group. Ethanol alcohol induces eyelid fibrosis and lower eyelid shortening. This may be a useful model in the future testing of novel surgical or pharmacologic treatments.

  11. New insights into the pathogenesis of cystic fibrosis sinusitis

    Science.gov (United States)

    Chang, Eugene H.

    2013-01-01

    People with cystic fibrosis (CF) sinus disease have developmental sinus abnormalities with airway bacterial infection, inflammation, impaired mucociliary clearance and thick obstructive mucus. The pathophysiology of airway disease in CF is not completely understood, and current treatments in CF sinus disease ameliorate symptoms but do not provide a cure. This manuscript reviews the history of CF, its manifestations in sinus disease, and the potential impact and relationship of CF on the upper and lower airway. We discuss recent discoveries in the pathophysiology of CF using the CF porcine animal model and exciting treatments that address the primary gene defect that may translate into improved outcomes in CF and non-CF sinusitis in humans. PMID:24282147

  12. What Are the Signs and Symptoms of Cystic Fibrosis?

    Science.gov (United States)

    ... Twitter. What Are the Signs and Symptoms of Cystic Fibrosis? The signs and symptoms of cystic fibrosis (CF) ... respiratory, digestive, or reproductive systems of the body. Cystic Fibrosis Figure A shows the organs that cystic fibrosis ...

  13. Reversal of hepatic fibrosis: pathophysiological basis of antifibrotic therapies

    Directory of Open Access Journals (Sweden)

    Ismail MH

    2011-07-01

    Full Text Available Mona H Ismail1, Massimo Pinzani21Department of Internal Medicine, Division of Gastroenterology, King Fahad University Hospital, Al-Khobar, Saudi Arabia; 2Dipartimento di Medicina Interna Center for Research, High Education and Transfer, Università degli Studi di Firenze, Florence, ItalyAbstract: Chronic liver injuries of different etiologies eventually lead to fibrosis, a scarring process associated with increased and altered deposition of extracellular matrix in the liver. Progression of fibrosis has a major worldwide clinical impact due to the high number of patients affected by chronic liver disease which can lead to severe complications, expensive treatment, a possible need for liver transplantation, and death. Liver fibrogenesis is characterized by activation of hepatic stellate cells and other extracellular matrix producing cells. Liver fibrosis may regress following specific therapeutic interventions. Other than removing agents causing chronic liver damage, no antifibrotic drug is currently available in clinical practice. The extent of liver fibrosis is variable between individuals, even after controlling for exogenous factors. Thus, host genetic factors are considered to play an important role in the process of liver scarring. Until recently it was believed that this process was irreversible. However, emerging experimental and clinical evidence is starting to show that even cirrhosis in its early stages is potentially reversible.Keywords: liver fibrosis, cirrhosis, fibrogenesis, antifibrotic agents

  14. Genotypes and phenotypes in cystic fibrosis and cystic fibrosis transmembrane regulator-related disorders.

    Science.gov (United States)

    Bombieri, Cristina; Seia, Manuela; Castellani, Carlo

    2015-04-01

    Cystic fibrosis (CF) is characterized by remarkable variability in severity, rate of disease progression, and organ involvement. In spite of the considerable amount of data collected on the relationship between genotype and phenotype in CF, this is still a challenging matter of debate. Barriers to the interpretation of this connection are the large number of mutations in the CF transmembrane regulator (CFTR) gene, the difficulties in attributing several of them to a specific mode of dysfunction, and a limited number of the almost 2,000 mutations so far detected, which have been clinically annotated. In addition to that, the heterogeneity of clinical manifestations in individuals with the same CFTR genotypes indicates that disease severity is modulated by other genes and by environmental factors, of which the most relevant is possibly treatment in its aspects of appropriateness, early start in life, and adherence. The phenotype variability extends to conditions, named CFTR-related disorders, which are connected with CFTR dysfunction, but do not satisfy diagnostic criteria for CF. The current level of knowledge does not allow use of the CFTR genotype to predict individual outcome and cannot be used as an indicator of CF prognosis. This might change with the development of treatments targeting specific mutations and possibly capable of changing the natural history of the disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Nephrogenic systemic fibrosis and gadolinium-based contrast media

    DEFF Research Database (Denmark)

    Thomsen, Henrik S; Morcos, Sameh K; Almén, Torsten

    2012-01-01

    PURPOSE: To update the guidelines of the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) on nephrogenic systemic fibrosis and gadolinium-based contrast media. AREAS COVERED: Topics reviewed include the history, clinical features and prevalence...... of nephrogenic systemic fibrosis and the current understanding of its pathophysiology. The risk factors for NSF are discussed and prophylactic measures are recommended. The stability of the different gadolinium-based contrast media and the potential long-term effects of gadolinium in the body have also been...... reviewed. KEY POINTS : • Clinical features, risk factors and prevention of nephrogenic systemic fibrosis are reviewed • Patients with GFR below 30 ml/min/1.73 m ( 2 ) have increased risk of developing NSF • Low stability gadolinium contrast media show the strongest association with NSF • Following...

  16. Birth distribution in cystic fibrosis in Saguenay-Lac-St-Jean, Quebec, Canada.

    Science.gov (United States)

    Daigneault, J; Aubin, G; Simard, F; De Braekeleer, M

    1991-09-01

    Although a seasonal trend in the birth distribution has been reported in cystic fibrosis (CF), this finding is still very controversial. The birth distribution of 113 patients with cystic fibrosis born in Saguenay-Lac-St-Jean (complete ascertainment) was analysed using two different statistical methods. Our results showed no monthly or seasonal birth variation. It is likely that a bias owing to incomplete ascertainment might explain why some previous studies found a seasonal trend in the birth distribution of cystic fibrosis.

  17. Role of endothelin in lung fibrosis

    Directory of Open Access Journals (Sweden)

    D. Abraham

    2008-12-01

    Full Text Available Accumulating evidence suggests that idiopathic pulmonary fibrosis (IPF results from lung injury primarily following an abnormal wound healing response towards epithelial cell damage. Thus, rather than resulting from chronic inflammation, as thought previously, the inflammatory response acts as a modifier of the fibrogenic response, which can also be influenced by the host’s genetic background and environmental triggers. Several key mediators, including endothelin (ET-1, have been implicated in the fibrosis and scarring associated with IPF. Elevated levels of ET-1 have been detected in bronchoalveolar lavage fluid and serum from patients with IPF and increased expression of ET-1 has been detected in small pulmonary blood vessels and macrophages. In vitro data show that ET-1 influences matrix production and degradation by promoting synthesis of collagen type I and III, inhibiting expression of matrix metalloproteinase-1 and promoting matrix remodelling. In addition, ET-1 promotes fibroblast differentiation to a myofibroblastic cell type, inducing the expression of proteins that contribute to a contractile phenotype including -smooth muscle actin. Moreover, ET-1 has been shown to initiate alveolar epithelial cell transition into fibroblast-like cells, a process termed epithelial–mesenchymal transition, and thereby contribute to pulmonary fibrosis. Furthermore, recently reported data from the BUILD (Bosentan Use in Interstitial Lung Disease-1 trial showed a trend towards a delay in time to disease progression or death following treatment with the endothelin receptor antagonist, bosentan, which was especially prominent in patients with biopsy-proven IPF. This adds to the evidence that ET-1 plays an important role in IPF. The present article examines recent evidence for the role of endothelin-1 in pulmonary fibrosis, and particularly, in the control of the function and differentiation of fibroblasts and myofibroblasts.

  18. Vitamin A intake and serum retinol levels in children and adolescents with cystic fibrosis

    NARCIS (Netherlands)

    Woestenenk, JW; Broos, Nancy; Stellato, Rebecca K; Arets, Hubertus G M; van der Ent, Cornelis K.; Houwen, RHJ

    2016-01-01

    BACKGROUND: Pancreatic insufficient cystic fibrosis (CF) patients receive vitamin A supplementation according to CF-specific recommendations to prevent deficiencies. Whether current recommendations are optimal for preventing both deficiency and toxicity is a subject of debate. We assessed the longit

  19. Inhalable Antimicrobials for Treatment of Bacterial Biofilm-Associated Sinusitis in Cystic Fibrosis Patients

    DEFF Research Database (Denmark)

    Klodzinska, Sylvia Natalie; Priemel, Petra Alexandra; Rades, Thomas

    2016-01-01

    Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa...

  20. [Are non-invasive tests going to replace liver biopsy for diagnosis of liver fibrosis?].

    Science.gov (United States)

    Restellini, Sophie; Spahr, Laurent

    2012-06-27

    Liver fibrosis is associated with chronic liver diseases, and may evolve into cirrhosis that may be complicated by liver failure and portal hypertension. Detection and quantification of liver fibrosis is a key point in the follow-up of patients with chronic liver diseases. Liver biopsy is the gold standard method to assess and quantify fibrosis, but its invasiveness is a limiting factor in everyday clinical practice. Non invasive markers using either biological or radiological parameters have been developed and may decrease the need for liver biopsy in some cases. However, information is limited to fibrosis, and cut-offs values and diagnostic accuracies for significant fibrosis may vary according to the etiology of liver disease. Liver biopsy allows the assessment of intermediate stages of fibrosis and describes accompanying lesions.

  1. [Treatment of Cystic Fibrosis with CFTR Modulators].

    Science.gov (United States)

    Tümmler, B

    2016-05-01

    Personalized medicine promises that medical decisions, practices and products are tailored to the individual patient. Cystic fibrosis, an inherited disorder of chloride and bicarbonate transport in exocrine glands, is the first successful example of customized drug development for mutation-specific therapy. There are two classes of CFTR modulators: potentiators that increase the activity of CFTR at the cell surface, and correctors that either promote the read-through of nonsense mutations or facilitate the translation, folding, maturation and trafficking of mutant CFTR to the cell surface. The potentiator ivacaftor and the corrector lumacaftor are approved in Germany for the treatment of people with cystic fibrosis who carry a gating mutation such as p.Gly551Asp or who are homozygous for the most common mutation p.Phe508del, respectively. This report provides an overview of the basic defect in cystic fibrosis, the population genetics of CFTR mutations in Germany and the bioassays to assess CFTR function in humans together with the major achievements of preclinical research and clinical trials to bring CFTR modulators to the clinic. Some practical information on the use of ivacaftor and lumacaftor in daily practice and an update on pitfalls, challenges and novel strategies of bench-to-bedside development of CFTR modulators are also provided.

  2. Correlation between ultrasound imaging and serum markers of liver fibrosis in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Jian-Xia Liu

    2016-01-01

    Objective:To investigate the clinical value of ultrasonic imaging in the assessment of liver fibrosis in patients with chronic hepatitis B. Methods:A total of 20 cases of liver biopsy in chronic hepatitis B, according to the degree of hepatic fibrosis were divided into mild hepatic fibrosis group, moderate fibrosis group, severe fibrosis group, the other selected healthy volunteers as control group, using color Doppler ultrasound, the use of imaging technology and automatic tracking. Strengthen the quantitative analysis, using the second generation microbubble contrast agent SonoVue contrast analysis, contrast agent reach the portal time (PVAT), hepatic artery time (HAAT), hepatic vein (HVVT), the calculation time of hepatic arteriovenous transit time (VAT) and hepatic portal vein transit time (VVT), using chemiluminescence detection of serum liver fiber hyaluronic acid (HA), laminin (LN) and collagen type IV (CIV) index. Results:there was no significant difference in HAAT, PVAT, VAT, VVT and HVAT in all groups, and there was no significant difference, mild, moderate and severe liver fibrosis group, and HA, LN and C levels were significantly higher than those in control group. Conclusion:serum liver fibrosis indexes can guide the degree of liver fibrosis. The ultrasound contrast can reflect the changes of liver blood flow dynamics, and it has a certain guiding significance to the assessment of the degree of liver fibrosis, the monitoring of the disease and the clinical treatment.

  3. Effects of Angiotensin Converting Enzyme Inhibitors on Liver Fibrosis in HIV and Hepatitis C Coinfection

    Directory of Open Access Journals (Sweden)

    Lindsey J. Reese

    2012-01-01

    Full Text Available Background. Liver fibrosis is accelerated in HIV and hepatitis C coinfection, mediated by profibrotic effects of angiotensin. The objective of this study was to determine if angiotensin converting enzyme inhibitors (ACE-Is attenuate liver fibrosis in coinfection. Methods. A retrospective review of 156 coinfected subjects was conducted to analyze the association between exposure to ACE-Is and liver fibrosis. Noninvasive indices of liver fibrosis (APRI, FIB-4, Forns indices were compared between subjects who had taken ACE-Is and controls who had not taken them. Linear regression was used to evaluate ACE-I use as an independent predictor of fibrosis. Results. Subjects taking ACE-Is for three years were no different than controls on the APRI and the FIB-4 but had significantly higher scores than controls on the Forns index, indicating more advanced fibrosis. The use of ACE-Is for three years remained independently associated with an elevated Forns score when adjusted for age, race, and HIV viral load (P<0.001. There were significant associations between all of the indices and significant fibrosis, as determined clinically and radiologically. Conclusions. There was not a protective association between angiotensin inhibition and liver fibrosis in coinfection. These noninvasive indices may be useful for ruling out significant fibrosis in coinfection.

  4. Land use change modelling: current practice and research priorities

    NARCIS (Netherlands)

    Verburg, P.H.; Schot, P.; Dijst, M.J.; Veldkamp, A.

    2004-01-01

    Land use change models are tools to support the analysis of the causes and consequences of land use dynamics. Scenario analysis with land use models can support land use planning and policy. Numerous land use models are available, developed from different disciplinary backgrounds. This paper reviews

  5. Evolutionary-driven support vector machines for determining the degree of liver fibrosis in chronic hepatitis C.

    Science.gov (United States)

    Stoean, Ruxandra; Stoean, Catalin; Lupsor, Monica; Stefanescu, Horia; Badea, Radu

    2011-01-01

    Hepatic fibrosis, the principal pointer to the development of a liver disease within chronic hepatitis C, can be measured through several stages. The correct evaluation of its degree, based on recent different non-invasive procedures, is of current major concern. The latest methodology for assessing it is the Fibroscan and the effect of its employment is impressive. However, the complex interaction between its stiffness indicator and the other biochemical and clinical examinations towards a respective degree of liver fibrosis is hard to be manually discovered. In this respect, the novel, well-performing evolutionary-powered support vector machines are proposed towards an automated learning of the relationship between medical attributes and fibrosis levels. The traditional support vector machines have been an often choice for addressing hepatic fibrosis, while the evolutionary option has been validated on many real-world tasks and proven flexibility and good performance. The evolutionary approach is simple and direct, resulting from the hybridization of the learning component within support vector machines and the optimization engine of evolutionary algorithms. It discovers the optimal coefficients of surfaces that separate instances of distinct classes. Apart from a detached manner of establishing the fibrosis degree for new cases, a resulting formula also offers insight upon the correspondence between the medical factors and the respective outcome. What is more, a feature selection genetic algorithm can be further embedded into the method structure, in order to dynamically concentrate search only on the most relevant attributes. The data set refers 722 patients with chronic hepatitis C infection and 24 indicators. The five possible degrees of fibrosis range from F0 (no fibrosis) to F4 (cirrhosis). Since the standard support vector machines are among the most frequently used methods in recent artificial intelligence studies for hepatic fibrosis staging, the

  6. Trap States in Copper Phthalocyanine Thin Films using Photogenerated Currents

    Science.gov (United States)

    Gredig, Thomas; Guerra, Jorge; Byrne, Matthew; Silverstein, Evan

    2010-03-01

    The efficiency of organic solar cells is limited by several factors including the photocurrent generation process. Copper phthalocyanine thin films with different grain structures are prepared via thermal evaporation onto interdigitated gold electrodes. The samples are analyzed with atomic force microscopy and then exposed to light pulses to explore the time dependence of photogenerated currents in phthalocyanine thin films. The average grain size is obtained from the correlation length of the height-height correlation function and varies from 30-200nm. The dependence of the recombination of photo-excited, dissociated charge pairs on the electric field is compared with the Onsager mechanism and a simple dual trap state model from which relevant time scales are extracted.

  7. Preparation of intravenous cholesterol tracer using current good manufacturing practices.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Swaney, William P; Ostlund, Richard E

    2015-12-01

    Studies of human reverse cholesterol transport require intravenous infusion of cholesterol tracers. Because insoluble lipids may pose risk and because it is desirable to have consistent doses of defined composition available over many months, we investigated the manufacture of cholesterol tracer under current good manufacturing practice (CGMP) conditions appropriate for phase 1 investigation. Cholesterol tracer was prepared by sterile admixture of unlabeled cholesterol or cholesterol-d7 in ethanol with 20% Intralipid(®). The resulting material was filtered through a 1.2 micron particulate filter, stored at 4°C, and tested at time 0, 1.5, 3, 6, and 9 months for sterility, pyrogenicity, autoxidation, and particle size and aggregation. The limiting factor for stability was a rise in thiobarbituric acid-reacting substances of 9.6-fold over 9 months (P postproduction. CGMP manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies.

  8. Operational advances in ring current modeling using RAM-SCB

    Energy Technology Data Exchange (ETDEWEB)

    Welling, Daniel T [Los Alamos National Laboratory; Jordanova, Vania K [Los Alamos National Laboratory; Zaharia, Sorin G [Los Alamos National Laboratory; Morley, Steven K [Los Alamos National Laboratory

    2010-12-03

    The Ring current Atmosphere interaction Model with Self-Consistently calculated 3D Magnetic field (RAM-SCB) combines a kinetic model of the ring current with a force-balanced model of the magnetospheric magnetic field to create an inner magnetospheric model that is magnetically self consistent. RAM-SCB produces a wealth of outputs that are valuable to space weather applications. For example, the anisotropic particle distribution of the KeV-energy population calculated by the code is key for predicting surface charging on spacecraft. Furthermore, radiation belt codes stand to benefit substantially from RAM-SCB calculated magnetic field values and plasma wave growth rates - both important for determining the evolution of relativistic electron populations. RAM-SCB is undergoing development to bring these benefits to the space weather community. Data-model validation efforts are underway to assess the performance of the system. 'Virtual Satellite' capability has been added to yield satellite-specific particle distribution and magnetic field output. The code's outer boundary is being expanded to 10 Earth Radii to encompass previously neglected geosynchronous orbits and allow the code to be driven completely by either empirical or first-principles based inputs. These advances are culminating towards a new, real-time version of the code, rtRAM-SCB, that can monitor the inner magnetosphere conditions on both a global and spacecraft-specific level. This paper summarizes these new features as well as the benefits they provide the space weather community.

  9. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis.

    Science.gov (United States)

    Lipson, Kenneth E; Wong, Carol; Teng, Yuchin; Spong, Suzanne

    2012-01-01

    CTGF is a secreted matricellular protein with very complex biology. It has been shown to modulate many signaling pathways leading to cell adhesion and migration, angiogenesis, myofibroblast activation, and extracellular matrix deposition and remodeling, which together lead to tissue remodeling and fibrosis. It has been reported in the literature that inhibition of CTGF expression by siRNA prevents CCl4-induced liver fibrosis and can reverse fibrosis when administered after significant collagen deposition is observed. A monoclonal antibody to CTGF that is currently in clinical development (FG-3019) has demonstrated the ability to reverse vascular stiffening and improve cardiac function in a rat model of diabetic complications. FG-3019 has also exhibited activity in a murine radiation-induced pulmonary fibrosis model. When FG-3019 was administered to mice after a significant radiation-induced increase in lung density could be observed by CT imaging, the density of the lungs was observed to decrease over the period during which the antibody was administered and to remain stable after therapy had ceased. When considered together, these data indicate that inhibition of CTGF can prevent and reverse the process of fibrosis.

  10. CFTR protein repair therapy in cystic fibrosis.

    Science.gov (United States)

    Quintana-Gallego, Esther; Delgado-Pecellín, Isabel; Calero Acuña, Carmen

    2014-04-01

    Cystic fibrosis is a single gene, autosomal recessive disorder, in which more than 1,900 mutations grouped into 6 classes have been described. It is an example a disease that could be well placed to benefit from personalised medicine. There are currently 2 very different approaches that aim to correct the basic defect: gene therapy, aimed at correcting the genetic alteration, and therapy aimed at correcting the defect in the CFTR protein. The latter is beginning to show promising results, with several molecules under development. Ataluren (PTC124) is a molecule designed to make the ribosomes become less sensitive to the premature stop codons responsible for class i mutations. Lumacaftor (VX-809) is a CFTR corrector directed at class ii mutations, among which Phe508del is the most frequent, with encouraging results. Ivacaftor (VX-770) is a potentiator, the only one marketed to date, which has shown good efficacy for the class iii mutation Gly551Asp in children over the age of 6 and adults. These drugs, or a combination of them, are currently undergoing various clinical trials for other less common genetic mutations. In the last 5 years, CFTR has been designated as a therapeutic target. Ivacaftor is the first drug to treat the basic defect in cystic fibrosis, but only provides a response in a small number of patients. New drugs capable of restoring the CFTR protein damaged by the most common mutations are required.

  11. Nephrogenic systemic fibrosis

    Directory of Open Access Journals (Sweden)

    Bhushan Madke

    2011-01-01

    Full Text Available Nephrogenic systemic fibrosis (NSF is a relatively new fibrosing disorder which has caught the attention of various specialities in the past decade. NSF is an extremely disabling and often painful condition, affecting up to 13% of the individuals with chronic kidney disease. The administration of a gadolinium chelate contrast agent has been reported to induce the development of NSF, particularly in patients who have acute or chronic renal disease with a glomerular filtration rate (GFR lower than 30-mL/min/1.73 m 2 and in those with acute renal insufficiency. Mass spectroscopy studies have demonstrated particles of gadolinium in the lesional tissue. The exact pathogenesis of this curious sclerosing condition is unknown. The role of the aberrant targeting of ′circulating fibrocytes′ to the peripheral tissues and viscera has been hypothesized. NSF has distinct clinicopathological features in the setting of renal failure and needs to be looked upon as a new entity on the block. The condition is characterized by irregular indurated plaques, with amoeba-like projections and islands of sparing, chiefly on the trunk and extremities. Flexion contractures of fingers, knees, and elbow joints are known to occur in advanced cases of NSF. The course is frequently associated with painful episodes and loss of ambulation. Histopathology shows haphazard arrangement of thickened bundles of collagen, varying amount of mucin, and increased population of fibroblast-like cells in the dermis. Immunohistochemistry shows increased deposition of type-I procollagen and CD 34+ cells having fibroblastic activity. The condition is refractory to treatment with corticosteroids and immunosuppressive agents. Various modalities of therapy such as UVA1 phototherapy, imatinib mesylate, photodynamic therapy, plasmapheresis, extracorporeal photochemotherapy, and high-dose intravenous immunoglobulin have shown a moderate degree of improvement in skin thickness scores. A prudent

  12. ENDOMYOCARDIAL FIBROSIS IN CHINA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Purpose.To introduce the epidemical, pathological, and clinical characteristics as well as the diagnostic and therapeutical experiences of endomyocardial fibrosis(EMF) in China. Data sources.A CMBdisc search was done of the Chinese-language literature published from January 1983 through June 1997 about EMF and/or restrictive cardiomyopathy. A manual search was then done for other contributions, including abstracts, between January 1965 and June 1997.Results. Eighty-seven Chinese cases of EMF were collected in this paper. There were 49 men and 38 women, with a mean age of 28±13 years(range, 8 to 68 years). The distribution of the cases is mainly in the south of China. Combined right and left ventricular disease occurs in 48 percent of cases, with pure right ventricular involvement occurring in 42 percent and pure left ventricular involvement in the remaining 10 percent of patients who are examined postmortem. The diagnosis of EMF was confirmed in 21 cases at autopsy, and in 66 cases by echocardiography, angiocardiography, and/or endomyocardial biopsy which showed the characteristic changes. Clinically, right-sided disease is the commonest variety. Endocardiectomy and tricuspid(n=7) or mitral(n=1) valves replacement have been performed in 8 patients. There were 2 operative deaths. Six patients had a satisfactory recovery postoperatively and living well in the follow-up duration. Conclusion.EMF has been diagnosed clinically and confirmed at necropsy in a number of cases in the south of China. The etiology, incidence and epidemiology are still unknown. The pathological and clinical features are similar to those in tropical areas, but right ventricular involvement is the commonest type in our country.

  13. Longitudinal survey of Staphylococcus aureus in cystic fibrosis patients using a multiple-locus variable-number of tandem-repeats analysis method

    Directory of Open Access Journals (Sweden)

    Vergnaud Gilles

    2010-01-01

    Full Text Available Abstract Background Staphylococcus aureus infection in patients with cystic fibrosis (CF is frequent and may be due to colonization by a few pathogenic lineages. Systematic genotyping of all isolates, methicillin-susceptible S. aureus (MSSA as well as methicillin-resistant S. aureus (MRSA is necessary to identify such lineages and follow their evolution in patients. Multiple-locus variable-number tandem repeat analysis (MLVA/VNTR was used to survey S. aureus clinical isolates in a French paediatric CF centre. Results During a 30 months period, 108 patients, aged 2 to 21 years, regularly followed up at the centre, provided sputum for culture. From 79 patients, a total of 278 isolates were genotyped by MLVA, resolving into 110 genotypes and 19 clonal complexes (CC composed of similar or closely related isolates. 71% of the strains were distributed into four main CCs, in term of number of isolates and number of genotypes. Spa (Staphylococcus protein A typing was performed on representative samples, showing an excellent concordance with MLVA. In 17 patients, strains from two to four different CCs were recovered over time. On six occasions, S. aureus isolates with the same genotype were shared by 2 different patients and they belonged to one of the four main clusters. Methicillin-resistance was observed in 60% of the isolates, 90% of which belonged to the main clonal complexes CC8, CC45 and CC5. In 5 patients, methicillin-resistance of S. aureus isolates was not associated with the mecA gene: for four patients, it was due to overproduction of β-lactamase, leading to BOR-SA (borderline S. aureus isolates, while a strain showing probably a new modified penicillin-binding capacity (MOD-SA was observed from one patient. Conclusion Systematic genotyping of S. aureus isolates recovered from sputum of CF children allows a thorough analysis of the strains responsible for sporadic as well as chronic colonization and the follow up of their evolution over time

  14. Liver fibrosis in chronic viral hepatitis: An ultrasonographic study

    Institute of Scientific and Technical Information of China (English)

    Rong-Qin Zheng; Qing-Hui Wang; Ming-De Lu; Shi-Bin Xie; Jie Ren; Zhong-Zhen Su; Yin-Ke Cai; Ji-Lu Yao

    2003-01-01

    AIM: To select valuable ultrasonographic predictors for the evaluation of hepatic inflammation and fibrosis degree in chronic hepatitis, and to study the value of ultrasonography in the evaluation of liver fibrosis and compensated liver cirrhosis in comparison with serology and histology.METHODS: Forty-four ultrasonographic variables were analyzed and screened using color Doppler ultrasound system in 225 patients with chronic viral hepatitis and compensated liver cirrhosis. The valuable ultrasonographic predictors were selected on the basis of a comparison with histopathological findings. The value of ultrasonography and serology in the evaluation of liver fibrosis degree and the diagnosis of compensated liver cirrhosis was also studied and compared. Meanwhile, the influencing factors on ultrasonographic diagnosis of compensated liver cirrhosis were also analyzed.RESULTS: By statistical analysis, the maximum velocity of portal vein and the degree of gall-bladder wall smoothness were selected as the valuable predictors for the inflammation grade (G), while liver surface, hepatic parenchymal echo pattern, and the wall thickness of gall-bladder were selected as the valuable predictors for the fibrosis stage (S). Three S-related independent ultrasonographyic predictors and three routine serum fibrosis markers (HA, HPCIII and CIV) were used to discriminate variables for the comparison of ultrasonography with serology. The diagnostic accuracy of ultrasonography in moderate fibrosis was higher than that of serology (P<0.01), while there were no significant differences in the general diagnostic accuracy of fibrosis as well as between mild and severe fibrosis (P<0.05). There were no significant differences between ultrasonography and serology in the diagnosis of compensated liver cirrhosis.However, the diagnostic accuracy of ultrasonography was higher in inactive liver cirrhosis and lower in active cirrhosis than that of serology (both P<0.05). False positive and false

  15. Systems level analysis and identification of pathways and networks associated with liver fibrosis.

    Directory of Open Access Journals (Sweden)

    Mohamed Diwan M AbdulHameed

    Full Text Available Toxic liver injury causes necrosis and fibrosis, which may lead to cirrhosis and liver failure. Despite recent progress in understanding the mechanism of liver fibrosis, our knowledge of the molecular-level details of this disease is still incomplete. The elucidation of networks and pathways associated with liver fibrosis can provide insight into the underlying molecular mechanisms of the disease, as well as identify potential diagnostic or prognostic biomarkers. Towards this end, we analyzed rat gene expression data from a range of chemical exposures that produced observable periportal liver fibrosis as documented in DrugMatrix, a publicly available toxicogenomics database. We identified genes relevant to liver fibrosis using standard differential expression and co-expression analyses, and then used these genes in pathway enrichment and protein-protein interaction (PPI network analyses. We identified a PPI network module associated with liver fibrosis that includes known liver fibrosis-relevant genes, such as tissue inhibitor of metalloproteinase-1, galectin-3, connective tissue growth factor, and lipocalin-2. We also identified several new genes, such as perilipin-3, legumain, and myocilin, which were associated with liver fibrosis. We further analyzed the expression pattern of the genes in the PPI network module across a wide range of 640 chemical exposure conditions in DrugMatrix and identified early indications of liver fibrosis for carbon tetrachloride and lipopolysaccharide exposures. Although it is well known that carbon tetrachloride and lipopolysaccharide can cause liver fibrosis, our network analysis was able to link these compounds to potential fibrotic damage before histopathological changes associated with liver fibrosis appeared. These results demonstrated that our approach is capable of identifying early-stage indicators of liver fibrosis and underscore its potential to aid in predictive toxicity, biomarker identification, and to

  16. Systems Level Analysis and Identification of Pathways and Networks Associated with Liver Fibrosis

    Science.gov (United States)

    AbdulHameed, Mohamed Diwan M.; Tawa, Gregory J.; Kumar, Kamal; Ippolito, Danielle L.; Lewis, John A.; Stallings, Jonathan D.; Wallqvist, Anders

    2014-01-01

    Toxic liver injury causes necrosis and fibrosis, which may lead to cirrhosis and liver failure. Despite recent progress in understanding the mechanism of liver fibrosis, our knowledge of the molecular-level details of this disease is still incomplete. The elucidation of networks and pathways associated with liver fibrosis can provide insight into the underlying molecular mechanisms of the disease, as well as identify potential diagnostic or prognostic biomarkers. Towards this end, we analyzed rat gene expression data from a range of chemical exposures that produced observable periportal liver fibrosis as documented in DrugMatrix, a publicly available toxicogenomics database. We identified genes relevant to liver fibrosis using standard differential expression and co-expression analyses, and then used these genes in pathway enrichment and protein-protein interaction (PPI) network analyses. We identified a PPI network module associated with liver fibrosis that includes known liver fibrosis-relevant genes, such as tissue inhibitor of metalloproteinase-1, galectin-3, connective tissue growth factor, and lipocalin-2. We also identified several new genes, such as perilipin-3, legumain, and myocilin, which were associated with liver fibrosis. We further analyzed the expression pattern of the genes in the PPI network module across a wide range of 640 chemical exposure conditions in DrugMatrix and identified early indications of liver fibrosis for carbon tetrachloride and lipopolysaccharide exposures. Although it is well known that carbon tetrachloride and lipopolysaccharide can cause liver fibrosis, our network analysis was able to link these compounds to potential fibrotic damage before histopathological changes associated with liver fibrosis appeared. These results demonstrated that our approach is capable of identifying early-stage indicators of liver fibrosis and underscore its potential to aid in predictive toxicity, biomarker identification, and to generally identify

  17. Measurements of current speed using an Aanderaa RCM4 current meter in the presence of surface waves

    Science.gov (United States)

    Sherwin, T. J.

    1988-02-01

    It is shown that the Aanderaa RCM4 with Savonius rotor integrates motions that have a period significantly smaller than the recording interval, thus causing a quantifiable amplification of the observed mean speed. The minimum speed that can be recorded is 2ν/;π, where ν is the amplitude of the speed of the oscillating motion. In general, the amplification factor decreases as the ratio of mean speed over ν increases. The theory appears to explain the difference in observations made by an Aanderaa RCM4 and a neighbouring EG&G VMCM when particle velocities due to swell are included. It is recommended that vector averaging current meters should be used for current measurement in the upper 50-100 m of shelf sea regions that experience small tidal currents and a large oceanic swell.

  18. Rikkunshito ameliorates cachexia associated with bleomycin-induced lung fibrosis in mice by stimulating ghrelin secretion.

    Science.gov (United States)

    Tsubouchi, Hironobu; Yanagi, Shigehisa; Miura, Ayako; Mogami, Sachiko; Yamada, Chihiro; Iizuka, Seiichi; Hattori, Tomohisa; Nakazato, Masamitsu

    2014-10-01

    Cachexia is a frequent complication in patients with respiratory failure, such as lung fibrosis, and it is a determining factor for functional capacity, health status, and mortality. Reductions in body weight and skeletal muscle mass are key features of cachexia that are resistant to current therapies. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment for patients with gastrointestinal symptoms and known to stimulate ghrelin secretion. By using bleomycin (BLM)-induced lung fibrosis mice in this study, we tested our hypothesis that RKT administration could ameliorate pulmonary cachexia. After BLM administration, mice were provided with either RKT or distilled water on a daily basis. Compared with the BLM-injected mice, the RKT-treated mice had smaller reductions of food intake and body weight. Skeletal muscle weights were retained in the RKT-treated mice, in conjunction with reduced expressions of MuRF-1 and atrogin-1 in the lysates of skeletal muscle found in lung fibrosis. Rikkunshito administration restored the plasma concentrations of ghrelin in BLM-injected mice. The anticachectic efficacies of RKT administration in BLM-injected mice were canceled by the concurrent treatment of a ghrelin receptor antagonist. Rikkunshito administration did not decrease the degree of loss of body weight or food intake reduction in either ghrelin-deficient mice or growth hormone secretagogue receptor-deficient mice. Our results indicate that RKT administration exerts protective effects on pulmonary cachexia by ameliorating skeletal muscle wasting and food intake reduction as mediated by the ghrelin system and, thus, highlight RKT as a potential therapeutic agent for the management of lung fibrosis.

  19. Analysis of Statistical Methods Currently used in Toxicology Journals

    OpenAIRE

    Na, Jihye; Yang, Hyeri; Bae, SeungJin; Lim, Kyung-Min

    2014-01-01

    Statistical methods are frequently used in toxicology, yet it is not clear whether the methods employed by the studies are used consistently and conducted based on sound statistical grounds. The purpose of this paper is to describe statistical methods used in top toxicology journals. More specifically, we sampled 30 papers published in 2014 from Toxicology and Applied Pharmacology, Archives of Toxicology, and Toxicological Science and described methodologies used to provide descriptive and in...

  20. Difficulties in diagnosing Marfan syndrome using current FBN1 databases.

    Science.gov (United States)

    Groth, Kristian A; Gaustadnes, Mette; Thorsen, Kasper; Østergaard, John R; Jensen, Uffe Birk; Gravholt, Claus H; Andersen, Niels H

    2016-01-01

    The diagnostic criteria of Marfan syndrome (MFS) highlight the importance of a FBN1 mutation test in diagnosing MFS. As genetic sequencing becomes better, cheaper, and more accessible, the expected increase in the number of genetic tests will become evident, resulting in numerous genetic variants that need to be evaluated for disease-causing effects based on database information. The aim of this study was to evaluate genetic variants in four databases and review the relevant literature. We assessed background data on 23 common variants registered in ESP6500 and classified as causing MFS in the Human Gene Mutation Database (HGMD). We evaluated data in four variant databases (HGMD, UMD-FBN1, ClinVar, and UniProt) according to the diagnostic criteria for MFS and compared the results with the classification of each variant in the four databases. None of the 23 variants was clearly associated with MFS, even though all classifications in the databases stated otherwise. A genetic diagnosis of MFS cannot reliably be based on current variant databases because they contain incorrectly interpreted conclusions on variants. Variants must be evaluated by time-consuming review of the background material in the databases and by combining these data with expert knowledge on MFS. This is a major problem because we expect even more genetic test results in the near future as a result of the reduced cost and process time for next-generation sequencing.Genet Med 18 1, 98-102.

  1. Evaluating the ameliorative potential of plant flavonoids and their nanocomposites in bleomycin induced idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Srabani Kar

    2016-07-01

    Full Text Available Introduction: Pulmonary Fibrosis can severely disrupt lung function. The cause of Idiopathic Pulmonary Fibrosis (IPF is still unclear. The treatment currently available for IPF provides minimal benefits. Bleomycin is used in research to induce experimental pulmonary fibrosis in animals. Plant flavonoids such as fisetin and curcumin are known for their anti-inflammatory properties. The aim was to demonstrate the path of physiological changes in bleomycin induced IPF and to further evaluate the reversal and ameliorative potentials of some plant flavonoids and their nanocomposites. Bleomycin administration is known to damage the lung epithelial cells resulting in lower cell numbers. Results: Our colony forming assay in BALF also demonstrated a reduction (1.65 fold in colony-forming unit after bleomycin administration. The number of colonies increased upon treatment with fisetin(1.20 fold and curcumin (1.13 fold respectively. MTT proliferation assay demonstrated a significant increase in the number of viable cells upon treatment with curcumin (1.42 fold and fisetin (1.74 fold respectively, in the lung. The NBT assay demonstrated a significant effect of curcumin in BALF, lung and peripheral blood. A significant effect of fisetin was observed in BALF and peripheral blood. Conclusion: These findings were also supported by the histological analyses of the lung samples. Curcumin showed highestpotential for the treatment of IPF and fisetin showed its ameliorative effect. [Biomed Res Ther 2016; 3(7.000: 707-722

  2. Oral calorie supplements for cystic fibrosis.

    Science.gov (United States)

    Smyth, Rosalind L; Rayner, Oli

    2017-05-04

    Poor nutrition occurs frequently in people with cystic fibrosis and is associated with other adverse outcomes. Oral calorie supplements are used to increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns they may reduce the amount of food eaten and not improve overall energy intake. This is an update of a previously published review. To establish whether in people with cystic fibrosis, oral calorie supplements: increase daily calorie intake; and improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess adverse effects associated with using these supplements. We searched the Cochrane Cystic Fibrosis Trials Register comprising references from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We contacted companies marketing oral calorie supplements.Last search: 18 October 2016. Randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in people with cystic fibrosis. We independently selected the included trials, assessed risk of bias and extracted data. We contacted the authors of included trials and obtained additional information for two trials. We identified 21 trials and included three, reporting results from 131 participants lasting between three months and one year. Two trials compared supplements to additional nutritional advice and one to no intervention. Two of the included trials recruited only children. In one trial the risk of bias was low across all domains, in a second trial the risk of bias was largely unclear and in the third mainly low. Blinding of participants was unclear in two of the trials. Also, in one trial the clinical condition of groups appeared to be unevenly balanced at baseline and in another trial there were

  3. Hepatosplenic volumetric assessment at MDCT for staging liver fibrosis.

    Science.gov (United States)

    Pickhardt, Perry J; Malecki, Kyle; Hunt, Oliver F; Beaumont, Claire; Kloke, John; Ziemlewicz, Timothy J; Lubner, Meghan G

    2017-07-01

    To investigate hepatosplenic volumetry at MDCT for non-invasive prediction of hepatic fibrosis. Hepatosplenic volume analysis in 624 patients (mean age, 48.8 years; 311 M/313 F) at MDCT was performed using dedicated software and compared against pathological fibrosis stage (F0 = 374; F1 = 48; F2 = 40; F3 = 65; F4 = 97). The liver segmental volume ratio (LSVR) was defined by Couinaud segments I-III over segments IV-VIII. All pre-cirrhotic fibrosis stages (METAVIR F1-F3) were based on liver biopsy within 1 year of MDCT. LSVR and total splenic volumes increased with stage of fibrosis, with mean(±SD) values of: F0: 0.26 ± 0.06 and 215.1 ± 88.5 mm(3); F1: 0.25 ± 0.08 and 294.8 ± 153.4 mm(3); F2: 0.331 ± 0.12 and 291.6 ± 197.1 mm(3); F3: 0.39 ± 0.15 and 509.6 ± 402.6 mm(3); F4: 0.56 ± 0.30 and 790.7 ± 450.3 mm(3), respectively. Total hepatic volumes showed poor discrimination (F0: 1674 ± 320 mm(3); F4: 1631 ± 691 mm(3)). For discriminating advanced fibrosis (≥F3), the ROC AUC values for LSVR, total liver volume, splenic volume and LSVR/spleen combined were 0.863, 0.506, 0.890 and 0.947, respectively. Relative changes in segmental liver volumes and total splenic volume allow for non-invasive staging of hepatic fibrosis, whereas total liver volume is a poor predictor. Unlike liver biopsy or elastography, these CT volumetric biomarkers can be obtained retrospectively on routine scans obtained for other indications. • Regional changes in hepatic volume (LSVR) correlate well with degree of fibrosis. • Total liver volume is a very poor predictor of underlying fibrosis. • Total splenic volume is associated with the degree of hepatic fibrosis. • Hepatosplenic volume assessment is comparable to elastography for staging fibrosis. • Unlike elastography, volumetric analysis can be performed retrospectively.

  4. Expression of integrin in hepatic fibrosis and intervention of resveratrol

    Institute of Scientific and Technical Information of China (English)

    Jianye WU; Chuanyong GUO; Jun LIU; Xuanfu XUAN

    2009-01-01

    The aim of this study was to explore the expression of integrin-β1 in different stages of hepatic fibrosis and intervention of resveratrol as well as the way by which integrin-β1 promoted hepatic fibrosis. Hepatic fibrosis models of male Sprague Dawley (SD) rats were created and intragastric administration of resveratrol was given in low (40 mg/kg), middle (120mg/kg) and high (200 mg/kg) dose groups. The expression of integrin-β1, transforming growth factor-β (TGF-β) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in different stages of hepatic fibrosis was detected by using RT-PCR. The expression of hexadecenoic acid (HA) and precollagen Ⅲ (pc Ⅲ) was assayed by radioimmunoassay. The expression of integrin-β1, TGF-β and TIMP-1 was determined in each group. Liver function and pathological sections of each group in different stages of hepatic fibrosis was tested to judge the therapeutic efficacy of resveratrol at different doses. The expression of integrin-β1 in normal control group was low and steady and was not increased with the development of hepatic fibrosis, but it was increased in other groups. The expression levels of integrin-β1 in the model control group (0.878±0.03, P 0.05). The expression levels of integrin-β1 and TGF-β in middle dose group and high dose group were higher than other groups (P<0.01). The expression levels of integrin-β1 and TGF-β in model control group and low dose group were lower than the normal control group (P < 0.01). The expression levels of TIMP-1 in the model control and low dose groups were higher than the other groups (P < 0.01). The expression levels of TIMP-1 in the middle dose group and the high dose group were lower than the normal control group (P<0.01). The expression of integrin-β1 existed in all stages of hepatic fibrosis of SD rats, and it was increased with the development of hepatic fibrosis. The expression of TGF-β and TIMP-1 was consistent with that ofintegrin-β1 in different stages of

  5. Relevance of activated hepatic stellate cells in predicting the development of pediatric liver allograft fibrosis.

    Science.gov (United States)

    Venturi, Carla; Reding, Raymond; Quinones, Jorge Abarca; Sokal, Etienne; Rahier, Jacques; Bueno, Javier; Sempoux, Christine

    2016-06-01

    Activated hepatic stellate cells (HSCs) are the main collagen-producing cells in liver fibrogenesis. With the purpose of analyzing their presence and relevance in predicting liver allograft fibrosis development, 162 liver biopsies of 54 pediatric liver transplantation (LT) recipients were assessed at 6 months, 3 years, and 7 years after LT. The proportion of activated HSCs, identified by α-smooth muscle actin (ASMA) immunostaining, and the amount of fibrosis, identified by picrosirius red (PSR%) staining, were determined by computer-based morphometric analysis. Fibrosis was also staged by using the semiquantitative liver allograft fibrosis score (LAFSc), specifically designed to score fibrosis in the pediatric LT population. Liver allograft fibrosis displayed progression over time by PSR% (P ASMA expression decreased in the long term, with inverse evolution with respect to fibrosis (P ASMA-positive HSCs area ≥ 8% at 6 months (n = 20) developed a higher fibrosis proportion compared to those with ASMA-positive HSCs area ≤ 8% (n = 34) at the same period of time and in the long term (P = 0.03 and P ASMA expression ≥ 8% at 6 months was found to be an independent risk factor for 7-year fibrosis development by PSR% (r(2) = 0.5; P ASMA expression ≥ 8% at 3 years showed an association with the development of fibrosis at 7 years (P = 0.02). In conclusion, there is a high proportion of activated HSCs in pediatric LT recipients. ASMA ≥ 8% at 6 months seems to be a risk factor for early and longterm fibrosis development. In addition, activated HSCs showed inverse evolution with respect to fibrosis in the long term. Liver Transplantation 22 822-829 2016 AASLD.

  6. Magnetic Field Due to a Finite Length Current-Carrying Wire Using the Concept of Displacement Current

    Science.gov (United States)

    Buschauer, Robert

    2014-01-01

    In undergraduate E&M courses the magnetic field due to a finite length, current-carrying wire can be calculated using the Biot-Savart law. However, to the author's knowledge, no textbook presents the calculation of this field using the Ampere-Maxwell law: ?B [multiplied by] dl = µ[subscript 0] (I + e[subscript 0] dF/dt) [multiplied by] 1

  7. Liver Fibrosis and Altered Matrix Synthesis

    Directory of Open Access Journals (Sweden)

    Katrin Neubauer

    2001-01-01

    Full Text Available Liver fibrosis represents the uniform response of liver to toxic, infectious or metabolic agents. The process leading to liver fibrosis resembles the process of wound healing, including the three phases following tissue injury: inflammation, synthesis of collagenous and noncollagenous extracellular matrix components, and tissue remodelling (scar formation. While a single liver tissue injury can be followed by an almost complete restitution ad integrum, the persistence of the original damaging noxa results in tissue damage. During the establishment of liver fibrosis, the basement membrane components collagen type IV, entactin and laminin increase and form a basement membrane-like structure within the space of Disse. The number of endothelial fenestrae of the sinusoids decreases. These changes of the sinusoids are called 'capillarization' because the altered structure of the sinusoids resembles that of capillaries. At the cellular level, origin of liver fibrogenesis is initiated by the damage of hepatocytes, resulting in the recruitment of inflammatory cells and platelets, and activation of Kupffer cells, with subsequent release of cytokines and growth factors. The hepatic stellate cells seem to be the primary target cells for these inflammatory stimuli, because during fibrogenesis, they undergo an activation process to a myofibroblast-like cell, which represents the major matrix-producing cell. Based on this pathophysiological mechanism, therapeutic methods are developed to inhibit matrix synthesis or stimulate matrix degradation. A number of substances are currently being tested that either neutralize fibrogenic stimuli and prevent the activation of hepatic stellate cells, or directly modulate the matrix metabolism. However, until now, the elimination of the hepatotoxins has been the sole therapeutic concept available for the treatment of liver fibrogenesis in humans.

  8. Current Procedures Used To Evaluate Teaching in Schools of Pharmacy.

    Science.gov (United States)

    Barnett, Candace W.; Matthews, Hewitt W.

    1998-01-01

    A survey of 72 pharmacy schools investigated methods of evaluating teaching, including use of student evaluations for both undergraduate and clinical teaching, peer evaluation, evaluation instruments, and use of the information for tenure/promotion decisions, faculty development activities, and determination of merit salary increases. Results are…

  9. Treatment and education reduce the severity of schistosomiasis periportal fibrosis

    Directory of Open Access Journals (Sweden)

    Paula Carolina Valenca Silva

    2013-07-01

    Full Text Available Introduction This study evaluates the factors associated with the development of severe periportal fibrosis in patients with Schistosoma mansoni. Methods A cross-sectional study was conducted from April to December 2012 involving 178 patients infected with S. mansoni who were treated in the Hospital das Clínicas of Pernambuco, Brazil. Information regarding risk factors was obtained using a questionnaire. Based on the patients' epidemiological history, clinical examination, and upper abdomen ultrasound evaluation, patients were divided into 2 groups: 137 with evidence of severe periportal fibrosis and 41 patients without fibrosis or with mild or moderate periportal fibrosis. Univariate and multivariate analyses were conducted using EpiInfo software version 3.5.5. Results Illiterate individuals (30.1% and patients who had more frequent contact with contaminated water in towns in the Zona da Mata of Pernambuco (33.2% were at greater risk for severe periportal fibrosis. Based on multivariate analysis, it was determined that an education level of up to 11 years of study and specific prior treatment for schistosomiasis were preventive factors for severe periportal fibrosis. Conclusions The prevailing sites of the severe forms of periportal fibrosis are still within the Zona da Mata of Pernambuco, although there has been an expansion to urban areas and the state coast. Specific treatment and an increased level of education were identified as protective factors, indicating the need for implementing social, sanitary, and health education interventions aimed at schistosomiasis to combat the risk factors for this major public health problem.

  10. Nephrogenic systemic fibrosis: epidemiology update

    DEFF Research Database (Denmark)

    Marckmann, P.

    2008-01-01

    Purpose of review The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. Recent findings Epidemiological and histochemical studies demonstrated that gadoli......Purpose of review The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. Recent findings Epidemiological and histochemical studies demonstrated...

  11. Transient elastography for liver fibrosis diagnosis

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Christensen, Peer Brehm; Weis, Nina

    2009-01-01

    fibrosis. Most of the studies have been conducted on patients with chronic hepatitis but a few studies have also covered fibrosis and cirrhosis due to other etiologies, and they also demonstrate the high sensitivity and specificity. Transient elastography for assessment of fibrosis may turn out...

  12. Cystic Fibrosis (CF): Chloride Sweat Test

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Cystic Fibrosis (CF) Chloride Sweat Test KidsHealth > For Parents > Cystic Fibrosis (CF) Chloride Sweat Test Print A A A ... It Is A chloride sweat test helps diagnose cystic fibrosis (CF) , an inherited disorder that makes kids sick ...

  13. What's it Like to Have Cystic Fibrosis?

    Science.gov (United States)

    ... Emergency Room? What Happens in the Operating Room? Cystic Fibrosis KidsHealth > For Kids > Cystic Fibrosis Print A A A What's in this article? ... with a condition she's known all her life — cystic fibrosis (say: SIS-tik fi-BRO-sus). Her parents ...

  14. Analysis of Statistical Methods Currently used in Toxicology Journals.

    Science.gov (United States)

    Na, Jihye; Yang, Hyeri; Bae, SeungJin; Lim, Kyung-Min

    2014-09-01

    Statistical methods are frequently used in toxicology, yet it is not clear whether the methods employed by the studies are used consistently and conducted based on sound statistical grounds. The purpose of this paper is to describe statistical methods used in top toxicology journals. More specifically, we sampled 30 papers published in 2014 from Toxicology and Applied Pharmacology, Archives of Toxicology, and Toxicological Science and described methodologies used to provide descriptive and inferential statistics. One hundred thirteen endpoints were observed in those 30 papers, and most studies had sample size less than 10, with the median and the mode being 6 and 3 & 6, respectively. Mean (105/113, 93%) was dominantly used to measure central tendency, and standard error of the mean (64/113, 57%) and standard deviation (39/113, 34%) were used to measure dispersion, while few studies provide justifications regarding why the methods being selected. Inferential statistics were frequently conducted (93/113, 82%), with one-way ANOVA being most popular (52/93, 56%), yet few studies conducted either normality or equal variance test. These results suggest that more consistent and appropriate use of statistical method is necessary which may enhance the role of toxicology in public health.

  15. Approach for Wide Use of Diagnostic Method for XLPE Cables Using Harmonics in AC Loss Current

    Science.gov (United States)

    Tsujimoto, Tomiyuki; Nakade, Masahiko; Yagi, Yukihiro; Ishii, Noboru

    Water tree is one of the degradation aspects of XLPE cables used for under-ground distribution or transmission lines. We have developed the loss current method using 3rd harmonic in AC loss current for cable diagnosis. Harmonic components in loss current arise as a result of the non-linear voltage-current characteristics of water trees. We confirmed that the 3rd harmonic in AC loss current had good correlation with water tree growth and break down strength. After that, we have applied this method to the actual 66kV XLPE cable lines. Up to now, the number of the application results is more than 130 lines. In case of cable lines terminated at gas-insulated switchgear (GIS), we have to remove the lightning arrestor (LA) and the potential transformer (PT) out of the test circuit. The reason is that we are afraid that each of LA and PT disturbs the degradation signal from cable lines. It takes extra time (1 or 2 days) and costs more to remove LA and PT in GIS out of a circuit. In order to achieve easy and reasonable diagnosis, we have developed a new method for cable lines terminated at GIS, by utilizing a technique, which enables to reduce signal of LA and PT from disturbed signal of cable lines. We confirmed the effect of the new method by experiments with actual cables.

  16. Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM) Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4) Induced Hepatic Fibrosis in Mice

    Science.gov (United States)

    Chow, Leola N.; Schreiner, Petra; Ng, Betina Y. Y.; Lo, Bernard; Hughes, Michael R.; Scott, R. Wilder; Gusti, Vionarica; Lecour, Samantha; Simonson, Eric; Manisali, Irina; Barta, Ingrid; McNagny, Kelly M.; Crawford, Jason; Webb, Murray; Underhill, T. Michael

    2016-01-01

    Modulation of chemokine CXCL12 and its receptor CXCR4 has been implicated in attenuation of bleomycin (BLM)-induced pulmonary fibrosis and carbon tetrachloride (CCl4)-induced hepatic injury. In pulmonary fibrosis, published reports suggest that collagen production in the injured lung is derived from fibrocytes recruited from the circulation in response to release of pulmonary CXCL12. Conversely, in hepatic fibrosis, resident hepatic stellate cells (HSC), the key cell type in progression of fibrosis, upregulate CXCR4 expression in response to activation. Further, CXCL12 induces HSC proliferation and subsequent production of collagen I. In the current study, we evaluated AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 in alleviating BLM-induced pulmonary and CCl4-induced hepatic fibrosis in mice. Similar to other CXCR4 antagonists, treatment with AMD070 significantly increased leukocyte mobilization. However, in these two models of fibrosis, AMD070 had a negligible impact on extracellular matrix deposition. Interestingly, our results indicated that CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage. Together, these findings indicate that the CXCL12-CXCR4 signaling axis is not an effective target for reducing fibrosis. PMID:26998906

  17. A comparison of methods currently used in inclusive design.

    Science.gov (United States)

    Goodman-Deane, Joy; Ward, James; Hosking, Ian; Clarkson, P John

    2014-07-01

    Inclusive design has unique challenges because it aims to improve usability for a wide range of users. This typically includes people with lower levels of ability, as well as mainstream users. This paper examines the effectiveness of two methods that are used in inclusive design: user trials and exclusion calculations (an inclusive design inspection method). A study examined three autoinjectors using both methods (n=30 for the user trials). The usability issues identified by each method are compared and the effectiveness of the methods is discussed. The study found that each method identified different kinds of issues, all of which are important for inclusive design. We therefore conclude that a combination of methods should be used in inclusive design rather than relying on a single method. Recommendations are also given for how the individual methods can be used more effectively in this context.

  18. Medical Applications for 3D Printing: Current and Projected Uses

    OpenAIRE

    Ventola, C. Lee

    2014-01-01

    3D printing is expected to revolutionize health care through uses in tissue and organ fabrication; creation of customized prosthetics, implants, and anatomical models; and pharmaceutical research regarding drug dosage forms, delivery, and discovery.

  19. Medical Applications for 3D Printing: Current and Projected Uses.

    Science.gov (United States)

    Ventola, C Lee

    2014-10-01

    3D printing is expected to revolutionize health care through uses in tissue and organ fabrication; creation of customized prosthetics, implants, and anatomical models; and pharmaceutical research regarding drug dosage forms, delivery, and discovery.

  20. The immediate effects of lidocaine iontophoresis using interferential current on pressure sense threshold and tactile sensation.

    Science.gov (United States)

    Yoosefinejad, Amin Kordi; Motealleh, Alireza; Abbasnia, Keramatollah

    2016-01-01

    Iontophoresis is the noninvasive delivery of ions using direct current. The direct current has some disadvantages such as skin burning. Interferential current is a kind of alternating current without limitations of direct current; so the purpose of this study is to investigate and compare the effects of lidocaine, interferential current and lidocaine iontophoresis using interferential current. 30 healthy women aged 20-24 years participated in this randomized clinical trial study. Pressure, tactile and pain thresholds were evaluated before and after the application of treatment methods. Pressure, tactile and pain sensitivity increased significantly after the application of lidocaine alone (p < 0.005) and lidocaine iontophoresis using interferential current (p < 0.0001). Lidocaine iontophoresis using interferential current can increase perception threshold of pain, tactile stimulus and pressure sense more significantly than lidocaine and interferential current alone.

  1. Current possibilities and prospects of using fungicides in forestry

    Directory of Open Access Journals (Sweden)

    Okorski Adam

    2015-06-01

    Full Text Available The possibility of using chemicals in European forestry is extremely limited due to the binding legal regulations and specific conditions concerning the market of plant protection products. This is reflected in the limited availability of active fungicides in forestry. Due to this limitation, practitioners using fungicides in forest nurseries and forest cultivation must have substantial knowledge of the biology of pathogens to ensure satisfactorily effective protection.

  2. The Preventive Effect of Atorvastatin on Paraquat-Induced Pulmonary Fibrosis in the Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Khodayar

    2014-12-01

    Full Text Available Purpose: Pulmonary fibrosis is a potentially lethal inflammatory disease and there has been no effective medication for this progressive disease up to now. As a model, different therapeutic approaches have been applied for paraquat-induced pulmonary injury and fibrosis. Atorvastatin besides cholesterol-lowering effects possesses anti-inflammatory and anti-oxidant properties. The current study was designed to investigate the preventive anti-fibrotic effects of atorvastatin on paraquat-induced pulmonary fibrosis in rats. Methods: The rats were randomly divided into five experimental groups. Group I, control group (saline, group II received a single oral dose of 20 mg/kg paraquat with no treatment and III, IV and V groups received atorvastatin at the doses of 10, 20, and 40 mg/kg/day orally one week before and three weeks after paraquat administration, respectively. The rats were sacrificed 21 days after paraquat. Lung hydroxyproline and serum levels of malondialdehyde (MDA were determined and lung indices and semi-quantitative histopathological changes were evaluated. Results: Paraquat could significantly increase the serum MDA and lung hydroxyproline levels. Elevated content of tissue hydroxyproline and serum levels of malondialdehyde induced by paraquat, attenuated by atorvastatin at the doses of 10, 20 and 40 mg/kg. Furthermore, histopathological findings and the amount of lung indices showed the beneficial preventive role of atorvastatin in rat pulmonary fibrosis induced by paraquat. Conclusion: In conclusion, the present data show that atorvastatin alleviate the toxic effects of paraquat under the experimental circumstances and may be a useful agent in cases who are in contact or poisoned with paraquat.

  3. Expression of leptin and leptin receptor during the development of liver fibrosis and cirrhosis.

    Science.gov (United States)

    Otte, C; Otte, J-M; Strodthoff, D; Bornstein, S R; Fölsch, U R; Mönig, H; Kloehn, S

    2004-01-01

    Leptin is involved in the regulation of food intake and is mainly secreted by adipocytes. Major secretagogues are cytokines such as TNF-alpha or IL-1. Leptin in turn upregulates inflammatory immune responses. Elevated leptin serum levels have been detected in patients with liver cirrhosis, a disease frequently associated with elevated levels of circulating cytokines as well as hypermetabolism and altered body weight. Recently, leptin has been detected in activated hepatic stellate cells in vitro and an involvement of leptin in liver fibrogenisis has been suggested. The current study was designed to further clarify the role of leptin in liver disease by characterizing leptin and leptin receptor expression in the development and onset of experimental liver fibrosis. Liver fibrosis and cirrhosis was induced in rats by use of phenobarbitone and increasing doses of CCl (4). Leptin and leptin receptor mRNA expression was determined by semiquantitative RT-PCR, protein expression by Western blot analysis and localization of leptin and its receptor by immunohistochemistry. Normal liver tissue does not express leptin, but leptin receptor mRNA. Increasing levels of leptin mRNA were detected in fibrotic and cirrhotic livers correlated to the degree of fibrosis. Leptin receptor mRNA expression was not significantly altered in damaged livers. Increasing levels of leptin were detected in fibrotic and cirrhotic livers, whereas protein expression of the receptor remained unchanged. Throughout different stages of liver fibrosis, leptin immunoreactivity was localized in activated hepatic stellate cells only, whereas immunoreactivity for the receptor was mainly seen on hepatocytes. In conclusion, leptin is expressed at increasing levels in activated hepatic stellate cells in vivo, which may therefore be a source of increased leptin tissue and serum levels contributing to the pathophysiology and morphological changes of chronic liver disease.

  4. Probiotic supplementation in children with cystic fibrosis-a systematic review.

    Science.gov (United States)

    Ananthan, Anitha; Balasubramanian, Haribalakrishna; Rao, Shripada; Patole, Sanjay

    2016-10-01

    Probiotics may benefit in cystic fibrosis (CF) as gut dysbiosis is associated with gastrointestinal symptoms and exacerbation of respiratory symptoms in CF. We conducted a systematic review of randomized controlled trials (RCTs) and non-RCTs of probiotic supplementation in children with CF, using the Cochrane methodology, preferred reporting items for systematic reviews (PRISMA) statement, and meta-analysis of observational studies in epidemiology (MOOSE) guidelines. Primary outcomes were pulmonary exacerbations, duration of hospitalization and antibiotics, and all-cause mortality. Secondary outcomes included gastrointestinal symptoms, markers of gut inflammation, and intestinal microbial balance. A total of nine studies (RCTs, 6, non-RCTs, 3; N = 275) with some methodological weaknesses were included in the review. The pooled estimate showed significant reduction in the rate of pulmonary exacerbation (fixed effects model, two parallel group RCTs and one cross-over trial: relative risk (RR) 0.25, (95 % confidence interval (95 % CI) 0.15,0.41); p Bacteroides in one RCT, one non-RCT). Limited low-quality evidence exists on the effects of probiotics in children with CF. Well-designed adequately powered RCTs assessing clinically meaningful outcomes are required to study this important issue. • Gut dysbiosis is frequent in children with cystic fibrosis due to frequent exposure to pathogens and antibiotics. • Probiotics decrease gut dysbiosis and improve gut maturity and function. What is New: • This comprehensive systematic review shows that current evidence on the safety and efficacy of probiotics in children with cystic fibrosis is limited and of low quality. • Well-designed and adequately powered trials assessing clinically important outcomes are required considering the health burden of cystic fibrosis and the potential benefits of probiotics.

  5. Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis.

    Science.gov (United States)

    Stribos, Elisabeth G D; Luangmonkong, Theerut; Leliveld, Anna M; de Jong, Igle J; van Son, Willem J; Hillebrands, Jan-Luuk; Seelen, Marc A; van Goor, Harry; Olinga, Peter; Mutsaers, Henricus A M

    2016-04-01

    Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue obtained from tumor nephrectomies and cultured up to 96 hours. Morphology, cell viability, and metabolic functionality (ie, uridine 5'-diphospho-glucuronosyltransferase and transporter activity) were determined to assess the integrity of PCKSs. Furthermore, inflammatory and fibrosis-related gene expressions were characterized. Finally, to validate the model, renal fibrogenesis was induced using transforming growth factor β1 (TGF-β1). Preparation of PCKSs induced an inflammatory tissue response, whereas long-term incubation (96 hours) induced fibrogenesis as shown by an increased expression of collagen type 1A1 (COL1A1) and fibronectin 1 (FN1). Importantly, PCKSs remained functional for more than 48 hours as evidenced by active glucuronidation and phenolsulfonphthalein uptake. In addition, cellular diversity appeared to be maintained, yet we observed a clear loss of nephrin messenger RNA levels suggesting that our model might not be suitable to study the role of podocytes in renal pathology. Moreover, TGF-β1 exposure augmented fibrosis, as illustrated by an increased expression of multiple fibrosis markers including COL1A1, FN1, and α-smooth muscle actin. In conclusion, PCKSs maintain their renal phenotype during culture and appear to be a promising model to investigate renal diseases, for example, renal fibrosis. Moreover, the human origin of PCKSs makes this model very suitable for translational research.

  6. The use of high resolution computerized tomography (HRCT) of the chest in evaluating the effect of tobramycin solution for inhalation in cystic fibrosis lung disease.

    Science.gov (United States)

    Nasr, Samya Z; Sakmar, Ermelinda; Christodoulou, Emmanuel; Eckhardt, Boris P; Streetman, Daniel S; Strouse, Peter J

    2010-05-01

    To compare the usefulness of HRCT of the chest versus spirometric measures (PFTs) in evaluating the effect of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF). Thirty-two CF patients with mostly mild lung disease age > or = 6 years, were enrolled in a double-blind, placebo-controlled pilot study. Patients were chronically colonized with Pseudomonas aeruginosa for at least 6 months prior to and at enrollment. If patients were on TSI, they were taken off for at least 3 months prior to enrollment. Duration was 6 months; 31 subjects completed the study. HRCT and PFTs were evaluated at baseline, after 28 days of treatment and at the end of the study. Study medication was administered as 5 ml nebulized treatment twice a day for 28 days followed by 28 days off (one cycle). Study consisted of three cycles. Two radiologists scored all films using a validated system. A total HRCT score consists of the sum of subscores: linear opacities, hyperinflation, nodular opacities, peribronchial thickening, mucous plugging, and bronchiectasis; each subscore could range from 0 to 80, with potential total scores varying from 0 to 480. The percent of the maximum possible HRCT score was then calculated and used for all comparisons. Using two tailed paired t-test, the percent maximum HRCT score decreased by 1.4 +/- 2.6% (mean +/- SD) (P = 0.049) and 0.3 +/- 2.8% (P = 0.63) for the TSI group and decreased by 0.1 +/- 1.5% (P = 0.74) and increased by 0.6 +/- 1.8% (P = 0.23) for the placebo group between visits 1 and 2, and visits 1 and 3, respectively. The data were then analyzed using a mixed model utilizing changes in scores over the durations of the study for each group. The change of HRCT score for the TSI group was -0.24/day (P = 0.02) and -0.03/day (P = 0.22), and for the control group the change was -0.01 (P = 0.93) and 0.02 (P = 0.29) between visits 1 and 2, and visits 1 and 3 respectively. FEF(25-75)% and FEV(1)% changes were not statistically significant using both

  7. Botulinum toxins: Pharmacology and its current therapeutic evidence for use

    Directory of Open Access Journals (Sweden)

    Muthane U

    2003-10-01

    Full Text Available Botulinum toxins are, as a group, among the most potent neuromuscular toxins known, yet they are clinically useful in the management of conditions associated with muscular and glandular over-activity. Botulinum toxins act by preventing release of acetylcholine into the neuromuscular junction. While botulinum toxin type A is commonly available, different manufacturers produce specific products, which are not directly interchangeable and should not be considered as generically equivalent formulations. Type B is also available in the market. Each formulation of botulinum toxin is unique with distinct dosing, efficacy and safety profiles for each use to which it is applied. Botulinum toxin type A is the treatment of choice based on its depth of evidence in dystonias and most other conditions. Botulinum toxin type A is established as useful in the management of spasticity, tremors, headache prophylaxis and several other neurological conditions. Active research is underway to determine the parameters for which the type B toxin can be used in these conditions, as covered in this review. Botulinum toxin use has spread to several fields of medicine.

  8. Gene delivery in peritoneal dialysis related peritoneal fibrosis research

    Institute of Scientific and Technical Information of China (English)

    LI Xie-jia; SUN Lin; XIAO Li; LIU Fu-you

    2012-01-01

    Objective To summarize the development of gene delivery vectors in peritoneal fibrosis research and discuss the feasibility and superiority of lentiviral vectors.Data sources The data in this article were collected from PubMed database with relevant English articles published from 1995 to 2011.Study selection Articles regarding the gene therapy in peritoneal fibrosis research using non-viral vectors,adenoviral vectors,ratroviral vectors,and lentiviral vectors were selected.Data were mainly extracted from 60 articles,which are listed in the reference section of this review.Results Non-viral vector-mediated gene delivery (including naked DNA for ex vivo,oligonucleotides,ultrasoundcontrast agent mediated naked gene delivery,etc.) and viral vector-mediated gene delivery (including adenovirus,helper-dependant adenovirus,and retrovirus vectors) have been successfully applied both in the mechanistic investigation and the potential prevention and treatment of peritoneal fibrosis.Conclusions Peritoneal fibrosis is a major complication of peritoneal dialysis (PD).Recently,the wide use of the gene delivery technique made it possible to access and further research peritoneal fibrosis.The use of lentiviral vector is expected to be widely used in PD research in the future due to its advantages in gene delivery.

  9. Results and current trends of nuclear methods used in agriculture

    Energy Technology Data Exchange (ETDEWEB)

    Horacek, P. (Ceskoslovenska Komise pro Atomovou Energii, Prague)

    1983-11-01

    The significance is evaluated of nuclear methods for agricultural research. The number of breeds induced by radiation mutations is increasing. The main importance of radiation mutation breeding consists in obtaining sources of the desired genetic properties for further hybridization. Radiostimulation is conducted with the aim of increasing yields. The irradiation of foods has not substantially increased worldwide. Very important is the irradiation of excrements and sludges which after such inactivation of pathogenic microorganisms may be used as humus-forming manure or as feed additives. In some countries the method is successfully being used of sexual sterilization for eradication of insect pests. The application of labelled compounds in the nutrition, physiology and protection of plants, farm animals and in food hygiene makes it possible to acquire new and accurate knowledge very quickly. Radioimmunoassay is a highly promising method in this respect. Labelling compounds with the stable /sup 15/N isotope is used for the research of nitrogen metabolism.

  10. Imprudent use of proton pump inhibitors in current practice

    Directory of Open Access Journals (Sweden)

    Manali Mangesh Mahajan

    2015-02-01

    Full Text Available In a developing country like India, where over 500 branded formulations of PPI are available, probability of misuse and abuse increases exponentially. Although a safe and very effective class of pharmaceutical agent, PPIs should be used only when there is documented evidence of a GI disorder that cannot be treated with an H2-receptor antagonist, and where a PPI use is clinically justified. Increased clinician awareness on appropriate PPI prescription will lead to better patient outcome at lower cost. [Int J Basic Clin Pharmacol 2015; 4(1.000: 184-185

  11. Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis.

    Science.gov (United States)

    Ippolito, Danielle L; AbdulHameed, Mohamed Diwan M; Tawa, Gregory J; Baer, Christine E; Permenter, Matthew G; McDyre, Bonna C; Dennis, William E; Boyle, Molly H; Hobbs, Cheryl A; Streicker, Michael A; Snowden, Bobbi S; Lewis, John A; Wallqvist, Anders; Stallings, Jonathan D

    2016-01-01

    Toxic industrial chemicals induce liver injury, which is difficult to diagnose without invasive procedures. Identifying indicators of end organ injury can complement exposure-based assays and improve predictive power. A multiplexed approach was used to experimentally evaluate a panel of 67 genes predicted to be associated with the fibrosis pathology by computationally mining DrugMatrix, a publicly available repository of gene microarray data. Five-day oral gavage studies in male Sprague Dawley rats dosed with varying concentrations of 3 fibrogenic compounds (allyl alcohol, carbon tetrachloride, and 4,4'-methylenedianiline) and 2 nonfibrogenic compounds (bromobenzene and dexamethasone) were conducted. Fibrosis was definitively diagnosed by histopathology. The 67-plex gene panel accurately diagnosed fibrosis in both microarray and multiplexed-gene expression assays. Necrosis and inflammatory infiltration were comorbid with fibrosis. ANOVA with contrasts identified that 51 of the 67 predicted genes were significantly associated with the fibrosis phenotype, with 24 of these specific to fibrosis alone. The protein product of the gene most strongly correlated with the fibrosis phenotype PCOLCE (Procollagen C-Endopeptidase Enhancer) was dose-dependently elevated in plasma from animals administered fibrogenic chemicals (P < .05). Semiquantitative global mass spectrometry analysis of the plasma identified an additional 5 protein products of the gene panel which increased after fibrogenic toxicant administration: fibronectin, ceruloplasmin, vitronectin, insulin-like growth factor binding protein, and α2-macroglobulin. These results support the data mining approach for identifying gene and/or protein panels for assessing liver injury and may suggest bridging biomarkers for molecular mediators linked to histopathology.

  12. Using Current Magazines as a Resource for Teaching Culture.

    Science.gov (United States)

    Griffin, Robert J.

    1987-01-01

    A slide/tape program, composed of photographs taken from Spanish magazines and a recorded commentary, was used to teach students of Spanish about the culture of Spain. The program also provided students with incentive and direction for exploring a wide range of cultural information in Spanish magazines. (CB)

  13. Teaching the Scientific Method Using Current News Articles

    Science.gov (United States)

    Palmer, Laura K.; Mahan, Carolyn G.

    2013-01-01

    We describe a short (less than 50 minutes) activity using news articles from sources such as "Science Daily" to teach students the steps of the scientific method and the difference between primary and secondary literature sources. The flexibility in choosing news articles to examine allowed us to tailor the activity to the specific interests of…

  14. CURRENT TRENDS IN THE USE OF SOLAR ENERGY

    Directory of Open Access Journals (Sweden)

    Vanya Zhivkova

    2013-06-01

    Full Text Available Solar energy represents the amount of solar radiation per unit time on unit area. Solar energy is used to obtain thermal energy through solar, and electrical energy through exist for solar energy: passive and active. The utilization of solar energy is essential for the development of human civilization.

  15. Dynamic phase-control of a rising sun magnetron using modulated and continuous current

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Gutierrez, Sulmer, E-mail: sulmer.a.fernandez.gutierrez@intel.com [Intel Corporation, 2111 NE 25th Ave, Hillsboro, Oregon 97214 (United States); Browning, Jim [Department of Electrical and Computer Engineering, Boise State University, Boise, Idaho 83725 (United States); Lin, Ming-Chieh [Department of Electrical and Biomedical Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Smithe, David N. [Tech-X Corporation, 5621 Arapahoe Ave, Boulder, Colorado 80303 (United States); Watrous, Jack [Confluent Sciences, LLC, Albuquerque, New Mexico 87111 (United States)

    2016-01-28

    Phase-control of a magnetron is studied via simulation using a combination of a continuous current source and a modulated current source. The addressable, modulated current source is turned ON and OFF at the magnetron operating frequency in order to control the electron injection and the spoke phase. Prior simulation work using a 2D model of a Rising Sun magnetron showed that the use of 100% modulated current controlled the magnetron phase and allowed for dynamic phase control. In this work, the minimum fraction of modulated current source needed to achieve a phase control is studied. The current fractions (modulated versus continuous) were varied from 10% modulated current to 100% modulated current to study the effects on phase control. Dynamic phase-control, stability, and start up time of the device were studied for all these cases showing that with 10% modulated current and 90% continuous current, a phase shift of 180° can be achieved demonstrating dynamic phase control.

  16. A COMPARATIVE STUDY BETWEEN MANAGEMENT OF ORAL SUBMUCOUS FIBROSIS

    Directory of Open Access Journals (Sweden)

    Nidhi

    2014-09-01

    Full Text Available : BACKGROUND: Oral Submucous Fibrosis is a potentially premalignant disorder well known for its chronic and resistant nature. Currently available treatment with local injection of corticosteroids with Hyaluronidase is effective to some extent. The aim of the study was to evaluate whether the efficacy of the current treatment modality for submucous fibrosis can be improved by adding either oral lycopene or oral anti-oxidants along with local injection of steroids. METHODS: This study was conducted from July 2012 to August 2014 A total of 38 patients were included under this study with either grade 3 or 4 submucous fibrosis they were randomly divided in to 2 groups consisting 19 patients each Group 1 were given oral lycopene of dose 16mg/day along with once weekly intralesional injection of steroids and Hyaluronidase. Group 2 were given only once weekly intralesional injection of steroids and Hyaluronidase. Mouth opening recorded from baseline to 6 weeks. Cases were followed up for 6 months thereafter. RESULTS: There was significant increase in mouth opening in both the groups. The results were statistically significant between Group 1 and Group 2. Group 1 patients responded better than the other group and P value <0.001. CONCLUSION: Lycopene in combination with intralesional steroids and Hyaluronidase, is highly efficacious in improving the mouth opening and reducing other symptoms in patients with Oral Submucous Fibrosis.

  17. Angiogenesis Inhibition in Prostate Cancer: Current Uses and Future Promises

    Directory of Open Access Journals (Sweden)

    Jeanny B. Aragon-Ching

    2010-01-01

    Full Text Available Angiogenesis has been well recognized as a fundamental part of a multistep process in the evolution of cancer progression, invasion, and metastasis. Strategies for inhibiting angiogenesis have been one of the most robust fields of cancer investigation, focusing on the vascular endothelial growth factor (VEGF family and its receptors. There are numerous regulatory drug approvals to date for the use of these agents in treating a variety of solid tumors. While therapeutic efficacy has been established, challenges remain with regards to overcoming resistance and assessing response to antiangiogenic therapies. Prostate cancer is the most common noncutaneous malignancy among American men and angiogenesis plays a role in disease progression. The use of antiangiogenesis agents in prostate cancer has been promising and is hereby explored.

  18. Overview on the Current Antibiotic Containing Agents Used in Endodontics

    Science.gov (United States)

    Bansal, Ramta; Jain, Aditya

    2014-01-01

    Antibiotics are systemically and locally used extensively in endodontics. However, local antibiotic application mode is considered more effective than systemic administration. The local mode enables the dentist to target bacteria in every nook and corner of root canal system, which is otherwise beyond reach if targeted by instrumentation or conventional root canal treatment protocols. Therefore, they are an important adjunct to conventional treatment of root canal. The present study reviews the various antibiotic containing dental agents used in endodontics. A web-based research on MedLine was performed with terms Review Articles published in the last 10 year's dental journals in English for literature researching, extracting, and synthesizing data. Relevant articles were shortlisted. Important cross-reference articles were also reviewed. PMID:25210667

  19. Parachute drawing standards currently in use at Sandia National Laboratories

    Energy Technology Data Exchange (ETDEWEB)

    Ronquillo, K.L.

    1988-01-01

    A need exists in the parachute industry for a standard method of defining and guiding the formation of textile drawings. Textile drawings have their own unique problems associated with their development. Unlike mechanical parts, textiles have no mass in cross section. Therefore, a cross-sectioned view has no hash marks. Hidden views are not usually incorporated in textile drawings as they are easily confused with stitch formations. Side views of textile parts are depicted using only one line to show thickness. This report will address these and other unique drawing problems associated with the development of parachute drawings and will offer, as a base, standards to be used when developing these drawings. 21 figs.

  20. Overview on the current antibiotic containing agents used in endodontics.

    Science.gov (United States)

    Bansal, Ramta; Jain, Aditya

    2014-08-01

    Antibiotics are systemically and locally used extensively in endodontics. However, local antibiotic application mode is considered more effective than systemic administration. The local mode enables the dentist to target bacteria in every nook and corner of root canal system, which is otherwise beyond reach if targeted by instrumentation or conventional root canal treatment protocols. Therefore, they are an important adjunct to conventional treatment of root canal. The present study reviews the various antibiotic containing dental agents used in endodontics. A web-based research on MedLine was performed with terms Review Articles published in the last 10 year's dental journals in English for literature researching, extracting, and synthesizing data. Relevant articles were shortlisted. Important cross-reference articles were also reviewed.