WorldWideScience

Sample records for fibrosis patients revealed

  1. Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation.

    Science.gov (United States)

    Kim, Sang Hu; Clark, Shawn T; Surendra, Anuradha; Copeland, Julia K; Wang, Pauline W; Ammar, Ron; Collins, Cathy; Tullis, D Elizabeth; Nislow, Corey; Hwang, David M; Guttman, David S; Cowen, Leah E

    2015-11-01

    The microbiome shapes diverse facets of human biology and disease, with the importance of fungi only beginning to be appreciated. Microbial communities infiltrate diverse anatomical sites as with the respiratory tract of healthy humans and those with diseases such as cystic fibrosis, where chronic colonization and infection lead to clinical decline. Although fungi are frequently recovered from cystic fibrosis patient sputum samples and have been associated with deterioration of lung function, understanding of species and population dynamics remains in its infancy. Here, we coupled high-throughput sequencing of the ribosomal RNA internal transcribed spacer 1 (ITS1) with phenotypic and genotypic analyses of fungi from 89 sputum samples from 28 cystic fibrosis patients. Fungal communities defined by sequencing were concordant with those defined by culture-based analyses of 1,603 isolates from the same samples. Different patients harbored distinct fungal communities. There were detectable trends, however, including colonization with Candida and Aspergillus species, which was not perturbed by clinical exacerbation or treatment. We identified considerable inter- and intra-species phenotypic variation in traits important for host adaptation, including antifungal drug resistance and morphogenesis. While variation in drug resistance was largely between species, striking variation in morphogenesis emerged within Candida species. Filamentation was uncoupled from inducing cues in 28 Candida isolates recovered from six patients. The filamentous isolates were resistant to the filamentation-repressive effects of Pseudomonas aeruginosa, implicating inter-kingdom interactions as the selective force. Genome sequencing revealed that all but one of the filamentous isolates harbored mutations in the transcriptional repressor NRG1; such mutations were necessary and sufficient for the filamentous phenotype. Six independent nrg1 mutations arose in Candida isolates from different patients

  2. Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation.

    Directory of Open Access Journals (Sweden)

    Sang Hu Kim

    2015-11-01

    Full Text Available The microbiome shapes diverse facets of human biology and disease, with the importance of fungi only beginning to be appreciated. Microbial communities infiltrate diverse anatomical sites as with the respiratory tract of healthy humans and those with diseases such as cystic fibrosis, where chronic colonization and infection lead to clinical decline. Although fungi are frequently recovered from cystic fibrosis patient sputum samples and have been associated with deterioration of lung function, understanding of species and population dynamics remains in its infancy. Here, we coupled high-throughput sequencing of the ribosomal RNA internal transcribed spacer 1 (ITS1 with phenotypic and genotypic analyses of fungi from 89 sputum samples from 28 cystic fibrosis patients. Fungal communities defined by sequencing were concordant with those defined by culture-based analyses of 1,603 isolates from the same samples. Different patients harbored distinct fungal communities. There were detectable trends, however, including colonization with Candida and Aspergillus species, which was not perturbed by clinical exacerbation or treatment. We identified considerable inter- and intra-species phenotypic variation in traits important for host adaptation, including antifungal drug resistance and morphogenesis. While variation in drug resistance was largely between species, striking variation in morphogenesis emerged within Candida species. Filamentation was uncoupled from inducing cues in 28 Candida isolates recovered from six patients. The filamentous isolates were resistant to the filamentation-repressive effects of Pseudomonas aeruginosa, implicating inter-kingdom interactions as the selective force. Genome sequencing revealed that all but one of the filamentous isolates harbored mutations in the transcriptional repressor NRG1; such mutations were necessary and sufficient for the filamentous phenotype. Six independent nrg1 mutations arose in Candida isolates from

  3. Cohort Study of Airway Mycobiome in Adult Cystic Fibrosis Patients: Differences in Community Structure between Fungi and Bacteria Reveal Predominance of Transient Fungal Elements

    Science.gov (United States)

    Sauer-Heilborn, Annette; Welte, Tobias; Guzman, Carlos A.; Abraham, Wolf-Rainer; Höfle, Manfred G.

    2015-01-01

    The respiratory mycobiome is an important but understudied component of the human microbiota. Like bacteria, fungi can cause severe lung diseases, but their infection rates are much lower. This study compared the bacterial and fungal communities of sputum samples from a large cohort of 56 adult patients with cystic fibrosis (CF) during nonexacerbation periods and under continuous antibiotic treatment. Molecular fingerprinting based on single-strand conformation polymorphism (SSCP) analysis revealed fundamental differences between bacterial and fungal communities. Both groups of microorganisms were taxonomically classified by identification of gene sequences (16S rRNA and internal transcript spacer), and prevalences of single taxa were determined for the entire cohort. Major bacterial pathogens were frequently observed, whereas fungi of known pathogenicity in CF were detected only in low numbers. Fungal species richness increased without reaching a constant level (saturation), whereas bacterial richness showed saturation after 50 patients were analyzed. In contrast to bacteria, a large number of fungal species were observed together with high fluctuations over time and among patients. These findings demonstrated that the mycobiome was dominated by transient species, which strongly suggested that the main driving force was their presence in inhaled air rather than colonization. Considering the high exposure of human airways to fungal spores, we concluded that fungi have low colonization abilities in CF, and colonization by pathogenic fungal species may be considered a rare event. A comprehensive understanding of the conditions promoting fungal colonization may offer the opportunity to prevent colonization and substantially reduce or even eliminate fungus-related disease progression in CF. PMID:26135861

  4. Voice Disorder in Cystic Fibrosis Patients

    Science.gov (United States)

    Lourenço, Bruna Mendes; Costa, Kauê Machado; da Silva Filho, Manoel

    2014-01-01

    Cystic fibrosis is a common autosomal recessive disorder with drastic respiratory symptoms, including shortness of breath and chronic cough. While most of cystic fibrosis treatment is dedicated to mitigating the effects of respiratory dysfunction, the potential effects of this disease on vocal parameters have not been systematically studied. We hypothesized that cystic fibrosis patients, given their characteristic respiratory disorders, would also present dysphonic symptoms. Given that voice disorders can severely impair quality of life, the identification of a potential cystic fibrosis-related dysphonia could be of great value for the clinical evaluation and treatment of this disease. We tested our hypothesis by measuring vocal parameters, using both objective physical measures and the GRBAS subjective evaluation method, in male and female cystic fibrosis patients undergoing conventional treatment and compared them to age and sex matched controls. We found that cystic fibrosis patients had a significantly lower vocal intensity and harmonic to noise ratio, as well as increased levels of jitter and shimmer. In addition, cystic fibrosis patients also showed higher scores of roughness, breathiness and asthenia, as well as a significantly altered general grade of dysphonia. When we segregated the results according to sex, we observed that, as a group, only female cystic fibrosis patients had significantly lower values of harmonic to noise ratio and an abnormal general grade of dysphonia in relation to matched controls, suggesting that cystic fibrosis exerts a more pronounced effect on vocal parameters of women in relation to men. Overall, the dysphonic characteristics of CF patients can be explained by dysfunctions in vocal fold movement and partial upper airway obstruction, potentially caused by the accumulation of mucus and chronic cough characteristic of CF symptomatology. Our results show that CF patients exhibit significant dysphonia and suggest they may

  5. Patient-reported Outcomes in Cystic Fibrosis

    OpenAIRE

    Goss, Christopher H.; Quittner, Alexandra L.

    2007-01-01

    Over the past 20 years, there has been tremendous progress in the area of patient-reported outcomes (PROs). A PRO instrument is defined as any measure of a patient's health status that is elicited directly from the patient and assesses how the patient “feels or functions with respect to his or her health condition.” The advances seen in clinical research regarding PROs has been mirrored in research in cystic fibrosis (CF). A large number of instruments have been used for both therapeutic and ...

  6. Microbiological surveillance in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Paola Gualdi

    2010-06-01

    Full Text Available Pulmonary infections in patients with cystic fibrosis (CF, are a major cause of morbidity and mortality. Prevention, diagnosis and therapy in cystic fibrosis, lead to the necessary collaboration between clinical and laboratory to identify effective strategies and appropriate solutions to address the problems inherent isolation micro-organisms, antibiotic strategies, overcoming of bacterial resistance and other problems management of these patients. The task of the microbiology laboratory and research in quickly and accurately, the agents responsible for these infectious processes, in order to isolate them from material, identify and determine their sensitivity antibiotics. A microbiological surveillance on 34 patients (13 males and 21 females with CF and related to the “Support Services Provincial Trento for the treatment of cystic fibrosis “in the period July 2005 - August 2008, was carried out. 180 Gram positive and 278 of Gram negative bacteria as well as 235 fungi wre collected. Staphylococcus aureus was the most frequently organism found in patients with CF with an incidence of 23% on 156 strains isolated, Pseudomonas aeruginosa was collected 19% of all microorganisms isolated corresponding to 131 strains, Candida albicans is the yeast often isolated with a frequency 22% equal to 149 isolates, Aspergillus fumigatus was isolated at a rate of 8%. From the data we collected and processed has been noted that the local epidemiology of CF patients reflects as reported in the scientific literature and national international consulting, both as a type microorganisms that frequency also isolated compared to age groups. Considering the score of Bartlett as discriminating respiratory fitness of the material, it has been observed that only 32 samples over 327 total (10% would materials insignificant. It follows therefore that the time of sample collection, followed by personnel (physiotherapists dedicated to CF patients, represents a crucial step

  7. Life-threatening systemic symptoms in a cystic fibrosis patient

    OpenAIRE

    Gohy, Sophie; Froidure, Antoine; Lebecque, Patrick; ECFS

    2014-01-01

    Case report A 20-year-old male patient with cystic fibrosis (CF) (F508del/F508del, last FEV1: 92% predicted) was admitted for the sudden occurrence of high-grade fever, FEV1 drop (72% predicted) without increased cough, malaise, diffuse pain and generalized lymphadenopathies. Initial check-up revealed the presence of very recent bilateral hilar lymphadenopathies along with a marked inflammatory syndrome (WBC: 35,680/µl, neutrophils: 28,220/µl, CRP: 163mg/L). Within 24 hours, the patient devel...

  8. Non-invasive measurement of liver and pancreas fibrosis in patients with cystic fibrosis.

    Science.gov (United States)

    Friedrich-Rust, Mireen; Schlueter, Nina; Smaczny, Christina; Eickmeier, Olaf; Rosewich, Martin; Feifel, Kirstin; Herrmann, Eva; Poynard, Thierry; Gleiber, Wolfgang; Lais, Christoph; Zielen, Stefan; Wagner, Thomas O F; Zeuzem, Stefan; Bojunga, Joerg

    2013-09-01

    Patients with cystic fibrosis (CF) have a relevant morbidity and mortality caused by CF-related liver-disease. While transient elastography (TE) is an established elastography method in hepatology centers, Acoustic-Radiation-Force-Impulse (ARFI)-Imaging is a novel ultrasound-based elastography method which is integrated in a conventional ultrasound-system. The aim of the present study was to evaluate the prevalence of liver-fibrosis in patients with CF using TE, ARFI-imaging and fibrosis blood tests. 106 patients with CF were prospectively included in the present study and received ARFI-imaging of the left and right liver-lobe, ARFI of the pancreas TE of the liver and laboratory evaluation. The prevalence of liver-fibrosis according to recently published best practice guidelines for CFLD was 22.6%. Prevalence of significant liver-fibrosis assessed by TE, ARFI-right-liver-lobe, ARFI-left-liver-lobe, Fibrotest, Fibrotest-corrected-by-haptoglobin was 17%, 24%, 40%, 7%, and 16%, respectively. The best agreement was found for TE, ARFI-right-liver-lobe and Fibrotest-corrected-by-haptoglobin. Patients with pancreatic-insufficiency had significantly lower pancreas-ARFI-values as compared to patients without. ARFI-imaging and TE seem to be promising non-invasive methods for detection of liver-fibrosis in patients with CF. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  9. Urinary incontinence in patients with cystic fibrosis.

    Science.gov (United States)

    Reichman, Gina; De Boe, Veerle; Braeckman, Johan; Michielsen, Dirk

    2016-01-01

    Owing to evolution in treatment, the average life expectancy of patients with cystic fibrosis (CF) has increased. This has been followed by an increase in urological complications such as urinary incontinence. As stress incontinence occurs during exercise, it may have a negative effect on the implementation of respiratory physiotherapy. The purpose of this study is to determine the prevalence of urinary incontinence and its effect on the quality of life and physiotherapy in a population with CF. Questionnaires were used to determine the prevalence of incontinence in patients of the Cystic Fibrosis Clinic of the University Hospital in Brussels. Two different surveys were used, depending on the age of the patients (incontinence were emphasized. Questionnaires were completed by 122 participants aged 6-59 years, showing an overall prevalence of 27% for urinary incontinence. Mainly adults reported urinary incontinence, with a prevalence of 11% in men and 68% in women aged 12 and above. The amount of urinary leakage was usually only a few drops and it was mainly triggered by coughing. Many of the participants had never mentioned this symptom to anyone. Doctors' and physical therapists' attention should be drawn to the fact that urinary incontinence is part of the complication spectrum of CF. A quarter of the study population refrained from coughing up phlegm and from physiotherapy. It is important to actively question and inform about this problem, to enable its detection and treatment.

  10. Maintaining Respiratory Health in Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    MR Modaresi

    2014-04-01

    Full Text Available Cystic fibrosis (CF is an inherited disease that primarily affects the lungs and the digestive system, however, it also affects a number of other organs and systems. More than 90% of mortality of  CF patients is due to lung complications.  Healthy lungs are important for a long life for people with CF, We will discuss two important topics for maintaining respiratory health. Chronic use of drugs for maintaining respiratory health There are a number of drugs available to keep CF lungs healthy. We will discuss the science behind the recommendations for use of: Inhaled antibiotics Dornase alfa Azithromycin Hypertonic saline High-dose ibuprofen Ivacaftor CF Airway Clearance Therapies Airway Clearance therapy is very important to keeping CF lungs healthy. Our discussions cover the following topics such as the: Daily airway clearance Different techniques of airway clearance Effect of aerobic exercise on airway clearance  

  11. Blood lipids analysis in patients with hepatitis and hepatic fibrosis

    International Nuclear Information System (INIS)

    Si Jianhong

    2007-01-01

    Objective: To investigate the correlationship between blood hepatic fibrosis markers and blood lipids levels. Methods: Serum hepatic fibrosis markers (HA, PC III, IV-C, LN) levels were determined with RIA and serum lipids (TG, TCh HDL; LDL, apoA1, apoB) were measured with biochemical methods in 98 patients with hepatitis in various stages and 50 controls. Liver biopsy was done in all the hepatitis patients. Results: Hepatic fibrosis was classified into 5 grades (S0-S4) according to the pathology shown in the biopsy specimen. The serum lipid levels decreased along with the increase of severity of fibrosis from S0 to S4. Levels in S4 patients were significantly lower than those in controls (P 0.05). Conclusion: The serum hepatic fibrosis markers levels increased and lipids levels decreased along with the progress of hepatitis from acute to cirrhosis. (authors)

  12. Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis

    Science.gov (United States)

    Mahavadi, Poornima; Sasikumar, Satish; Cushing, Leah; Hyland, Tessa; Rosser, Ann E.; Riccardi, Daniela; Lu, Jining; Kalin, Tanya V.; Kalinichenko, Vladimir V.; Guenther, Andreas; Ramirez, Maria I.; Pardo, Annie; Selman, Moisés; Warburton, David

    2013-01-01

    Chronic injury of alveolar lung epithelium leads to epithelial disintegrity in idiopathic pulmonary fibrosis (IPF). We had reported earlier that Grhl2, a transcriptional factor, maintains alveolar epithelial cell integrity by directly regulating components of adherens and tight junctions and thus hypothesized an important role of GRHL2 in pathogenesis of IPF. Comparison of GRHL2 distribution at different stages of human lung development showed its abundance in developing lung epithelium and in adult lung epithelium. However, GRHL2 is detected in normal human lung mesenchyme only at early fetal stage (week 9). Similar mesenchymal reexpression of GRHL2 was also observed in IPF. Immunofluorescence analysis in serial sections from three IPF patients revealed at least two subsets of alveolar epithelial cells (AEC), based on differential GRHL2 expression and the converse fluorescence intensities for epithelial vs. mesenchymal markers. Grhl2 was not detected in mesenchyme in intraperitoneal bleomycin-induced injury as well as in spontaneously occurring fibrosis in double-mutant HPS1 and HPS2 mice, whereas in contrast in a radiation-induced fibrosis model, with forced Forkhead box M1 (Foxm1) expression, an overlap of Grhl2 with a mesenchymal marker was observed in fibrotic regions. Grhl2's role in alveolar epithelial cell plasticity was confirmed by altered Grhl2 gene expression analysis in IPF and further validated by in vitro manipulation of its expression in alveolar epithelial cell lines. Our findings reveal important pathophysiological differences between human IPF and specific mouse models of fibrosis and support a crucial role of GRHL2 in epithelial activation in lung fibrosis and perhaps also in epithelial plasticity. PMID:24375798

  13. Viruses in cystic fibrosis patients' airways.

    Science.gov (United States)

    Billard, Lisa; Le Berre, Rozenn; Pilorgé, Léa; Payan, Christopher; Héry-Arnaud, Geneviève; Vallet, Sophie

    2017-11-01

    Although bacteria have historically been considered to play a major role in cystic fibrosis (CF) airway damage, a strong impact of respiratory viral infections (RVI) is also now recognized. Emerging evidence confirms that respiratory viruses are associated with deterioration of pulmonary function and exacerbation and facilitation of bacterial colonization in CF patients. The aim of this review is to provide an overview of the current knowledge on respiratory viruses in CF airways, to discuss the resulting inflammation and RVI response, to determine how to detect the viruses, and to assess their clinical consequences, prevalence, and interactions with bacteria. The most predominant are Rhinoviruses (RVs), significantly associated with CF exacerbation. Molecular techniques, and especially multiplex PCR, help to diagnose viral infections, and the coming rise of metagenomics will extend knowledge of viral populations in the complex ecosystem of CF airways. Prophylaxis and vaccination are currently available only for Respiratory syncytial and Influenza virus (IV), but antiviral molecules are being tested to improve CF patients' care. All the points raised in this review highlight the importance of taking account of RVIs and their potential impact on the CF airway ecosystem.

  14. Archetypal analysis of diverse Pseudomonas aeruginosa transcriptomes reveals adaptation in cystic fibrosis airways

    Science.gov (United States)

    2013-01-01

    Background Analysis of global gene expression by DNA microarrays is widely used in experimental molecular biology. However, the complexity of such high-dimensional data sets makes it difficult to fully understand the underlying biological features present in the data. The aim of this study is to introduce a method for DNA microarray analysis that provides an intuitive interpretation of data through dimension reduction and pattern recognition. We present the first “Archetypal Analysis” of global gene expression. The analysis is based on microarray data from five integrated studies of Pseudomonas aeruginosa isolated from the airways of cystic fibrosis patients. Results Our analysis clustered samples into distinct groups with comprehensible characteristics since the archetypes representing the individual groups are closely related to samples present in the data set. Significant changes in gene expression between different groups identified adaptive changes of the bacteria residing in the cystic fibrosis lung. The analysis suggests a similar gene expression pattern between isolates with a high mutation rate (hypermutators) despite accumulation of different mutations for these isolates. This suggests positive selection in the cystic fibrosis lung environment, and changes in gene expression for these isolates are therefore most likely related to adaptation of the bacteria. Conclusions Archetypal analysis succeeded in identifying adaptive changes of P. aeruginosa. The combination of clustering and matrix factorization made it possible to reveal minor similarities among different groups of data, which other analytical methods failed to identify. We suggest that this analysis could be used to supplement current methods used to analyze DNA microarray data. PMID:24059747

  15. Phenotypes selected during chronic lung infection in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang

    2012-01-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by g...... the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis....

  16. Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance

    Directory of Open Access Journals (Sweden)

    E.R. Parra

    2012-07-01

    Full Text Available In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1 and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF. Telomerase+, myofibroblasts α-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci, severe (mural fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.

  17. Oral Pirfenidone in patients with chronic fibrosis resulting from radiotherapy: a pilot study

    International Nuclear Information System (INIS)

    Simone, Nicole L; Soule, Benjamin P; Gerber, Lynn; Augustine, Elizabeth; Smith, Sharon; Altemus, Rosemary M; Mitchell, James B; Camphausen, Kevin A

    2007-01-01

    Fibrosis is a common side effect after treatment with ionizing radiation. Several methods to ameliorate debilitating fibrosis have been employed but without consistent results. The goal of this pilot study is to determine if Pirfenidone, a novel regulator of cytokine gene expression, has the potential to ameliorate established radiation-induced fibrosis. Open label, prospective pilot study of 800 mg three times/day, orally administered Pirfenidone was administered to enrolled patients who were had completed radiation therapy and who had established radiation-induced fibrosis. Range of motion (ROM) was assessed using standard measures, and subjective measures of pain, fatigue, disability and global health were measured every three months. Seven patients were enrolled of whom 3 had ROM assessments of 1 site and 2 had ROM assessments of 2 sites. Of these assessments, 6 revealed increased ROM during drug intervention while 1 revealed a decreased ROM. There was an overall improvement in the mental composite score of the SF36 while physical composite score was decreased and the vitality score was unchanged. Two patients were removed from the study because of syncopal episodes. Several patients experienced improved function of at least 25% and reported subjective improvement. Pirfenidone may benefit patients with radiation-induced fibrosis and is worthy of a larger well controlled trial

  18. Impaired Lymphocyte Profile in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Luciana Santos Cardoso

    2013-01-01

    Full Text Available The Th2 immune response in chronic schistosomiasis is associated with the development of periportal fibrosis. However, little is known about the phenotype and activation status of T cells in the process. Objective. To evaluate the profile of T cells in schistosomiasis patients with periportal fibrosis. Methods. It was a cross-sectional study, conducted in the village of Agua Preta, Bahia, Brazil, which included 37 subjects with periportal fibrosis determined by ultrasound. Peripheral blood mononuclear cells were obtained by the Ficcol-hypaque gradient and the frequency of T cells expressing the surface markers CD28, CD69, CD25, and CTLA-4 was determined by flow cytometry. Results. The frequency of CD4+CD28+ T lymphocytes was higher in individuals with moderate to severe fibrosis compared to patients with incipient fibrosis. We did not observe any significant difference in the frequency of CD4+ T cells expressing CD69 among groups of individuals. There was also no significant difference in the frequency of CD8+ T cells expressing CD28 or CD69 among the studied groups. Individuals with moderate to severe fibrosis presented a lower frequency of CD8+ T cells, CD4+CD25high T cells, and CD4+CTLA-4+ T cells when compared to patients without fibrosis or incipient fibrosis. The frequency of CD4+CD25low cells did not differ between groups. Conclusion. The high frequency of activated T cells coinciding with a low frequency of putative Treg cells may account for the development of periportal fibrosis in human schistosomiasis.

  19. Pulmonary Artery Occlusion and Mediastinal Fibrosis in a Patient on Dopamine Agonist Treatment for Hyperprolactinemia

    DEFF Research Database (Denmark)

    Su, Junjing; Simonsen, Ulf; Carlsen, Jørn

    2017-01-01

    Unusual forms of pulmonary hypertension include pulmonary hypertension related to mediastinal fibrosis and the use of serotonergic drugs. Here, we describe a patient with diffuse mediastinal fibrosis and pulmonary hypertension while she was on dopamine agonist therapy. A young woman, who...... showed fibrosis and chronic inflammation. Subsequent investigations revealed that diffuse mediastinal fibrosis with concurrent pulmonary hypertension, and not CTEPH, was the most likely diagnosis and cabergoline and bromocriptine may have triggered the fibrotic changes. Both drugs are ergot...... was treated with cabergoline and bromocriptine for hyperprolactinemia, presented with progressive dyspnea over several months. Based on the clinical investigation results, in particular, elevated pulmonary arterial pressures and significant perfusion defects on computed tomography (CT) pulmonary angiography...

  20. An adult cystic fibrosis patient presenting with persistent dyspnea: case report

    Directory of Open Access Journals (Sweden)

    Farinet Catherine L

    2006-05-01

    Full Text Available Abstract Background Persistent dyspnea is a common finding in the cystic fibrosis patient that typically leads to further work up of an alternative pulmonary etiology. Adult cystic fibrosis patients; however, are growing in numbers and they are living into the ages in which coronary artery disease becomes prevalent. Coronary disease should be included in the consideration of diagnostic possibilities. Case presentation A 52-year-old white male with cystic fibrosis was evaluated for exertional dyspnea associated with vague chest discomfort. Diagnostic testing revealed normal white blood cell, hemoglobin and platelet count, basic metabolic panel, fasting lipid profile, HbA1c, with chest radiograph confirming chronic cystic findings unchanged from prior radiographs and an electrocardiogram that revealed sinus rhythm with left anterior fascicular block. Stress thallium testing demonstrated a reversible anteroseptal perfusion defect with a 55% left ventricular ejection fraction. Heart catheterization found a 99% occlusion of the left anterior descending artery extending into the two diagonal branches, with 100% obstruction of the left anterior descending artery at the trifurcation and 70% lesion affecting the first posterior lateral branch of the circumflex artery. Conclusion This case report represents the first description in the medical literature of a cystic fibrosis patient diagnosed with symptomatic coronary artery disease. Applying a standard clinical practice guide proved useful toward evaluating a differential diagnosis for a cystic fibrosis patient presenting with dyspnea and chest discomfort.

  1. 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.

  2. Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Fluge, Gjermund; Olesen, Hanne Vebert; Giljam, Marita

    2009-01-01

    Background: The co-morbidity of cystic fibrosis (CF) and celiac disease (CD) has been reported sporadically since the 1960s. To our knowledge, this is the first time a systematic screening is performed in a large cohort of CF patients. Methods: Transglutaminase-IgA (TGA), endomysium-IgA (EMA...

  3. Radiation-induced neck fibrosis in patients with nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Li Jian; Wang Rensheng; Gan Langge; Liu Wenqi; Zhang Yong

    2005-01-01

    Objective: To investigate the post-irradiation neck fibrosis in patients with nasopharyngeal carcinoma and its related factors. Methods: A total of 267 patients received conventional fractionated radiotherapy with D T 50-72 Gy on the neck a half year to 10 years ago were observed for the changes of cervical shape and functions. Results: Different degrees of post-irradiation neck fibrosis were seen in all patients. The rate of heavy degree of neck radiation fibrosis was 24.34 %, and it was 2.74% when received preventive dose on the neck. There was a very significant difference between patients who received late course of tangential irradiation on the neck and those who didn't receive (P=0.0001). The incidence of post-irradiation neck fibrosis didn't increase when patients received radiotherapy combined with chemotherapy (P=0.2678). The function of cervical muscles turned weak in patients received radiotherapy delivered by 6 MV accelerator in late course of tangential irradiation, whereas skin damage was severer in patients treated with 60 Co γ-rays. Conclusions: The incidence of heavy degree of post-irradiation neck fibrosis is high ,and is related closely to late course of tangential irradiation. The authors should avoid adopting this sort of irradiation on the neck. (authors)

  4. Pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Myung Jin; Goo, Jin Mo E-mail: jmgoo@plaza.snu.ac.kr; Im, Jung-Gi

    2004-11-01

    Objectives: Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk of pulmonary tuberculosis. However, detecting pulmonary tuberculosis may be difficult due to the underlying fibrosis. The aim of this report is to describe the radiological and clinical findings of pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis. Materials and methods: We reviewed 143 consecutive patients in whom IPF was diagnosed by either the histological or radio-clinical criteria. Among them, nine patients were histologically (n=2) or bacteriologically (n=7) confirmed to have active pulmonary tuberculosis. The location and patterns of pulmonary tuberculosis were examined on a thin section CT scan. Results: The most common thin section CT findings were subpleural nodules (n=6; mean diameter, 3.2 cm) and a lobar or segmental consolidation (n=3). The lesions were located most commonly in the right lower lobe (n=4). The incidence of tuberculosis in patients with idiopathic pulmonary fibrosis was more than five times higher than that of the general population. Conclusion: The atypical manifestation of pulmonary tuberculosis is common in patients with idiopathic pulmonary fibrosis, which may mimic lung cancer or bacterial pneumonia.

  5. Pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis

    International Nuclear Information System (INIS)

    Chung, Myung Jin; Goo, Jin Mo; Im, Jung-Gi

    2004-01-01

    Objectives: Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk of pulmonary tuberculosis. However, detecting pulmonary tuberculosis may be difficult due to the underlying fibrosis. The aim of this report is to describe the radiological and clinical findings of pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis. Materials and methods: We reviewed 143 consecutive patients in whom IPF was diagnosed by either the histological or radio-clinical criteria. Among them, nine patients were histologically (n=2) or bacteriologically (n=7) confirmed to have active pulmonary tuberculosis. The location and patterns of pulmonary tuberculosis were examined on a thin section CT scan. Results: The most common thin section CT findings were subpleural nodules (n=6; mean diameter, 3.2 cm) and a lobar or segmental consolidation (n=3). The lesions were located most commonly in the right lower lobe (n=4). The incidence of tuberculosis in patients with idiopathic pulmonary fibrosis was more than five times higher than that of the general population. Conclusion: The atypical manifestation of pulmonary tuberculosis is common in patients with idiopathic pulmonary fibrosis, which may mimic lung cancer or bacterial pneumonia

  6. Typing of Pseudomonas aeruginosa strains in Norwegian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Fluge, G; Ojeniyi, B; Høiby, N

    2001-01-01

    OBJECTIVES: Typing of Pseudomonas aeruginosa isolates from Norwegian cystic fibrosis (CF) patients with chronic Pseudomonas lung infection in order to see whether cross-infection might have occurred. METHODS: Isolates from 60 patients were collected during the years 1994-98, and typed by pulsed...

  7. Inspiratory muscle training in patients with cystic fibrosis

    NARCIS (Netherlands)

    de Jong, W.; van Aalderen, W.M.C.; Kraan, J.; Koeter, G.H.; van der Schans, C.P.

    Little information is available about the effects of inspiratory muscle training in patients with cystic fibrosis (CF). In this study the effects of inspiratory-threshold loading in patients with CF on strength and endurance of the inspiratory muscles, pulmonary function, exercise capacity, dyspnoea

  8. TINF2 Gene Mutation in a Patient with Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    T. W. Hoffman

    2016-01-01

    Full Text Available Pulmonary fibrosis is a frequent manifestation of telomere syndromes. Telomere gene mutations are found in up to 25% and 3% of patients with familial disease and sporadic disease, respectively. The telomere gene TINF2 encodes an eponymous protein that is part of the shelterin complex, a complex involved in telomere protection and maintenance. A TINF2 gene mutation was recently reported in a family with pulmonary fibrosis. We identified a heterozygous Ser245Tyr mutation in the TINF2 gene of previously healthy female patient that presented with progressive cough due to pulmonary fibrosis as well as panhypogammaglobulinemia at age 52. Retrospective multidisciplinary evaluation classified her as a case of possible idiopathic pulmonary fibrosis. Telomere length-measurement indicated normal telomere length in the peripheral blood compartment. This is the first report of a TINF2 mutation in a patient with sporadic pulmonary fibrosis, which represents another association between TINF2 mutations and this disease. Furthermore, this case underlines the importance of telomere dysfunction and not telomere length alone in telomere syndromes and draws attention to hypogammaglobulinemia as a manifestation of telomere syndromes.

  9. Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis

    Science.gov (United States)

    Liu, Longwei; You, Zhifeng; Yu, Hongsheng; Zhou, Lyu; Zhao, Hui; Yan, Xiaojun; Li, Dulei; Wang, Bingjie; Zhu, Lu; Xu, Yuzhou; Xia, Tie; Shi, Yan; Huang, Chenyu; Hou, Wei; Du, Yanan

    2017-12-01

    The role of pathological angiogenesis on liver fibrogenesis is still unknown. Here, we developed fibrotic microniches (FμNs) that recapitulate the interaction of liver sinusoid endothelial cells (LSECs) and hepatic stellate cells (HSCs). We investigated how the mechanical properties of their substrates affect the formation of capillary-like structures and how they relate to the progression of angiogenesis during liver fibrosis. Differences in cell response in the FμNs were synonymous of the early and late stages of liver fibrosis. The stiffness of the early-stage FμNs was significantly elevated due to condensation of collagen fibrils induced by angiogenesis, and led to activation of HSCs by LSECs. We utilized these FμNs to understand the response to anti-angiogenic drugs, and it was evident that these drugs were effective only for early-stage liver fibrosis in vitro and in an in vivo mouse model of liver fibrosis. Late-stage liver fibrosis was not reversed following treatment with anti-angiogenic drugs but rather with inhibitors of collagen condensation. Our work reveals stage-specific angiogenesis-induced liver fibrogenesis via a previously unrevealed mechanotransduction mechanism which may offer precise intervention strategies targeting stage-specific disease progression.

  10. Trace incorporation of heavy water reveals slow and heterogeneous pathogen growth rates in cystic fibrosis sputum

    Science.gov (United States)

    Kopf, Sebastian H.; Sessions, Alex L.; Cowley, Elise S.; Reyes, Carmen; Van Sambeek, Lindsey; Hu, Yang; Orphan, Victoria J.; Kato, Roberta; Newman, Dianne K.

    2016-01-01

    Effective treatment for chronic infections is undermined by a significant gap in understanding of the physiological state of pathogens at the site of infection. Chronic pulmonary infections are responsible for the morbidity and mortality of millions of immunocompromised individuals worldwide, yet drugs that are successful in laboratory culture are far less effective against pathogen populations persisting in vivo. Laboratory models, upon which preclinical development of new drugs is based, can only replicate host conditions when we understand the metabolic state of the pathogens and the degree of heterogeneity within the population. In this study, we measured the anabolic activity of the pathogen Staphylococcus aureus directly in the sputum of pediatric patients with cystic fibrosis (CF), by combining the high sensitivity of isotope ratio mass spectrometry with a heavy water labeling approach to capture the full range of in situ growth rates. Our results reveal S. aureus generation times with a median of 2.1 d, with extensive growth rate heterogeneity at the single-cell level. These growth rates are far below the detection limit of previous estimates of CF pathogen growth rates, and the rates are slowest in acutely sick patients undergoing pulmonary exacerbations; nevertheless, they are accessible to experimental replication within laboratory models. Treatment regimens that include specific antibiotics (vancomycin, piperacillin/tazobactam, tobramycin) further appear to correlate with slow growth of S. aureus on average, but follow-up longitudinal studies must be performed to determine whether this effect holds for individual patients.

  11. Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Fluge, G; Olesen, H V; Gilljam, M

    2009-01-01

    BACKGROUND: The co-morbidity of cystic fibrosis (CF) and celiac disease (CD) has been reported sporadically since the 1960s. To our knowledge, this is the first time a systematic screening is performed in a large cohort of CF patients. METHODS: Transglutaminase-IgA (TGA), endomysium-IgA (EMA...... patients were detected in the Danish CF cohort. Patients diagnosed with untreated CD reported symptoms typical of both CF and CD (poor weight gain, loose and/or fatty stools, fatigue, irritability, abdominal pain). They improved after introduction of a gluten-free diet. CONCLUSIONS: Systematic screening...

  12. Clinicopathological characteristics of patients with combined pulmonary fibrosis and emphysema

    International Nuclear Information System (INIS)

    Ito, Takafumi; Sugino, Keishi; Sakamoto, Susumu; Homma, Sakae; Kurosaki, Atsuko; Uekusa, Toshimasa

    2012-01-01

    The aim of this study was to clarify the clinicopathological characteristics and the prognostic factors of combined pulmonary fibrosis and emphysema (CPFE), which is defined as pulmonary emphysema associated with idiopathic pulmonary fibrosis (IPF). Of 92 IPF patients admitted to our hospital during the past 6 years, 35 were diagnosed as CPFE (Group E) and 57 as IPF without emphysema (Group F). We retrospectively compared the clinical features between these 2 groups. Furthermore, we investigated the histopathological localization and characteristic background parenchymal architecture of lung cancer in 6 patients with CPFE who had undergone surgical lung resection for complications of lung cancer. Lastly, we compared the histopathological differences in background lung structures of the origins of the lung cancers in the following 3 groups: Group E, Group F, and pulmonary emphysema. The smoking index values and the incidence of lung cancer were higher in patients in Group E than in Group F, but the survival times were significantly lower in Group E patients. The prognostic factors included emphysema, lung cancer, pulmonary arterial hypertension, increased composite physiological index, and acute exacerbation. Histopathologically, the localization of lung cancer in Group E patients was adjacent to emphysematous lesions with or without associated fibrosis, which showed a more marked architectural distortion with less significant fibroblastic foci, collapse of alveoli, and subpleural fibrosis than in Group F patients. In conclusion, this study demonstrated that the incidence of lung cancer was extremely high in patients with CPFE. However, the prognosis was unfavorable regardless of the presence of lung cancer, with the chief adverse prognostic factor being complications of pulmonary emphysema. Emphysematous lesions with fibrosis in Group E that are different from those seen in Group F may be background lung structures characteristic of the carcinogenesis of lung

  13. The Role of Vitamin A in Patients with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    N.V. Rogovyk

    2013-10-01

    Full Text Available Cystic fibrosis is hereditary monogenic exocrine disease, which manifests itself most often by disorders in bronchopulmonary and digestive systems. The affection of the latter leads to deficiency of liposoluble vitamins A, D, E and K in the body of the patient. The lack and excess of vitamin A in this disease may contribute to a number of pathological states and aggravate the disease. Therefore, in the records of all European centers of cystic fibrosis it is recommended to carry out annual determination of the levels of vitamin A, followed by individual dose adjustment.

  14. Serum YKL-40 is increased in patients with hepatic fibrosis

    DEFF Research Database (Denmark)

    Johansen, J S; Christoffersen, P; Møller, S

    2000-01-01

    BACKGROUND/AIMS: YKL-40, a mammalian member of the chitinase family, is a lectin that binds heparin and chitin. The function of YKL-40 is unknown, but it may function in tissue remodelling. The aims of this study were to assess the level of circulating YKL-40 in patients with various kinds...... with the blood sample. RESULTS: The median serum YKL-40 was highest in patients with alcoholic cirrhosis (532 microg/l), in particular in patients with additional alcoholic hepatitis (740 microg/l). Patients with alcoholic cirrhosis, post-hepatitic cirrhosis (425 microg/l) and non-cirrhotic fibrosis (330 microg/l......) had significantly higher serum YKL-40 than normal subjects (102 microg/l), patients with fatty liver (195 microg/l) or patients with viral hepatitis without fibrosis (174 microg/l). Serum YKL-40 was significantly (p

  15. Pharmacokinetics of aerosolized tobramycin in adult patients with cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J; Jacobs, F A; Brimicombe, R W; Heijerman, H G; Bakker, W; Briemer, D D

    This study was performed to determine the clinical pharmacokinetics of tobramycin in six patients with cystic fibrosis (CF) after inhalation of 600 mg. Tobramycin was administered with an ultrasonic nebulizer (WISTO SENIOR). Blood and urine were sampled until 24 h after inhalation. Maximum

  16. Treatment of lung infection in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Döring, Gerd; Flume, Patrick; Heijerman, Harry

    2012-01-01

    In patients with cystic fibrosis (CF) lung damage secondary to chronic infection is the main cause of death. Treatment of lung disease to reduce the impact of infection, inflammation and subsequent lung injury is therefore of major importance. Here we discuss the present status of antibiotic...

  17. Diagnosis of biofilm infections in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Høiby, Niels; Bjarnsholt, Thomas; Moser, Claus

    2017-01-01

    Chronic Pseudomonas aeruginosa biofilm lung infection in cystic fibrosis patients is the best described biofilm infection in medicine. The initial focus can be the paranasal sinuses and then follows repeated colonization and infection of the lungs by aspiration. The matrix of the biofilms is domi...... by other pathogens e.g., Stenotrophomonas, Burkholderia multivorans, Achromobacter xylosoxidans and Mycobacterium abscessus complex....

  18. Fatty acyltranferases in serum in cystic fibrosis (CF) patients

    International Nuclear Information System (INIS)

    Zielenski, J.; Newman, L.J.; Slomiany, B.L.; Slomiany, A.

    1987-01-01

    Studies on serum and gastrointestinal secretion from CF patient is suggest that defective accumulation of mucus in gastrointestinal tract and excessive amount of a protease resistant peptides in serum are related to the abnormal activity of enzymes responsible for fatty acylation of proteins. Here, the authors investigated the fatty acyltransferase activities in serum of normal and CF patients. A 15μl of serum was mixed with 0.85 nmol [ 14 C]palmitoyl CoA, 200μg of serine and threonine and incubated at 37 0 C for 30 min. The incubates were immediately frozen, dried extracted with C/M and chromatographed in chloroform/methanol/water. The incorporation of [ 14 C]palmitate was determined using linear radioscanner and authoradiography. The results of HPTLC revealed that CF serum in addition of ACAT and LCAT contained enzymes responsible for the transfer of [ 14 C]palmitate to monoacylphosphoglycerides, and serine and threonine. In normal serum the formation of a small amount of palmitoyl serine and palmitoyl threonine was also observed but the acylation of monoacylphosphoglycerides was not detectable. The authors conclude that in cystic fibrosis the abnormal fatty acyltransferases are responsible for the occurrence of protease resistant glycoprotein, unusual peptides in serum and possibly for the modification of membrane proteins and lipids

  19. Fibrosis index based on four factors better predicts advanced fibrosis or cirrhosis than aspartate aminotransferase/platelet ratio index in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Chia-Chi Wang

    2015-10-01

    Conclusion: FIB-4 could predict hepatic fibrosis in CHC patients. By adding two parameters (age and alanine aminotransferase, FIB-4 better predicts advanced fibrosis and cirrhosis than APRI in CHC patients.

  20. The Efficacy of MAG-DHA for Correcting AA/DHA Imbalance of Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    Caroline Morin

    2018-05-01

    Full Text Available Omega-3 polyunsaturated fatty acid (n-3 PUFA supplementations are thought to improve essential fatty acid deficiency (EFAD as well as reduce inflammation in Cystic Fibrosis (CF, but their effectiveness in clinical studies remains unknown. The aim of the study was to determine how the medical food containing docosahexaenoic acid monoglyceride (MAG-DHA influenced erythrocyte fatty acid profiles and the expression levels of inflammatory circulating mediators. We conducted a randomized, double blind, pilot trial including fifteen outpatients with Cystic Fibrosis, ages 18–48. The patients were divided into 2 groups and received MAG-DHA or a placebo (sunflower oil for 60 days. Patients took 8 × 625 mg MAG-DHA softgels or 8 × 625 mg placebo softgels every day at bedtime for 60 days. Lipid analyses revealed that MAG-DHA increased docosahexaenoic acid (DHA levels and decrease arachidonic acid (AA ratio (AA/DHA in erythrocytes of CF patients following 1 month of daily supplementation. Data also revealed a reduction in plasma human leukocyte elastase (pHLE complexes and interleukin-6 (IL-6 expression levels in blood samples of MAG-DHA supplemented CF patients. This pilot study indicates that MAG-DHA supplementation corrects erythrocyte AA/DHA imbalance and may exert anti-inflammatory properties through the reduction of pHLE complexes and IL6 in blood samples of CF patients. Trial registration: Pro-resolving Effect of MAG-DHA in Cystic Fibrosis (PREMDIC, NCT02518672.

  1. Lack of effect of delta F508 mutation on aerobic capacity in patients with cystic fibrosis.

    Science.gov (United States)

    Kaplan, T A; Moccia-Loos, G; Rabin, M; McKey, R M

    1996-10-01

    As aerobic exercise capacity, as defined by VO2max, is associated with patient functioning and possibly prognosis in cystic fibrosis (CF), correlations between VO2max phenotype and genotype may be of value. Retrospective clinical series. Cystic fibrosis referral clinic. Convenience sample of 35 patients with CF consecutively referred for exercise testing. Blood samples were examined for mutations of cystic fibrosis transmembrane regulator (CFTR), Height, wight, pulmonary function, resting-energy expenditure, VO2max, and other exercise variables were assessed in each referred patient. Statistical comparison of 10 patients who were homozygous for the dF508 mutation of CFTR with 20 patients heterozygous for dF508 revealed no significant differences for height, weight, pulmonary function, resting-energy expenditure, VO2max, or any other exercise variables. These results imply a limited effect of the mutation status on overall patient functioning and prognosis. Future identification of more rare CFTR mutations and other genes and subsequent classification of patients in a manner reflective of the cellular physiology may lead to different results.

  2. Nutritional Assesment in Cystic Fibrosis Patients( Iran and Newzeland

    Directory of Open Access Journals (Sweden)

    V Moeeni

    2014-04-01

    Full Text Available Introduction: Patients with Cystic Fibrosis have increased risk of malnutrition. Early detection of nutritional deterioration enables prompt intervention and correction. The aims of this project were to: - Define the nutritional status of CF patients in Iran and New Zealand -    Compare and contrast the MacDonald Nutritional Screening tool  with the Australasian guidelines for Nutrition in Cystic Fibrosis -    Validate these results in comparison with patient’s evaluation by their CF clinical team.   Materials and Methods: 69 CF patients (2-18 years were assessed during routine outpatient visits over one year. Anthropometric measurements were obtained. Both tools were applied for each patient and the results compared to their clinical evaluation (as gold standard with calculation of specificity and sensitivity. Results: Under-nutrition was more frequent in Iranian than NZ patients (39% versus 0%, p=0.0001, whereas over-nutrition was more prevalent in NZ children (9% versus 17%, p=0.05. At the first visit, MacDonald and Australasian guidelines were able to recognize 77% and 61% of under-nourished Iranian patients, respectively. The mean sensitivity and specificity for all visits for the MacDonald tool were 83% & 73% (Iran and 65% & 86% (NZ. Sensitivity and specificity for the Australasian guidelines were 79% & 79% (Iran and 70% & 90% (NZ. Conclusions: Both tools successfully recognised patients at risk of malnutrition. The MacDonald tool had comparable sensitivity and specificity to that described previously, especially in Iranian patients. This tool may be helpful in recognizing at risk CF patients, particularly in developing countries with fewer resources. Key words: Iran, Cystic Fibrosis Patient, Newzeland, Nutritional Assesment.

  3. Archetypal analysis of diverse Pseudomonas aeruginosa transcriptomes reveals adaptation in cystic fibrosis airways

    DEFF Research Database (Denmark)

    Thøgersen, Juliane Charlotte; Mørup, Morten; Pedersen, Søren Damkiær

    2013-01-01

    is to introduce a method for DNA microarray analysis that provides an intuitive interpretation of data through dimension reduction and pattern recognition. We present the first “Archetypal Analysis” of global gene expression. The analysis is based on microarray data from five integrated studies of Pseudomonas...... aeruginosa isolated from the airways of cystic fibrosis patients. RESULTS: Our analysis clustered samples into distinct groups with comprehensible characteristics since the archetypes representing the individual groups are closely related to samples present in the data set. Significant changes in gene....... This suggests positive selection in the cystic fibrosis lung environment, and changes in gene expression for these isolates are therefore most likely related to adaptation of the bacteria. CONCLUSIONS: Archetypal analysis succeeded in identifying adaptive changes of P. aeruginosa. The combination of clustering...

  4. Clinical Meaning of Ascites in Patients with Endomyocardial Fibrosis

    Directory of Open Access Journals (Sweden)

    Barretto Antonio Carlos Pereira

    2002-01-01

    Full Text Available OBJECTIVE: To evaluate the clinical meaning of ascites and the main features of patients with ascites and endomyocardial fibrosis. METHODS: We studied 166 patients with endomyocardial fibrosis (mean age 37 years, 114 women treated over the last 20 years. Ventriculography findings, surgery or necropsy confirmed the diagnosis in all patients. Most patients belonged to New York Heart Association Functional Class III/IV (134, 83.7%. Eighty-one (50.6% had biventricular, 28 (17.5% had right ventricular, and 51 (31.8% had left ventricular involvement. During follow-up, 56 patients died. RESULTS: Ascites was present in 67 (41.8% patients, and right ventricular involvement was present in 59 (88%. In the comparison between patients with or without ascites, those with ascites had higher mortality (49.2% and 24.7%, respectively. Patients with ascites had a higher incidence of edema (95% vs. 43%, hepatomegaly (5.8cm vs. 4.1cm, mean right atrium pressure (19.3 vs. 12mmHg, and final right ventricle diastolic pressure (18.7 vs. 12.9mmHg. Also, patients with ascites had a longer history of illness (5.1 and 3.9 years, respectively and had atrial fibrillation more frequently (44.7% vs. 30.1%. CONCLUSION: Ascites was observed in less than 50% of cases of endomyocardial fibrosis and was associated with greater involvement of the right ventricle and with a longer duration of the disease, thus being a characteristic of a worse prognosis.

  5. Cystic fibrosis transmembrane regulator haplotypes in households of patients with cystic fibrosis.

    Science.gov (United States)

    Furgeri, Daniela Tenório; Marson, Fernando Augusto Lima; Correia, Cyntia Arivabeni Araújo; Ribeiro, José Dirceu; Bertuzzo, Carmen Sílvia

    2018-01-30

    Nearly 2000 mutations in the cystic fibrosis transmembrane regulator (CFTR) gene have been reported. The F508del mutation occurs in approximately 50-65% of patients with cystic fibrosis (CF). However, molecular diagnosis is not always possible. Therefore, silent polymorphisms can be used to label the mutant allele in households of patients with CF. To verify the haplotypes of four polymorphisms at the CFTR locus in households of patients with CF for pre-fertilization, pre-implantation, and prenatal indirect mutation diagnosis to provide better genetic counseling for families and patients with CF and to associate the genotypes/haplotypes with the F508del mutation screening. GATT polymorphism analysis was performed using direct polymerase chain reaction amplification, and the MP6-D9, TUB09 and TUB18 polymorphism analyses were performed using restriction fragment length polymorphism. Nine haplotypes were found in 37 CFTR alleles, and of those, 24 were linked with the F508del mutation and 13 with other CFTR mutations. The 6 (GATT), C (MP6-D9), G (TUB09), and C (TUB18) haplotypes showed the highest prevalence (48%) of the mutant CFTR allele and were linked to the F508del mutation (64%). In 43% of households analyzed, at least one informative polymorphism can be used for the indirect diagnostic test. CFTR polymorphisms are genetic markers that are useful for identifying the mutant CFTR alleles in households of patients with CF when it is not possible to establish the complete CFTR genotype. Moreover, the polymorphisms can be used for indirect CFTR mutation identification in cases of pre-fertilization, pre-implantation and prenatal analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. The association between insulin resistance and hepatic fibrosis in patients with chronic hepatitis C: an observational, multicenter study in Turkey.

    Science.gov (United States)

    Dökmeci, Abdulkadir; Ustündağ, Yücel; Hulagu, Saadettin; Tuncer, Ilyas; Akdoğan, Meral; Demirsoy, Hüseyin; Köklü, Seyfettin; Güzelbulut, Fatih; Doğan, Ibrahim; Demir, Ali; Akarsu, Mesut; Yüceyar, Hakan; Ozdoğan, Osman Cavit; Ozdener, Fatih; Erdoğan, Seda

    2014-10-01

    To evaluate the association between insulin resistance and hepatic fibrosis in patients with chronic hepatitis C. A total of 104 chronic hepatitis C patients were included in this non-interventional, open-label, observational, multicenter, cross-sectional study conducted at 20 gastroenterology clinics in Turkey. The primary end point was the correlation between stage of hepatic fibrosis and insulin resistance evaluated via the homeostasis model of assessment-insulin resistance index. Confounders of hepatic fibrosis and insulin resistance were the secondary end points. The mean age of patients was 52.8 years; 65.4% were female. Type 2 diabetes was present in 6.8% and insulin resistance noted in 38.0% of patients. Further, 45.7% of the patients had mild (A0/A1) and the remaining had moderate/severe (A2/A3) hepatic necroinflammatory activity. Patient distribution according to Metavir fibrosis stage was as follows: F0/F1 (57.0%); F2 (6.5%); F3 (23.7%); and F4 (12.9%). A univariate analysis revealed significant positive correlations between Metavir fibrosis stage and insulin resistance (r=0.297; p=0.007). Logistic regression analysis showed that significant predictors of insulin resistance were high alanine transaminase levels (odds ratio, 0.97; 95% confidence interval, 0.944-0.997) and liver fibrosis stage (odds ratio, 0.114; 95% confidence interval, 0.021-0.607). Our findings revealed significant associations between insulin resistance and hepatic fibrosis.

  7. Integrated analysis of microRNA and gene expression profiles reveals a functional regulatory module associated with liver fibrosis.

    Science.gov (United States)

    Chen, Wei; Zhao, Wenshan; Yang, Aiting; Xu, Anjian; Wang, Huan; Cong, Min; Liu, Tianhui; Wang, Ping; You, Hong

    2017-12-15

    Liver fibrosis, characterized with the excessive accumulation of extracellular matrix (ECM) proteins, represents the final common pathway of chronic liver inflammation. Ever-increasing evidence indicates microRNAs (miRNAs) dysregulation has important implications in the different stages of liver fibrosis. However, our knowledge of miRNA-gene regulation details pertaining to such disease remains unclear. The publicly available Gene Expression Omnibus (GEO) datasets of patients suffered from cirrhosis were extracted for integrated analysis. Differentially expressed miRNAs (DEMs) and genes (DEGs) were identified using GEO2R web tool. Putative target gene prediction of DEMs was carried out using the intersection of five major algorithms: DIANA-microT, TargetScan, miRanda, PICTAR5 and miRWalk. Functional miRNA-gene regulatory network (FMGRN) was constructed based on the computational target predictions at the sequence level and the inverse expression relationships between DEMs and DEGs. DAVID web server was selected to perform KEGG pathway enrichment analysis. Functional miRNA-gene regulatory module was generated based on the biological interpretation. Internal connections among genes in liver fibrosis-related module were determined using String database. MiRNA-gene regulatory modules related to liver fibrosis were experimentally verified in recombinant human TGFβ1 stimulated and specific miRNA inhibitor treated LX-2 cells. We totally identified 85 and 923 dysregulated miRNAs and genes in liver cirrhosis biopsy samples compared to their normal controls. All evident miRNA-gene pairs were identified and assembled into FMGRN which consisted of 990 regulations between 51 miRNAs and 275 genes, forming two big sub-networks that were defined as down-network and up-network, respectively. KEGG pathway enrichment analysis revealed that up-network was prominently involved in several KEGG pathways, in which "Focal adhesion", "PI3K-Akt signaling pathway" and "ECM

  8. Raman spectroscopy as a new tool for early detection of bacteria in patients with cystic fibrosis

    International Nuclear Information System (INIS)

    Rusciano, Giulia; Capriglione, Paola; Pesce, Giuseppe; Sasso, Antonio; Abete, Pasquale; Carnovale, Vincenzo

    2013-01-01

    Respiratory infections represent a major threat for people affected by cystic fibrosis, leading to pulmonary deterioration and lung transplantation as a therapeutic option for end-stage patients. A fast and correct identification of pathogens in airway fluid of these patients is crucial to establish appropriate therapies, to prevent cross-infections and, ultimately, to preserve lung function. In this study, we used Raman spectroscopy to reveal bacteria in the sputa of patients such as Pseudomonas aeruginosa and Staphylococcus aureus, which are among the earliest and the most frequent bacteria affecting cystic fibrosis patients. We found that Raman analysis, combined with principal component analysis, is able to provide a correct identification of these bacteria, with a global accuracy higher than 95%. Interestingly, bacterial identification is performed by analysing patients’ sputa as a whole, avoiding, therefore, time-consuming procedures involving bacterial isolation or even bacterial cultures. This study suggests that Raman spectroscopy could be a suitable candidate for the development of innovative and non-invasive procedures for a fast and reliable identification of respiratory infections in cystic fibrosis patients. (letter)

  9. Raman spectroscopy as a new tool for early detection of bacteria in patients with cystic fibrosis

    Science.gov (United States)

    Rusciano, Giulia; Capriglione, Paola; Pesce, Giuseppe; Abete, Pasquale; Carnovale, Vincenzo; Sasso, Antonio

    2013-07-01

    Respiratory infections represent a major threat for people affected by cystic fibrosis, leading to pulmonary deterioration and lung transplantation as a therapeutic option for end-stage patients. A fast and correct identification of pathogens in airway fluid of these patients is crucial to establish appropriate therapies, to prevent cross-infections and, ultimately, to preserve lung function. In this study, we used Raman spectroscopy to reveal bacteria in the sputa of patients such as Pseudomonas aeruginosa and Staphylococcus aureus, which are among the earliest and the most frequent bacteria affecting cystic fibrosis patients. We found that Raman analysis, combined with principal component analysis, is able to provide a correct identification of these bacteria, with a global accuracy higher than 95%. Interestingly, bacterial identification is performed by analysing patients’ sputa as a whole, avoiding, therefore, time-consuming procedures involving bacterial isolation or even bacterial cultures. This study suggests that Raman spectroscopy could be a suitable candidate for the development of innovative and non-invasive procedures for a fast and reliable identification of respiratory infections in cystic fibrosis patients.

  10. Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains

    NARCIS (Netherlands)

    Varga, J.J.; Barbier, Mariette; Mulet, Xavier; Bielecki, Piotr; Bartell, J.A.; Owings, J.P.; Martinez-Ramos, Inmaculada; Hittle, L.E.; Davis, M.R.; Damron, F.H.; Liechti, G.W.; Puchałka, Jacek; Martins dos Santos, Vitor; Ernst, R.K.; Papin, J.A.; Albertí, Sebastian; Oliver, Antonio; Goldberg, J.B.

    2015-01-01

    Background: Pseudomonas aeruginosa is an environmentally ubiquitous Gram-negative bacterium and important opportunistic human pathogen, causing severe chronic respiratory infections in patients with underlying conditions such as cystic fibrosis (CF) or bronchiectasis. In order to identify

  11. Patient factors associated with lung transplant referral and waitlist for patients with cystic fibrosis and pulmonary fibrosis.

    Science.gov (United States)

    Liu, Yuan; Vela, Monica; Rudakevych, Tanya; Wigfield, Christopher; Garrity, Edward; Saunders, Milda R

    2017-03-01

    Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to fibrosis (CF) and pulmonary fibrosis (PF). We analyzed the times from transplant eligibility to referral, work-up and waitlisting using Kaplan-Meier curves and log-rank tests. Overall, the referral rate for transplant-eligible patients was 64%. Of those referred, approximately 36% reach the lung transplant waitlist. Referred CF patients were significantly more likely to reach the transplant waitlist than PF patients (CF 60% vs PF 22%, p < 0.05). In addition, CF patients had a shorter wait from transplant eligibility to waitlist than PF patients (329 vs 2,369 days, respectively [25th percentile], p < 0.05). Patients with PF and CF both faced delays from eligibility to referral and waitlist. Quality improvement efforts are needed to better identify and refer appropriate patients for lung transplant evaluation. Targeted interventions may facilitate more efficient evaluation completion and waitlist appearance. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Costa Luciano Bello

    2002-01-01

    Full Text Available There is increasing interest in the identification of factors associated with liver disease progression in patients infected with hepatitis C virus (HCV. We assessed host-related factors associated with a histologically advanced stage of this disease and determined the rate of liver fibrosis progression in HCV-infected patients. We included patients submitted to liver biopsy, who were anti-HCV and HCV RNA positive, who showed a parenteral risk factor (blood transfusion or intravenous drug use, and who gave information about alcohol consumption.Patients were divided into two groups for analysis: group 1 - grades 0 to 2; group 2 - grades 3 to 4. The groups were compared in terms of sex, age at the time of infection, estimated duration of infection and alcoholism. The rate of fibrosis progression (index of fibrosis was determined based on the relationship between disease stage and duration of infection (years. Logistic regression analysis revealed that age at the time of infection (P or = 40 years (median = 0.47. The main factors associated with a more rapid fibrosis progression were age at the time of infection and the estimated duration of infection. Patients who acquired HCV after 40 years of age showed a higher rate of fibrosis progression.

  13. Second Harmonic Generation Reveals Subtle Fibrosis Differences in Adult and Pediatric Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Liu, Feng; Zhao, Jing-Min; Rao, Hui-Ying; Yu, Wei-Miao; Zhang, Wei; Theise, Neil D; Wee, Aileen; Wei, Lai

    2017-11-20

    Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system in 62 adult and 36 pediatric NAFLD liver specimens. Six distinct parameters identified differences among the NASH CRN stages with high accuracy (area under the curve, 0835-0.982 vs 0.885-0.981, adult and pediatric). All portal region parameters showed similar changes across early stages 0, 1C, and 2, in both groups. Parameter values decreased in adults with progression from stage 1A/B to 2 in the central vein region. In children, aggregated collagen parameters decreased, but nearly all distributed collagen parameters increased from stage 1A/B to 2. SHG analysis accurately reproduces NASH CRN staging in NAFLD, as well as reveals differences and similarities between adult and pediatric collagen deposition not captured by currently available quantitative methods. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  14. Practical Guidelines: Lung Transplantation in Patients with Cystic Fibrosis

    Science.gov (United States)

    Hirche, T. O.; Knoop, C.; Hebestreit, H.; Shimmin, D.; Solé, A.; Elborn, J. S.; Ellemunter, H.; Aurora, P.; Hogardt, M.; Wagner, T. O. F.; ECORN-CF Study Group

    2014-01-01

    There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation. PMID:24800072

  15. Lung cancer in patients with idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Karampitsakos, Theodoros; Tzilas, Vasilios; Tringidou, Rodoula; Steiropoulos, Paschalis; Aidinis, Vasilis; Papiris, Spyros A; Bouros, Demosthenes; Tzouvelekis, Argyris

    2017-08-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease of unknown etiology. With a gradually increasing worldwide prevalence and a mortality rate exceeding that of many cancers, IPF diagnosis and management are critically important and require a comprehensive multidisciplinary approach. This approach also involves assessment of comorbid conditions, such as lung cancer, that exerts a dramatic impact on disease survival. Emerging evidence suggests that progressive lung scarring in the context of IPF represents a risk factor for lung carcinogenesis. Both disease entities present with major similarities in terms of pathogenetic pathways, as well as potential causative factors, such as smoking and viral infections. Besides disease pathogenesis, anti-cancer agents, including nintedanib, have been successfully applied in the treatment of patients with IPF while an oncologic approach with a cocktail of several pleiotropic anti-fibrotic agents is currently in the therapeutic pipeline of IPF. Nevertheless, epidemiologic association between IPF and lung cancer does not prove causality. Currently there is significant lack of knowledge supporting a direct association between lung fibrosis and cancer reflecting to disappointing therapeutic algorithms. An optimal therapeutic strategy for patients with both IPF and lung cancer represents an amenable need. This review article synthesizes the current state of knowledge regarding pathogenetic commonalities between IPF and lung cancer and focuses on clinical and therapeutic data that involve both disease entities. Copyright © 2017. Published by Elsevier Ltd.

  16. Increased amount of atrial fibrosis in patients with atrial fibrillation secondary to mitral valve disease

    NARCIS (Netherlands)

    Geuzebroek, Guillaume S. C.; van Amersfoorth, Shirley C. M.; Hoogendijk, Mark G.; Kelder, Johannes C.; van Hemel, Norbert M.; de Bakker, Jacques M. T.; Coronel, Ruben

    2012-01-01

    Objective: Atrial fibrosis is related to atrial fibrillation but may differ in patients with mitral valve disease or lone atrial fibrillation. Therefore, we studied atrial fibrosis in patients with atrial fibrillation + mitral valve disease or with lone atrial fibrillation and compared it with

  17. Clinical presentation of metabolic alkalosis in an adult patient with cystic fibrosis.

    Science.gov (United States)

    Sweetser, Lisel J; Douglas, James A; Riha, Renata L; Bell, Scott C

    2005-03-01

    In subtropical and tropical climates, dehydration is common in cystic fibrosis patients with respiratory exacerbations. This may lead to a clinical presentation of metabolic alkalosis with associated hyponatraemia and hypochloraemia. An adult cystic fibrosis patient who presented with a severe respiratory exacerbation accompanied by metabolic alkalosis is presented and the effects of volume correction are reported.

  18. Subclinical anaemia of chronic disease in adult patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    O'connor, T M

    2012-02-03

    Patients with chronic hypoxaemia develop secondary polycythaemia that improves oxygen-carrying capacity. Therefore, normal haemoglobin and haematocrit values in the presence of chronic arterial hypoxaemia in cystic fibrosis constitute \\'relative anaemia\\'. We sought to determine the cause of this relative anaemia in patients with cystic fibrosis. We studied haematological indices and oxygen saturation in healthy volunteers (n=17) and in adult patients with cystic fibrosis (n=15). Patients with cystic fibrosis had lower resting arterial oxygen saturation when compared with normal volunteers (P<0.0001), and exercise led to a greater reduction in arterial oxygen saturation (P<0.0001). However, haemoglobin and haematocrit values in patients with cystic fibrosis did not significantly differ from normal volunteers. Serum iron (P=0.002), transferrin (P=0.02), and total iron-binding capacity (P=0.01) were lower in patients with cystic fibrosis. There were no significant differences in serum ferritin, percentage iron saturation, serum erythropoietin or red cell volume between the groups. The data presented demonstrate a characteristic picture of anaemia of chronic disease in adult patients with cystic fibrosis, except for normal haemoglobin and haematocrit values. Normal haemoglobin and haematocrit values in patients with cystic fibrosis appear to represent a combination of the effects of arterial hypoxaemia promoting polycythaemia, counterbalanced by chronic inflammation promoting anaemia of chronic disease.

  19. Pharmacokinetic variability of clarithromycin and differences in CYP3A4 activity in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Dalbøge, C S; Nielsen, X C; Dalhoff, K

    2014-01-01

    3A4-activity and clarithromycin metabolism was demonstrated (P cystic fibrosis patients may cause treatment failure. The Erythromycin Breath Test could be valuable in identifying cystic fibrosis patients in risk...

  20. Evolution and Pathoadaptation of Pseudomonas aeruginosa in Cystic Fibrosis Patients

    DEFF Research Database (Denmark)

    Marvig, Rasmus Lykke

    , which is a transmissible clone isolated from chronically infected Danish CF patients over a period of 38 years. Whole-genome analysis of DK2 isolates enabled a finegrained reconstruction of the recent evolutionary history of the DK2 lineage and an identification of bacterial genes targeted by mutations...... to optimize pathogen fitness. The identification of such pathoadaptive genes gives new insight into how the pathogen evolves under the selective pressures of the host immune system and drug therapies. Furthermore, isolates with increased rates of mutation (hypermutator phenotype) emerged in the DK lineage...... is the dominating pathogen of chronic airway infections in patients with cystic fibrosis (CF), and the bacterial long-term persistence in CF hosts involves mutation and selection of genetic variants with increased fitness in the CF airways. We performed a retrospective study of the P. aeruginosa DK2 clone type...

  1. Pseudomonas aeruginosa host-adaptation in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Rau, Martin Holm

    Pseudomonas aeruginosa is an opportunistic pathogen capable of transition from an environmental lifestyle to a host-associated lifestyle, as exemplified in the life-long airway infection of cystic fibrosis (CF) patients. Long-term infection is associated with extensive genetic adaptation of P...... the framework upon which this thesis is based. Early P. aeruginosa colonization of the CF airways is the period in which the outcome of infection is determined, i.e. if the bacteria are eventually eradicated or persist. In three patient cases the evolutionary events from initiation of infection were explored...... to unravel the early adaptive processes possibly securing bacterial persistence. In this early stage, clinical isolates displayed few adaptive events however these included phenotypes often observed in late chronic infection isolates including the conversion to a mucoid phenotype and increased antibiotic...

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

    Directory of Open Access Journals (Sweden)

    Aarti Shakkottai MD

    2017-02-01

    Full Text Available 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.

  3. Microbiota present in cystic fibrosis lungs as revealed by whole genome sequencing.

    Directory of Open Access Journals (Sweden)

    Philippe M Hauser

    Full Text Available Determination of the precise composition and variation of microbiota in cystic fibrosis lungs is crucial since chronic inflammation due to microorganisms leads to lung damage and ultimately, death. However, this constitutes a major technical challenge. Culturing of microorganisms does not provide a complete representation of a microbiota, even when using culturomics (high-throughput culture. So far, only PCR-based metagenomics have been investigated. However, these methods are biased towards certain microbial groups, and suffer from uncertain quantification of the different microbial domains. We have explored whole genome sequencing (WGS using the Illumina high-throughput technology applied directly to DNA extracted from sputa obtained from two cystic fibrosis patients. To detect all microorganism groups, we used four procedures for DNA extraction, each with a different lysis protocol. We avoided biases due to whole DNA amplification thanks to the high efficiency of current Illumina technology. Phylogenomic classification of the reads by three different methods produced similar results. Our results suggest that WGS provides, in a single analysis, a better qualitative and quantitative assessment of microbiota compositions than cultures and PCRs. WGS identified a high quantity of Haemophilus spp. (patient 1 or Staphylococcus spp. plus Streptococcus spp. (patient 2 together with low amounts of anaerobic (Veillonella, Prevotella, Fusobacterium and aerobic bacteria (Gemella, Moraxella, Granulicatella. WGS suggested that fungal members represented very low proportions of the microbiota, which were detected by cultures and PCRs because of their selectivity. The future increase of reads' sizes and decrease in cost should ensure the usefulness of WGS for the characterisation of microbiota.

  4. Noninvasive Assessment of Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Elena Buzzetti

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is prevalent in 20–25% of the general population and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. Histologically, NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH, fibrosis, and cirrhosis. As NASH develops in only 10–15% of patients with NAFLD, it is not practical to biopsy all patients who present with NAFLD. Noninvasive fibrosis tests have been extensively developed recently and offer alternatives for staging fibrosis. Despite their increasing use, such tests cannot adequately differentiate simple steatosis from NASH. At present, such tests can be used as first line tests to rule out patients without advanced fibrosis and thus prevent unnecessary secondary care referrals in a significant number of patients. In this review we present the evidence for the use of noninvasive fibrosis tests in patients with NAFLD.

  5. Primary structure determination of five sialylated oligosaccharides derived from bronchial- mucus glycoproteins of patients suffering from cystic fibrosis. The occurrence of the NeuAcα(2→3)Galα(1→4)[Fucα(1→3)]GlcNAcα(1→.) structural element revealed by 500-MHz 1H NMR spectroscopy

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Lamblin, G.; Boersma, A.; Klein, A.; Roussel, P.; Halbeek, H. van

    1984-01-01

    The structure of sialylated carbohydrate units of bronchial mucins obtained from cystic fibrosis patients was investigated by 500-MHz 1H NMR spectroscopy in conjunction with sugar analysis. After subjecting the mucins to alkaline borohydride degradation, sialylated oligosaccharide-alditols were

  6. Molecular epidemiology of Aspergillus collected from cystic fibrosis patients.

    Science.gov (United States)

    Sabino, Raquel; Ferreira, Jose A G; Moss, Richard B; Valente, Joana; Veríssimo, Cristina; Carolino, Elisabete; Clemons, Karl V; Everson, Cassie; Banaei, Niaz; Penner, John; Stevens, David A

    2015-07-01

    Aspergillus respiratory infection is a common complication in cystic fibrosis (CF) and is associated with loss of pulmonary function and allergic disease. Fifty-three Aspergillus isolates recovered from CF patients were identified to species by Internal Transcribed Spacer Region (ITS), β-tubulin, and calmodulin sequencing. Three species complexes (Terrei, Nigri, and Fumigati) were found. Identification to species level gave a single Aspergillus terreus sensu stricto, one Aspergillus niger sensu stricto and 51 Aspergillus fumigatus sensu stricto isolates. No cryptic species were found. To our knowledge, this is the first prospective study of Aspergillus species in CF using molecular methods. The paucity of non-A. fumigatus and of cryptic species of A. fumigatus suggests a special association of A. fumigatus sensu stricto with CF airways, indicating it likely displays unique characteristics making it suitable for chronic residence in that milieu. These findings could refine an epidemiologic and therapeutic approach geared to this pathogen. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  7. Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Ibrahim Ahmed Janahi

    2017-01-01

    Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is a pulmonary disorder that often occurs in patients with asthma or cystic fibrosis (CF and is characterized by a hypersensitivity response to the allergens of the fungus Aspergillus fumigatus. In patients with CF, growth of A. fumigatus hyphae within the bronchial lumen triggers an immunoglobulin E (IgE-mediated hypersensitivity response that results in airway inflammation, bronchospasm, and bronchiectasis. In most published studies, the prevalence of ABPA is about 8.9% in patients with CF. Since the clinical features of this condition overlap significantly with that of CF, ABPA is challenging to diagnose and remains underdiagnosed in many patients. Diagnosis of ABPA in CF patients should be sought in those with evidence of clinical and radiologic deterioration that is not attributable to another etiology, a markedly elevated total serum IgE level (while off steroid therapy and evidence of A. fumigatus sensitization. Management of ABPA involves the use of systemic steroids to reduce inflammation and modulate the immune response. In patients who do not respond to steroids or cannot tolerate them, antifungal agents should be used to reduce the burden of A. fumigatus allergens. Recent studies suggest that omalizumab may be an effective option to reduce the frequency of ABPA exacerbations in patients with CF. Further randomized controlled trials are needed to better establish the efficacy of omalizumab in managing patients with CF and ABPA.

  8. Sphingobacterium respiratory tract infection in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    de Gregorio Fabiola

    2009-12-01

    Full Text Available Abstract Background Bacteria that belong to the genus Sphingobacterium are Gram-negative, non-fermentative bacilli, ubiquitous in nature and rarely involved in human infections. The aims of this study were to evaluate the epidemiology of infection by Sphingobacterium in a cohort of patients affected by Cystic Fibrosis (CF, the antibiotic susceptibility and the DNA fingerprinting of the isolated strains and to analyze some clinical outcomes of the infected patients. Findings Between January 2006 and June 2008, patients (n = 332 attending the Regional CF Unit in Naples, Italy, were enrolled. Sputum samples were processed for microscopic, cultural, phenotypic identification and antibiotic susceptibility testing. DNA fingerprinting was performed by pulsed-field gel electrophoresis (PFGE. A total of 21 strains of Sphingobacterium were isolated from 7 patients (13 of S. spiritovorum, 8 of S. multivorum. S. multivorum isolates were more resistant than those of S. spiritovorum. PFGE profiles were in general heterogeneous, which suggested independent circulation. Conclusions This is the first Italian report about respiratory tract infections by Sphingobacterium in CF patients. In our cohort, these infections were not associated with a deterioration of pulmonary function during the follow-up period. Although the exact role of this microorganism in CF lung disease is unknown and the number of infected patients was small, this study could represent an important starting-point for understanding the epidemiology and the possible pathogenic role of Sphingobacterium in CF patients.

  9. Emergence of respiratory Streptococcus agalactiae isolates in cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Vera Eickel

    Full Text Available Streptococcus agalactiae is a well-known pathogen for neonates and immunocompromized adults. Beyond the neonatal period, S. agalactiae is rarely found in the respiratory tract. During 2002-2008 we noticed S. agalactiae in respiratory secretions of 30/185 (16% of cystic fibrosis (CF patients. The median age of these patients was 3-6 years older than the median age CF patients not harboring S. agalactiae. To analyze, if the S. agalactiae isolates from CF patients were clonal, further characterization of the strains was achieved by capsular serotyping, surface protein determination and multilocus sequence typing (MLST. We found a variety of sequence types (ST among the isolates, which did not substantially differ from the MLST patterns of colonizing strains from Germany. However serotype III, which is often seen in colonizing strains and invasive infections was rare among CF patients. The emergence of S. agalactiae in the respiratory tract of CF patients may represent the adaptation to a novel host environment, supported by the altered surfactant composition in older CF patients.

  10. Evaluation of Fucosylated Haptoglobin and Mac-2 Binding Protein as Serum Biomarkers to Estimate Liver Fibrosis in Patients with Chronic Hepatitis C.

    Directory of Open Access Journals (Sweden)

    Seiichi Tawara

    Full Text Available Fucosylated haptoglobin (Fuc-Hpt and Mac-2 binding protein (Mac-2 bp are identified as cancer biomarkers, based on the results from a glyco-proteomic analysis. Recently, we reported that these glyco-biomarkers were associated with liver fibrosis and/or ballooning hepatocytes in patients with nonalcoholic fatty liver disease (NAFLD. We evaluated the ability of these glycoproteins to estimate liver fibrosis in 317 patients with chronic hepatitis C. We measured the serum Fuc-Hpt and Mac-2 bp levels using a lectin-antibody ELISA and ELISA, respectively. The serum levels of both Fuc-Hpt and Mac-2 bp increased with the progression of liver fibrosis. The multivariate analysis revealed that Mac-2 bp was an independent factor associated with moderate liver fibrosis (F ≥ 2. In contrast, Fuc-Hpt was an independent factor associated with advanced liver fibrosis (F ≥ 3. In terms of evaluating liver fibrosis, the serum levels of these glycomarkers were correlated with well-known liver fibrosis indexes, such as the aspartate aminotransferase to platelet ratio index (APRI and Fibrosis-4 (FIB4 index. An assay that combined the APRI or FIB4 index and the Fuc-Hpt or Mac-2 bp levels increased the AUC value for diagnosing hepatic fibrosis. Interestingly, the cumulative incidence of hepatocellular carcinoma (HCC was significantly higher in the patients with elevated serum levels of Fuc-Hpt and Mac-2 bp. In conclusion, both Fuc-Hpt and Mac-2 bp could be useful glyco-biomarkers of liver fibrosis and predictors of HCC in patients with chronic hepatitis C.

  11. Genetic testing for cystic fibrosis in adult patients

    Directory of Open Access Journals (Sweden)

    Marina Mencinger

    2006-02-01

    Full Text Available Background: Cystic fibrosis (CF is an autosomal recessive disease caused by mutations in gene encoding cystic fibrosis transmembrane regulator (CFTR protein. Over 1400 mutations found in the gene contribute to the complexity of the CF phenotypes ranging from a classic multiorgan disease commonly involving respiratory, gastrointestinal and reproductive tract to mild and monosymptomatic presentations. Pilocarpine iontophoresis is considered as standard diagnostic test for CF, but it often fails in atypical forms of CF.Methods: In order to provide an additional diagnostic test to assure the diagnosis and provide patients with a proper medical care, we performed a genetic testing on 16 adults suspected to have atypical form of CF. Following counselling, parents of patients with possible homozygote variant of mutations were tested. On a personal request testing was also performed in an adult sibling of a patient with two known mutations to investigate possible carrier hood. The allele specific polymerase chain reaction method (PCR was used to detect 29 most common mutations in the cftr gene.Results: The diagnosis was proved in 3 individuals, a homozygote for Δ F508, and two compound heterozygotes Δ F508/R1162X and Δ F508/3849+10kbC>T. In three cases only one mutation was found: I148T, 2789+5G>A and Δ F508 in a heterozygote form.Conclusions: The genetic testing for CF is a valuable diagnostic tool in atypical forms of CF. Exclusion of possible differential diagnosis is warranted because of a variable CF phenotype. In cases where only one or no mutation was detected a necessity of whole gene sequencing is indicated to exclude rare mutations and polymorphisms that could be implicated in the pathogenesis of atypical CF.

  12. The Role of Computed Tomography in Monitoring Patients with Cystic Fibrosis

    International Nuclear Information System (INIS)

    Rybacka, Anna; Karmelita-Katulska, Katarzyna

    2016-01-01

    Cystic fibrosis is the most common lethal autosomal recessive disorder in the Caucasian population. Although the survival rate in patients constantly improves, lung damage is still the major cause of morbidity and mortality in patients with cystic fibrosis. In clinical practice, evaluation of patients’ pulmonary state is made by combination of monitoring of lung function and more directly by assessing the lung structure in imaging studies. Studies showed that computed tomography findings are more sensitive as compared to the pulmonary function tests. Computed tomography can identify a wide range of morphological abnormalities in patients with cystic fibrosis, such as bronchiectasis (which is progressive, irreversible and probably the most relevant structural change in cystic fibrosis) peribronchial thickening, mucous plugging and many other disorders that occur in the course of the disease. Computed tomography has a crucial role in the assessment of pulmonary damage over time, detecting complications and monitoring treatment effects in patients with cystic fibrosis

  13. Volumetric capnography for the evaluation of pulmonary disease in adult patients with cystic fibrosis and noncystic fibrosis bronchiectasis.

    Science.gov (United States)

    Veronez, L; Moreira, M M; Soares, S T P; Pereira, M C; Ribeiro, M A G O; Ribeiro, J D; Terzi, R G G; Martins, L C; Paschoal, I A

    2010-06-01

    This study was designed to use volumetric capnography to evaluate the breathing pattern and ventilation inhomogeneities in patients with chronic sputum production and bronchiectasis and to correlate the phase 3 slope of the capnographic curve to spirometric measurements. Twenty-four patients with cystic fibrosis (CF) and 21 patients with noncystic fibrosis idiopathic bronchiectasis (BC) were serially enrolled. The diagnosis of cystic fibrosis was based on the finding of at least two abnormal sweat chloride concentrations (iontophoresis sweat test). The diagnosis of bronchiectasis was made when the patient had a complaint of chronic sputum production and compatible findings at high-resolution computed tomography (HRCT) scan of the thorax. Spirometric tests and volumetric capnography were performed. The 114 subjects of the control group for capnographic variables were nonsmoker volunteers, who had no respiratory symptoms whatsoever and no past or present history of lung disease. Compared with controls, patients in CF group had lower SpO(2) (P volumes normalized for weight (V(E)/kg) (P volume (P3Slp/V(E)) (P capacities and both groups had very similar abnormalities. The capnographic variables in the patient group suggest a restrictive respiratory pattern (greater respiratory rates, smaller expiratory times and expiratory volumes, normal peak expiratory flows). Both groups of patients showed increased phase III slopes compared with controls, which probably indicates the presence of diffuse disease of small airways in both conditions leading to inhomogeneities of ventilation.

  14. Hemoglobin oxygen affinity in patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Dieter Böning

    Full Text Available In patients with cystic fibrosis lung damages cause arterial hypoxia. As a typical compensatory reaction one might expect changes in oxygen affinity of hemoglobin. Therefore position (standard half saturation pressure P50st and slope (Hill's n of the O2 dissociation curve as well as the Bohr coefficients (BC for CO2 and lactic acid were determined in blood of 14 adult patients (8 males, 6 females and 14 healthy controls (6 males, 8 females. While Hill's n amounted to approximately 2.6 in all subjects, P50st was slightly increased by 1 mmHg in both patient groups (controls male 26.7 ± 0.2, controls female 27.0 ± 0.1, patients male 27.7 ± 0.5, patients female 28.0 ± 0.3 mmHg; mean and standard error, overall p<0.01. Main cause was a rise of 1-2 µmol/g hemoglobin in erythrocytic 2,3-biphosphoglycerate concentration. One patient only, clearly identified as an outlier and with the mutation G551D, showed a reduction of both P50st (24.5 mmHg and [2,3-biphosphoglycerate] (9.8 µmol/g hemoglobin. There were no differences in BCCO2, but small sex differences in the BC for lactic acid in the controls which were not detectable in the patients. Causes for the right shift of the O2 dissociation curve might be hypoxic stimulation of erythrocytic glycolysis and an increased red cell turnover both causing increased [2,3-biphosphoglycerate]. However, for situations with additional hypercapnia as observed in exercising patients a left shift seems to be a more favourable adaptation in cystic fibrosis. Additionally when in vivo PO2 values were corrected to the standard conditions they mostly lay left of the in vitro O2 dissociation curve in both patients and controls. This hints to unknown fugitive factors influencing oxygen affinity.

  15. Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Sakugawa; Fukunori Kinjo; Atsushi Saito; Tomofumi Nakayoshi; Kasen Kobashigawa; Tsuyoshi Yamashiro; Tatsuji Maeshiro; Satoru Miyagi; Joji Shiroma; Akiyo Toyama; Tomokuni Nakayoshi

    2005-01-01

    AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), and progresses to the end stage of liver disease. Biochemical markers of liver fibrosis are strongly associated with the degree of histological liver fibrosis in patients with chronic liver disease.However, data are few on the usefulness of markers in NAFLD patients. The aim of this study was to identify better noninvasive predictors of hepatic fibrosis, with special focus on markers of liver fibrosis, type Ⅵ collagen 7S domain and hyaluronic acid.METHODS: One hundred and twelve patients with histologically proven NAFLD were studied.RESULTS: The histological stage of NAFLD correlated with several clinical and biochemical variables, the extent of hepatic fibrosis and the markers of liver fibrosis were relatively strong associated. The best cutoff values to detect NASH were assessed by using receiver operating characteristic analysis: type Ⅵ collagen 7S domain ≥5.0 ng/mL, hyaluronic acid ≥43 ng/mL. Both markers had a high positive predictive value: type Ⅵ collagen 7S domain, 86% and hyaluronic acid,92%. Diagnostic accuracies of these markers were evaluated to detect severe fibrosis. Both markers showed high negative predictive values: type Ⅵ collagen 7S domain (≥5.0 ng/mL),84% and hyaluronic acid (≥50 ng/mL), 78%, and were significantly and independently associated with the presence of NASH or severe fibrosis by logistic regression analysis.CONCLUSION: Both markers of liver fibrosis are useful in discriminating NASH from fatty liver alone or patients with severe fibrosis from patients with non-severe fibrosis.

  16. Short-term effects of splenectomy on serum fibrosis indexes in liver cirrhosis patients.

    Science.gov (United States)

    Kong, Degang; Chen, Xiuli; Lu, Shichun; Guo, Qingliang; Lai, Wei; Wu, Jushan; Lin, Dongdong; Zeng, Daobing; Duan, Binwei; Jiang, Tao; Cao, Jilei

    2015-01-01

    To determine the changing patterns of 4 liver fibrosis markers pre and post splenectomy (combined with pericardial devascularization [PCDV]) and to examine the short-term effects of splenectomy on liver fibrosis. Four liver fibrosis markers of 39 liver cirrhosis patients were examined pre, immediately post, 2 days post, and 1 week post (15 cases) splenectomy (combined with PCDV). The laminin (LN) level decreased immediately post surgery compared with the preoperative LN level (P splenectomy showed characteristic changes, splenectomy may transiently initiate the degradation process of liver fibrosis.

  17. Isolation of Pseudomonas cepacia in cystic fibrosis patient

    Directory of Open Access Journals (Sweden)

    Elizabeth de Andrade Marques

    1993-03-01

    Full Text Available Pulmonary infection on cystic fibrosis (CF patients are associated with a limited qualitative number of microorganisms. During the colonization process, Staphylococcus aureus usually preceedes Pseudomonas aeruginosa. This latter is at first non-mucoid, being replaced or associated to a mucoid morphotype which is rare in other diseases. In 1980, Pseudomonas cepacia appeared as an important agent in CF pulmonary infections with a mean frequency of about 6.1% isolations in different parts of the world. The primus colonization mainly occurs in the presence of pre-existent tissue lesions and the clinical progress of the disease is variable. In some patients it can be fulminant; in others it can cause a gradual and slow decrease in their pulmonary functions. The concern with this germ isolation is justified by its antibiotic multiple resistence and the possibility of direct transmission from a colonized patient to a non-colonized one. We reported the first case of P. cepacia infection in a CF patient in our area. The microbiological attendance to this patient had been made from 1986 to 1991 and the first positive culture appeared in 1988. The sensitivity profile showed that the primus colonization strain was sensitive to 9 of 17 tested antibiotics, however in the last culture the strain was resistent to all antibiotics. These data corroborate the need for monitoring the bacterial flora on CF patients respiratory system.

  18. [Peripherally inserted central catheter antibiotic therapy for cystic fibrosis patients].

    Science.gov (United States)

    Betegnie, A-L; Cracowski, C; Bedouch, P; Segond, C; Robein-Dobremez, M-J; Pin, I; Allenet, B

    2014-11-01

    Peripherally inserted central catheters (PICC) are more and more used for intravenous antibiotic infusions in cystic fibrosis (CF) patients in the Grenoble area (France). The aim of this study was to assess the use of this technique in this indication. 1. Retrospective evaluation of 102 consecutive PICC insertions over 3years and the incidence of adverse events during the therapy. 2. Prospective evaluation of 12 patient's satisfaction and their nurses over a 3-month period. 3. Comparative analysis of single domiciliary treatment costs using PICC versus peripheral catheter (PC). 102 PICC insertions were attempted in 31 patients. Seven failures and 7 complications occurred during the treatment requiring removal of the PICC, i.e. an overall success rate of 86.2% (88/102). Pain during PICC introduction was 4.2/10 (visual analogical scale). Mean satisfaction levels during therapy were 9.3/10 for patients and 8.7/10 for nurses. Compared with PC, all the patients said that PICC was "more comfortable". Differential costs of treatment with PC and with PICC at home were estimated at 57.15€ and 590.16€ respectively. PICC is an alternative to CP for intravenous antibiotherapy in CF patients, providing better safety and comfort. PICC use should be promoted in this indication. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  19. Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients

    DEFF Research Database (Denmark)

    Hansen, C. R.; Pressler, T.; Nielsen, K. G.

    2010-01-01

    BACKGROUND: Achromobacter xylosoxidans infection may cause conspicuous chronic pulmonary inflammation in cystic fibrosis (CF) patients similar to Pseudomonas aeruginosa and the Burkholderia cepacia complex (Bcc). Evolution in lung function was compared in chronically infected patients. Cytokine...

  20. Comparative genomics of non-pseudomonal bacterial species colonising paediatric cystic fibrosis patients

    Directory of Open Access Journals (Sweden)

    Kate L. Ormerod

    2015-09-01

    Full Text Available The genetic disorder cystic fibrosis is a life-limiting condition affecting ∼70,000 people worldwide. Targeted, early, treatment of the dominant infecting species, Pseudomonas aeruginosa, has improved patient outcomes; however, there is concern that other species are now stepping in to take its place. In addition, the necessarily long-term antibiotic therapy received by these patients may be providing a suitable environment for the emergence of antibiotic resistance. To investigate these issues, we employed whole-genome sequencing of 28 non-Pseudomonas bacterial strains isolated from three paediatric patients. We did not find any trend of increasing antibiotic resistance (either by mutation or lateral gene transfer in these isolates in comparison with other examples of the same species. In addition, each isolate contained a virulence gene repertoire that was similar to other examples of the relevant species. These results support the impaired clearance of the CF lung not demanding extensive virulence for survival in this habitat. By analysing serial isolates of the same species we uncovered several examples of strain persistence. The same strain of Staphylococcus aureus persisted for nearly a year, despite administration of antibiotics to which it was shown to be sensitive. This is consistent with previous studies showing antibiotic therapy to be inadequate in cystic fibrosis patients, which may also explain the lack of increasing antibiotic resistance over time. Serial isolates of two naturally multi-drug resistant organisms, Achromobacter xylosoxidans and Stenotrophomonas maltophilia, revealed that while all S. maltophilia strains were unique, A. xylosoxidans persisted for nearly five years, making this a species of particular concern. The data generated by this study will assist in developing an understanding of the non-Pseudomonas species associated with cystic fibrosis.

  1. Surgical Outcomes of Lung Cancer Patients with Combined Pulmonary Fibrosis and Emphysema and Those with Idiopathic Pulmonary Fibrosis without Emphysema.

    Science.gov (United States)

    Sato, Seijiro; Koike, Terumoto; Hashimoto, Takehisa; Ishikawa, Hiroyuki; Okada, Akira; Watanabe, Takehiro; Tsuchida, Masanori

    2016-08-23

    Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder. The aim of this study was to compare the surgical outcomes of lung cancer patients with CPFE and those with idiopathic pulmonary fibrosis (IPF) without emphysema. A total of 1548 patients who underwent surgery for primary lung cancer between January 2001 and December 2012 were retrospectively reviewed. Of the 1548 patients, 55 (3.6%) had CPFE on computed tomography (CT), and 45 (2.9%) had IPF without emphysema. The overall and disease-free 5-year survival rates for patients with CPFE were not significantly worse than those for patients with IPF without emphysema (24.9% vs. 36.8%, p = 0.814; 39.8% vs. 39.3%, p = 0.653, respectively). Overall, 21 (38.1%) patients with CPFE and nine patients (20.0%) with IPF without emphysema developed postoperative cardiopulmonary complications. Patients with CPFE had significantly more postoperative cardiopulmonary complications involving pulmonary air leakage for >6 days, hypoxemia, and arrhythmia than patients with IPF without emphysema (p = 0.048). There was no significant difference in survival after surgical treatment between CPFE patients and IPF patients without emphysema, but CPFE patients had significantly higher morbidity than IPF patients without emphysema.

  2. Optimizing quality of life in patients with idiopathic pulmonary fibrosis

    Science.gov (United States)

    van Manen, Mirjam J. G.; Geelhoed, J. J. Miranda.; Tak, Nelleke C.; Wijsenbeek, Marlies S.

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating, progressive and ultimately fatal lung disease. The combination of poor prognosis, uncertainty of disease course and severe symptom burden heavily impacts patients’ and their families’ quality of life. Though new antifibrotic drugs have been shown to decrease disease progression, the effect on health-related quality of life (HRQOL) has not been convincingly demonstrated. In a relentless disease such as IPF, striving to optimize HRQOL should complement the endeavour to prolong life. Unfortunately, there is a paucity of interventions improving symptoms and functionality for patients with IPF, and research focusing on symptom improvement, and assessing and optimizing HRQOL, is limited. This review summarizes the most recent insights into measuring and improving quality of life for patients with IPF, and discusses challenges in the management of this devastating disease. Moreover, we postulate a new model for continuous care in IPF – ‘the ABCDE of IPF care’: Assessing patients’ needs; Backing patients by giving information and support; delivering Comfort care by focusing on treating symptoms and taking into account Comorbidities; striving to prolong life by Disease modification; helping and preparing patients and their caregivers for the eventual End-of-life events that are likely to occur. PMID:28134007

  3. Clinical characteristics in patients with asymmetric idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Callahan, Sean J; Xia, Meng; Murray, Susan; Flaherty, Kevin R

    2016-10-01

    A group of patients with idiopathic pulmonary fibrosis (IPF) presents with disease affecting one lung markedly more than the other. At this time, it is unclear how this population differs from those who present with more symmetric disease. We sought to explain the characteristics of the asymmetric group and how their disease progresses. In this retrospective case-control study we accessed an interstitial lung disease (ILD) database and identified 14 asymmetric IPF cases via high-resolution computed tomography (HRCT) scoring of each lung lobe's disease severity. We identified 28 symmetric IPF controls from the same database using the same methods, and compared the clinical features of each group. Patients with asymmetric disease exhibited similar demographics as those in the general IPF population; they were predominantly male (64%), elderly (69 years old), and used tobacco (57%). We found a trend toward significantly increased all-cause mortality in the case population two years following diagnosis (p = 0.089). Pulmonary function tests were significantly lower in the case group at the time of diagnosis, then both groups experienced gradual decline. We found no statistically significant differences in number of IPF exacerbations (cases 43%, controls 39%, p = 0.824) and gastro-esophageal reflux (both groups 50%). Patients with asymmetric IPF resemble patients in the general IPF population but may have a lower overall survival rate. Further systemic factors may be studied to identify reasons for disease asymmetry and clinical decline in this population. Published by Elsevier Ltd.

  4. [The profile of caregivers to pediatric patients with cystic fibrosis].

    Science.gov (United States)

    Alves, Stella Pegoraro; Bueno, Denise

    2018-05-01

    The scope of this study was to establish the profile of caregivers of pediatric patients diagnosed with Cystic Fibrosis (CF). It was a cross-sectional, descriptive and prospective study in which the caregivers of fibrocystic patients were interviewed during pharmaceutical consultation in a reference center of a University Hospital in southern Brazil. General information was obtained about the caregivers and about their understanding of the disease, drug consumption and dynamics of treatment at home and at school. Seventy-five caregivers were interviewed. Most of them were female, 37.3 years old on average, mothers of the patients who did not work outside the home. Seventy-one caregivers declared difficulties in drug acquisition and patient support associations were highlighted as the main alternative to avoid the interruption of treatment. Another fact observed was the overload of the caregiving process on the shoulders of only one caregiver resulting in social and economic impacts and changes to the family's daily routine. This fact emphasizes the need of intervention by a qualified multidisciplinary team to identify and alleviate difficulties, investing in interpersonal relations and administering care.

  5. Independent predictors of fibrosis in patients with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Hossain, Noreen; Afendy, Arian; Stepanova, Maria; Nader, Fatema; Srishord, Manirath; Rafiq, Nila; Goodman, Zachary; Younossi, Zobair

    2009-11-01

    Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We investigated factors associated with advanced fibrosis in NAFLD. The study included 432 patients with histologically proven NAFLD (26.8% with nonalcoholic steatohepatitis [NASH] and 17.4% with moderate-to severe fibrosis). NASH was defined as steatosis, lobular inflammation, and ballooning degeneration with or without Mallory-Denk bodies and/or fibrosis. Fibrosis was classified into 2 groups: those with no or minimal fibrosis and those with moderate-to-severe fibrosis. Groups were compared using Mann-Whitney and chi-square method analyses. A model was constructed using a stepwise bidirectional method; its predictive power was measured using a 10-fold cross-validation technique. Patients with NASH were more likely to be male (P < .0001); have lower hip-to-waist ratios (P = .03); were less likely to be African American (P = .06); have higher levels of alanine aminotransferase (ALT; P < .0001), aspartate aminotransferase (AST; P < .0001), and serum triglycerides (P = .0154), but lower levels of high-density lipoprotein cholesterol (P < .0001). Patients with moderate-to-severe fibrosis were older (P = .0245); more likely to be male (P = .0189), Caucasian (P = .0382), have diabetes mellitus (P = .0238), and hypertension (P = .0375); and have a lower hip-to-waist ratio (P = .0077) but higher serum AST (P < .0001) and ALT (P < .0001) levels. The multivariate analysis model to predict moderate-to-severe fibrosis included male sex, Caucasian ethnicity, diabetes mellitus, and increased AST and ALT levels (model P value < .0001). In patients with NAFLD, diabetes mellitus and aminotransferase levels are independent predictors of moderate-to-severe fibrosis. They can be used to identify NAFLD patients at risk for advanced fibrosis.

  6. Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease

    Directory of Open Access Journals (Sweden)

    Robert A. Quinn

    2016-08-01

    Full Text Available Background. Cystic fibrosis (CF is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy. Methods. Longitudinal sputum samples were collected from 11 patients (n = 44 samples to assess the effect of exacerbations on the sputum metabolome using liquid chromatography-tandem mass spectrometry (LC-MS/MS. The data was analyzed with MS/MS molecular networking and multivariate statistics. Results. The individual patient source had a larger influence on the metabolome of sputum than the clinical state (exacerbation, treatment, post-treatment, or stable. Of the 4,369 metabolites detected, 12% were unique to CFPE samples; however, the only known metabolites significantly elevated at exacerbation across the dataset were platelet activating factor (PAF and a related monacylglycerophosphocholine lipid. Due to the personalized nature of the sputum metabolome, a single patient was followed for 4.2 years (capturing four separate exacerbation events as a case study for the detection of personalized biomarkers with metabolomics. PAF and related lipids were significantly elevated during CFPEs of this patient and ceramide was elevated during CFPE treatment. Correlating the abundance of bacterial 16S rRNA gene amplicons to metabolomics data from the same samples during a CFPE demonstrated that antibiotics were positively correlated to Stenotrophomonas and Pseudomonas, while ceramides and other lipids were correlated with Streptococcus, Rothia, and anaerobes. Conclusions. This study identified PAF and other inflammatory lipids as potential biomarkers of CFPE, but overall, the metabolome of CF sputum was patient specific, supporting a personalized approach to molecular detection of CFPE onset.

  7. Pandoraea pnomenusa Isolated from an Australian Patient with Cystic Fibrosis.

    Science.gov (United States)

    Ambrose, Mark; Malley, Roslyn C; Warren, Sanchia J C; Beggs, Sean A; Swallow, Oliver F E; McEwan, Belinda; Stock, David; Roddam, Louise F

    2016-01-01

    Pandoraea species are considered as emerging pathogens in people with cystic fibrosis (CF). The contribution of these organisms to disease progression in CF patients is not fully understood owing in large measure to the scant reports in clinical and research literature describing their colonization of CF patients and their associated virulence determinants. In an effort to increase awareness and evidence for Pandoraea spp. infection in people with CF, and to stimulate research aimed at unraveling the pathogenic properties of Pandoraea, we report a case of a 26-year-old Australian (Tasmanian) man with CF who was chronically infected with Pandoraea pnomenusa for at least one year prior to his death from respiratory failure. In addition, we describe for the first time evidence suggesting that this bacterium is a facultative anaerobe and report on the availability of a whole genome sequence for this organism. To the best of our knowledge, this report represents only the second clinical case study of P. pnomenusa infection in the world, and the first in an Australian CF patient.

  8. Sleep-disordered breathing in patients with cystic fibrosis *

    Science.gov (United States)

    Veronezi, Jefferson; Carvalho, Ana Paula; Ricachinewsky, Claudio; Hoffmann, Anneliese; Kobayashi, Danielle Yuka; Piltcher, Otavio Bejzman; Silva, Fernando Antonio Abreu e; Martinez, Denis

    2015-01-01

    Abstract Objective: To test the hypothesis that disease severity in patients with cystic fibrosis (CF) is correlated with an increased risk of sleep apnea. Methods: A total of 34 CF patients underwent clinical and functional evaluation, as well as portable polysomnography, spirometry, and determination of IL-1β levels. Results: Mean apnea-hypopnea index (AHI), SpO2 on room air, and Epworth Sleepiness Scale score were 4.8 ± 2.6, 95.9 ± 1.9%, and 7.6 ± 3.8 points, respectively. Of the 34 patients, 19 were well-nourished, 6 were at nutritional risk, and 9 were malnourished. In the multivariate model to predict the AHI, the following variables remained significant: nutritional status (β = −0.386; p = 0.014); SpO2 (β = −0.453; p = 0.005), and the Epworth Sleepiness Scale score (β = 0.429; p = 0.006). The model explained 51% of the variation in the AHI. Conclusions: The major determinants of sleep apnea were nutritional status, SpO2, and daytime sleepiness. This knowledge not only provides an opportunity to define the clinical risk of having sleep apnea but also creates an avenue for the treatment and prevention of the disease. PMID:26398755

  9. Noninvasive Assessment of Advanced Fibrosis Based on Hepatic Volume in Patients with Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Hayashi, Tatsuya; Saitoh, Satoshi; Fukuzawa, Kei; Tsuji, Yoshinori; Takahashi, Junji; Kawamura, Yusuke; Akuta, Norio; Kobayashi, Masahiro; Ikeda, Kenji; Fujii, Takeshi; Miyati, Tosiaki; Kumada, Hiromitsu

    2017-09-15

    Noninvasive liver fibrosis evaluation was performed in patients with nonalcoholic fatty liver disease (NAFLD). We used a quantitative method based on the hepatic volume acquired from gadoxetate disodium-enhanced (Gd-EOB-DTPA-enhanced) magnetic resonance imaging (MRI) for diagnosing advanced fibrosis in patients with NAFLD. A total of 130 patients who were diagnosed with NAFLD and underwent Gd-EOB-DTPA-enhanced MRI were retrospectively included. Histological data were available for 118 patients. Hepatic volumetric parameters, including the left hepatic lobe to right hepatic lobe volume ratio (L/R ratio), were measured. The usefulness of the L/R ratio for diagnosing fibrosis ≥F3-4 and F4 was assessed using the area under the receiver operating characteristic (AUROC) curve. Multiple regression analysis was performed to identify variables (age, body mass index, serum fibrosis markers, and histological features) that were associated with the L/R ratio. The L/R ratio demonstrated good performance in differentiating advanced fibrosis (AUROC, 0.80; 95% confidence interval, 0.72 to 0.88) from cirrhosis (AUROC, 0.87; 95% confidence interval, 0.75 to 0.99). Multiple regression analysis showed that only fibrosis was significantly associated with the L/R ratio (coefficient, 0.121; p<0.0001). The L/R ratio, which is not influenced by pathological parameters other than fibrosis, is useful for diagnosing cirrhosis in patients with NAFLD.

  10. Improving the care of patients with cystic fibrosis (CF)

    Science.gov (United States)

    Khan, Ahsan Aftab; Nash, Edward F; Whitehouse, Joanna; Rashid, Rifat

    2017-01-01

    Background The West Midlands Adult Cystic Fibrosis (CF) Centre based at Birmingham Heartlands Hospital provides care for adults with CF in the West Midlands. People with CF are prone to pulmonary exacerbations, which often require inpatient admission for intravenous antibiotics. We observed that the admission process was efficient during working hours (9:00–17:00, Monday–Friday) when the CF team are routinely available, but out-of-working hours, there were delays in these patients being clerked and receiving their first antibiotic dose. We were concerned that this was resulting in quality and potential safety issues by causing delays in starting treatment and prolonging hospital inpatient stays. We therefore undertook a quality improvement project (QIP) aimed at addressing these issues. An initial survey showed median time to clerk of 5 hours, with 60% of patients missing their first dose of antibiotics and mean length of stay of 16 days. Methods We applied the Plan-Do-Study-Act (PDSA) cycle approach, with the first PDSA cycle involving raising awareness of the issue through education to doctors, nurses and patients. Results This led to a reduction of median time to clerk from 5 to 2 hours with 23% of patients missing their first antibiotic dose and mean length of stay reducing to 14 days. The second cycle involved introducing an admissions checklist and displaying education posters around the hospital, resulting in median time to clerk remaining at 2 hours but only 20% of patients missing their first antibiotic dose and the mean length of stay remaining at 14 days. Conclusion This QIP has improved the out-of-hours admissions process for adults with CF in our centre. We plan to review the longer term effects of the project including sustainability, effects on clinical outcomes and patient satisfaction. PMID:28959778

  11. Blunted perception of neural respiratory drive and breathlessness in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Charles C. Reilly

    2016-03-01

    Full Text Available The electromyogram recorded from the diaphragm (EMGdi and parasternal intercostal muscle using surface electrodes (sEMGpara provides a measure of neural respiratory drive (NRD, the magnitude of which reflects lung disease severity in stable cystic fibrosis. The aim of this study was to explore perception of NRD and breathlessness in both healthy individuals and patients with cystic fibrosis. Given chronic respiratory loading and increased NRD in cystic fibrosis, often in the absence of breathlessness at rest, we hypothesised that patients with cystic fibrosis would be able to tolerate higher levels of NRD for a given level of breathlessness compared to healthy individuals during exercise. 15 cystic fibrosis patients (mean forced expiratory volume in 1 s (FEV1 53.5% predicted and 15 age-matched, healthy controls were studied. Spirometry was measured in all subjects and lung volumes measured in the cystic fibrosis patients. EMGdi and sEMGpara were recorded at rest and during incremental cycle exercise to exhaustion and expressed as a percentage of maximum (% max obtained from maximum respiratory manoeuvres. Borg breathlessness scores were recorded at rest and during each minute of exercise. EMGdi % max and sEMGpara % max and associated Borg breathlessness scores differed significantly between healthy subjects and cystic fibrosis patients at rest and during exercise. The relationship between EMGdi % max and sEMGpara % max and Borg score was shifted to the right in the cystic fibrosis patients, such that at comparable levels of EMGdi % max and sEMGpara % max the cystic fibrosis patients reported significantly lower Borg breathlessness scores compared to the healthy individuals. At Borg score 1 (clinically significant increase in breathlessness from baseline corresponding levels of EMGdi % max (20.2±12% versus 32.15±15%, p=0.02 and sEMGpara % max (18.9±8% versus 29.2±15%, p=0.04 were lower in the healthy individuals compared to the cystic

  12. Acute appendicitis mimicking intestinal obstruction in a patient with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Chun-Han Chen

    2012-10-01

    Full Text Available Cystic fibrosis (CF is an inherited disease of the secretory glands caused by mutations of the cystic fibrosis transmembrane regulator (CFTR gene. The clinical manifestations of CF are repetitive lung infections, biliary cirrhosis, pancreatic abnormalities, and gastrointestinal disorders. We report a 21-year-old Taiwanese man with CF who had abdominal pain for 2 days. The diagnosis of CF had been confirmed by peripheral blood analysis of the CFTR gene 5 years before admission. He presented to the emergency department with nausea, vomiting, abdominal distension, and crampy abdominal pain, which is atypical for acute appendicitis. The physical examination and a series of studies revealed intestinal obstruction, but acute appendicitis could not be ruled out. After conservative treatment, together with empiric antibiotics, the refractory abdominal pain and leukocytosis with a left-shift warranted surgical intervention. A diagnostic laparoscopy revealed a swollen, hyperemic appendix, a severely distended small intestine, and serous ascites. The laparoscopic procedure was converted to a laparotomy for open disimpaction and appendectomy. He was discharged on the eighth postoperative day. The histologic examination of the appendix was consistent with early appendicitis. In conclusion, acute abdominal pain in adult CF patients is often associated with intestinal obstruction syndrome. The presentation of concurrent appendicitis may be indolent and lead not only to diagnostic difficulties, but also a number of therapeutic choices.

  13. Acute appendicitis mimicking intestinal obstruction in a patient with cystic fibrosis.

    Science.gov (United States)

    Chen, Chun-Han; Chang, Cheng-Chih; Yang, Bor-Yau; Lin, Paul Y; Wang, Chia-Siu

    2012-10-01

    Cystic fibrosis (CF) is an inherited disease of the secretory glands caused by mutations of the cystic fibrosis transmembrane regulator (CFTR) gene. The clinical manifestations of CF are repetitive lung infections, biliary cirrhosis, pancreatic abnormalities, and gastrointestinal disorders. We report a 21-year-old Taiwanese man with CF who had abdominal pain for 2 days. The diagnosis of CF had been confirmed by peripheral blood analysis of the CFTR gene 5 years before admission. He presented to the emergency department with nausea, vomiting, abdominal distension, and crampy abdominal pain, which is atypical for acute appendicitis. The physical examination and a series of studies revealed intestinal obstruction, but acute appendicitis could not be ruled out. After conservative treatment, together with empiric antibiotics, the refractory abdominal pain and leukocytosis with a left-shift warranted surgical intervention. A diagnostic laparoscopy revealed a swollen, hyperemic appendix, a severely distended small intestine, and serous ascites. The laparoscopic procedure was converted to a laparotomy for open disimpaction and appendectomy. He was discharged on the eighth postoperative day. The histologic examination of the appendix was consistent with early appendicitis. In conclusion, acute abdominal pain in adult CF patients is often associated with intestinal obstruction syndrome. The presentation of concurrent appendicitis may be indolent and lead not only to diagnostic difficulties, but also a number of therapeutic choices. Copyright © 2012. Published by Elsevier B.V.

  14. The Prognosis of Small Cell Lung Cancer in Patients with Pulmonary Fibrosis.

    Science.gov (United States)

    Matsumoto, Yoko; Ohara, Sayaka; Furukawa, Ryutaro; Usui, Kazuhiro

    2017-10-01

    The purpose of this study was to assess the prognosis of small cell lung cancer (SCLC) based on the underlying pulmonary disease. A total of 204 patients with SCLC were reviewed and categorized into three groups: normal, emphysema and fibrosis. The median overall survival duration (OS) in patients with normal lungs (n=57), with emphysema (n=105) and fibrosis (n=42) was 21.3, 16.4 and 10.8 months (p=0.063). In limited-stage disease (LD), the median OS in patients with fibrosis (7.4 months) was shorter than normal (52.7 months) or emphysema patients (26.4 months) (p=0.034). In extensive-stage disease (ED), the median OS in patients with fibrosis (12.7 months) was not significantly different from normal (11.4 months) or emphysema patients (13.5 months) (p=0.600). Patients with fibrosis had a poorer prognosis than normal or emphysema patients in LD-SCLC, but the coexistence of pulmonary fibrosis did not affect the prognostic outcomes in ED-SCLC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Maintenance of nutritional status in patients with cystic fibrosis: new and emerging therapies

    Directory of Open Access Journals (Sweden)

    Kalnins D

    2012-06-01

    Full Text Available Daina Kalnins,1 Michael Wilschanski21Clinical Dietetics, Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada; 2Pediatric Gastroenterology Unit, Hadassah University Hospitals, Jerusalem, IsraelAbstract: Poor clinical outcomes in cystic fibrosis are often associated with undernutrition. Normal growth and development should be achieved in cystic fibrosis, and nutritional counseling is paramount at all ages. Prevention and early detection of growth failure is the key to successful nutritional intervention. The advance in nutritional management is certainly one factor that has contributed to the improved survival in recent decades. This review outlines the major nutritional parameters in the management of the patient with cystic fibrosis, including recent advances in pancreatic enzyme replacement therapy and fat-soluble vitamin therapy. There are sections on complicated clinical situations which directly affect nutrition, for example, before and after lung transplantation, cystic fibrosis-related diabetes, and bone health.Keywords: cystic fibrosis, nutrition, fat-soluble vitamins, pancreatic enzymes

  16. Anesthesia for Lobectomy in a Pediatric Patient` with Cystic Fibrosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Seyedhejazi Mahin

    2014-07-01

    Full Text Available Cystic Fibrosis is the most common autosomal recessive disease which causes a lot of complications and there are some needed operations in lifelong of such patients. Anesthesia in these patients requires particular attention and a full cooperation of surgeon, anesthetist and pediatrician .We reported a case of lobectomy with lung separation in a 4.5 years old child with cystic fibrosis which was performed with minor complications in the hope that an awareness of such situations may turn up similar cases of study. Keywords: Cystic Fibrosis, Anesthesia, Pulmonic Lobectomy

  17. Role of hyaluronic acid and laminin as serum markers for predicting significant fibrosis in patients with chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    Feng Li

    Full Text Available OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of serum HA and LN as serum markers for predicting significant fibrosis in CHB patients. METHODS: Serum HA and LN levels of 87 patients with chronic hepatitis B and 19 blood donors were assayed by RIA. Liver fibrosis stages were determined according to the Metavir scoring-system. The diagnostic performances of all indexes were evaluated by the receiver operating characteristic (ROC curves. RESULTS: Serum HA and LN concentrations increased significantly with the stage of hepatic fibrosis, which showed positive correlation with the stages of liver fibrosis (HA: r = 0.875, p < 0.001; LN: r = 0.610, p < 0.001. There were significant differences of serum HA and LN levels between F2-4 group in comparison with those in F0-F1 group (p < 0.001 and controls (p < 0.001, respectively. From ROC curves, 185.3 ng/mL as the optimal cut-off value of serum HA for diagnosis of significant fibrosis, giving its sensitivity, specificity, PPV, NPV, LR+, LR- and AC of 84.2%, 83.3%, 90.6%, 73.5%, 5.04, 0.19 and 83.9, respectively. While 132.7 ng/mL was the optimal cut-off value of serum LN, the sensitivity, specificity, PPV, NPV, LR+, LR- and AC were 71.9%, 80.0%, 87.2%, 60.0%, 3.59%, 0.35% and 74.7, respectively. Combinations of HA and LN by serial tests showed a perfect specificity and PPV of 100%, at the same time sensitivity declined to 63.2% and LR+ increased to 18.9, while parallel tests revealed a good sensitivity of 94.7%, NPV to 86.4%, and LR- declined to 0.08. CONCLUSIONS: Serum HA and LN concentrations showed positive correlation with the stages of liver fibrosis. Detection of serum HA and LN in predicting significant fibrosis showed good diagnostic performance, which would be further optimized by combination of the two indices. HA and LN would be clinically useful serum markers for predicting significant fibrosis in patients with chronic hepatitis B, when liver biopsy is

  18. Serum Mac-2 binding protein glycosylation isomer predicts grade F4 liver fibrosis in patients with biliary atresia.

    Science.gov (United States)

    Yamada, Naoya; Sanada, Yukihiro; Tashiro, Masahisa; Hirata, Yuta; Okada, Noriki; Ihara, Yoshiyuki; Urahashi, Taizen; Mizuta, Koichi

    2017-02-01

    Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) is a novel fibrosis marker. We examined the ability of M2BPGi to predict liver fibrosis in patients with biliary atresia. Sixty-four patients who underwent living donor liver transplantation (LDLT) were included [median age, 1.1 years (range 0.4-16.0), male 16 patients (25.0 %)]. We examined M2BPGi levels in serum obtained the day before LDLT, and we compared the value of the preoperative M2BPGi levels with the histological evaluation of fibrosis using the METAVIR fibrosis score. Subsequently, we assessed the ability of M2BPGi levels to predict fibrosis. The median M2BPGi level in patients with BA was 6.02 (range, 0.36-20.0), and 0, 1, 1, 11, and 51 patients had METAVIR fibrosis scores of F0, F1, F2, F3, and F4, respectively. In patients with F4 fibrosis, the median M2BPGi level was 6.88 (quartile; 5.235, 12.10), significantly higher than that in patients with F3 fibrosis who had a median level of 2.42 (quartile; 1.93, 2.895, p F4 fibrosis. M2BPGi is a novel fibrosis marker for evaluating the status of the liver in patients with BA, especially when predicting grade F4 fibrosis.

  19. Molecular detection of an atypical, highly resistant, clonal Pseudomonas aeruginosa isolate in cystic fibrosis patients.

    LENUS (Irish Health Repository)

    Keating, Deirdre

    2013-03-01

    The identification of Pseudomonas aeruginosa (P. aeruginosa) isolates in sputum from cystic fibrosis (CF) patients can be challenging due to the multitude of phenotypic changes isolates undergo during adaptation to the microenvironment of the CF lung.

  20. Anterior uveitis and congenital fibrosis of the extraocular muscles in a patient with Noonan syndrome

    Directory of Open Access Journals (Sweden)

    Elgohary Mostafa

    2005-01-01

    Full Text Available We describe a patient with Noonan syndrome who presented with Human Leukocyte Antigen B27-associated recurrent acute anterior uveitis and manifestations of congenital fibrosis of the extraocular muscles, which has not been reported before.

  1. FEATURES OF METABOLIC INDEXES OF BLOOD LYMPHOCYTES IN THE PATIENTS WITH EPIDURAL FIBROSIS FOLLOWING LUMBAR MICRODISCECTOMY

    Directory of Open Access Journals (Sweden)

    N. V. Isaeva

    2008-01-01

    Full Text Available Abstract. A complex immunologic examination of fifty patients with clinically significant postoperative fibrosis has been performed. Immunogram indexes were determined, and activities of basic oxidation-reduction enzymes were investigated in blood lymphocytes. What concerned immune status of the patients under study, some peculiar features have been revealed, with respect to cellular and humoral compartments, i.e., relative increase in CD3+ population, a shift to CD4+ cells in the ratio of lymphocyte subpopulations, higher indexes of immune regulation and phagocytosis, increased IgG level, and lower content of IgA, as compared to appropriate controls. Metabolic parameters of lymphocytes reflect their functional activation, being expressed as an enhanced ability for intracellular synthetic processes, elevated functional activity of lymphocytes, and increased immune response. The general pattern of changes in immune status and metabolic indexes of lymphocytes allow us to assume participation of autoimmune component in progression of epidural fibrosis. The data obtained may be used in combined diagnostics and correction of this disorder. (Med. Immunol., vol. 10, N 6, pp 589-592.

  2. Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Todd NW

    2013-03-01

    Full Text Available Nevins W Todd,1,2 Rachel G Scheraga,1,3 Jeffrey R Galvin,1,4 Aldo T Iacono,1 E James Britt,1 Irina G Luzina,1,2 Allen P Burke,5,* Sergei P Atamas1,2,* 1Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; 2Baltimore VA Medical Center, Baltimore, MD, USA; 3Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; 4Department of Diagnostic Radiology, University of Maryland School of Medicine, Baltimore, MD, USA; 5Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA *These authors contributed equally to this work Background: Idiopathic pulmonary fibrosis (IPF is a fatal lung disease with no known effective therapy. It is often assumed, but has not been objectively evaluated, that pulmonary inflammation subsides as IPF progresses. The goal of this work was to assess changes in the degree of inflammatory cell infiltration, particularly lymphocytic infiltration, over the duration of illness in IPF. Methods: Sixteen patients with confirmed IPF were identified in patients whom surgical lung biopsy (SLB was performed in early disease, and in patients whom lung transplantation was subsequently performed in end stage disease. A numerical scoring system was used to histologically quantify the amount of fibrosis, honeycomb change, fibroblastic foci, and lymphocyte aggregates in each SLB and lung explant tissue sample. Analyses of quantitative scores were performed by comparing paired, matched samples of SLB to lung explant tissue. Results: Median time [1st, 3rd quartiles] from SLB to lung transplantation was 24 [15, 29] months. Histologic fibrosis and honeycomb change were more pronounced in the explant samples compared with SLB (P < 0.001 and P < 0.01, respectively, and most notably, higher numbers of lymphocyte aggregates were observed in the explant samples compared to SLB (P = 0.013. Immunohistochemical analyses revealed abundant CD3+ (T lymphocyte and CD20+ (B

  3. Emerging potential treatments: new hope for idiopathic pulmonary fibrosis patients?

    Directory of Open Access Journals (Sweden)

    U. Costabel

    2011-09-01

    Full Text Available Currently, there are no approved pharmacological treatments for the management of patients with idiopathic pulmonary fibrosis (IPF in the USA or Europe. Pirfenidone is an orally bio-available small molecule that exhibits antifibrotic and anti-inflammatory properties in a variety of in vitro and animal models. Pirfenidone has been evaluated in four randomised, double-blind, placebo-controlled clinical trials conducted in Japan, North America and Europe. The totality of the data from these trials indicates that pirfenidone is able to reduce the rate of decline in lung function, measured as change in per cent predicted forced vital capacity (FVC or vital capacity. There was also an effect on secondary end-points of progression free survival, categorical change in per cent predicted FVC, and the 6-min walk test. A recent meta-analysis of the three phase III studies in IPF demonstrated that pirfenidone significantly reduced the risk of disease progression by 30%. The efficacy of pirfenidone is associated with an acceptable tolerability and safety profile.

  4. Multiorgan gadolinium (Gd) deposition and fibrosis in a patient with nephrogenic systemic fibrosis--an autopsy-based review

    DEFF Research Database (Denmark)

    Sanyal, Soma; Marckmann, Peter; Scherer, Susanne

    2011-01-01

    tissues of NSF patients, predominantly at the bulk chemical level. The distribution of Gd at the histologic level of organs other than skin has not been reported previously. METHODS: We analysed tissues from an autopsy case with verified advanced NSF by light microscopy and scanning electron microscopy......), kidney, lymph node, skeletal muscle, dura mater and cerebellum of the NSF autopsy case, primarily in vascular walls. Some, but not all, Gd deposits were seen in fibrotic areas. Literature review highlighted that non-specific tissue fibrosis and calcification are frequent findings in tissues of patients...

  5. [Cystic fibrosis--initial diagnosis in a 39-year-old patient].

    Science.gov (United States)

    Bargon, J; Rickmann, J; Jacobi, V; Straub, R; Arnemann, J; Wagner, T O

    2000-12-15

    Cystic fibrosis is the most common hereditary disorder among Caucasians. Most of the patients are diagnosed as children. However, some cases are going undiagnosed into adulthood and are then often misdiagnosed because the non-pediatricians do not know cystic fibrosis very well and do not consider this diagnosis in adult patients. We present the medical history of a woman, who was diagnosed with cystic fibrosis at the age of 39 years, although she had suffered from bronchiectasis, pancreatic insufficiency and liver cirrhosis since many years. Her medical history was long with some diagnosis, but because of her age nobody considered the final diagnosis. In adult patients with bronchiectasis, liver cirrhosis and pancreatic insufficiency in combination or with only one of these symptoms, cystic fibrosis should be included into the differential diagnosis.

  6. Liver shear-wave velocity and serum fibrosis markers to diagnose hepatic fibrosis in patients with chronic viral hepatitis B

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jian Xue; Ji, Yong Hao; Zhao Junzhi; Zhang, Yao Ren; Dun, Guo Liang; Ning, Bo [Dept. of Ultrasonography, Baoji Central Hospital, Baoji (China); Ai, Hong [Dept. of Ultrasonography, The First Affiliated Hospital of Medical College, Xi' an Jiaotong University, Xi' an (China)

    2016-06-15

    To compare several noninvasive indices of fibrosis in chronic viral hepatitis B, including liver shear-wave velocity (SWV), hyaluronic acid (HA), collagen type IV (CIV), procollagen type III (PCIII), and laminin (LN). Acoustic radiation force impulse (ARFI) was performed in 157 patients with chronic viral hepatitis B and in 30 healthy volunteers to measure hepatic SWV (m/s) in a prospective study. Serum markers were acquired on the morning of the same day of the ARFI evaluation. Receiver operating characteristic (ROC) analysis was performed to evaluate and compare the accuracies of SWV and serum markers using METAVIR scoring from liver biopsy as a reference standard. The most accurate test for diagnosing fibrosis F ≥ 1 was SWV with the area under the ROC curve (AUC) of 0.913, followed by LN (0.744), HA (0.701), CIV (0.690), and PCIII (0.524). The best test for diagnosing F ≥ 2 was SWV (AUC of 0.851), followed by CIV (0.671), HA (0.668), LN (0.562), and PCIII (0.550). The best test for diagnosing F ≥ 3 was SWV (0.854), followed by CIV (0.693), HA (0.675), PCIII (0.591), and LN (0.548). The best test for diagnosing F = 4 was SWV (0.965), followed by CIV (0.804), PCIII (0.752), HA (0.744), and LN (0.662). SWV combined with HA and CIV did not improve diagnostic accuracy (AUC = 0.931 for F ≥ 1, 0.863 for F ≥ 2, 0.855 for F ≥ 3, 0.960 for F = 4). The performance of SWV in diagnosing liver fibrosis is superior to that of serum markers. However, the combination of SWV, HA, and CIV does not increase the accuracy of diagnosing liver fibrosis and cirrhosis.

  7. Liver shear-wave velocity and serum fibrosis markers to diagnose hepatic fibrosis in patients with chronic viral hepatitis B

    International Nuclear Information System (INIS)

    Liu, Jian Xue; Ji, Yong Hao; Zhao Junzhi; Zhang, Yao Ren; Dun, Guo Liang; Ning, Bo; Ai, Hong

    2016-01-01

    To compare several noninvasive indices of fibrosis in chronic viral hepatitis B, including liver shear-wave velocity (SWV), hyaluronic acid (HA), collagen type IV (CIV), procollagen type III (PCIII), and laminin (LN). Acoustic radiation force impulse (ARFI) was performed in 157 patients with chronic viral hepatitis B and in 30 healthy volunteers to measure hepatic SWV (m/s) in a prospective study. Serum markers were acquired on the morning of the same day of the ARFI evaluation. Receiver operating characteristic (ROC) analysis was performed to evaluate and compare the accuracies of SWV and serum markers using METAVIR scoring from liver biopsy as a reference standard. The most accurate test for diagnosing fibrosis F ≥ 1 was SWV with the area under the ROC curve (AUC) of 0.913, followed by LN (0.744), HA (0.701), CIV (0.690), and PCIII (0.524). The best test for diagnosing F ≥ 2 was SWV (AUC of 0.851), followed by CIV (0.671), HA (0.668), LN (0.562), and PCIII (0.550). The best test for diagnosing F ≥ 3 was SWV (0.854), followed by CIV (0.693), HA (0.675), PCIII (0.591), and LN (0.548). The best test for diagnosing F = 4 was SWV (0.965), followed by CIV (0.804), PCIII (0.752), HA (0.744), and LN (0.662). SWV combined with HA and CIV did not improve diagnostic accuracy (AUC = 0.931 for F ≥ 1, 0.863 for F ≥ 2, 0.855 for F ≥ 3, 0.960 for F = 4). The performance of SWV in diagnosing liver fibrosis is superior to that of serum markers. However, the combination of SWV, HA, and CIV does not increase the accuracy of diagnosing liver fibrosis and cirrhosis

  8. Cystic fibrosis - Comparison between patients in paediatric and adult age.

    Science.gov (United States)

    Santos, V; Cardoso, A V; Lopes, C; Azevedo, P; Gamboa, F; Amorim, A

    Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Although most cases are diagnosed in childhood, diagnosis in adults is apparently increasing. Evaluate the adult population with CF, comparing patients who were diagnosed before and after 18 years of age. Retrospective analysis of patients followed in three main medical centres in Portugal in 2012. Comparison of two groups: G1 - patients diagnosed at <18 years and G2 - patients diagnosed at ≥18 years. 89 adults were identified: 61.8% in G1, 38.2% in G2. Gender distribution was similar in both groups. Average age in G2 was higher (38.3±8.4 vs. 26.8±6.1 years, p<0.001). Respiratory symptoms most frequently led to CF diagnosis in all patients, mainly in adulthood. There was a greater percentage of patients homozygous for the mutation delF508 in G1 (43.6 vs. 8.8%, p=0.02). Respiratory and pancreatic function, and body mass index (BMI) showed a higher severity in G1 (G1 vs. G2: FEV1: 54.6±27.3 vs. 29.9±64.6%, p=0.177; pancreatic insufficiency 72.7 vs. 26.5%, p<0.001; BMI 20.2±3.4 vs. 22.2±4.8, p=0.018). Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus were the most frequently isolated microorganisms. Lung transplantation rate was higher in G2 (20.6 vs. 10.9%, p=0.231) while mortality rate was higher in G1 (0 vs. 3.6%, p=0.261). Hospital admission rate was higher in G1 as well as mortality rate. The results suggest that patients with CF diagnosed in childhood have characteristics that distinguish them from those diagnosed in adulthood, and these differences may have implications for diagnosis, prognosis and life expectancy. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

  9. TNF-alpha 308 SNP Rs3091256 GG Genotype is Strongly Associated with Fibrosis in Patients with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Özgür GÜNAL

    2017-12-01

    Full Text Available Objective: We aimed to review the influence of host genetic factors on the clinical course, treatment response as well as fibrosis progression in patients with viral hepatitis C genotype 1. Materials and Methods: Ninety-five patients with chronic hepatitis C virus (HCV infection and 97 controls were enrolled. The patients received pegylated interferon (Peg-IFN+ribavirin therapy for 48 weeks and were followed up for the next 48 weeks. Aspartat aminotransferase/platelet ratio (APRI was used to detect liver fibrosis DNA specimens were extracted from the peripheral blood mononuclear cells and the tumor necrosis factor-alpha (TNF-α 308 rs3091256 was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Results: All patients included in the study were infected with HCV genotype 1. of the 95 HCV-positive patients, spontaneous viral clearence was observed in 25.5%, rapid viral response in 44.2%, early viral response in 91.8%, and sustained viral response was found in 73.3% of patients. The allele and genotype were not significant between patients and controls. There was no significant difference in virologic response as well. However, TNF-α-308 single nucleotide polymorphisms (SNP rs3091256 GG genotype was strongly associated with fibrosis and alanine aminotransferase (ALT levels (p=0.006 and p=0.017, respectively. Conclusion: TNF-α-308 polymorphisms may reveal different results among countries. Patients having SNP rs3091256 GG are prone to have higher ALT levels and fibrosis score but have better treatment outcome.

  10. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    International Nuclear Information System (INIS)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell'Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto; Pellegrino, Teresa; Petretta, Mario; Riccio, Eleonora; Pisani, Antonio

    2017-01-01

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by 123 I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by 123 I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r 2 = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, 123 I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  11. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell' Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy); Riccio, Eleonora; Pisani, Antonio [University of Naples Federico II, Department of Public Health, Naples (Italy)

    2017-12-15

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by {sup 123}I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by {sup 123}I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r{sup 2} = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, {sup 123}I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  12. Ursodeoxycholic acid treatment in patients with cystic fibrosis at risk for liver disease.

    Science.gov (United States)

    Siano, Maria; De Gregorio, Fabiola; Boggia, Bartolo; Sepe, Angela; Ferri, Pasqualina; Buonpensiero, Paolo; Di Pasqua, Antonio; Raia, Valeria

    2010-06-01

    Meconium ileus has been detected as a risk factor for development of liver disease in cystic fibrosis, with influence on morbidity and mortality. To evaluate the effect of early treatment with ursodeoxycholic acid in patients with cystic fibrosis and meconium ileus to prevent chronic hepatic involvement and to explore the potential role of therapy on clinical outcomes. 26 cystic fibrosis patients with meconium ileus (16 M, mean age 8,4 years, range 3,5-9) were assigned to two groups: group 1 (14 patients) treated early with ursodeoxycholic acid (UDCAe); group 2 (12 patients) treated with ursodeoxycholic acid at the onset of cystic fibrosis liver disease (UDCAd). Anthropometric data, pulmonary function tests, pancreatic status, complications such as diabetes, hepatic involvement and Pseudomonas aeruginosa colonisation were compared among groups. A higher prevalence of cystic fibrosis chronic liver disease was observed in the UDCAd group with a statistically significant difference at 9 years of age (p<0.05). Chronic infection by P. aeruginosa was found in 7% of UDCAe and 33% of UDCAd (p<0.05). No differences were observed in nutritional status and other complications. Early treatment with ursodeoxycholic acid may be beneficial in patients at risk of developing cystic fibrosis chronic liver disease such as those with meconium ileus. Multicentre studies should be encouraged to confirm these data. Copyright 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. [Cystic Fibrosis Cloud database: An information system for storage and management of clinical and microbiological data of cystic fibrosis patients].

    Science.gov (United States)

    Prieto, Claudia I; Palau, María J; Martina, Pablo; Achiary, Carlos; Achiary, Andrés; Bettiol, Marisa; Montanaro, Patricia; Cazzola, María L; Leguizamón, Mariana; Massillo, Cintia; Figoli, Cecilia; Valeiras, Brenda; Perez, Silvia; Rentería, Fernando; Diez, Graciela; Yantorno, Osvaldo M; Bosch, Alejandra

    2016-01-01

    The epidemiological and clinical management of cystic fibrosis (CF) patients suffering from acute pulmonary exacerbations or chronic lung infections demands continuous updating of medical and microbiological processes associated with the constant evolution of pathogens during host colonization. In order to monitor the dynamics of these processes, it is essential to have expert systems capable of storing and subsequently extracting the information generated from different studies of the patients and microorganisms isolated from them. In this work we have designed and developed an on-line database based on an information system that allows to store, manage and visualize data from clinical studies and microbiological analysis of bacteria obtained from the respiratory tract of patients suffering from cystic fibrosis. The information system, named Cystic Fibrosis Cloud database is available on the http://servoy.infocomsa.com/cfc_database site and is composed of a main database and a web-based interface, which uses Servoy's product architecture based on Java technology. Although the CFC database system can be implemented as a local program for private use in CF centers, it can also be used, updated and shared by different users who can access the stored information in a systematic, practical and safe manner. The implementation of the CFC database could have a significant impact on the monitoring of respiratory infections, the prevention of exacerbations, the detection of emerging organisms, and the adequacy of control strategies for lung infections in CF patients. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Risk of gastrointestinal cancers in patients with cystic fibrosis: a systematic review and meta-analysis.

    Science.gov (United States)

    Yamada, Akihiro; Komaki, Yuga; Komaki, Fukiko; Micic, Dejan; Zullow, Samantha; Sakuraba, Atsushi

    2018-04-26

    The management and life expectancy of patients with cystic fibrosis have improved substantially in the past three decades, which has resulted in an increased number of these patients being diagnosed with malignancies. Our aim was to assess the risk of gastrointestinal cancers in patients with cystic fibrosis. In this systematic review and meta-analysis, we searched PubMed, MEDLINE, Google Scholar, Scopus, Embase, and Cochrane databases with no language restrictions for studies published from inception of the databases to Aug 1, 2017, assessing the risk of gastrointestinal cancers in patients with cystic fibrosis. We also searched abstracts from scientific meetings and the bibliographies of identified articles for additional references. Studies were included if they reported the standardised incidence ratio (SIR) or incidence ratio per person-years. No exclusion criteria with regard to patient characteristics (age, sex, comorbidities, cystic fibrosis mutation type), study setting (location and time period), or method of reporting cancer diagnoses were applied. The primary outcome was risk of gastrointestinal cancer and site-specific gastrointestinal cancers in patients with cystic fibrosis compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of gastrointestinal cancer varied according to patient lung transplant status. The study is registered with PROSPERO, number CRD42017075396. Our search identified 95 681 records, of which six cohort studies including 99 925 patients (544 695 person-years) were eligible for the meta-analysis. The overall risk of gastrointestinal cancer was significantly higher in patients with cystic fibrosis than in the general population (pooled SIR 8·13, 95% CI 6·48-10·21; pcystic fibrosis who had a lung transplant was increased compared with that of patients who did not receive a transplant (pooled SIR 21·13, 95% CI 14

  15. Integrated Genomics Reveals Convergent Transcriptomic Networks Underlying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Kusko, Rebecca L; Brothers, John F; Tedrow, John; Pandit, Kusum; Huleihel, Luai; Perdomo, Catalina; Liu, Gang; Juan-Guardela, Brenda; Kass, Daniel; Zhang, Sherry; Lenburg, Marc; Martinez, Fernando; Quackenbush, John; Sciurba, Frank; Limper, Andrew; Geraci, Mark; Yang, Ivana; Schwartz, David A; Beane, Jennifer; Spira, Avrum; Kaminski, Naftali

    2016-10-15

    Despite shared environmental exposures, idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease are usually studied in isolation, and the presence of shared molecular mechanisms is unknown. We applied an integrative genomic approach to identify convergent transcriptomic pathways in emphysema and IPF. We defined the transcriptional repertoire of chronic obstructive pulmonary disease, IPF, or normal histology lungs using RNA-seq (n = 87). Genes increased in both emphysema and IPF relative to control were enriched for the p53/hypoxia pathway, a finding confirmed in an independent cohort using both gene expression arrays and the nCounter Analysis System (n = 193). Immunohistochemistry confirmed overexpression of HIF1A, MDM2, and NFKBIB members of this pathway in tissues from patients with emphysema or IPF. Using reads aligned across splice junctions, we determined that alternative splicing of p53/hypoxia pathway-associated molecules NUMB and PDGFA occurred more frequently in IPF or emphysema compared with control and validated these findings by quantitative polymerase chain reaction and the nCounter Analysis System on an independent sample set (n = 193). Finally, by integrating parallel microRNA and mRNA-Seq data on the same samples, we identified MIR96 as a key novel regulatory hub in the p53/hypoxia gene-expression network and confirmed that modulation of MIR96 in vitro recapitulates the disease-associated gene-expression network. Our results suggest convergent transcriptional regulatory hubs in diseases as varied phenotypically as chronic obstructive pulmonary disease and IPF and suggest that these hubs may represent shared key responses of the lung to environmental stresses.

  16. Prevalence of gastric varices and portal hypertensive gastropathy in patients with Symmer's periportal fibrosis

    International Nuclear Information System (INIS)

    Mudawi, H.; Ali, Y.; El-Tahir, M.

    2008-01-01

    Symmer's periportal fibrosis secondary to schistosomiasis is a common cause of portal hypertension worldwide. Data on the prevalence of gastric variances and portal hypertensive gastropathy in this group of patients with portal of hypertension is relatively scarce. The aim of this study was to determine the prevalence of gastric varices and portal hypertensive gastropathy in patients presenting with portal hypertension secondary to Symmer's periportal fibrosis. In a prospective study, upper gastrointestinal endoscopy was carried out to determine the prevalence of gastric varices and portal hypertensive gastropathy in patients with portal hypertension secondary to Symmer's fibrosis. Of 143 patients studied, 24 patients (16.8%) had gastric varices (grade I in 10.5%, grade Ii in 6.3%) and 31 patients (21.7%) had portal hypertensive gastropathy (mild in 11.2%, severe in 10.5%). Gastric varices were more prevalent in patients with grade I and II esophageal varices and portal hypertensive gastropathy was more prevalent in those with grade III and IV esophageal varices, but the differences were not statistically significant. We conclude that both gastric varices and portal hypertensive gastropathy seem to have a lower prevalence in patients with portal hypertension secondary to Symmer's periportal fibrosis when compared to reported data in patients with portal hypertension secondary to liver cirrhosis and non-cirrhotic portal fibrosis. (author)

  17. Hepatic fibrosis in patients with chronic hepatitis C assessed by transient elastography: implications for determining the efficacy of antiviral therapy Evaluación de la fibrosis hepática en pacientes con hepatopatía crónica C mediante elastografía transitoria: implicaciones para determinar la eficacia del tratamiento antiviral

    Directory of Open Access Journals (Sweden)

    J. Mendoza

    2010-07-01

    Full Text Available Background: the efficacy of combination therapy with peginterferon plus ribavirin to eradicate viral infection in patients with chronic hepatitis C (CHC is well established; moreover, it is able to arrest or even reverse liver fibrosis. Aims: to analyze the measurements of hepatic stiffness as an index of liver fibrosis using transient elastography (TE in patients who underwent a sustained virological response (SVR during long-term follow-up; comparing the changes in the severity of fibrosis with non-responders patients. Material and methods: after hepatic fibrosis was studied in three patients with CHC who underwent a SVR during long-term follow up, a prospective study was initiated in 24 patients with CHC who received combination therapy to compare the evolution of fibrosis in those with SVR and those who were non-responders. The genotype of hepatitis C virus (HCV and the degree of viremia were determined. METAVIR scoring system was used for liver fibrosis. Hepatic stiffness was measured by TE. Results: of the initial three patients pre-treatment liver biopsies revealed active disease and fibrosis (stage 3 in two and mild fibrosis (stage 1 in one. After several years of follow up serum AST/ALT levels were normal and HCV RNA was undetectable in each case; in contrast to the baseline histological assessments of fibrosis, values for hepatic stiffness (3.4-6.9 KPa were compatible with an absence of any appreciable hepatic fibrosis. In the prospective study, 8 patients underwent a SVR and 16 were non-responders. TE indicated that the severity of hepatic fibrosis in the SVR group improved in 7 (88% patients, whereas in the non-responder it improved in only 4 (25% (p < 0.05. The difference between development of severe fibrosis (F ≥ 3 in responders and non-responders was not significant (p = 0.23, possibly due to the small sample size. Conclusions: regression of hepatic fibrosis appears to be common in patients with CHC who undergo a SVR. TE is a

  18. Identification and Fibrosis Staging of Hepatitis C Patients Using the Electronic Medical Record System.

    Science.gov (United States)

    Anand, Vijay; Hyun, Christian; Khan, Qasim M; Hall, Curtis; Hessefort, Norbert; Sonnenberg, Amnon; Fimmel, Claus J

    2016-09-01

    The aim of this study was to noninvasively assess the severity of chronic hepatitis C virus (HCV) in large patient populations. It would be helpful if fibrosis scores could be calculated solely on the basis of data contained in the patients' electronic medical records (EMR). We performed a pilot study to identify all HCV-infected patients in a large health care system, and predict their fibrosis stage on the basis of demographic and laboratory data using common data from their EMR. HCV-infected patients were identified using the EMR. The liver biopsies of 191 HCV patients were graded using the Ishak and Metavir scoring systems. Demographic and laboratory data were extracted from the EMR and used to calculate the aminotransferase to platelet ratio index, Fib-4, Fibrosis Index, Forns, Göteborg University Cirrhosis Index, Lok Index, and Vira-HepC. In total, 869 HCV-infected patients were identified from a population of over 1 million. In the subgroup of patients with liver biopsies, all 7 algorithms were significantly correlated with the fibrosis stage. The degree of correlation was moderate, with correlation coefficients ranging from 0.22 to 0.60. For the detection of advanced fibrosis (Metavir 3 or 4), the areas under the receiver operating characteristic curve ranged from 0.71 to 0.84, with no significant differences between the individual scores. Sensitivities, specificities, and positive and negative predictive values were within the previously reported range. All scores tended to perform better for higher fibrosis stages. Our study demonstrates that HCV-infected patients can be identified and their fibrosis staged using commonly available EMR-based algorithms.

  19. Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization

    Energy Technology Data Exchange (ETDEWEB)

    Keravec, Marlene; Mounier, Jerome; Prestat , Emmanuel; Vallet, Sophie; Jansson, Janet K.; Bergaud , Gaetaqn; Rosec, Silvain; Gourious, Stephanie; Rault, Gilles; Coton, Emmanuel; Barbier, George; Hery-Arnaud, Geneveieve

    2015-08-09

    Abstract Pseudomonas aeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state.

  20. Significant fibrosis after radiation therapy in a patient with Marfan Syndrome

    International Nuclear Information System (INIS)

    Suarez, Eva M.; Knackstedt, Rebecca J.; Jenrette, Joseph M.

    2014-01-01

    Marfan syndrome is one of the collagen vascular diseases that theoretically predisposes patients to excessive radiation-induced fibrosis yet there is minimal published literature regarding this clinical scenario. We present a patient with a history of Marfan syndrome requiring radiation for a diagnosis of a right brachial plexus malignant nerve sheath tumor. It has been suggested that plasma transforming growth factor beta 1 (TGF-beta1) can be monitored as a predictor of subsequent fibrosis in this population of high risk patients. We therefore monitored the patient's TGF-beta1 level during and after treatment. Despite maintaining stable levels of plasma TGF-beta1, our patient still developed extensive fibrosis resulting in impaired range of motion. Our case reports presents a review of the literature of patients with Marfan syndrome requiring radiation therapy and the limitations of serum markers on predicting long-term toxicity.

  1. Significant fibrosis after radiation therapy in a patient with Marfan Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, Eva M.; Knackstedt, Rebecca J.; Jenrette, Joseph M. [Medical University of South Carolina, Charleston (United States)

    2014-09-15

    Marfan syndrome is one of the collagen vascular diseases that theoretically predisposes patients to excessive radiation-induced fibrosis yet there is minimal published literature regarding this clinical scenario. We present a patient with a history of Marfan syndrome requiring radiation for a diagnosis of a right brachial plexus malignant nerve sheath tumor. It has been suggested that plasma transforming growth factor beta 1 (TGF-beta1) can be monitored as a predictor of subsequent fibrosis in this population of high risk patients. We therefore monitored the patient's TGF-beta1 level during and after treatment. Despite maintaining stable levels of plasma TGF-beta1, our patient still developed extensive fibrosis resulting in impaired range of motion. Our case reports presents a review of the literature of patients with Marfan syndrome requiring radiation therapy and the limitations of serum markers on predicting long-term toxicity.

  2. Rapid emergence of a ceftazidime-resistant Burkholderia multivorans strain in a cystic fibrosis patient.

    Science.gov (United States)

    Stokell, Joshua R; Gharaibeh, Raad Z; Steck, Todd R

    2013-12-01

    Burkholderia multivorans poses a serious health threat to cystic fibrosis patients due to innate resistance to multiple antibiotics and acquisition of resistance to a range of antibiotics due to the frequent use of antibiotics to treat chronic infections. Monitoring antibiotic susceptibility is crucial to managing patient care. We identified the rapid emergence of a ceftazidime-resistant strain in a single patient within four days during a hospitalization for treatment of an exacerbation. B. multivorans was isolated from expectorated sputum samples using Burkholderia cepacia selective agar. A macrodilution assay was performed on all isolates to determine the minimum inhibitory concentration of ceftazidime. Approximately 4000 colonies were scored to identify the percent of ceftazidime-resistant colonies. Extracted DNA was used to determine the total bacterial counts and abundance of B. multivorans using quantitative PCR. An increase from no detectable B. multivorans ceftazidime-resistant colonies to over 75% of all colonies tested occurred within a four-day period. The resistant population remained dominant in 6 of the 8 samples in the following 17 months of the study. qPCR revealed an association between change in the percent of resistant colonies and abundance of B. multivorans, but not of total bacteria. No association was found between the acquisition of resistance to ceftazidime and other antibiotics commonly used to treat B. multivorans infections. The rapid emergence of a ceftazidime-resistant by B. multivorans strain occurred during a hospitalization while under selective pressure of antibiotics. The resistant strain maintained dominance in the B. multivorans population which resulted in an overall decline in a patient health and treatment efficacy. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  3. Ten years' of experience in patient education of families with a child/adolescent suffering from cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke

    2007-01-01

    Aims: The patient education programme for families with children or adolescents with cystic fibrosis (the CF school) was established ten years ago to enable patients to make choices in their lives as CF patients. The CF school provides patients with knowledge about cystic fibrosis (CF), teaches...

  4. Lung cancer in patients with idiopathic pulmonary fibrosis: frequency and CT findings

    International Nuclear Information System (INIS)

    Lee, Hak Jong; Im, Jung Gi; Ahn, Joong Mo; Yeon, Kyung Mo

    1994-01-01

    The incidence of lung cancer in patients with idiopathic pulmonary fibrosis(lPF) is higher than that of general population. To evaluate the frequency and CT findings of lung cancer associated with idiopathic pulmonary fibrosis, we analyzed 19 patients with lung cancer associated with idiopathic pulmonary fibrosis. We analyzed retrospectively 19 patients with histologically confirmed lung cancer out of 208 patients diagnosed as IPF either by CT and clinical findings(n=188) or histologically(n=20). All 19 patients were male, aged 40-85 years (mean 66 years). Scanning techniques were conventional CT in 12 patients, HRCT in 1 patient and both conventional CT and HRCT in 6 patients. We analyzed the CT patterns of lung cancer and IPF, locations of the tumor and histologic types of lung cancer. The incidence of lung cancer in patients with idiopathic pulmonary fibrosis was 9.1%(19/208). In 11 of 19 patients, CT findings of lung cancer were ill-defined consolidation-like mass. Lung cancer was located mainly in lower lobes(right lower lobe; 10/19, left lower lobe; 5/19) and at the periphery(12/19). Histologically, squamous cell carcinoma was the most common cell type (11/19). The incidence of lung cancer in patients with idiopathic pulmonary fibrosis was much higher than that of general population. Typical CT findings of lung cancer were predominantly ill-defined consolidation like mass at the peripheral lung portion which is the location where the most advanced fibrosis occur

  5. Lung cancer in patients with idiopathic pulmonary fibrosis: frequency and CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hak Jong; Im, Jung Gi; Ahn, Joong Mo; Yeon, Kyung Mo [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1994-12-15

    The incidence of lung cancer in patients with idiopathic pulmonary fibrosis(lPF) is higher than that of general population. To evaluate the frequency and CT findings of lung cancer associated with idiopathic pulmonary fibrosis, we analyzed 19 patients with lung cancer associated with idiopathic pulmonary fibrosis. We analyzed retrospectively 19 patients with histologically confirmed lung cancer out of 208 patients diagnosed as IPF either by CT and clinical findings(n=188) or histologically(n=20). All 19 patients were male, aged 40-85 years (mean 66 years). Scanning techniques were conventional CT in 12 patients, HRCT in 1 patient and both conventional CT and HRCT in 6 patients. We analyzed the CT patterns of lung cancer and IPF, locations of the tumor and histologic types of lung cancer. The incidence of lung cancer in patients with idiopathic pulmonary fibrosis was 9.1%(19/208). In 11 of 19 patients, CT findings of lung cancer were ill-defined consolidation-like mass. Lung cancer was located mainly in lower lobes(right lower lobe; 10/19, left lower lobe; 5/19) and at the periphery(12/19). Histologically, squamous cell carcinoma was the most common cell type (11/19). The incidence of lung cancer in patients with idiopathic pulmonary fibrosis was much higher than that of general population. Typical CT findings of lung cancer were predominantly ill-defined consolidation like mass at the peripheral lung portion which is the location where the most advanced fibrosis occur.

  6. Molecular mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients

    DEFF Research Database (Denmark)

    Jalal, S; Ciofu, O; Høiby, Niels

    2000-01-01

    Twenty P. aeruginosa isolates were collected from six cystic fibrosis (CF) patients, aged 27 to 33, in 1994 (9 isolates) and 1997 (11 isolates) at the CF Center, Copenhagen, Denmark, and were typed by pulse-field gel electrophoresis (PFGE) or ribotyping. Five of the patients had isolates with the......Twenty P. aeruginosa isolates were collected from six cystic fibrosis (CF) patients, aged 27 to 33, in 1994 (9 isolates) and 1997 (11 isolates) at the CF Center, Copenhagen, Denmark, and were typed by pulse-field gel electrophoresis (PFGE) or ribotyping. Five of the patients had isolates...

  7. T helper cell subsets specific for Pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Hannah K Bayes

    Full Text Available We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis.Peripheral blood human memory CD4(+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines.Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4(+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6(+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood.Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions.

  8. Evaluation of bone mineral density in cystic fibrosis patients

    Directory of Open Access Journals (Sweden)

    Jessica Cemlyn-Jones

    2008-09-01

    Full Text Available Patients with cystic fibrosis (CF have an increasing life span and osteoporosis has become a more recognised problem in these patients. The pathogenesis of low bone mineral density (BMD in CF seems to be multifactorial and the aim of this study was to assess the prevalence of low BMD in a group of CF outpatients and to relate the findings with the variables studied.The study included 22 patients aged between 14 and 45 years (mean age 26.3. Two of the subjects were lung transplant patients. BMD was assessed by dualenergy X-ray absorptiometry (DEXA at the lumbar spine (LS and femoral neck (FN. This data was correlated with serum 25-hydroxy vitamin D (25-OHD levels, BMI and the forced expiratory volume in one second (FEV1.BMD (Z-score and T-score ranged from 0.6 to -6 and from 0.5 to -6.7 at LS; at FN the scores ranged from 0.6 to -3.9 and from 0.6 to -4.1. The mean serum 25-OHD concentration (12,57 ng/ml was at the low end of the normal range (10-60 ng/ml. On average patients did not present with malnutrition, however BMI ranged from 15.2 to 33.7 kg/m2. Lung function status was assessed by FEV1; 64% of patients had FEV1 below 80% and within this group four patients had a FEV1 under 40%.There was a positive correlation between low BMD and 25-OHD concentrations and also between BMD and FEV1. There was no linear correlation between BMD and BMI. Resumo: A esperança de vida dos doentes com fibrose quística (FQ tem vindo a aumentar, sendo mais frequente a identificação de osteoporose. A patogénese de uma baixa densidade mineral óssea (DMO na FQ parece ser multifactorial e o objectivo deste trabalho foi avaliar a prevalência de baixa DMO num grupo de doentes com FQ e a sua correlação com outros parâmetros avaliados.O estudo incluiu 22 doentes com FQ com idades compreendidas entre os 14 e os 45 anos (média 26,3, dois dos quais transplantados pulmonares. A DMO foi avaliada por densitometria óssea ao nível da coluna lombar e do colo do f

  9. Uptake of genetic counselling services by patients with cystic fibrosis ...

    African Journals Online (AJOL)

    Background: Although cystic fibrosis (CF) is a common genetic condition, genetic counselling services appear to be underutilised by affected families. The aim of this study was to determine the uptake of genetic counselling and mutation testing for CF by relatives of affected individuals, and the impact of introducing ...

  10. Uptake of genetic counselling services by patients with cystic fibrosis ...

    African Journals Online (AJOL)

    2011-05-09

    May 9, 2011 ... Cystic fibrosis (CF) is a chronic, inherited disorder that affects the respiratory tract, pancreas, .... 18%) themselves and other individuals, such as nurses (20 out of 153, 13%), general practitioners (15 out of 153, 10%) .... considered to be rare in this ethnic group, it is likely that. CF is still under-recognised and ...

  11. Sequential occurrence of combined pulmonary fibrosis and emphysema syndrome in a non-smoker female patient.

    Science.gov (United States)

    Gupta, Pawan; Dash, Devijyoti; Mittal, Richa; Chhabra, Sunil K

    2017-05-01

    The combined pulmonary fibrosis and emphysema (CPFE) syndrome is a unique and an under-recognized disorder characterized by emphysema in the upper lobes and interstitial fibrosis in the lower lobes of the lung. It occurs predominantly in males and almost exclusively in smokers. This rare combination of a restrictive and an obstructive mechanical defect carries a poorer prognosis than either of the two components. We present a case of CPFE syndrome in a non-smoker female patient who developed lower lobe emphysema subsequent to development of interstitial fibrosis. The case was remarkable for the extreme rarity of several presenting features, namely, a lower lobe occurrence of emphysema subsequent to pre-existent interstitial fibrosis, female gender and absence of a history of smoking. © 2015 John Wiley & Sons Ltd.

  12. Chronic pulmonary infection with Stenotrophomonas maltophilia and lung function in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Dalbøge, C S; Hansen, C R; Pressler, T

    2011-01-01

    Background The clinical consequences of chronic Stenotrophomonas maltophilia infection in cystic fibrosis (CF) patient are still unclear. Method All patients treated in the Copenhagen CF centre (N=278) from 1 January 2008 to 31 December 2009 were included. Each patient chronically infected with S...

  13. Acupuncture in the rehabilitation of patients with radiation fibrosis ans secondary neuritis

    International Nuclear Information System (INIS)

    Subova, N.D.; Bardychev, M.S.; Guseva, L.I.

    1980-01-01

    Acupuncture application experience as effective method of rehabilitation of patients with radiation fibrosis and neuritis is presented. Acupuncture results are more efficient in patients with treatment course after irradiation not more than 3 years, that is why its inclusion in the complex of medicaleasures of presentive treatment of patients with delayed radiation injuries should be considered advisable

  14. Young patients with cystic fibrosis demonstrate subtle alterations of the cardiovascular system.

    Science.gov (United States)

    Eising, Jacobien B; van der Ent, Cornelis K; Teske, Arco J; Vanderschuren, Maaike M; Uiterwaal, Cuno S P M; Meijboom, Folkert J

    2018-02-02

    As life expectancy increases in patients with cystic fibrosis, it is important to pay attention to extra-pulmonary comorbidities. Several studies have shown signs of myocardial dysfunction in adult patients, but little is known about onset and development of these changes over time. In this prospective study, cardiac function in children with cystic fibrosis was compared to that of healthy children. 33 children, aged 3-12years, with cystic fibrosis were recruited from the Wilhelmina Children's hospital and 33 age-matched healthy children were selected from the WHISTLER study, a population-based cohort study. Measurements of lung function, arterial stiffness, and echocardiography (conventional measures and myocardial deformation imaging) were performed. There were no differences in anthropometrics, lung function and blood pressure between the two groups. The cystic fibrosis children had a higher arterial stiffness compared to the healthy children (pulse wave velocity respectively 5.76±0.57m/s versus 5.43±0.61m/s, p-value 0.049). Using conventional echocardiographic parameters for right ventricular function, Tricuspid Annular Plane Systolic Excursion) and Tissue Doppler Imaging, cystic fibrosis children had a reduced right ventricular systolic function when compared to the healthy children. After adjustment for lung function, global strains of both right and left ventricles were significantly lower in the cystic fibrosis group than in healthy children (linear regression coefficient 1.45% left ventricle, p-value 0.022 and 4.42% right ventricle, p-value cystic fibrosis children than in healthy controls. Our study suggests that already at a very young age, children with cystic fibrosis show an increased arterial stiffness and some signs of diminished both right and left ventricular function. Copyright © 2018. Published by Elsevier B.V.

  15. Abdominal CT predictors of fibrosis in patients with chronic pancreatitis undergoing surgery

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Amitasha; Afghani, Elham [Johns Hopkins Medical Institutions, Division of Gastroenterology, Baltimore, MD (United States); Singh, Vikesh K. [Johns Hopkins Medical Institutions, Division of Gastroenterology, Baltimore, MD (United States); Johns Hopkins Medical Institutions, Pancreatitis Center, Baltimore, MD (United States); Cruise, Michael; Matsukuma, Karen [Johns Hopkins Medical Institutions, Department of Pathology, Baltimore, MD (United States); Ali, Sumera; Raman, Siva P.; Fishman, Elliot K. [Johns Hopkins Medical Institutions, The Russel H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Andersen, Dana K. [National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States); Makary, Martin A. [Johns Hopkins Medical Institutions, Department of Surgery, Baltimore, MD (United States); Johns Hopkins Medical Institutions, Pancreatitis Center, Baltimore, MD (United States); Zaheer, Atif [Johns Hopkins Medical Institutions, The Russel H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Johns Hopkins Medical Institutions, Pancreatitis Center, Baltimore, MD (United States); Johns Hopkins Medical Institutions, Baltimore, MD (United States)

    2015-05-01

    To determine which abdominal CT findings predict severe fibrosis and post-operative pain relief in chronic pancreatitis (CP). Pre-operative abdominal CTs of 66 patients (mean age 52 ± 12 years, 53 % males) with painful CP who underwent the Whipple procedure (n = 32), Frey procedure (n = 32) or pancreatic head biopsy (n = 2), between 1/2003-3/2014, were evaluated. CT was evaluated for parenchymal calcifications, intraductal calculi, main pancreatic duct dilation (>5 mm), main pancreatic duct stricture, and abnormal side branch(es). The surgical histopathology was graded for fibrosis. CT findings were evaluated as predictors of severe fibrosis and post-operative pain relief using regression and area under receiver operating curve (AUC) analysis. Thirty-eight (58 %) patients had severe fibrosis. Parenchymal calcification(s) were an independent predictor of severe fibrosis (p = 0.03), and post-operative pain relief over a mean follow-up of 1-year (p = 0.04). Presence of >10 parenchymal calcifications had higher predictive accuracy for severe fibrosis than 1-10 parenchymal calcification(s) (AUC 0.88 vs. 0.59, p = 0.003). The predictive accuracy of >10 versus 1-10 parenchymal calcifications increased after adjusting for all other CT findings (AUC 0.89 vs. 0.63, p = 0.01). Parenchymal calcification(s) independently predict severe fibrosis and are significantly associated with post-operative pain relief in CP. The presence of >10 parenchymal calcifications is a better predictor of severe fibrosis than 1-10 parenchymal calcification(s). (orig.)

  16. Abdominal CT predictors of fibrosis in patients with chronic pancreatitis undergoing surgery

    International Nuclear Information System (INIS)

    Sinha, Amitasha; Afghani, Elham; Singh, Vikesh K.; Cruise, Michael; Matsukuma, Karen; Ali, Sumera; Raman, Siva P.; Fishman, Elliot K.; Andersen, Dana K.; Makary, Martin A.; Zaheer, Atif

    2015-01-01

    To determine which abdominal CT findings predict severe fibrosis and post-operative pain relief in chronic pancreatitis (CP). Pre-operative abdominal CTs of 66 patients (mean age 52 ± 12 years, 53 % males) with painful CP who underwent the Whipple procedure (n = 32), Frey procedure (n = 32) or pancreatic head biopsy (n = 2), between 1/2003-3/2014, were evaluated. CT was evaluated for parenchymal calcifications, intraductal calculi, main pancreatic duct dilation (>5 mm), main pancreatic duct stricture, and abnormal side branch(es). The surgical histopathology was graded for fibrosis. CT findings were evaluated as predictors of severe fibrosis and post-operative pain relief using regression and area under receiver operating curve (AUC) analysis. Thirty-eight (58 %) patients had severe fibrosis. Parenchymal calcification(s) were an independent predictor of severe fibrosis (p = 0.03), and post-operative pain relief over a mean follow-up of 1-year (p = 0.04). Presence of >10 parenchymal calcifications had higher predictive accuracy for severe fibrosis than 1-10 parenchymal calcification(s) (AUC 0.88 vs. 0.59, p = 0.003). The predictive accuracy of >10 versus 1-10 parenchymal calcifications increased after adjusting for all other CT findings (AUC 0.89 vs. 0.63, p = 0.01). Parenchymal calcification(s) independently predict severe fibrosis and are significantly associated with post-operative pain relief in CP. The presence of >10 parenchymal calcifications is a better predictor of severe fibrosis than 1-10 parenchymal calcification(s). (orig.)

  17. Cost-effectiveness analysis of ledipasvir/sofosbuvir in patients with chronic hepatitis C: Treatment of patients with absence or mild fibrosis compared to patients with advanced fibrosis.

    Science.gov (United States)

    Buti, M; Domínguez-Hernández, R; Oyagüez, I; Casado, M A; Esteban, R

    2017-09-01

    To evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment-naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0-F1) versus advanced fibrosis (F2-F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality-adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0-F1 compared with F2-F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load rates were obtained from real-world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0-F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2-F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0-F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver-related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2-F4 patients. In CHC treatment-naïve GT1 patients, starting treatment with LDV/SOF in patients with F0-F1 compared to those with F2-F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings. © 2017 John Wiley & Sons Ltd.

  18. Cystic fibrosis transmembrane conductance regulator (CFTR allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Serena Schippa

    Full Text Available INTRODUCTION: In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF. CFTR mutations (F508del is the most common lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age. METHODS: Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure. RESULTS: Patients were classified by two different criteria: 1 presence/absence of F508del mutation; 2 disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum were reduced. CONCLUSIONS: This is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a 'systemic disease', linking the lung and the gut in a joined axis.

  19. Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients.

    Science.gov (United States)

    Schippa, Serena; Iebba, Valerio; Santangelo, Floriana; Gagliardi, Antonella; De Biase, Riccardo Valerio; Stamato, Antonella; Bertasi, Serenella; Lucarelli, Marco; Conte, Maria Pia; Quattrucci, Serena

    2013-01-01

    In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF). CFTR mutations (F508del is the most common) lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age. Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure. Patients were classified by two different criteria: 1) presence/absence of F508del mutation; 2) disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme) were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum) were reduced. This is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a 'systemic disease', linking the lung and the gut in a joined axis.

  20. [Normal lung volumes in patients with idiopathic pulmonary fibrosis and emphysema].

    Science.gov (United States)

    Casas, Juan Pablo; Abbona, Horacio; Robles, Adriana; López, Ana María

    2008-01-01

    Pulmonary function tests in idiopathic pulmonary fibrosis characteristically show a restrictive pattern, resulting from reduction of pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. Previous reports suggest that when both diseases coexist, pulmonary volumes are compensated and a smaller than expected reduction or even normal lung volumes can be found. We report 4 male patients of 64, 60, 73 and 70 years, all with heavy cigarette smoking history and progressive breathlessness. Three of them had severe limitation in their quality of life. All four showed advanced lung interstitial involvement, at high resolution CT scan, fibrotic changes predominantly in the subpleural areas of lower lung fields and concomitant emphysema in the upper lobes. Emphysema and pulmonary fibrosis was confirmed by open lung biopsy in one patient. The four patients showed normal spirometry and lung volumes with severe compromise of gas exchange and poor exercise tolerance evaluated by 6 minute walk test. Severe pulmonary arterial hypertension was also confirmed in three patients. Normal lung volumes does not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  1. Clinical significance of determination of serum MMP9 and P III P levels in patients with pulmonary interstitial fibrosis

    International Nuclear Information System (INIS)

    Jia Cuiying

    2008-01-01

    Objective: To assess the clinical value of determination of serum matrix metallo-proteinase-9 (MMP 9 ) and type III pro-collagen peptide (PIIIP) levels in patients with pulmonary interstitial fibrosis. Methods: Serum MMP 9 (with ELISA) and PIIIP(with RIA) levels were determined in 46 patients with pulmonary interstitial fibrosis and 30 controls. Results: Serum MMP 9 and PIIIP levels in patients with pulmonary interstitial fibrosis were significantly higher than those in controls (P 9 and PIIIP might be used as clinical diagnostic markers for pulmonary interstitial fibrosis. (authors)

  2. Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients

    DEFF Research Database (Denmark)

    Nielsen, Mette J; Kazankov, Konstantin; Leeming, Diana J

    2015-01-01

    as potential biomarkers for clinically significant and advanced fibrosis. METHODS: Specific protein fragments of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3 and P4NP7S) were assessed in plasma from 403 chronic hepatitis C...... patients by specific ELISAs. Patients were stratified according to Metavir Fibrosis stage; F0 (n = 46), F1 (n = 161), F2 (n = 95), F3 (n = 44) and F4 (n = 33) based on liver biopsy. RESULTS: Pro-C3 was significantly elevated in patients with significant fibrosis (≥F2) compared to F0-F1 (p... the markers C3M, C4M, C6M and P4NP7S were significantly elevated in patients with advanced fibrosis (≥F3) compared to F0-F2 (pC1M showed no difference between fibrosis stages. Using Receiver Operating Characteristics analysis, the best marker for detecting ≥F2 and ≥F3 was Pro-C3 with AUC = 0...

  3. Shear wave elastography (SWE) of the spleen in patients with hepatitis B and C but without significant liver fibrosis.

    Science.gov (United States)

    Pawluś, Aleksander; Inglot, Marcin; Chabowski, Mariusz; Szymańska, Kinga; Inglot, Małgorzata; Patyk, Mateusz; Słonina, Joanna; Caseiro-Alves, Filipe; Janczak, Dariusz; Zaleska-Dorobisz, Urszula

    2016-10-01

    The aim of the study was to compare the elasticity of the spleen in patients with hepatitis B and C but without liver fibrosis with that of healthy subjects using a shear wave elastography (SWE) examination. Between December 2014 and December 2015, 35 patients with hepatitis B virus (HBV) infections and 45 patients with (hepatitis C virus) HCV infections and liver stiffness below 7.1 kPa were included in the study. The control group was composed of 53 healthy volunteers without any chronic liver disease, with no abnormal findings in their ultrasound examinations and with an SWE of the liver below 6.5 kPa. The SWE measurements were a part of routine ultrasound abdominal examinations. The examinations were performed using an Aixplorer device by two radiologists with at least 6 years' experience. To compare spleen stiffness between the groups, the Mann-Whitney U-test was applied. To analyze the dependency between liver and spleen elasticity, Spearman's rank correlation coefficient was calculated. A total of 133 SWE findings were analyzed. Stiffness of the spleen was significantly higher in patients with HBV and HCV but without significant liver fibrosis than it was in the healthy controls (p = 0.0018 and 0.0000, respectively). This correlation was also present in patients with liver stiffness below 6.5 kPa (p = 0.0041 and 0.0000, respectively). Analysis revealed no significant correlation between liver and spleen stiffness in patients with hepatitis B and C and without significant fibrosis (p = 0.3216 and 0.0626, respectively). Patients with hepatitis B and C but without significant liver fibrosis have stiffer spleens than healthy controls. There is no dependency between liver and spleen elasticity in patients without significant fibrosis. The SWE examination might be an important tool and could be used in addition to conventional imaging. Our study may become a starting point in further investigations into the role of the spleen in HCV and HBV

  4. Aquagenic Wrinkling of the Palms in Patients with Cystic Fibrosis

    DEFF Research Database (Denmark)

    Kaiser, H; Brustad, N; Pressler, T

    2018-01-01

    Aquagenic wrinkling of the palms (AWP) is a condition characterized by oedema, confluent white papules and excessive wrinkling of the palms after few minutes exposure to water. The phenomenon may be associated with pain, numbness and pruritus1,2. It was first noticed and described in 1974 in chil...... in children with cystic fibrosis (CF) by a paediatrician R.B. Elliott3. This article is protected by copyright. All rights reserved....

  5. Cytokine levels as biomarkers of radiation fibrosis in patients treated with breast radiotherapy

    International Nuclear Information System (INIS)

    Westbury, Charlotte B; Yarnold, John R; Haviland, Joanne; Davies, Sue; Gothard, Lone; Abdi, Bahja Ahmed; Sydenham, Mark; Bowen, Jo; Stratton, Richard; Short, Susan C

    2014-01-01

    Radiation fibrosis is not easily measurable although clinical scores have been developed for this purpose. Biomarkers present an alternative more objective approach to quantification, and estimation in blood provides accessible samples. We investigated if blood cytokines could be used to measure established fibrosis in patients who have undergone radiotherapy for breast cancer. We studied two cohorts treated by breast-conserving surgery and radiotherapy in the UK START Trial A, one with breast fibrosis (cases) and one with no or minimal fibrosis (controls). Two candidate cytokines, plasma connective tissue growth factor (CTGF) and serum interleukin-6 (IL6) were estimated by ELISA. Comparisons between cases and controls used the t-test or Mann–Whitney test and associations between blood concentration and clinical factors were assessed using the Spearman rank correlation coefficient. Seventy patients were included (26 cases, 44 controls). Mean time since radiotherapy was 9.9 years (range 8.3-12.0). No statistically significant differences between cases and controls in serum IL6 (median (IQR) 0.84 pg/ml (0.57-1.14), 0.75 pg/ml (0.41-1.43) respectively) or plasma CTGF (331.4 pg/ml (234.8-602.9), 334.5 pg/ml (270.0-452.8) were identified. There were no significant associations between blood cytokine concentration and age, fibrosis severity, breast size or time since radiotherapy. No significant difference in IL6 or CTGF concentrations was detected between patients with breast fibrosis and controls with minimal or no fibrosis

  6. Plasma YKL-40: a new potential marker of fibrosis in patients with alcoholic cirrhosis?

    DEFF Research Database (Denmark)

    Johansen, J S; Møller, S; Price, P A

    1997-01-01

    YKL-40 is released or extracted in the hepatosplanchnic system and to localize YKL-40 in liver tissue. METHODS: Plasma YKL-40 was determined by radioimmunoassay in 25 patients with liver diseases (alcoholic cirrhosis (n = 20), chronic active hepatitis (n = 2), cirrhosis of unknown aetiology (n = 2...... with alcoholic liver disease. RESULTS: Plasma YKL-40 was significantly increased in patients with alcoholic cirrhosis (median, 523 micrograms/l; P ... with a moderate or severe degree of liver fibrosis, and immunohistochemical studies showed positive staining for YKL-40 antigen in areas of the liver biopsy with fibrosis. CONCLUSIONS: The increased plasma YKL-40 in patients with alcoholic cirrhosis may reflect the remodelling of liver fibrosis....

  7. Factors associated with worse lung function in cystic fibrosis patients with persistent staphylococcus aureus

    NARCIS (Netherlands)

    Junge, S. (Sibylle); Görlich, D. (Dennis); Reijer, M.D. (Martijn Den); B. Wiedemann (Baerbel); B. Tümmler (Burkhard); H. Ellemunter; Dübbers, A. (Angelika); Küster, P. (Peter); M. Ballmann; Koerner-Rettberg, C. (Cordula); Große-Onnebrink, J. (Jörg); Heuer, E. (Eberhardt); Sextro, W. (Wolfgang); Mainz, J.G. (Jochen G.); Hammermann, J. (Jutta); Riethmüller, J. (Joachim); Graepler-Mainka, U.M. (Ute M.); Staab, D. (Doris); Wollschläger, B. (Bettina); Szczepanski, R. (Rüdiger); A. Schuster (Antje); Tegtmeyer, F.-K. (Friedrich-Karl); Sutharsan, S. (Sivagurunathan); Wald, A. (Alexandra); Nofer, J.-R. (Jerzy-Roch); W.J.B. van Wamel (Willem); Becker, K. (Karsten); Peters, G. (Georg); Kahl, B.C. (Barbara C.)

    2016-01-01

    textabstractBackground Staphylococcus aureus is an important pathogen in cystic fibrosis (CF). However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures. Our main hypothesis was that patients with high S. aureus density in

  8. The microorganisms in chronically infected end-stage and non-end-stage cystic fibrosis patients

    DEFF Research Database (Denmark)

    Rudkjøbing, Vibeke B; Thomsen, Trine R; Alhede, Morten

    2011-01-01

    Patients suffering from cystic fibrosis (CF) develop chronic lung infections because of highly viscous mucus, where bacteria can form biofilms. In this study, we investigated the microorganisms present in the lungs of end-stage and non-end-stage patients using standard culturing techniques and mo...

  9. Epidemiology of nontuberculous mycobacteria among patients with cystic fibrosis in Scandinavia

    DEFF Research Database (Denmark)

    Qvist, Tavs; Gilljam, Marita; Jönsson, Bodil

    2015-01-01

    BACKGROUND: Nontuberculous mycobacteria (NTM) are an emerging threat to cystic fibrosis (CF) patients but their epidemiology is not well described. METHODS: In this retrospective observational study we identified all Scandinavian CF patients with a positive NTM culture from airway secretions from...

  10. Burkholderia pseudomallei Infection in a Cystic Fibrosis Patient from the Caribbean: A Case Report

    Directory of Open Access Journals (Sweden)

    Dimas Mateos Corral

    2008-01-01

    Full Text Available Burkholderia pseudomallei is a pathogen identified with increasing frequency in the respiratory tracts of cystic fibrosis (CF patients from endemic areas such as Southeast Asia and northern Australia. The following report describes the first known reported case in a CF patient from the Caribbean attending a North American CF clinic.

  11. Burkholderia pseudomallei infection in a cystic fibrosis patient from the Caribbean: A case report

    Science.gov (United States)

    Corral, Dimas Mateos; Coates, Allan L; Yau, Yvonne CW; Tellier, Raymond; Glass, Mindy; Jones, Steven M; Waters, Valerie J

    2008-01-01

    Burkholderia pseudomallei is a pathogen identified with increasing frequency in the respiratory tracts of cystic fibrosis (CF) patients from endemic areas such as Southeast Asia and northern Australia. The following report describes the first known reported case in a CF patient from the Caribbean attending a North American CF clinic. PMID:18716683

  12. Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation.

    Science.gov (United States)

    Porteous, Mary K; Rivera-Lebron, Belinda N; Kreider, Maryl; Lee, James; Kawut, Steven M

    2016-03-01

    Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4-93.3) in 6-minute walk distance ([Formula: see text]). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0-21.1; [Formula: see text]). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1-29.5; [Formula: see text]). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis.

  13. Effect of Emphysema Extent on Serial Lung Function in Patients with Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Cottin, Vincent; Hansell, David M; Sverzellati, Nicola; Weycker, Derek; Antoniou, Katerina M; Atwood, Mark; Oster, Gerry; Kirchgaessler, Klaus-Uwe; Collard, Harold R; Wells, Athol U

    2017-11-01

    Patients with idiopathic pulmonary fibrosis and emphysema may have artificially preserved lung volumes. In this post hoc analysis, we investigated the relationship between baseline emphysema and fibrosis extents, as well as pulmonary function changes, over 48 weeks. Data were pooled from two phase III, randomized, double-blind, placebo-controlled trials of IFN-γ-1b in idiopathic pulmonary fibrosis (GIPF-001 [NCT00047645] and GIPF-007 [NCT00075998]). Patients with Week 48 data, baseline high-resolution computed tomographic images, and FEV 1 /FVC ratios less than 0.8 or greater than 0.9 (0.9 in GIPF-007), as well as randomly selected patients with ratios of 0.8-0.9 and 0.7-0.8, were included. Changes from baseline in pulmonary function at Week 48 were analyzed by emphysema extent. The relationship between emphysema and fibrosis extents and change in pulmonary function was assessed using multivariate linear regression. Emphysema was identified in 38% of patients. A negative correlation was observed between fibrosis and emphysema extents (r = -0.232; P emphysema extent (28 to 65%) showed the smallest FVC decline, with a difference of 3.32% at Week 48 versus patients with no emphysema (P = 0.047). In multivariate analyses, emphysema extent greater than or equal to 15% was associated with significantly reduced FVC decline over 48 weeks versus no emphysema or emphysema less than 15%. No such association was observed for diffusing capacity of the lung for carbon monoxide or composite physiologic index. FVC measurements may not be appropriate for monitoring disease progression in patients with idiopathic pulmonary fibrosis and emphysema extent greater than or equal to 15%.

  14. Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Alazawi, William; Bernabe, Eduardo; Tai, David; Janicki, Tomasz; Kemos, Polychronis; Samsuddin, Salma; Syn, Wing-Kin; Gillam, David; Turner, Wendy

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) has a bidirectional association with metabolic syndrome. It affects up to 30% of the general population, 70% of individuals with diabetes and 90% with obesity. The main histological hallmark of progressive NAFLD is fibrosis. There is a bidirectional epidemiological link between periodontitis and metabolic syndrome. NAFLD, periodontitis and diabetes share common risk factors, are characterised by inflammation and associated with changes in commensal bacteria. Therefore we tested the hypothesis that periodontitis is associated with NAFLD and with significant fibrosis in two study groups. We analyzed data from a population-based survey and a patient-based study. NHANES III participants with abdominal ultrasound and sociodemographic, clinical, and oral examination data were extracted and appropriate weighting applied. In a separate patient-based study, consenting patients with biopsy-proved NAFLD (or with liver indices too mild to justify biopsy) underwent dental examination. Basic Periodontal Examination score was recorded. In NHANES, periodontitis was significantly associated with steatosis in 8172 adults even after adjusting for sociodemographic factors. However, associations were fully explained after accounting for features of metabolic syndrome. In the patient-based study, periodontitis was significantly more common in patients with biopsy-proven NASH and any fibrosis (F0-F4) than without NASH (p = 0.009). Periodontitis was more common in patients with NASH and significant fibrosis (F2-4) than mild or no fibrosis (F0-1, p = 0.04). Complementary evidence from an epidemiological survey and a clinical study show that NAFLD is associated with periodontitis and that the association is stronger with significant liver fibrosis.

  15. Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    William Alazawi

    Full Text Available Non-alcoholic fatty liver disease (NAFLD has a bidirectional association with metabolic syndrome. It affects up to 30% of the general population, 70% of individuals with diabetes and 90% with obesity. The main histological hallmark of progressive NAFLD is fibrosis. There is a bidirectional epidemiological link between periodontitis and metabolic syndrome. NAFLD, periodontitis and diabetes share common risk factors, are characterised by inflammation and associated with changes in commensal bacteria. Therefore we tested the hypothesis that periodontitis is associated with NAFLD and with significant fibrosis in two study groups.We analyzed data from a population-based survey and a patient-based study. NHANES III participants with abdominal ultrasound and sociodemographic, clinical, and oral examination data were extracted and appropriate weighting applied. In a separate patient-based study, consenting patients with biopsy-proved NAFLD (or with liver indices too mild to justify biopsy underwent dental examination. Basic Periodontal Examination score was recorded.In NHANES, periodontitis was significantly associated with steatosis in 8172 adults even after adjusting for sociodemographic factors. However, associations were fully explained after accounting for features of metabolic syndrome. In the patient-based study, periodontitis was significantly more common in patients with biopsy-proven NASH and any fibrosis (F0-F4 than without NASH (p = 0.009. Periodontitis was more common in patients with NASH and significant fibrosis (F2-4 than mild or no fibrosis (F0-1, p = 0.04.Complementary evidence from an epidemiological survey and a clinical study show that NAFLD is associated with periodontitis and that the association is stronger with significant liver fibrosis.

  16. Longevity of Patients With Cystic Fibrosis in 2000 to 2010 and Beyond: Survival Analysis of the Cystic Fibrosis Foundation Patient Registry

    Science.gov (United States)

    MacKenzie, Todd; Gifford, Alex H.; Sabadosa, Kathryn A.; Quinton, Hebe B.; Knapp, Emily A.; Goss, Christopher H.; Marshall, Bruce C.

    2015-01-01

    Background Advances in treatments for cystic fibrosis (CF) continue to extend survival. An updated estimate of survival is needed for better prognostication and to anticipate evolving adult care needs. Objective To characterize trends in CF survival between 2000 and 2010 and to project survival for children born and diagnosed with the disease in 2010. Design Registry-based study. Setting 110 Cystic Fibrosis Foundation–accredited care centers in the United States. Patients All patients represented in the Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2000 and 2010. Measurements Survival was modeled with respect to age, age at diagnosis, gender, race or ethnicity, F508del mutation status, and symptoms at diagnosis. Results Between 2000 and 2010, the number of patients in the CFFPR increased from 21 000 to 26 000, median age increased from 14.3 to 16.7 years, and adjusted mortality decreased by 1.8% per year (95% CI, 0.5% to 2.7%). Males had a 19% (CI, 13% to 24%) lower adjusted risk for death than females. Median survival of children born and diagnosed with CF in 2010 is projected to be 37 years (CI, 35 to 39 years) for females and 40 years (CI, 39 to 42 years) for males if mortality remains at 2010 levels and more than 50 years if mortality continues to decrease at the rate observed between 2000 and 2010. Limitations The CFFPR does not include all patients with CF in the United States, and loss to follow-up and missing data were observed. Additional analyses to address these limitations suggest that the survival projections are conservative. Conclusion Children born and diagnosed with CF in the United States in 2010 are expected to live longer than those born earlier. This has important implications for prognostic discussions and suggests that the health care system should anticipate greater numbers of adults with CF. Primary Funding Source Cystic Fibrosis Foundation. PMID:25133359

  17. Gadolinium enhancement of the cerebrospinal fluid in a patient with meningeal fibrosis and cryptococcal infection

    International Nuclear Information System (INIS)

    Sakamoto, S.; Kitagaki, H.; Ishii, K.; Yamaji, S.; Ikejiri, Y.; Mori, E.

    1997-01-01

    We describe the case of a 52-year-old man, with cryptococcal meningitis and meningeal fibrosis who had undergone ventricular shunting. Gd-DTPA-enhanced T1-weighted MRI revealed diffuse meningeal enhancement. Remarkably, there was enhancement of the pia mater and posterior fossa subarachnoid space. (orig.). With 3 figs

  18. Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

    Science.gov (United States)

    Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang; Detlefsen, Sönke; Antonsen, Steen; Krag, Aleksander

    2018-04-01

    Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for

  19. Trajectories of caregiver burden in families of adult cystic fibrosis patients.

    Science.gov (United States)

    Wojtaszczyk, Ann; Glajchen, Myra; Portenoy, Russell K; Berdella, Maria; Walker, Patricia; Barrett, Malcolm; Chen, Jack; Plachta, Amy; Balzano, Julie; Fresenius, Ashley; Wilder, Kenya; Langfelder-Schwind, Elinor; Dhingra, Lara

    2017-10-17

    Little is known about the experience of family caregivers of adults with cystic fibrosis (CF). This information is important for the identification of caregivers at risk for burden. This was a longitudinal analysis of survey data obtained from caregivers of adult CF patients participating in an early intervention palliative care trial. Caregivers completed the validated Brief Assessment Scale for Caregivers (BASC) repeatedly over a 28-month period. Mixed-effects modeling evaluated multivariate associations with positive and negative caregiver perceptions over time. Of the 54 caregivers, 47.9% were spouses. The mean age was 50.9 years (SD = 13.2); 72.2% were women; 75.9% were married; and 63.0% were employed. At baseline, the BASC revealed large variations in positive and negative perceptions of caregiving. Although average scores over time were unchanging, variation was greater across caregivers than within caregivers (0.49 vs. 0.27, respectively). At baseline, the positive impact of caregiving in the sample was higher than the negative impact. Multivariate analysis revealed that patients' baseline pulmonary function and their full-time employment status predicted caregiver burden over time. Caregivers of CF patients varied in their positive and negative caregiving experiences, although burden levels in individual caregivers were stable over time. When the disease was advanced, caregivers of CF patients experienced more overall burden but also more positive impact. This suggests that the role of caregivers may become more meaningful as disease severity worsens. In addition, full-time patient employment was associated with lower caregiver burden regardless of disease severity. This suggests that burden in CF caregivers may be predicted by financial strain or benefits conferred by patient employment. These associations require further investigation to determine whether highly burdened caregivers can be identified and assisted using tailored interventions.

  20. Calcium Stone Growth in Urine from Cystic Fibrosis Patients and Healthy Controls

    Science.gov (United States)

    McSorley, Anita; Jones, Andrew M.; Webb, A. Kevin; Rao, P. Nagaraj; Kavanagh, John P.

    2007-04-01

    Cystic fibrosis patients have an increased risk of renal stone disease. There is some evidence that this may be related to a different excretory pattern of stone risk factors, but an alternative hypothesis, that the urine of cystic fibrosis patients is deficient in urinary inhibitors of crystallization and stone formation has not been tested. Here we have grown calcium stones, in vitro, in the presence of urine from healthy controls and compared this with growth in the presence of urine from cystic fibrosis patients. A stone farm was used to grow twelve calcium stones simultaneously, firstly in artificial urine for about 200 hours and then in 90% whole human urine for another 500 hours. Six of the stones received urine from healthy controls and six received urine from adult cystic fibrosis patients. There were no significant differences in stone mass at any of the key time points or in the overall growth pattern (p>0.05) between stones destined for, or treated with, urine from CF patients and the controls. Human urine greatly inhibited stone growth in vitro but there was no difference in the growth rate in urine from healthy controls and CF patients. This refutes the hypothesis that a tendency for a higher prevalence of urinary stones in CF patients is related to a deficiency in inhibitory activity.

  1. Analysis of the CFTR gene in Venezuelan cystic fibrosis patients, identification of six novel cystic fibrosis-causing genetic variants.

    Science.gov (United States)

    Sánchez, Karen; de Mendonca, Elizabeth; Matute, Xiorama; Chaustre, Ismenia; Villalón, Marlene; Takiff, Howard

    2016-01-01

    The mutations in the CFTR gene found in patients with cystic fibrosis (CF) have geographic differences, but there are scant data on their prevalence in Venezuelan patients. This study determined the frequency of common CFTR gene mutations in a group of Venezuelan patients with CF. The 27 exons of the CFTR gene from 110 Venezuelan patients in the National CF Program were amplified and sequenced. A total of 36 different mutations were identified, seven with frequencies greater than 1%: p.Phe508del (27.27%), p.Gly542* (3.18%), c.2988+1G>A (3.18%), p.Arg334Trp (1.36%), p.Arg1162* (1.36%), c.1-8G>C (1.36%), and p.[Gly628Arg;Ser1235Arg](1.36). In 40% of patients, all with a clinical diagnosis of CF, no mutations were found. This report represents the largest cohort of Venezuelan patients with CF ever examined, and includes a wider mutation panel than has been previously studied in this population. Mutations common in Southern European populations predominate, and several new mutations were discovered, but no mutations were found in 40% of the cohort.

  2. ASSOCIATION OF CAFFEINE INTAKE AND LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C

    Directory of Open Access Journals (Sweden)

    Kalinca da Silva OLIVEIRA

    2015-03-01

    Full Text Available Background Caffeine consumption has been associated to decreased levels of liver enzymes and lower risk of fibrosis in patients with hepatitis C virus. Objectives This study aimed to evaluate the association between caffeine consumption and inflammatory activity or degree of liver fibrosis in patients with hepatitis C virus infection. Methods A cross-sectional study of patients with chronic hepatitis C virus infection treated in an outpatient Gastroenterology Unit of Santa Casa Hospital (Porto Alegre - Brasil. Patients were interviewed regarding the consumption of caffeine and anthropometric assessment was performed. Liver biopsy was performed in a maximum period of 36 months before inclusion in the study Results There were 113 patients, 67 (59.3% females, 48 (42.5% were aged between 52 and 62 years, and 101 (89.4% were white. The average caffeine consumption was 251.41 ± 232.32 mg/day, and 70 (62% patients consumed up to 250 mg/day of caffeine. There was no association between caffeine consumption and inflammatory activity on liver biopsy. On the other hand, when evaluating the caffeine consumption liver fibrosis an inverse association was observed. Conclusions The greater consumption of caffeine was associated with lower liver fibrosis. There was no association between caffeine consumption and inflammatory activity.

  3. Frequency of common CFTR gene mutations in Venezuelan patients with cystic fibrosis

    OpenAIRE

    Sánchez, Karen; Arcia, Orlando; Matute, Xiorama; Mindiola, Luz; Chaustre, Ismenia; Takiff, Howard

    2014-01-01

    Mutations in the CFTR gene in Cystic Fibrosis (CF) patients have geographic differences and there is scant data on their prevalence in Venezuelan patients. This study determined the frequency of common CFTR gene mutations in these patients. We amplified and sequenced exons 7, 10, 11, 19, 20 and 21, which contain the most common CFTR mutations, from 105 Venezuelan patients in the National CF Program. Eleven different mutations were identified, four with frequencies greater than 1%: p.Phe508del...

  4. PROGRESSION OF LIVER FIBROSIS IN MONOINFECTED PATIENTS BY HEPATITIS C VIRUS AND COINFECTED BY HCV AND HUMAN IMMUNODEFICIENCY VIRUS

    Directory of Open Access Journals (Sweden)

    Cristiane Valle TOVO

    2013-03-01

    Full Text Available Context The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. Objective To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected Methods Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. Conclusion The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations.

  5. Diagnostic value of fibronectin discriminant score for predicting liver fibrosis stages in chronic hepatitis C virus patients.

    Science.gov (United States)

    Attallah, Abdelfattah M; Abdallah, Sanaa O; Attallah, Ahmed A; Omran, Mohamed M; Farid, Khaled; Nasif, Wesam A; Shiha, Gamal E; Abdel-Aziz, Abdel-Aziz F; Rasafy, Nancy; Shaker, Yehia M

    2013-01-01

    Several noninvasive predictive models were developed to substitute liver biopsy for fibrosis assessment. To evaluate the diagnostic value of fibronectin which reflect extracellular matrix metabolism and standard liver functions tests which reflect alterations in hepatic functions. Chronic hepatitis C (CHC) patients (n = 145) were evaluated using ROC curves and stepwise multivariate discriminant analysis (MDA) and was validated in 180 additional patients. Liver biochemical profile including transaminases, bilirubin, alkaline phosphatase, albumin, complete blood count were estimated. Fibronectin concentration was determined using monoclonal antibody and ELISA. A novel index named fibronectin discriminant score (FDS) based on fibronectin, APRI and albumin was developed. FDS produced areas under ROC curves (AUC) of 0.91 for significant fibrosis and 0.81 for advanced fibrosis. The FDS correctly classified 79% of the significant liver fibrosis patients (F2-F4) with 87% sensitivity and 75% specificity. The relative risk [odds ratio (OR)] of having significant liver fibrosis using the cut-off values determined by ROC curve analyses were 6.1 for fibronectin, 4.9 for APRI, and 4.2 for albumin. FDS predicted liver fibrosis with an OR of 16.8 for significant fibrosis and 8.6 for advanced fibrosis. The FDS had similar AUC and OR in the validation group to the estimation group without statistically significant difference. FDS predicted liver fibrosis with high degree of accuracy, potentially decreasing the number of liver biopsy required.

  6. Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Tolker-Nielsen, Tim; Jensen, Peter Østrup

    2015-01-01

    Lung infection is the main cause of morbidity and mortality in patients with cystic fibrosis and is mainly dominated by Pseudomonas aeruginosa. The biofilm mode of growth makes eradication of the infection impossible, and it causes a chronic inflammation in the airways. The general mechanisms...

  7. Pulmonary bacterial pathogens in cystic fibrosis patients and antibiotic therapy: a tool for the health workers

    Directory of Open Access Journals (Sweden)

    Coutinho Henrique

    2008-11-01

    Full Text Available Abstract Cystic fibrosis is the most common and best known genetic disease involving a defect in transepithelial Cl- transport by mutations in the CF gene on chromosome 7, which codes for the cystic fibrosis transmembrane conductance regulator protein (CFTR. The most serious symptoms are observed in the lungs, augmenting the risk of bacterial infection. The objective of this review was to describe the bacterial pathogens colonizing patients with cystic fibrosis. A systematic search was conducted using the international bibliographic databanks SCIELO, HIGHWIRE, PUBMED, SCIRUS and LILACS to provide a useful and practical review for healthcare workers to make them aware of these microorganisms. Today, B. cepacia, P. aeruginosa and S. aureus are the most important infectious agents in cystic fibrosis patients. However, healthcare professionals must pay attention to emerging infectious agents in these patients, because they represent a potentially serious future problem. Therefore, these pathogens should be pointed out as a risk to these patients, and hospitals all over the world must be prepared to detect and combat these bacteria.

  8. Decreased mucosal oxygen tension in the maxillary sinuses in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Aanæs, Kasper; Rickelt, Lars Fledelius; Johansen, Helle Krogh

    2011-01-01

    Pseudomonas aeruginosa in the sinuses plays a role in the lungs in cystic fibrosis (CF) patients, but little is known about the sinus environment where the bacteria adapt. Anoxic areas are found in the lower respiratory airways but it is unknown if the same conditions exist in the sinuses....

  9. Within-host microevolution of Pseudomonas aeruginosa in Italian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Marvig, Rasmus Lykke; Dolce, Daniela; Madsen Sommer, Lea Mette

    2015-01-01

    Chronic infection with Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis (CF) patients, and a more complete understanding of P. aeruginosa within-host genomic evolution, transmission, and population genomics may provide a basis for improving intervention strate...

  10. Serum hyaluronic acid as a marker of hepatic fibrosis

    International Nuclear Information System (INIS)

    Khan, J.A.; Khan, F.A.; Ijaz, A.; Khan, N.A.; Mehmood, T.

    2007-01-01

    To determine the serum hyaluronic acid (HA) levels as biochemical marker of hepatic fibrosis and cirrhosis and correlate it with the degree of hepatic fibrosis and cirrhosis. This study was performed on 100 patients of chronic liver disease whose liver biopsies had been carried out. Fifty healthy controls were also included in the study. Routine liver function tests, hepatitis serology and serum hyaluronic acid levels were carried out on patients and controls. Liver biopsy of 100 patients revealed that 21 were in stage 0 fibrosis, 38 in stage 1 fibrosis, 26 in stage 3 fibrosis and 15 in stage 4 fibrosis. Mean Serum HA (mean +- SD) concentration in patients were 189 +- 98 mg/L vs. 21 +- 10 mg/L of healthy controls. The difference observed was statistically significant (p < 0.001). Patients in stage 4 fibrosis had significantly higher (p <0.001) mean serum HA concentration as compared to other stages of liver fibrosis. Diagnostic accuracy of serum HA at marginally elevated level of 60 mg/L determined the sensitivity 78.4 %, specificity 80.9%, positive predicted value 93.9% and negative predicted value of 50%. Serum HA is a useful non-invasive marker of liver fibrosis. There is a strong positive correlation between serum HA levels and degree of liver fibrosis. The concentration of serum HA rises according to progression of liver fibrosis and levels are highest in patients with liver cirrhosis. (author)

  11. Individual radiosensitivity measured with lymphocytes can be used to predict the risk of fibrosis after radiotherapy of breast cancer patients

    International Nuclear Information System (INIS)

    Hoeller, U.; Borgmann, K.; Alberti, W.; Dikomey, E.

    2003-01-01

    To analyse the relationship of individual cellular radiosensitivity and fibrosis after breast conserving therapy. A new model was used describing the percentage of patients developing fibrosis per year per patients at risk . In a retrospective study, 86 patients were included, who had undergone breast conserving surgery and irradiation of the breast with a median dose of 55 Gy (54-55Gy), 2.5 Gy/fraction (n=57) or 2 Gy/fraction (n=29). Median age was 62 years (range: 44-86) and median follow up was 7.5 years (range 5-16). Patients were examined for fibrosis according to the LENT/SOMA score. For analysis, fibrosis was classified as none (G0-1) or present (G2-3). The time to complete development of fibrosis was determined by analysis of yearly mammograms. Individual cellular radiosensitivity was determined by scoring lethal chromosomal aberrations in in vitro irradiated (6 Gy) lymphocytes using metaphase technique. Patients with low/intermediate cellular radiosensitivity were compared with patients with high cellular radiosensitivity with actuarial methods. Ten patients developed fibrosis at 1-8 years after radiotherapy. Individual cellular radiosensitivity was described by normal distribution of lethal chromosomal aberrations, average 5.47 lethal aberrations per cell (standard deviation 0.71). Cellular radiosensitivity was defined as low/intermediate (le 6.18 lethal aberrations) in 73 patients and as high (> 6.18 lethal aberrations ) in 13 patients. In both groups the actuarial rate of fibrosis-free patients declined exponentially with time after radiotherapy. Patients with high cellular radiosensitivity showed a 2.3 fold higher annual rate for fibrosis than patients with intermediate and low radiosensitivity (3.6±0.1 vs. 1.6±0.3). In breast cancer patients, high individual cellular radiosensitivity as determined by the number of lethal chromosome aberrations in in vitro irradiated lymphocytes was correlated with an enhanced annual rate of fibrosis

  12. Possibilities of computed bronchophonography in the diagnosis of external respiratory dysfunction in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    E. B. Pavlinova

    2016-01-01

    Full Text Available The degree of respiratory organ injury in cystic fibrosis determines the prognosis of the disease. Objective: to evaluate external respiratory function in children with cystic fibrosis. The study enrolled 48 children followed up at the Omsk Cystic Fibrosis Center. A control group consisted of 42 non-addicted smoking children with no evidence for respiratory diseases in the history. External respiratory function was evaluated using computed bronchophonography; spirography was additionally carried out in children over 6 years of age. Computed bronchophonography revealed obstructive respiratory failure in all children with severe cystic fibrosis. Chronic respiratory tract infection with Pseudomonas aeruginosa and bronchiectasis were associated with the higher values of the acoustic work of breathing at frequencies over 5000 Hz. It was established that there was a moderate negative correlation between the value of the acoustic work of breathing in the high frequency range and the forced expiratory volume in 1 second in %. Conclusion. Computed bronchophonography could reveal obstructive external respiratory dysfunction in children less than 6 years of age. 

  13. Factors associated with worse lung function in cystic fibrosis patients with persistent staphylococcus aureus

    OpenAIRE

    Junge, S. (Sibylle); Görlich, D. (Dennis); Reijer, M.D. (Martijn Den); Wiedemann, Baerbel; Tümmler, Burkhard; Ellemunter, H.; Dübbers, A. (Angelika); Küster, P. (Peter); Ballmann, M.; Koerner-Rettberg, C. (Cordula); Große-Onnebrink, J. (Jörg); Heuer, E. (Eberhardt); Sextro, W. (Wolfgang); Mainz, J.G. (Jochen G.); Hammermann, J. (Jutta)

    2016-01-01

    textabstractBackground Staphylococcus aureus is an important pathogen in cystic fibrosis (CF). However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures. Our main hypothesis was that patients with high S. aureus density in their respiratory specimens would more likely experience worsening of their lung disease than patients with low bacterial loads. Methods Therefore, we conducted an observational prospective longitudi...

  14. Factors Associated with Worse Lung Function in Cystic Fibrosis Patients with Persistent Staphylococcus aureus

    OpenAIRE

    Junge, Sibylle; G?rlich, Dennis; den Reijer, Martijn; Wiedemann, B?rbel; T?mmler, Burkhard; Ellemunter, Helmut; D?bbers, Angelika; K?ster, Peter; Ballmann, Manfred; Koerner-Rettberg, Cordula; Gro?e-Onnebrink, J?rg; Heuer, Eberhardt; Sextro, Wolfgang; Mainz, Jochen G.; Hammermann, Jutta

    2016-01-01

    Background Staphylococcus aureus is an important pathogen in cystic fibrosis (CF). However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures. Our main hypothesis was that patients with high S. aureus density in their respiratory specimens would more likely experience worsening of their lung disease than patients with low bacterial loads. Methods Therefore, we conducted an observational prospective longitudinal multi-ce...

  15. Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients

    Science.gov (United States)

    Khattab, Mahmoud; Sakr, Mohamed Amin; Fattah, Mohamed Abdel; Mousa, Youssef; Soliman, Elwy; Breedy, Ashraf; Fathi, Mona; Gaber, Salwa; Altaweil, Ahmed; Osman, Ashraf; Hassouna, Ahmed; Motawea, Ibrahim

    2016-01-01

    AIM To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy. METHODS A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR). RESULTS Fibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage (P < 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤ -0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis. CONCLUSION Our predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy. PMID:27917265

  16. Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients.

    Science.gov (United States)

    Khattab, Mahmoud; Sakr, Mohamed Amin; Fattah, Mohamed Abdel; Mousa, Youssef; Soliman, Elwy; Breedy, Ashraf; Fathi, Mona; Gaber, Salwa; Altaweil, Ahmed; Osman, Ashraf; Hassouna, Ahmed; Motawea, Ibrahim

    2016-11-18

    To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy. A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR). Fibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage ( P < 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤ -0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis. Our predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy.

  17. Multidimensional clinical phenotyping of an adult cystic fibrosis patient population.

    Directory of Open Access Journals (Sweden)

    Douglas J Conrad

    Full Text Available Cystic Fibrosis (CF is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease.The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier.Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1 a low lung health scores phenotype, 2 a younger, well-nourished, male-dominated class, 3 various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency.This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study.

  18. Frequency of steatosis and its relation with the grade of fibrosis in patients with hepatitis C

    International Nuclear Information System (INIS)

    Shaikh, S.; Sadik, M.; Hussain, B.G.

    2009-01-01

    To study the frequency of steatosis and observe the relation between steatosis and grade of fibrosis in patients with hepatitis C. This descriptive case series study was undertaken at Liaquat University of Medical and Health Sciences hospital from July 2005 to November 2007. It included 158 PCR-positive hepatitis C cases with genotype 3. Patients demographic data was enrolled in well designed proforma BMI was calculated and history of diabetes mellitus was obtained. Liver biopsy was done after written consent and was sent for grading of fibrosis and steatosis. T-test was applied for Continuous variables whereas stage of fibrosis was compared with grade of steatosis, BMI and age by chi-square test. 0.05 was made a level of Significance. This study included 158 patients out of which 109 (69%) were male and 49(31%) were female. The mean age of the patient was 36.8 +- 9.8.The BMI was 30 in 19 (12%) of cases. The steatosis was found in 71(45%) of cases. Mild ( 60% hepatocytes involved) steatosis in 12(7.5%) cases. A strong correlation between steatosis score and fibrosis stage was observed in our study (P= < 0.001) whereas no relationship was observed between BMI (P 0.67) or age (P =0.39) with stage of steatosis. This study showed that increased steatosis is associated with worsening fibrosis suggesting a possible role for steatosis in the acceleration of liver disease in HCV Patients and efforts to control steatosis may therefore have an important role in halting HCV liver disease progression. (author)

  19. Fibrosis and electrophysiological characteristics of the atrial appendage in patients with atrial fibrillation and structural heart disease

    NARCIS (Netherlands)

    Brakel, T.J. van; Krieken, T. van der; Westra, S.W.; Laak, J.A.W.M. van der; Smeets, J.L.R.M.; Swieten, H.A. van

    2013-01-01

    PURPOSE: This study was conducted to investigate the degree of fibrosis in atrial appendages of patients with and without atrial fibrillation (AF) undergoing cardiac surgery. In addition, we hypothesized that areas of atrial fibrosis can be identified by electrogram fractionation and low voltage for

  20. Draft Genome Sequences of Pseudomonas aeruginosa B3 Strains Isolated from a Cystic Fibrosis Patient Undergoing Antibiotic Chemotherapy

    DEFF Research Database (Denmark)

    Marvig, Rasmus Lykke; Jochumsen, Nicholas; Johansen, Helle Krogh

    2013-01-01

    Pseudomonas aeruginosa frequently establishes chronic infections in the airways of patients suffering from cystic fibrosis (CF). Here, we report the draft genome sequences of four P. aeruginosa B3 strains isolated from a chronically infected CF patient undergoing antibiotic chemotherapy.......Pseudomonas aeruginosa frequently establishes chronic infections in the airways of patients suffering from cystic fibrosis (CF). Here, we report the draft genome sequences of four P. aeruginosa B3 strains isolated from a chronically infected CF patient undergoing antibiotic chemotherapy....

  1. Hemostatic dysfunction is increased in patients with hepatosplenic schistosomiasis mansoni and advanced periportal fibrosis.

    Directory of Open Access Journals (Sweden)

    Luiz Arthur Calheiros Leite

    Full Text Available BACKGROUND: Schistosomiasis mansoni is an endemic parasitic disease and a public health problem in Northeast Brazil. In some patients, hepatic abnormalities lead to periportal fibrosis and result in the most severe clinical form, hepatosplenic schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation and liver function tests in patients with hepatosplenic schistosomiasis (n = 55 correlate with the severity of their periportal fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples were used for liver function tests, hemogram and prothrombin time (International Normalized Ratio, INR. The blood coagulation factors (II, VII, VIII, IX and X, protein C and antithrombin IIa (ATIIa, plasminogen activator inhibitor 1 (PAI-1 and D-dimer were measured by photometry or enzyme linked immunosorbent assay. Hyperfibrinolysis was defined on the basis of PAI-1 levels and a D-dimer concentration greater than a standard cut-off of 483 ng/mL. Standard liver function tests were all abnormal in the patient group compared to healthy controls (n = 29, including raised serum transaminases (p<0.001 and lower levels of albumin (p = 0.0156. Platelet counts were 50% lower in patients, while for coagulation factors there was a 40% increase in the INR (p<0.001 and reduced levels of Factor VII and protein C in patients compared to the controls (both p<0.001. Additionally, patients with more advanced fibrosis (n = 38 had lower levels of protein C compared to those with only central fibrosis (p = 0.0124. The concentration of plasma PAI-1 in patients was one-third that of the control group (p<0.001, and D-dimer levels 2.2 times higher (p<0.001 with 13 of the 55 patients having levels above the cut-off. CONCLUSION/SIGNIFICANCE: This study confirms that hemostatic abnormalities are associated with reduced liver function and increased liver fibrosis. Of note was the finding that a quarter of patients with hepatosplenic schistosomiasis and

  2. Profiling of antioxidant superoxide dismutase in saliva of oral submucous fibrosis patients to categorize its diagnosis in varying stages

    International Nuclear Information System (INIS)

    Sirohi, Y.; Shetty, D.C.; Urs, A.B.; Rai, H.C.

    2011-01-01

    Background: Oral submucous fibrosis is a pre malignant condition in Indian and South-East Asia. Role of oxidant-antioxidant in causation and progression of cancer and pre cancers is known. Reactive oxygen species are generated in the oral cavity during chewing areca nut, the major etiological agent in oral submucous fibrosis. Objectives: To see the alterations in the salivary superoxide dismutase levels in various clinical and histopathological grades of oral submucous fibrosis. Materials and Methods: Unstimulated saliva was collected from 25 oral submucous fibrosis patients and age and gender matched controls. The saliva was assessed for superoxide dismutase value by spectrophotometric method using assay kit (Bio Vision Catalog number K335-100). The oral submucous fibrosis cases were grouped into clinical stages and histopathological grades and superoxide dismutase values were compared in different clinical stages and histopathological grades. Results: The superoxide dismutase levels were reduced in oral submucous fibrosis as compared to controls. A steady decline in the levels was seen as the clinical stage and histopathological grade of oral submucous fibrosis advanced. Conclusions: Salivary superoxide dismutase levels can be alternatively used as a surrogate marker for the diagnosis of oral submucous fibrosis. Policy message: Oral physicians should advise the pan chewers to regularly check their salivary superoxide dismutase levels so as to ease the early diagnosis of oral submucous fibrosis. (author)

  3. Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    McPherson, Stuart; Henderson, Elsbeth; Burt, Alastair D; Day, Christopher P; Anstee, Quentin M

    2014-05-01

    A third of the population are estimated to have NAFLD of varying severity. Serum immunoglobulins are frequently elevated in patients with chronic liver disease, but little is known about serum immunoglobulin levels in patients with NAFLD. Aim of this study was to evaluate serum immunoglobulin levels (IgA, IgG, and IgM) in a large cohort of patients with biopsy-proven NAFLD and determine if immunoglobulin levels are associated with clinical or histological features. Patients seen in a tertiary fatty liver clinic between 1999 and 2009 were included. Liver biopsies were assessed using the Kleiner score. Immunoglobulin levels and other blood tests were taken at time of biopsy. 285 patients (110 simple steatosis and 175 NASH) had serum immunoglobulins measured within 6months of liver biopsy. 130 (46%) patients had elevated (>1× upper limit of normal) serum IgA levels, 28 (10%) patients had elevated IgG and 22 (8%) raised IgM. Serum IgA levels were elevated more frequently in patients with NASH compared with subjects with simple steatosis (55% vs. 31%, pliver fibrosis (Kleiner stage 3-4). There was a significant positive association between serum IgA levels and the stage of fibrosis (pfibrosis following multivariate analysis. A model constructed from these independent predictors accurately predicted advanced fibrosis (AUROC 0.87). The serum IgA level was frequently elevated in patients with NAFLD and was an independent predictor of advanced fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. Effect of Obstructive airway disease in patients with non-cystic fibrosis bronchiectasis

    International Nuclear Information System (INIS)

    Khalid, Mohammad; Saleemi, Sarfraz; Zeitouni, Mohammed; Al-Dammas, Saleh; Khaliq, Mohammad Rehan

    2004-01-01

    Extensive research has been devoted to cystic fibrosis-related brochiectasis compared with noncystic fibrosis brochiectasis but the latter is more common and results in significant morbidity and mortality. We assessed the relationship between pulmonary function test (PFT) findings and sputum bacteriology, blood gases, number of hospital admissions and mortality in patients with non-cystic fibrosis brochiectasis (NCFB). we conducted a retrospective review of 88 consecutive patients admitted with exacerbation of brochiectasis over 5 years from 1996 to 2001. Demographic and clinical data collected included gender, age, pulmonary functions, arterial blood gases, sputum bacteriology during stable and exacerbation periods and number of hospital admissions due to exacerbation of brochiectasis. A comparison was made between patients having obstructive airway disease (OAD group) and patients with normal or restrictive pulmonaru functions (non-OAD group). OAD patients with NCFB adversely affected clinical outcome.There was a significant increase in Pseuomonas colonization (60.3% vs. 16%; P<0.0003), hypercapnic respiratory failure (63.4% vs. 20%; P<0.0003) and mean number of admissons due to exacerbation (6 vs. 2; P<0.0001)in the OAD group as compared with the non OAD group, the difference was not statistically significant. Patients with NCFB who have OAD have a significantly higher rate of colonization with Pseuomonas aeruginosa (PSA) hypercapric respiratory failure, a greater number of hospital admissions due to exacerbation of brochiectasis and a a higher mortality compared with patients with restrictive or normal pulmonary functions. (author)

  5. Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline

    Directory of Open Access Journals (Sweden)

    Constantin Adams

    2016-07-01

    Full Text Available Background/Aims: Several recent clinical studies revealed an accumulation of ceramide in bronchial epithelial cells of patients with cystic fibrosis (CF. Degradation of ceramide concentrations in lungs of CF patients employing the functional acid sphingomyelinase inhibitor amitriptyline revealed a benefit in lung function, weight and exacerbation rates. Methods: To test for a beneficial effect of amitriptyline in vivo, we performed two phase II randomised, double-blind, placebo-controlled studies. CF patients were treated with 25 mg amitriptyline twice daily, i.e. a total dose of 50 mg/d. After those two studies part of the patients used amitriptyline in an off-lable-use for routine treatment. These patients were observed after one, two and three years after continuous use of amitriptyline and were matched with those patients who were not treated. These patients were used as a control group. Results: After one year of treatment, forced expiratory volume in 1 sec predicted (FEV1 increased significantly by 7.6±7.0%, p=1 decreased significantly in the control group by 1.8±3.3%, p=0.010, and weight increased by 1.1±2.7kg, p=0.010 (n=14. After two years of treatment, FEV1 increased significantly by 5.6±10.3%, p=0.009, and weight increased by 3.6±2.9kg, p=1 decreased in the control group by 2.1±3.7%, p=0.051 and weight increased by only 0.4±2.9kg, p=0.31 (n=10. After three years of treatment, FEV1 increased significantly by 7.7±8%, p=0.050, and weight increased by 7.3±3.8kg, p=0.016, in the amitriptyline population (n=5, whereas FEV1 decreased in the control group by 1.0±1.3%, p=0.075 and weight increased by 0.4±1.5kg, p=0.29 (n=5. Conclusion: Amitriptyline significantly increases FEV1, reduces ceramide in lung cells and increases weight of CF patients.

  6. Establishing ultrasound based transient elastography cutoffs for different stages of hepatic fibrosis and cirrhosis in Egyptian chronic hepatitis C patients.

    Science.gov (United States)

    Elsharkawy, Aisha; Alboraie, Mohamed; Fouad, Rabab; Asem, Noha; Abdo, Mahmoud; Elmakhzangy, Hesham; Mehrez, Mai; Khattab, Hany; Esmat, Gamal

    2017-12-01

    Transient elastography is widely used to assess fibrosis stage in chronic hepatitis C (CHC). We aimed to establish and validate different transient elastography cut-off values for significant fibrosis and cirrhosis in CHC genotype 4 patients. The data of 100 treatment-naive CHC patients (training set) and 652 patients (validation set) were analysed. The patients were subjected to routine pretreatment laboratory investigations, liver biopsy and histopathological staging of hepatic fibrosis according to the METAVIR scoring system. Transient elastography was performed before and in the same week as liver biopsy using FibroScan (Echosens, Paris, France). Transient elastography results were correlated to different stages of hepatic fibrosis in both the training and validation sets. ROC curves were constructed. In the training set, the best transient elastography cut-off values for significant hepatic fibrosis (≥F2 METAVIR), advanced hepatic fibrosis (≥F3 METAVIR) and cirrhosis (F4 METAVIR) were 7.1, 9 and 12.2 kPa, with sensitivities of 87%, 87.5% and 90.9% and specificities of 100%, 99.9% and 99.9%, respectively. The application of these cut-offs in the validation set showed sensitivities of 85.5%, 82.8% and 92% and specificities of 86%, 89.4% and 99.01% for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, respectively. Transient elastography performs well for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, with validated cut-offs of 7.1, 9 and 12.2 kPa, respectively, in genotype 4 CHC patients. Copyright © 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

  7. Long term prognosis of patients with cystic fibrosis in relation to early detection by neonatal screening and treatment in a cystic fibrosis centre

    NARCIS (Netherlands)

    Dankert-Roelse, J E; te Meerman, G J

    BACKGROUND: A study was undertaken to evaluate whether an early diagnosis by neonatal screening may improve the long term prognosis of patients with cystic fibrosis and to assess the influence of expert management started immediately after the diagnosis. METHODS: Comparative clinical follow up in

  8. Accuracy of the Enhanced Liver Fibrosis Test vs Fibrotest, Elastography and Indirect Markers in Detection of Advanced Fibrosis in Patients with Alcoholic Liver Disease

    DEFF Research Database (Denmark)

    Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang

    2018-01-01

    BACKGROUND & AIMS: Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2......-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). METHODS: We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal...... significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P=.521 and .004 for comparison with ELF). Adding a serum marker to transient elastography...

  9. Spontaneous pneumothorax associated with pulmonary fibrosis in a patient with neurofibromatosis type 2

    International Nuclear Information System (INIS)

    Alcala Cerra, Gabriel; Moscote-Salazar, Luis Rafael; Lozano Tagua, Carlos Fernando; Sabogal Barrios, Ruben

    2010-01-01

    Pulmonary involvement in patients with neurofibromatosis has been repetitively reported as a very rare complication in type 1 variety. It is characterized by pulmonary interstitial disease, pulmonary fibrosis and bullaes, the last with high risk of rupture. We described a case of spontaneous pneumothorax in a patient with type 2 neurofibromatosis, as consequence of pulmonary fibrotic changes. To our knowledge this association had not been reported.

  10. Patient knowledge and pulmonary medication adherence in adult patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Lin AH

    2017-03-01

    Full Text Available Ann Hsu-An Lin,1 Jennifer G Kendrick,2,3 Pearce G Wilcox,4,5 Bradley S Quon4,51Faculty of Medicine, 2Faculty of Pharmaceutical Sciences, University of British Columbia, 3Department of Pharmacy, Children’s and Women’s Health Centre of British Columbia, 4Department of Medicine, Division of Respiratory Medicine, University of British Columbia, 5Centre for Heart Lung Innovation, St Paul’s Hospital, Vancouver, BC, CanadaBackground and objectives: Patient knowledge of lung function (ie, forced expiratory volume in 1 s [FEV1]% predicted and the intended benefits of their prescribed pulmonary medications might play an important role in medication adherence, but this relationship has not been examined previously in patients with cystic fibrosis (CF.Methods: All patients diagnosed with CF and without prior lung transplantation were invited to complete knowledge and self-reported medication adherence questionnaires during routine outpatient visits to the Adult CF Clinic, St Paul’s Hospital, Vancouver, Canada from June 2013 to August 2014.Results: A total of 142 out of 167 (85% consecutive adults attending CF clinic completed patient knowledge and medication adherence survey questionnaires. Sixty-four percent of the patients recalled their last FEV1% predicted value within 5%, and 70% knew the intended benefits of all their prescribed medications. Self-reported adherence rates were highest for inhaled antibiotics (81%, azithromycin (87%, and dornase alpha (76% and lowest for hypertonic saline (47%. Individuals who knew their FEV1% predicted value within 5% were more likely to self-report adherence to dornase alpha (84% vs 62%, P=0.06 and inhaled antibiotics (88% vs 64%, P=0.06 compared to those who did not, but these associations were not statistically significant. There were no significant associations observed between patient knowledge of intended medication benefits and self-reported medication adherence.Conclusion: Contrary to our hypothesis

  11. Radiological characteristics, histological features and clinical outcomes of lung cancer patients with coexistent idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Khan, K A; Kennedy, M P; Moore, E; Crush, L; Prendeville, S; Maher, M M; Burke, L; Henry, M T

    2015-02-01

    Despite advances in diagnosis and management, the outcomes for both lung cancer and idiopathic pulmonary fibrosis (IPF) are still unfavourable. The pathophysiology and outcomes for patients with concomitant lung cancer and IPF remains unclear. A retrospective analysis was performed of all patients presenting with concomitant IPF and lung cancer to our centre over a 3-year period. Patients with connective tissue disease, asbestos exposure, sarcoidosis, previous thoracic radiation, radiological evidence of fibrosis but no histological confirmation of lung cancer, or the use of medications known to cause pulmonary fibrosis were excluded. We describe clinical, radiological and pathological characteristics of this group. We also report the response to standardized lung cancer therapy in this cohort. Of 637 lung cancer patients, 34 were identified with concomitant IPF (5.3 %) and all were smokers. 85 % had non-small cell lung cancer, 41 % were squamous cell cancers. The majority of tumours were located in the lower lobes, peripheral and present in an area of honeycombing. Despite the fact that approximately 2/3rds of the patients had localised or locally advanced lung cancer, the outcome of therapy for lung cancer was extremely poor regardless of tumour stage or severity of IPF. At our centre, 1/20 patients with lung cancer have concomitant IPF. The majority of these tumours are small in size, peripheral in location and squamous cell carcinoma; in an area of honey combing. The outcome for concomitant lung cancer and IPF regardless of stage or therapy is poor.

  12. Non-invasive assessment of liver fibrosis using two-dimensional shear wave elastography in patients with autoimmune liver diseases.

    Science.gov (United States)

    Zeng, Jie; Huang, Ze-Ping; Zheng, Jian; Wu, Tao; Zheng, Rong-Qin

    2017-07-14

    To determine the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE) for the non-invasive assessment of liver fibrosis in patients with autoimmune liver diseases (AILD) using liver biopsy as the reference standard. Patients with AILD who underwent liver biopsy and 2D-SWE were consecutively enrolled. Receiver operating characteristic (ROC) curves were constructed to assess the overall accuracy and to identify optimal cut-off values. The characteristics of the diagnostic performance were determined for 114 patients with AILD. The areas under the ROC curves for significant fibrosis, severe fibrosis, and cirrhosis were 0.85, 0.85, and 0.86, respectively, and the optimal cut-off values associated with significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 9.7 kPa, 13.2 kPa and 16.3 kPa, respectively. 2D-SWE showed sensitivity values of 81.7% for significant fibrosis, 83.0% for severe fibrosis, and 87.0% for cirrhosis, and the respective specificity values were 81.3%, 74.6%, and 80.2%. The overall concordance rate of the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages was 53.5%. 2D-SWE showed promising diagnostic performance for assessing liver fibrosis stages and exhibited high cut-off values in patients with AILD. Low overall concordance rate was observed in the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages.

  13. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.

    Science.gov (United States)

    Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor; Wood, Tammara A; Christmann, Romy B; Farber, Harrison W; Lafyatis, Robert A; Denton, Christopher P; Hinchcliff, Monique E; Pioli, Patricia A; Mahoney, J Matthew; Whitfield, Michael L

    2017-03-23

    Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune

  14. Follow-up and nonpharmacological management of the idiopathic pulmonary fibrosis patient

    Directory of Open Access Journals (Sweden)

    J.J. Egan

    2011-06-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic, progressive, fatal form of diffuse interstitial lung disease. Management of IPF requires an orderly approach, with regular evaluations and implementation of both pharmacological and nonpharmacological treatments. Pulmonary rehabilitation can relieve patients from the distressing symptoms of IPF and improve quality of life. Oxygen therapy is central to treatment of all patients. Lung transplantation enhances survival in selected patients. Mechanical ventilation may be used in patients with acute exacerbations, but the prognosis is poor in these cases. Palliative care focuses on symptom management, advance directives and end-of-life planning. Patient support groups may also play an important role.

  15. Intra-abdominal fibrosis in a recent cohort of patients with neuroendocrine ('carcinoid') tumours of the small bowel.

    Science.gov (United States)

    Druce, M R; Bharwani, N; Akker, S A; Drake, W M; Rockall, A; Grossman, A B

    2010-03-01

    Fibrosis is a hallmark of neuroendocrine tumours (NETs) arising in the jejunum and ileum and may manifest in the mesentery and elsewhere. It is clinically important and once-established, there are few effective therapies. To examine the frequency, radiological manifestations and clinical significance of intra-abdominal fibrosis in a patient cohort using modern cross-sectional imaging. Current prevalence is compared to historical series and correlation with cardiac fibrosis evaluated. Cross-sectional, retrospective survey of a cohort of patients with mid-gut NETs from a single centre. Review of clinical features, biochemistry and imaging of patients with sporadic mid-gut NET and available imaging between 2002 and 2008. Thirty-one patients were included: 26 (83.9%) had liver metastases and 11 (35.4%) had small-bowel wall thickening; 17 patients (55%) had mesenteric involvement, with a mass, which contained coarse calcification in seven patients and fine calcification in a further two. There was soft-tissue stranding in 13 patients (plus in a further patient with no mass) and 'indrawing' of tissues in 11 patients. Two patients had a 'misty' mesentery and two had early retroperitoneal fibrosis. Mesenteric involvement was unrelated to gender and urinary 5HIAA excretion. Intra-abdominal fibrosis can be detected radiologically in around half of patients with mid-gut NET using contemporary cross-sectional imaging. Although not statistically significant, small-bowel obstruction was seen more frequently in the group with fibrosis. There was no relationship with cardiac fibrosis. Prospective studies are needed to evaluate predictors of fibrosis onset and clinical course and determine optimal methods of prevention and treatment.

  16. PFGE and antibiotic susceptibility phenotype analysis of Pseudomonas aeruginosa strain chronically infecting Cystic Fibrosis patients

    Directory of Open Access Journals (Sweden)

    Giovanna Pulcrano

    2008-09-01

    Full Text Available Pseudomonas aeruginosa is the leading cause of chronic lung infection and following pulmonary worsening of cystic fibrosis patients. To verify whether bacterial modifications regarding motility, mucoidy, and serum susceptibility proceeded from an adaptation to chronic infection or a replacement with a new strain, sequential P. aeruginosa isolates of known phenotype collected from 5 cystic fibrosis patients were typed by pulsed-field gel electophoresis (PFGE. Antimicrobial susceptibility testing of all isolates was performed by the disc diffusion method. PFGE typing demonstrated that strains dissimilar in colony morphotype and of different antibiotic susceptibility patterns could be of the same genotype. Some patients were colonized with a rather constant P. aeruginosa flora, with strains of different phenotypes but of one genotype. Instead, some patients may be colonized by more than one genotype. Secretion of mucoid exopolysaccharide and acquisition of a new antibiotic susceptibility phenotype in these strain appear to evolve during chronic colonization in cystic fibrosis patients from specific adaptation to infection rather than from acquisition of new bacterial strains.

  17. Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review.

    Science.gov (United States)

    Pu, Mariana Zorrón Mei Hsia; Christensen-Adad, Flávia Corrêa; Gonçalves, Aline Cristina; Minicucci, Walter José; Ribeiro, José Dirceu; Ribeiro, Antonio Fernando

    2016-09-01

    To elucidate whether insulin is effective or not in patients with cystic fibrosis before the diabetes mellitus phase. The study was performed according to the Prisma method between August and September 2014, using the PubMed, Embase, Lilacs and SciELO databases. Prospective studies published in English, Portuguese and Spanish from 2002 to 2014, evaluating the effect of insulin on weight parameters, body mass index and pulmonary function in patients with cystic fibrosis, with a mean age of 17.37 years before the diabetes mellitus phase were included. Eight articles were identified that included 180 patients undergoing insulin use. Sample size ranged from 4 to 54 patients, with a mean age ranging from 12.4 to 28 years. The type of follow-up, time of insulin use, the dose and implementation schedule were very heterogeneous between studies. There are theoretical reasons to believe that insulin has a beneficial effect in the studied population. The different methods and populations assessed in the studies do not allow us to state whether early insulin therapy should or should not be carried out in patients with cystic fibrosis prior to the diagnosis of diabetes. Therefore, studies with larger samples and insulin use standardization are required. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  18. Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review

    Directory of Open Access Journals (Sweden)

    Mariana Zorrón Mei Hsia Pu

    Full Text Available Abstract Objective: To elucidate whether insulin is effective or not in patients with cystic fibrosis before the diabetes mellitus phase. Data source: The study was performed according to the Prisma method between August and September 2014, using the PubMed, Embase, Lilacs and SciELO databases. Prospective studies published in English, Portuguese and Spanish from 2002 to 2014, evaluating the effect of insulin on weight parameters, body mass index and pulmonary function in patients with cystic fibrosis, with a mean age of 17.37 years before the diabetes mellitus phase were included. Data synthesis: Eight articles were identified that included 180 patients undergoing insulin use. Sample size ranged from 4 to 54 patients, with a mean age ranging from 12.4 to 28 years. The type of follow-up, time of insulin use, the dose and implementation schedule were very heterogeneous between studies. Conclusions: There are theoretical reasons to believe that insulin has a beneficial effect in the studied population. The different methods and populations assessed in the studies do not allow us to state whether early insulin therapy should or should not be carried out in patients with cystic fibrosis prior to the diagnosis of diabetes. Therefore, studies with larger samples and insulin use standardization are required.

  19. Validation and comparison of seventeen noninvasive models for evaluating liver fibrosis in Chinese hepatitis B patients.

    Science.gov (United States)

    Dong, Minhui; Wu, Jingwen; Yu, Xueping; Li, Jing; Yang, Sisi; Qi, Xun; Mao, Richeng; Zhang, Yongmei; Yu, Jie; Zhu, Haoxiang; Yang, Feifei; Qin, Yanli; Zhang, Jiming

    2018-01-03

    To avoid liver biopsy, many noninvasive models comprised of serum markers for liver fibrosis assessment have been developed. Given that most of them were developed in hepatitis C cohorts and few of them have been validated in Chinese hepatitis B patients, we aim to conduct this validation and compare their diagnostic accuracies in such a population. A total of 937 HBV-infected patients who underwent liver biopsy were included in this single-centre retrospective study. The diagnostic accuracies of the 17 noninvasive models were assessed by areas under the receiver-operating characteristic curves (AUROCs), using histologically evaluated fibrotic stages of the biopsy specimens as standards. To compare efficiencies of the models, a grading system based on AUROC levels was developed. For discriminating significant fibrosis in all patients, the best three noninvasive models were King's score (AUROC = 0.756), Virahep-C model (AUROC = 0.756) and GPR (AUROC = 0.744); and for diagnosing cirrhosis, Lok index (AUROC = 0.832), FI (AUROC = 0.820) and FIB-4 (AUROC = 0.818) got the first three places. AUROCs in HBeAg-positive group were generally higher than those in HBeAg-negative group. In addition, based on the grading system, Virahep-C and GPR outstood others in evaluating liver fibrosis in all patients. In Chinese HBV-infected patients, Virahep-C models and GPR had high accuracies in diagnosing liver fibrosis and cirrhosis, while the most discussed models like APRI and FIB-4 did not outstand. Assessment should take into account the HBeAg sero-status, since these noninvasive models were more appropriate for HBeAg-positive patients than HBeAg-negative ones. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Lung Cancer in Patients With Combined Pulmonary Fibrosis and Emphysema and Idiopathic Pulmonary Fibrosis. A Descriptive Study in a Spanish Series.

    Science.gov (United States)

    Portillo, Karina; Perez-Rodas, Nancy; García-Olivé, Ignasi; Guasch-Arriaga, Ignasi; Centeno, Carmen; Serra, Pere; Becker-Lejuez, Caroline; Sanz-Santos, José; Andreo García, Felip; Ruiz-Manzano, Juan

    2017-06-01

    Information on the association of lung cancer (LC) and combined pulmonary fibrosis and emphysema (CPFE) is limited and derived almost exclusively from series in Asian populations. The main objective of the study was to assess the impact of LC on survival in CPFE patients and in patients with idiopathic pulmonary fibrosis (IPF). A retrospective study was performed with data from patients with CFPE and IPF diagnosed in our hospital over a period of 5 years. Sixty-six patients were included, 29 with CPFE and 37 with IPF. Nine had a diagnosis of LC (6 with CPFE and 3 with IPF). Six patients (67%) received palliative treatment even though 3 of them were diagnosed atstage i-ii. Overall mortality did not differ significantly between groups; however, in patients with LC, survival was significantly lower compared to those without LC (P=.044). The most frequent cause of death was respiratory failure secondary to pulmonary fibrosis exacerbation (44%). In a multivariate analysis, the odds ratio of death among patients with LC compared to patients without LC was 6.20 (P=.037, 95% confidence interval: 1.11 to 34.48). Lung cancer reduces survival in both entities. The diagnostic and therapeutic management of LC is hampered by the increased risk of complications after any treatment modality, even after palliative treatment. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Expression of transforming growth factor-beta 1 in dystrophic patient muscles correlates with fibrosis. Pathogenetic role of a fibrogenic cytokine.

    OpenAIRE

    Bernasconi, P; Torchiana, E; Confalonieri, P; Brugnoni, R; Barresi, R; Mora, M; Cornelio, F; Morandi, L; Mantegazza, R

    1995-01-01

    Duchenne muscular dystrophy is a fatal disorder characterized by progressive muscular weakness, wasting, and severe muscle contractures in later disease stages. Muscle biopsy reveals conspicuous myofiber degeneration and fibrosis substituting muscle tissue. We quantitatively determined mRNA of the potent fibrogenic cytokine transforming growth factor-beta 1 by quantitative PCR in 15 Duchenne muscular dystrophy, 13 Becker muscular dystrophy, 11 spinal muscular atrophy patients, and 16 controls...

  2. The distribution of immunomodulatory cells in the lungs of patients with idiopathic pulmonary fibrosis

    Science.gov (United States)

    Nuovo, Gerard J.; Hagood, James S.; Magro, Cynthia M.; Chin, Nena; Kapil, Rubina; Davis, Luke; Marsh, Clay B.; Folcik, Virginia A.

    2011-01-01

    We have characterized the immune system involvement in the disease processes of idiopathic pulmonary fibrosis in novel ways. To do so, we analyzed lung tissue from 21 cases of idiopathic pulmonary fibrosis and 21 (non-fibrotic, non-cancerous) controls for immune cell and inflammation-related markers. The immunohistochemical analysis of the tissue was grouped by patterns of severity in disease pathology. There were significantly greater numbers of CD68+ and CD80+ cells, and significantly fewer CD3+, CD4+, and CD45RO+ cells in areas of relatively (histologically) normal lung in biopsies from idiopathic pulmonary fibrosis patients compared to controls. In zones of active disease, characterized by epithelial cell regeneration and fibrosis, there were significantly more cells expressing CD4, CD8, CD20, CD68, CD80, CCR6, S100, IL-17, tumor necrosis factor-α, and retinoic acid-related orphan receptors compared to histologically normal lung areas from idiopathic pulmonary fibrosis patients. Inflammation was implicated in these active regions by the cells that expressed retinoid orphan receptor-α, -β, and -γ, CCR6, and IL-17. The regenerating epithelial cells predominantly expressed these pro-inflammatory molecules, as evidenced by co-expression analyses with epithelial cytokeratins. Macrophages in pseudo-alveoli and CD3+ T cells in the fibrotic interstitium also expressed IL-17. Co-expression of IL-17 with retinoid orphan receptors, and epithelial cytoskeletal proteins, CD68, and CD3 in epithelial cells, macrophages, and T-cells, respectively, confirmed the production of IL-17 by these cell types. There was little staining for Foxp3, CD56, or CD34 in any idiopathic pulmonary fibrosis lung regions. The fibrotic regions had fewer immune cells overall. In summary, our study shows participation of innate and adaptive mononuclear cells in active-disease regions of idiopathic pulmonary fibrosis lung, where the regenerating epithelial cells appear to propagate inflammation

  3. Diagnosis of Fibrosis and Activity by a Combined Use of Strain and Shear Wave Imaging in Patients with Liver Disease.

    Science.gov (United States)

    Yada, Norihisa; Tamaki, Nobuhura; Koizumi, Yohei; Hirooka, Masashi; Nakashima, Osamu; Hiasa, Yoichi; Izumi, Namiki; Kudo, Masatoshi

    2017-01-01

    Performing shear wave imaging is simple, but can be difficult when inflammation, jaundice, and congestion are present. Therefore, the correct diagnosis of liver fibrosis using shear wave imaging alone might be difficult in mild-to-moderate fibrosis cases. Strain imaging can diagnose liver fibrosis without the influence of inflammation. Therefore, the combined use of strain and shear wave imaging (combinational elastography) for cases without jaundice and congestion might be useful for evaluating fibrosis and inflammation. We enrolled consecutive patients with liver disease, without jaundice or liver congestion. Strain and shear wave imaging, blood tests, and liver biopsy were performed on the same day. The liver fibrosis index (LF index) was calculated by strain imaging; real-time tissue elastography, and the shear wave velocity (Vs) was calculated by shear wave imaging. Fibrosis index (F index) and activity index (A index) were calculated as a multiple regression equation for determining hepatic fibrosis and inflammation using histopathological diagnosis as the gold standard. The diagnostic ability of F index for fibrosis and A index for inflammation were compared using LF index and Vs. The total number of enrolled cases was 388. The area under the receiver operating characteristic (AUROC) was 0.87, 0.80, 0.83, and 0.80, at diagnosis of fibrosis stage with an F index of F1 or higher, F2 or higher, F3 or higher, and F4, respectively. The AUROC was 0.94, 0.74, and 0.76 at diagnosis of activity grade with an A index of A1 or higher, A2 or higher, and A3, respectively. The diagnostic ability of F index for liver fibrosis and A index for inflammation was higher than for other conventional diagnostic values. The combined use of strain and shear wave imaging (combinational elastography) might increase the positive diagnosis of liver fibrosis and inflammation. © 2017 S. Karger AG, Basel.

  4. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui

    2002-01-01

    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

  5. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui

    2002-01-01

    Cystic fibrosis is a 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

  6. Enhanced liver fibrosis test using ELISA assay accurately discriminates advanced stage of liver fibrosis as determined by transient elastography fibroscan in treatment naïve chronic HCV patients.

    Science.gov (United States)

    Omran, Dalia; Yosry, Ayman; Darweesh, Samar K; Nabeel, Mohammed M; El-Beshlawey, Mohammed; Saif, Sameh; Fared, Azza; Hassany, Mohamed; Zayed, Rania A

    2018-02-01

    Evaluation of liver fibrosis stage is crucial in the assessment of chronic HCV patients, regarding decision to start treatment and during follow-up. Our aim was to assess the validity of the enhanced liver fibrosis (ELF) score in discrimination of advanced stage of liver fibrosis in naïve chronic HCV patients. We prospectively evaluated liver fibrosis stage in one hundred eighty-one naïve chronic HCV Egyptian patients by transient elastography (TE)-FibroScan. Patients were categorized into mild to moderate fibrosis (≤F2) group and advanced fibrosis (≥F3) group. The ELF score components, hyaluronic acid (HA), amino-terminal propeptide of type-III-procollagen (PIIINP) and tissue inhibitor of metalloproteinase type-1 (TIMP-1), were done using ELISA test. The mean values of ELF and its individual components significantly correlated with the hepatic fibrosis stage as measured by TE-FibroScan (P value 0.001). ELF cutoff value of 9.8 generated a sensitivity of 77.8%, specificity of 67.1%, area under the receiver operator characteristic curve (AUROC) of 0.76 with 95% confidence interval [CI] (0.68-0.83) for detecting advanced fibrosis (F ≥ 3). ELF panel is a good, reliable noninvasive test and showed comparable results to TE-FibroScan in detecting liver fibrosis stage in treatment naïve chronic HCV patients.

  7. Lung fibrosis-associated soluble mediators and bronchoalveolar lavage from idiopathic pulmonary fibrosis patients promote the expression of fibrogenic factors in subepithelial lung myofibroblasts.

    Science.gov (United States)

    Bouros, Evangelos; Filidou, Eirini; Arvanitidis, Konstantinos; Mikroulis, Dimitrios; Steiropoulos, Paschalis; Bamias, George; Bouros, Demosthenes; Kolios, George

    2017-10-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by infiltration of inflammatory cells, excessive collagen production and accumulation of myofibroblasts. We explored the possible role of subepithelial lung myofibroblasts (SELMs) in the development of fibrosis in IPF. SELMs, isolated from surgical specimens of healthy lung tissue, were cultured with pro-inflammatory factors or bronchoalveolar lavage fluid (BALF) from patients with IPF or idiopathic non-specific interstitial pneumonia (iNSIP) and their fibrotic activity was assessed. Stimulation of SELMs with pro-inflammatory factors induced a significant increase of Tissue Factor (TF) and Tumor necrosis factor-Like cytokine 1 A (TL1A) expression and collagen production in culture supernatants. Stimulation with BALF from IPF patients with mild to moderate, but not severe disease, and from iNSIP patients induced a significant increase of TF expression. BALF from all IPF patients induced a significant increase of TL1A expression and collagen production, while BALF from iNSIP patients induced a significant increase of TL1A, but not of collagen production. Interestingly, TGF-β1 and BALF from all IPF, but not iNSIP patients, induced a significant increase in SELMs migration. In conclusion, BALF from IPF patients induces fibrotic activity in lung myofibroblasts, similar to mediators associated with lung fibrosis, indicating a key role of SELMs in IPF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Hearing thresholds at high frequency in patients with cystic fibrosis: a systematic review

    Directory of Open Access Journals (Sweden)

    Debora T.M. Caumo

    Full Text Available Abstract Introduction: High-frequency audiometry may contribute to the early detection of hearing loss caused by ototoxic medications. Many ototoxic drugs are widely used in the treatment of patients with cystic fibrosis. Early detection of hearing loss should allow known harmful drugs to be identified before the damage affects speech frequencies. The damage caused by ototoxicity is irreversible, resulting in important social and psychological consequences. In children, hearing loss, even when restricted to high frequencies, can affect the development of language. Objective: To investigate the efficacy and effectiveness of hearing monitoring through high-frequency audiometry in pediatric patients with cystic fibrosis. Methods: Electronic databases PubMed, MedLine, Web of Science and LILACS were searched, from January to November 2015. The selected studies included those in which high-frequency audiometry was performed in patients with cystic fibrosis, undergoing treatment with ototoxic drugs and published in Portuguese, English and Spanish. The GRADE system was chosen for the evaluation of the methodological quality of the articles. Results: During the search process carried out from January 2015 to November 2015, 512 publications were identified, of which 250 were found in PubMed, 118 in MedLine, 142 in Web of Science and 2 in LILACS. Of these, nine articles were selected. Conclusion: The incidence of hearing loss was identified at high frequencies in cystic fibrosis patients without hearing complaints. It is assumed that high-frequency audiometry can be an early diagnostic method to be recommended for hearing investigation of patients at risk of ototoxicity.

  9. Do all patients with idiopathic pulmonary fibrosis warrant a trial of therapeutic intervention? A pro-con perspective.

    Science.gov (United States)

    Moodley, Yuben; Corte, Tamera; Richeldi, Luca; King, Talmadge E

    2015-04-01

    Idiopathic pulmonary fibrosis (IPF) is an incurable condition that is characterized by progressive pulmonary fibrosis, architectural distortion of the lung and loss of gas exchange units. Until recently, there was no effective treatment for this condition. However, there were two landmark trials published earlier this year, which have changed the management of this condition. Pirfenidone (Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis trial) and nintedanib (Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis-1 and -2 trials) have both demonstrated positive outcomes in patients with IPF. In this perspective, we critically discuss the role of these agents in IPF and in the broader pulmonary fibrosis population. © 2015 Asian Pacific Society of Respirology.

  10. Pentoxifylline and vitamin E for treatment or prevention of radiation-induced fibrosis in patients with breast cancer.

    Science.gov (United States)

    Kaidar-Person, Orit; Marks, Lawrence B; Jones, Ellen L

    2018-04-23

    Radiation therapy (RT) plays an important role in the management of breast cancer. Radiation-induced fibrosis is a side effect of radiation therapy and may occur in up to 13% of the cases in patients (Radiother Oncol, 2009;90:80), fortunately usually is modest/localized and not associated with marked symptoms. However, occasionally, fibrosis can be moderate-to-severe, and cause clinically-meaningful symptoms. The current review summarizes the use of pentoxifylline and vitamin E of treatment or prevention of radiation-induced fibrosis in breast cancer patients. Even though data are limited, this regimen may reduce RT-associated toxicity. © 2018 Wiley Periodicals, Inc.

  11. Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation.

    Science.gov (United States)

    El-Chemaly, Souheil; O'Brien, Kevin J; Nathan, Steven D; Weinhouse, Gerald L; Goldberg, Hilary J; Connors, Jean M; Cui, Ye; Astor, Todd L; Camp, Philip C; Rosas, Ivan O; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A; Gahl, William A; Gochuico, Bernadette R

    2018-01-01

    Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants.

  12. Occurrence of hypermutable Pseudomonas aeruginosa in cystic fibrosis patients is associated with the oxidative stress caused by chronic lung inflammation

    DEFF Research Database (Denmark)

    Ciofu, Oana; Riis, Bente; Pressler, Tacjana

    2005-01-01

    Oxidative stress caused by chronic lung inflammation in patients with cystic fibrosis (CF) and chronic lung infection with Pseudomonas aeruginosa is characterized by the reactive oxygen species (ROS) liberated by polymorphonuclear leukocytes (PMNs). We formulated the hypothesis that oxidation...

  13. Relative contribution of Prevotella intermedia and Pseudomonas aeruginosa to lung pathology in airways of patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Beer, Isabelle; Braitmaier, Peter

    2010-01-01

    Patients with cystic fibrosis (CF) with Pseudomonas aeruginosa lung infections produce endobronchial mucus plugs allowing growth of obligate anaerobes including Prevotella spp. Whether obligate anaerobes contribute to the pathophysiology of CF lung disease is unknown....

  14. Development of low-dose protocols for thin-section CT assessment of cystic fibrosis in pediatric patients.

    LENUS (Irish Health Repository)

    O'Connor, Owen J

    2010-12-01

    To develop low-dose thin-section computed tomographic (CT) protocols for assessment of cystic fibrosis (CF) in pediatric patients and determine the clinical usefulness thereof compared with chest radiography.

  15. The adult cystic fibrosis patient with abdominal pain: what the radiologist needs to know

    Energy Technology Data Exchange (ETDEWEB)

    Liong, S.Y.; Awad, D. [Department of Radiology, University Hospital of South Manchester, Wythenshawe Hospital, Manchester (United Kingdom); Jones, A.M. [Department of Respiratory Medicine, University Hospital of South Manchester, Wythenshawe Hospital, Manchester (United Kingdom); Manchester Academic Health Science Centre, University of Manchester, Manchester (United Kingdom); Sukumar, S.A., E-mail: Sathi.Sukumar@uhsm.nhs.u [Department of Radiology, University Hospital of South Manchester, Wythenshawe Hospital, Manchester (United Kingdom)

    2011-02-15

    As the life expectancy of cystic fibrosis (CF) patients continues to increase, abdominal manifestations of CF are increasingly being encountered by clinicians and radiologists. Imaging plays an important role in the evaluation of adult CF patients with abdominal pain as a cause is often not discernable clinically. Accurate diagnosis is crucial in these patients as some causes may be managed conservatively, whilst others may require surgical intervention. In this review, we describe clinical presentation, imaging findings, and management of adult CF patients presenting with abdominal pain.

  16. 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 infec...... and management of biofilm infections caused by P. aeruginosa and discusses critical issues related to novel antimicrobial drug formulation design approaches.......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....... aeruginosa from the respiratory tract after a first infection has been shown to delay chronic pulmonary infection with the bacteria for up to two years. The challenges with providing a suitable treatment for bacterial sinusitis include: (i) identifying a suitable antimicrobial compound; (ii) selecting...

  17. Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del.

    Science.gov (United States)

    Taylor-Cousar, Jennifer L; Munck, Anne; McKone, Edward F; van der Ent, Cornelis K; Moeller, Alexander; Simard, Christopher; Wang, Linda T; Ingenito, Edward P; McKee, Charlotte; Lu, Yimeng; Lekstrom-Himes, Julie; Elborn, J Stuart

    2017-11-23

    Combination treatment with the cystic fibrosis transmembrane conductance regulator (CFTR) modulators tezacaftor (VX-661) and ivacaftor (VX-770) was designed to target the underlying cause of disease in patients with cystic fibrosis. In this phase 3, randomized, double-blind, multicenter, placebo-controlled, parallel-group trial, we evaluated combination therapy with tezacaftor and ivacaftor in patients 12 years of age or older who had cystic fibrosis and were homozygous for the CFTR Phe508del mutation. Patients were randomly assigned in a 1:1 ratio to receive either 100 mg of tezacaftor once daily and 150 mg of ivacaftor twice daily or matched placebo for 24 weeks. The primary end point was the absolute change in the percentage of the predicted forced expiratory volume in 1 second (FEV 1 ) through week 24 (calculated in percentage points); relative change in the percentage of the predicted FEV 1 through week 24 (calculated as a percentage) was a key secondary end point. Of the 510 patients who underwent randomization, 509 received tezacaftor-ivacaftor or placebo, and 475 completed 24 weeks of the trial regimen. The mean FEV 1 at baseline was 60.0% of the predicted value. The effects on the absolute and relative changes in the percentage of the predicted FEV 1 in favor of tezacaftor-ivacaftor over placebo were 4.0 percentage points and 6.8%, respectively (Pcystic fibrosis and were homozygous for the CFTR Phe508del mutation. (Funded by Vertex Pharmaceuticals; EVOLVE ClinicalTrials.gov number, NCT02347657 .).

  18. Psychological impact of working with patients with cystic fibrosis at end-of-life, pre-transplant stage.

    Science.gov (United States)

    Clisby, Nicola; Shaw, Samantha; Cormack, Maggie

    2013-04-01

    Multidisciplinary staff who work with end-of-life, pre-transplant patients with cystic fibrosis (CF) have to juggle two seemingly opposing care approaches; active care to maintain their patients' health and condition in anticipation of a transplant, and sensitive palliative care that takes their end-of-life wishes into consideration should they not receive a transplant. Little is known about the psychological impact on staff working within this care dichotomy. The aim of this study is to explore staff's experiences and understand more about the psychological impact of this work on them professionally and personally, and how this affects their ability to provide appropriate care for their patients. A qualitative explorative research design was used. Ten semistructured interviews with multidisciplinary staff working in cystic fibrosis centers and units across the United Kingdom were analyzed using interpretative phenomenological analysis (IPA). Two superordinate themes emerged from the analysis: factors contributing to the "juggle" of active and palliative care, and extent of emotional impact on staff. The study indicates that there is an emotional impact on staff working with patients with CF at end-of-life, pre-transplant stages. Specifically, it reveals the extent of the unpredictability that staff work with, and the range of emotions that staff experience, including uncertainty about professional identity and anxiety about working practices. The depth and intimacy of professional-patient relationships is highlighted, particularly for staff in close contact with and similar in age to their patients. Additionally, the strength of staff's commitment and desire to care for patients within broader humanistic terms that mesh with their own personal values is brought to light. Despite the difficulties with their work, the majority of staff adopted numerous coping strategies to manage their emotions, many of which emphasized the link between their professional and

  19. Ursodeoxycholic acid treatment is associated with improvement of liver stiffness in cystic fibrosis patients.

    Science.gov (United States)

    van der Feen, Cathelijne; van der Doef, Hubert P J; van der Ent, Cornelis K; Houwen, Roderick H J

    2016-11-01

    Ursodeoxycholic acid (UDCA) might prevent progression of cystic fibrosis liver disease, but objective parameters for its effect are lacking. We used liver stiffness measurements to evaluate the effect of Ursodeoxycholic acid. Paired measurements of liver stiffness were done in 73 patients without UDCA and in 32 patients with UDCA. In the latter group, 6 patients had cirrhosis; in 15 patients, UDCA was started based on Colombo criteria, and in 11 patients for other reasons. In patients without UDCA, liver stiffness increased: 0.19 (-0.03 to 0.59)kPa/year. Liver stiffness also increased in patients with cirrhosis: 4.6 (0.67-12.4)kPa/year. In patients who had UDCA based on Colombo criteria, a decrease of liver stiffness was observed: 0.70 (-1.6 to 0.55)kPa/year (P=0.01). In patients on UDCA for other reasons, liver stiffness increased: 0.23 (-0.20 to 0.51)kPa/year. UDCA reduced liver stiffness in patients with well-defined, mild liver disease. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. Point shear wave elastography of the pancreas in patients with cystic fibrosis: a comparison with healthy controls.

    Science.gov (United States)

    Pfahler, Matthias Hermann Christian; Kratzer, Wolfgang; Leichsenring, Michael; Graeter, Tilmann; Schmidt, Stefan Andreas; Wendlik, Inka; Lormes, Elisabeth; Schmidberger, Julian; Fabricius, Dorit

    2018-02-19

    Manifestations of cystic fibrosis in the pancreas are gaining in clinical importance as patients live longer. Conventional ultrasonography and point shear wave elastography (pSWE) imaging are non-invasive and readily available diagnostic methods that are easy to perform. The aim of this study was to perform conventional ultrasonography and obtain pSWE values in the pancreases of patients with cystic fibrosis and to compare the findings with those of healthy controls. 27 patients with cystic fibrosis (13 women/14 men; mean age 27.7 ± 13.7 years; range 9-58 years) and 60 healthy control subjects (30 women/30 men; mean age 30.3 ± 10.0 years; range 22-55 years) underwent examinations of the pancreas with conventional ultrasound and pSWE imaging. Patients with cystic fibrosis have an echogenic pancreatic parenchyma. We found cystic lesions of the pancreas in six patients. pSWE imaging of the pancreatic parenchyma gave significantly lower shear wave velocities in patients with cystic fibrosis than in the control group (1.01 m/s vs 1.30 m/s; p cystic fibrosis than in a healthy control population.

  1. Microbiology of airway disease in a cohort of patients with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Carnovale Vincenzo

    2006-01-01

    Full Text Available Abstract Background Recent reports document an increasing incidence of new Gram-negative pathogens such as Stenotrophomonas maltophilia and Alcaligenes xylosoxidans isolated from patients with Cystic Fibrosis, along with an increase in common Gram-negative pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex. Furthermore, the increase in multidrug-resistance of such organisms makes the therapeutic management of these patients more problematic. Therefore, careful isolation and identification, and accurate studies of susceptibility to antibiotics are critical for predicting the spread of strains, improving therapeutic measures and facilitating our understanding of the epidemiology of emerging pathogens. The first aim of this study was to determine the incidence and the prevalence of colonization by Gram-negative organisms isolated from respiratory samples of Cystic Fibrosis patients in the Regional Referral Cystic Fibrosis Centre of Naples; the second was to evaluate the spectrum of multidrug-resistance of these organisms. Methods Patients (n = 300 attending the Regional Cystic Fibrosis Unit were enrolled in this study over 3 years. Sputum was processed for microscopic tests and culture. An automated system, Phoenix (Becton Dickinson, Sparks, Maryland, USA, was used for phenotypic identification of all strains; the API 20 NE identification system (bioMérieux, Marcy l'Etoile, France was used when the identification with the Phoenix system was inaccurate. A PCR-RFLP method was used to characterize the organisms in the Burkholderia cepacia complex. A chemosusceptibility test on microbroth dilutions (Phoenix was used. Primary outcomes such as FEV1 were correlate with different pathogens. Results During the period of study, 40% of patients was infected by Pseudomonas aeruginosa, 7% by Burkholderia cepacia complex, 11% by Stenotrophomonas maltophilia and 7% by Alcaligenes xylosoxidans. Of the strains isolated, 460 were multidrug

  2. Increased serum concentration of G-CSF in cystic fibrosis patients with chronic Pseudomonas aeruginosa pneumonia

    DEFF Research Database (Denmark)

    Jensen, Peter Østrup; Moser, C; Kharazmi, A

    2006-01-01

    BACKGROUND: Chronic Pseudomonas aeruginosa lung infection is the major reason for premature death in patients with cystic fibrosis (CF). Infected patients experience a progressive deterioration of the lung tissue caused by a persistent accumulation of PMNs. We investigated if the pulmonary...... was reduced. CONCLUSION: G-CSF in the sera may contribute to the pulmonary inflammation in CF patients with chronic P. aeruginosa lung infection by regulating the number of PMNs available for migration and may be considered as an indicator of clinical status....

  3. Muscular strength after different types of training in physically active patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Sahlberg, M.; Svantesson, U.; Magnusson, Thomas E.

    2008-01-01

    Physical training is important in the treatment of patients with cystic fibrosis (CF). Optimal types of training and intensity are unknown. The aim of the study was to evaluate the effect on muscular strength after 6 months of endurance training (ET) and/or resistance training (RT). Twenty patients....... Vitamin E and cytokines were analyzed. Fifteen tests of muscular strength were used. Handgrip strength in females and quadriceps strength in males were significantly decreased compared with healthy age- and sex-matched controls and positively associated with lung function. Sixteen patients completed...

  4. 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.

  5. Doppler ultrasonography combined with transient elastography improves the non-invasive assessment of fibrosis in patients with chronic liver diseases.

    Science.gov (United States)

    Alempijevic, Tamara; Zec, Simon; Nikolic, Vladimir; Veljkovic, Aleksandar; Stojanovic, Zoran; Matovic, Vera; Milosavljevic, Tomica

    2017-01-31

    Accurate clinical assessment of liver fibrosis is essential and the aim of our study was to compare and combine hemodynamic Doppler ultrasonography, liver stiffness by transient elastography, and non-invasive serum biomarkers with the degree of fibrosis confirmed by liver biopsy, and thereby to determine the value of combining non-invasive method in the prediction significant liver fibrosis. We included 102 patients with chronic liver disease of various etiology. Each patient was evaluated using Doppler ultrasonography measurements of the velocity and flow pattern at portal trunk, hepatic and splenic artery, serum fibrosis biomarkers, and transient elastography. These parameters were then input into a multilayer perceptron artificial neural network with two hidden layers, and used to create models for predicting significant fibrosis. According to METAVIR score, clinically significant fibrosis (≥F2) was detected in 57.8% of patients. A model based only on Doppler parameters (hepatic artery diameter, hepatic artery systolic and diastolic velocity, splenic artery systolic velocity and splenic artery Resistance Index), predicted significant liver fibrosis with a sensitivity and specificity of75.0% and 60.0%. The addition of unrelated non-invasive tests improved the diagnostic accuracy of Doppler examination. The best model for prediction of significant fibrosis was obtained by combining Doppler parameters, non-invasive markers (APRI, ASPRI, and FIB-4) and transient elastography, with a sensitivity and specificity of 88.9% and 100%. Doppler parameters alone predict the presence of ≥F2 fibrosis with fair accuracy. Better prediction rates are achieved by combining Doppler variables with non-invasive markers and liver stiffness by transient elastography.

  6. Diagnostic value of real-time tissue elastography for liver fibrosis in patients with chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    ZHANG Guosheng

    2014-07-01

    Full Text Available ObjectiveTo investigate the diagnostic value of real-time tissue elastography (RTE in evaluating liver fibrosis in patients with chronic hepatitis B (CHB. MethodsEighty-six patients with CHB, who visited Beijing Tiantan Hospital and Beijing You′an Hospital from March to August, 2013, were grouped according to the pathological stages of liver fibrosis. They were examined by RTE, biochemical tests, and liver biopsy. Then, liver fibrosis index (LFI and aspartate aminotransferase-to-platelet ratio index (APRI were calculated. Comparison between groups was made by one-way analysis of variance, followed by LSD t-test for multiple comparisons. The correlation between LFI and pathological stage of liver fibrosis was analyzed by Spearman correlation test. The sensitivity and specificity of LFI for the diagnosis of liver fibrosis were calculated. Regarding S≥2 (significant liver fibrosis and S≥4 (early liver cirrhosis as the positive standards, the receiver operating characteristic (ROC curve was drawn and compared with APRI. ResultsLFI differed significantly across the groups (P=0.000, except the comparison between S0 and S1 (P=0.298. LFI was significantly correlated with pathological stage (r=0.831, P<0.001. The areas under the ROC curve of LFI in diagnosing significant liver fibrosis and early liver cirrhosis were 0873 (P<0.001 and 0.923 (P=0002, respectively; the diagnostic thresholds were 2.74 and 3.61, respectively; the sensitivity and specificity were 0.766/0.872 and 0.833/0.878, respectively. LFI was significantly superior to APRI. ConclusionRTE has high diagnostic values for significant liver fibrosis and early liver cirrhosis and is an important noninvasive diagnostic method for liver fibrosis in patients with CHB.

  7. Four case reports of Chinese cystic fibrosis patients and literature review.

    Science.gov (United States)

    Xu, Juan; Yin, Yong; Zhang, Lei; Zhang, Jing; Yuan, Shuhua; Zhang, Hao

    2017-08-01

    Cystic fibrosis (CF) is an extremely rare disease in Asians. Here, we report four Chinese children with CF and review the literature about Chinese CF patients. The cystic fibrosis transmembrane conductance regulator (CFTR) gene testing was performed on four suspected patients for CF screening. We also reviewed the literature about Chinese CF patients from 1970s. The clinical data of all these CF patients were summarized. We diagnosed four CF patients who had mutations in the CFTR gene. We identified six different mutations in the four patients. The c.1766+5G>T, c.595C>T, c.2909G>A, and c.4056G>C had been reported already. The two splicing mutations of c.579+1_579+2insACAT and c.1117-1G>C were novel mutations. There have been 46 Chinese CF patients reported in literature from 1974 up to present (2016.12). The clinical manifestations of CF involved several systems. The most common symptom was recurrent pulmonary infections. Thirty-three different mutations were identified; c.1766 + 5G>T was the most common mutation among Chinese CF patients. Only one of these mutations (R553X) was in the Caucasian CF screening panel. The spectrum of CFTR mutations in Chinese was highly different from that of Caucasian. There was a high risk of misdiagnosis or delayed diagnosis of CF even in suspected cases in China. It is necessary to educate Chinese clinicians about the signs, symptoms, and diagnosis of cystic fibrosis and promote the implementation of the sweat chloride test. © 2017 Wiley Periodicals, Inc.

  8. Aspartate aminotransferase-to-platelet ratio index for fibrosis and cirrhosis prediction in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Roberto Gomes da Silva Junior

    Full Text Available In chronic hepatitis C (CHC, liver biopsy is the gold standard method for assessing liver histology, however it is invasive and can have complications. Non-invasive markers have been proposed and aspartate aminotransferase (AST-to-platelet ratio index (APRI has been shown as an easy and inexpensive marker of liver fibrosis. This study evaluated the diagnostic performance of APRI for significant fibrosis and cirrhosis prediction in CHC patients. This study included treatment-naive CHC patients who had undergone liver biopsy from January 2000 to August 2006. All histological slides were reviewed according to the METAVIR system. APRI was calculated based on laboratory results performed within four months from the biopsy. Twenty-eight (56% patients had significant fibrosis (F2-F4 and 13 (26% had cirrhosis (F4. The area under ROC curves of APRI for predicting significant fibrosis and cirrhosis were 0.92 (0.83-1.00 and 0.92 (0.85-1.00, respectively. Using cut-off values recommended by prior studies, significant fibrosis could be identified, in accordance with liver biopsy, in 44% and cirrhosis in 66% of patients. APRI could identify significant fibrosis and cirrhosis at a high degree of accuracy in studied patients.

  9. Influence of Pulmonary Hypertension on Patients With Idiopathic Pulmonary Fibrosis Awaiting Lung Transplantation.

    Science.gov (United States)

    Hayes, Don; Black, Sylvester M; Tobias, Joseph D; Kirkby, Stephen; Mansour, Heidi M; Whitson, Bryan A

    2016-01-01

    The influence of varying levels of pulmonary hypertension (PH) on survival in idiopathic pulmonary fibrosis is not well defined. The United Network for Organ Sharing database was queried from 2005 to 2013 to identify first-time lung transplant candidates listed for lung transplantation who were tracked from waitlist entry date until death or censoring to determine the influence of PH on patients with advanced lung disease. Using data for right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure of 25 mm Hg or more, and severe as 35 mm Hg or more. Of 6,657 idiopathic pulmonary fibrosis patients, 6,651 were used for univariate analysis, 6,126 for Kaplan-Meier survival function, 6,013 for multivariate Cox models, and 5,186 (mild PH) and 2,014 (severe PH) for propensity score matching, respectively. Univariate Cox proportional hazards analysis found significant differences in survival for mild PH (hazard ratio [HR] 1.689, 95% confidence interval [CI]: 1.434 to 1.988, p idiopathic pulmonary fibrosis awaiting lung transplantation, so referral should be considered early in the disease course. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis.

    Science.gov (United States)

    Marvig, Rasmus Lykke; Sommer, Lea Mette; Molin, Søren; Johansen, Helle Krogh

    2015-01-01

    Little is known about how within-host evolution compares between genotypically different strains of the same pathogenic species. We sequenced the whole genomes of 474 longitudinally collected clinical isolates of Pseudomonas aeruginosa sampled from 34 children and young individuals with cystic fibrosis. Our analysis of 36 P. aeruginosa lineages identified convergent molecular evolution in 52 genes. This list of genes suggests a role in host adaptation for remodeling of regulatory networks and central metabolism, acquisition of antibiotic resistance and loss of extracellular virulence factors. Furthermore, we find an ordered succession of mutations in key regulatory networks. Accordingly, mutations in downstream transcriptional regulators were contingent upon mutations in upstream regulators, suggesting that remodeling of regulatory networks might be important in adaptation. The characterization of genes involved in host adaptation may help in predicting bacterial evolution in patients with cystic fibrosis and in the design of future intervention strategies.

  11. Non-coding keratin variants associate with liver fibrosis progression in patients with hemochromatosis.

    Directory of Open Access Journals (Sweden)

    Pavel Strnad

    Full Text Available BACKGROUND: Keratins 8 and 18 (K8/K18 are intermediate filament proteins that protect the liver from various forms of injury. Exonic K8/K18 variants associate with adverse outcome in acute liver failure and with liver fibrosis progression in patients with chronic hepatitis C infection or primary biliary cirrhosis. Given the association of K8/K18 variants with end-stage liver disease and progression in several chronic liver disorders, we studied the importance of keratin variants in patients with hemochromatosis. METHODS: The entire K8/K18 exonic regions were analyzed in 162 hemochromatosis patients carrying homozygous C282Y HFE (hemochromatosis gene mutations. 234 liver-healthy subjects were used as controls. Exonic regions were PCR-amplified and analyzed using denaturing high-performance liquid chromatography and DNA sequencing. Previously-generated transgenic mice overexpressing K8 G62C were studied for their susceptibility to iron overload. Susceptibility to iron toxicity of primary hepatocytes that express K8 wild-type and G62C was also assessed. RESULTS: We identified amino-acid-altering keratin heterozygous variants in 10 of 162 hemochromatosis patients (6.2% and non-coding heterozygous variants in 6 additional patients (3.7%. Two novel K8 variants (Q169E/R275W were found. K8 R341H was the most common amino-acid altering variant (4 patients, and exclusively associated with an intronic KRT8 IVS7+10delC deletion. Intronic, but not amino-acid-altering variants associated with the development of liver fibrosis. In mice, or ex vivo, the K8 G62C variant did not affect iron-accumulation in response to iron-rich diet or the extent of iron-induced hepatocellular injury. CONCLUSION: In patients with hemochromatosis, intronic but not exonic K8/K18 variants associate with liver fibrosis development.

  12. What patients with pulmonary fibrosis and their partners think: a live, educative survey in the Netherlands and Germany

    Science.gov (United States)

    van Manen, Mirjam J.G.; Kreuter, Michael; van den Blink, Bernt; Oltmanns, Ute; Palmowski, Karin; Brunnemer, Eva; Hummler, Simone; Tak, Nelleke C.; van den Toorn, Leon; Miedema, Jelle; Hoogsteden, Henk C.

    2017-01-01

    Pulmonary fibrosis greatly impacts patients and their partners. Unmet needs of patients are increasingly acknowledged; the needs of partners often remain unnoticed. Little is known about the best way to educate patients and partners. We investigated pulmonary fibrosis patients' and partners' perspectives and preferences in care, and the differences in these between the Netherlands and Germany. Additionally, we evaluated whether interactive interviewing could be a novel education method in this population. Patients and partners were interviewed during pulmonary fibrosis patient information meetings. In the Netherlands, voting boxes were used and results were projected directly. In Germany, questionnaires were used. In the Netherlands, 278 patients and partners participated; in Germany, 51. Many participants experienced anxiety. Almost all experienced misunderstanding, because people do not know what pulmonary fibrosis is. All expressed a need for information, psychological support and care for partners. Use of the interactive voting system was found to be pleasant (70%) and informative (94%). This study improves the knowledge of care needs of patients with pulmonary fibrosis and their partners. There were no major differences between the Netherlands and Germany. Interactive interviewing could be an attractive method to acquire insights into the needs and preferences of patients and partners, while providing them with information at the same time. PMID:28229083

  13. What patients with pulmonary fibrosis and their partners think: a live, educative survey in the Netherlands and Germany

    Directory of Open Access Journals (Sweden)

    Mirjam J.G. van Manen

    2017-02-01

    Full Text Available Pulmonary fibrosis greatly impacts patients and their partners. Unmet needs of patients are increasingly acknowledged; the needs of partners often remain unnoticed. Little is known about the best way to educate patients and partners. We investigated pulmonary fibrosis patients' and partners' perspectives and preferences in care, and the differences in these between the Netherlands and Germany. Additionally, we evaluated whether interactive interviewing could be a novel education method in this population. Patients and partners were interviewed during pulmonary fibrosis patient information meetings. In the Netherlands, voting boxes were used and results were projected directly. In Germany, questionnaires were used. In the Netherlands, 278 patients and partners participated; in Germany, 51. Many participants experienced anxiety. Almost all experienced misunderstanding, because people do not know what pulmonary fibrosis is. All expressed a need for information, psychological support and care for partners. Use of the interactive voting system was found to be pleasant (70% and informative (94%. This study improves the knowledge of care needs of patients with pulmonary fibrosis and their partners. There were no major differences between the Netherlands and Germany. Interactive interviewing could be an attractive method to acquire insights into the needs and preferences of patients and partners, while providing them with information at the same time.

  14. A sigmoidal fit for pressure-volume curves of idiopathic pulmonary fibrosis patients on mechanical ventilation: clinical implications

    Directory of Open Access Journals (Sweden)

    Juliana C. Ferreira

    2011-01-01

    Full Text Available OBJECTIVE: Respiratory pressure-volume curves fitted to exponential equations have been used to assess disease severity and prognosis in spontaneously breathing patients with idiopathic pulmonary fibrosis. Sigmoidal equations have been used to fit pressure-volume curves for mechanically ventilated patients but not for idiopathic pulmonary fibrosis patients. We compared a sigmoidal model and an exponential model to fit pressure-volume curves from mechanically ventilated patients with idiopathic pulmonary fibrosis. METHODS: Six idiopathic pulmonary fibrosis patients and five controls underwent inflation pressure-volume curves using the constant-flow technique during general anesthesia prior to open lung biopsy or thymectomy. We identified the lower and upper inflection points and fit the curves with an exponential equation, V = A-B.e-k.P, and a sigmoid equation, V = a+b/(1+e-(P-c/d. RESULTS: The mean lower inflection point for idiopathic pulmonary fibrosis patients was significantly higher (10.5 ± 5.7 cm H2O than that of controls (3.6 ± 2.4 cm H2O. The sigmoidal equation fit the pressure-volume curves of the fibrotic and control patients well, but the exponential equation fit the data well only when points below 50% of the inspiratory capacity were excluded. CONCLUSION: The elevated lower inflection point and the sigmoidal shape of the pressure-volume curves suggest that respiratory system compliance is decreased close to end-expiratory lung volume in idiopathic pulmonary fibrosis patients under general anesthesia and mechanical ventilation. The sigmoidal fit was superior to the exponential fit for inflation pressure-volume curves of anesthetized patients with idiopathic pulmonary fibrosis and could be useful for guiding mechanical ventilation during general anesthesia in this condition.

  15. Assessment of liver fibrosis stage influence on clinical course of periodontal diseases in patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    О. М. Slaba

    2017-08-01

    Full Text Available The aim. To assess the influence of liver fibrosis stage on the clinical course of periodontal diseases in patients with chronic hepatitis C. Material and Methods. 122 patients with chronic hepatitis C, treated at the 7th department ofLvivRegionalInfectiousDiseasesHospital during 2013 – 2015 were included into dental investigation. The periodontal disease was diagnosed in accordance with the classification of M. F. Danilevsky (1994. The clinical condition of periodontium was assessed by the papillary marginal alveolar index (PMA in the modification ofParma, by the periodontal index – PI (AL Russel, 1956, by the Muhlemann and Son index – the degree of bleeding in the region of the gingival papilla (PBI. The stage of liver fibrosis was determined according to the medical history. The significance of the difference between two or more relative indicators was calculated using the Fisher test with the Metropolis algorithm. The correlation dependence between the clinical condition of periodontal tissues and the stage of liver fibrosis in patients with viral hepatitis C was studied using the Spearman rank correlation coefficient. Results. The highest percentage of patients with stage of liver fibrosis F0 (70.00 ± 15.28 % was registered in patients with healthy periodont, the lowest - in patients with generalized periodontitis of the third stage (7.89 ± 4.37 %. The highest frequency of patients with the stage of liver fibrosis F3 (73.68 ± 7.14 % was also observed in persons suffering from generalized periodontitis stage III (73.68 ± 7.14 %. Conclusions. The distribution of periodontal lesion severity statistically significant (p < 0.001 depended on the stage of liver fibrosis in patients with chronic hepatitis C. Direct (R = 0.70; p < 0.001 strong correlation between the clinical state of periodontal tissues and the stage of liver fibrosis in patients with chronic hepatitis C (using the Spearman rank correlation coefficient has been determined

  16. Pentraxin 3 Is a Predictor for Fibrosis and Arterial Stiffness in Patients with Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Kadir Ozturk

    2016-01-01

    Full Text Available Objective. The aim of the present study was to investigate whether pentraxin 3 (PTX3 can be a new noninvasive marker for prediction of liver fibrosis in patients with NAFLD. We also aimed to evaluate the relationship between PTX3 and atherosclerosis in patients with NAFLD. Method. Fifty-four male patients with biopsy-proven NAFLD and 20 apparently healthy male volunteers were included. PTX3 levels were determined, using an ELISA method (R&D Sysytems, Quantikine ELISA, USA. To detect the presence of subclinical atherosclerosis in NAFLD, measurements of CIMT, FMD, and cf-PWV levels were performed. Results. PTX3 levels in NAFLD patients with fibrosis were higher than both NAFLD patients without fibrosis and controls (P=0.032 and P=0.028, respectively, but there was no difference between controls and NAFLD patients without fibrosis in terms of PTX3 levels (P=0.903. PTX3 levels were strongly correlated with cf-PWV (r=0.359, P=0.003, whereas no significant correlation was found with other atherosclerosis markers, CIMT and FMD. Conclusion. Elevated plasma PTX3 levels are associated with the presence of fibrosis in patients with NAFLD, independently of metabolic syndrome components. This study demonstrated that for the first time there is a close association between elevated PTX3 levels and increased arterial stiffness in patients with NAFLD.

  17. Molecular epidemiology and dynamics of Pseudomonas aeruginosa populations in lungs of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Jelsbak, Lars; Johansen, Helle Krogh; Frost, Anne Louise Viborg

    2007-01-01

    The ability to establish lifelong persistent infections is a fundamental aspect of the interactions between many pathogenic microorganisms and their mammalian hosts. One example is chronic lung infections by the opportunistic pathogen Pseudomonas aeruginosa in cystic fibrosis (CF) patients....... This infection process is associated with extensive genetic adaptation and microevolution of the infecting bacteria. Through investigations of P. aeruginosa populations and infection dynamics in a group of CF patients followed at the Danish CF Clinic in Copenhagen, we have identified two distinct and dominant...

  18. Critical evaluation of lung scintigraphy in cystic fibrosis: study of 113 patients

    International Nuclear Information System (INIS)

    Piepsz, A.; Wetzburger, C.; Spehl, M.; Machin, D.; Dab, I.; Ham, H.R.; Vandevivere, J.; Baran, D.

    1980-01-01

    A long-term study has been performed on 285 lung perfusion scintigrams obtained from 113 patients with cystic fibrosis. Transverse and longitudinal comparisons with clinical and radiological scores, as well as retrospective analysis of the deceased patients, were the methods used in order to evaluate the importance of the scintigraphic images. It appears that lung scintigraphy is the best index of the regional lung impairment, and contributes, as does a chest radiograph, to the early detection of lung lesions, the two methods being complementary

  19. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR

    DEFF Research Database (Denmark)

    Wainwright, Claire E; Elborn, J Stuart; Ramsey, Bonnie W

    2015-01-01

    was 30 to 39% lower in the lumacaftor-ivacaftor groups than in the placebo group; the rate of events leading to hospitalization or the use of intravenous antibiotics was lower in the lumacaftor-ivacaftor groups as well. The incidence of adverse events was generally similar in the lumacaftor......-ivacaftor and placebo groups. The rate of discontinuation due to an adverse event was 4.2% among patients who received lumacaftor-ivacaftor versus 1.6% among those who received placebo. CONCLUSIONS: These data show that lumacaftor in combination with ivacaftor provided a benefit for patients with cystic fibrosis...

  20. Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Psuedomonas aeruginosa infection

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S S; Nielsen, K G

    1997-01-01

    The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis (CF) and complicating chronic Pseudomonas aeruginosa (P.a.) lung infection was studied in a placebo-controlled, parallel, double-blind single center trial. Active treatment...... consisted of budesonide dry powder, 800 microg twice daily, delivered from a Turbuhaler. The study period covered two successive 3-mo intervals between elective courses of intravenous anti-Pseudomonas antibiotics. Fifty-five patients entered the study, with a mean age of 20 yr and a mean FEV1 of 63...

  1. Trampoline use as physiotherapy for cystic fibrosis patients.

    Science.gov (United States)

    Barak, A; Wexler, I D; Efrati, O; Bentur, L; Augarten, A; Mussaffi, H; Avital, A; Rivlin, J; Aviram, M; Yahav, Y; Kerem, E

    2005-01-01

    Physicians and physiotherapists who care for CF patients have recommended the use of trampolines as a physiotherapeutic tool for enhancing cardiopulmonary performance, encouraging sputum production, and improving general well-being. Despite some therapeutic and recreational benefits associated with trampoline use, papers in the general pediatric population mostly document an increased incidence of injuries, ranging from minor trauma to spinal cord injuries and even death. The aim of this review is to examine the accumulated published data regarding the use of trampolines, to assess their potential contributions and disadvantages for CF patients, and to define whether trampoline use should be recommended. An extensive search in the published medical literature retrieved approximately 60 articles that primarily dealt with trampolines, out of which only two dealt with CF. The preponderance of these articles are reports pertaining to injuries related to the use of trampolines, with only a few describing the medical, physiologic, and/or psychological benefits of trampolines. Based on the accumulated data, the presumed benefits of trampoline use for CF patients are not proven. Furthermore, the suggested benefits could be acquired using other types of exercise. Weighing the known risks of trampolines against the potential benefits that are not unique to this modality suggests that the use of trampolines for CF should not be recommended.

  2. An atypical presentation of sinus mucopyocele in a pediatric cystic fibrosis patient

    Directory of Open Access Journals (Sweden)

    Horesh E

    2015-05-01

    Full Text Available Elan Horesh, Andrew A Colin, Roy Casiano, Sara T WesterBascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: This case report details an association of chronic allergic conjunctivitis and respiratory tract colonization in a cystic fibrosis (CF patient due to an ethmoidal mucocele infected with Escherichia coli. A 3-year-old CF patient presented for evaluation with complaints of chronic periocular erythema, conjunctival injection, and irritation for 2 years. He was treated for presumed allergic conjunctivitis with no improvement and continued to have overall worsening of symptoms on the right greater than the left eye in a waxing and waning pattern. On presentation to the Bascom Palmer Eye Institute, he was noted to have telecanthus and prominent erythema in the region of the medial canthus. Orbital imaging disclosed a mucocele in the right ethmoid sinus. The patient underwent functional endoscopic sinus surgery, with successful marsupialization of the ethmoidal mucocele, which was found on culture to be infected with E. coli. Post-operatively with continuous pulmonary care, the patient remains free of allergic conjunctivitis and E. coli colonization of the upper airway. This case highlights the importance of analyzing the adjacent sinus in patients with chronic, relapsing allergic conjunctivitis refractory to medical management, particularly in patients with underlying systemic diseases such as CF.Keywords: allergic conjuncitivitis, Escherichia Coli, cystic fibrosis, mucocele

  3. Serum Levels of Surfactant Proteins in Patients with Combined Pulmonary Fibrosis and Emphysema (CPFE.

    Directory of Open Access Journals (Sweden)

    Andriana I Papaioannou

    Full Text Available Emphysema and idiopathic pulmonary fibrosis (IPF present either per se or coexist in combined pulmonary fibrosis and emphysema (CPFE. Serum surfactant proteins (SPs A, B, C and D levels may reflect lung damage. We evaluated serum SP levels in healthy controls, emphysema, IPF, and CPFE patients and their associations to disease severity and survival.122 consecutive patients (31 emphysema, 62 IPF, and 29 CPFE and 25 healthy controls underwent PFTs, ABG-measurements, 6MWT and chest HRCT. Serum levels of SPs were measured. Patients were followed-up for 1-year.SP-A and SP-D levels differed between groups (p = 0.006 and p<0.001 respectively. In post-hoc analysis, SP-A levels differed only between controls and CPFE (p<0.05 and CPFE and emphysema (p<0.05. SP-D differed between controls and IPF or CPFE (p<0.001 for both comparisons. In IPF SP-B correlated to pulmonary function while SP-A, correlated to the Composite Physiological Index (CPI. Controls current smokers had higher SP-A and SP-D levels compared to non-smokers (p = 0.026 and p = 0.023 respectively. SP-D levels were higher in CPFE patients with extended emphysema (p = 0.042. In patients with IPF, SP-B levels at the upper quartile of its range (≥26 ng/mL presented a weak association with reduced survival (p = 0.05.In conclusion, serum SP-A and SP-D levels were higher where fibrosis exists or coexists and related to disease severity, suggesting that serum SPs relate to alveolar damage in fibrotic lungs and may reflect either local overproduction or overleakage. The weak association between high levels of SP-B and survival needs further validation in clinical trials.

  4. Lung fibrosis in deceased HIV-infected patients with Pneumocystis pneumonia

    Directory of Open Access Journals (Sweden)

    Erica J Shaddock

    2012-06-01

    Full Text Available Background. Pneumocystis pneumonia (PcP is one of the most common opportunistic infections found in patients with HIV. The prognosis if ventilation is required is poor, with mortality of 36 - 80%. Although more recent studies have shown improved survival, our experience has been that close to 100% of such patients die, and we therefore decided to investigate further. Methods. All patients with confirmed or suspected PcP who died owing to respiratory failure were eligible for the study. Where consent was obtained, trucut lung biopsies were performed post mortem, stored in formalin and sent for histopathological assessment. Results. Twelve adequate lung biopsies were obtained from 1 July 2008 to 28 February 2011 – 3 from men and 9 from women. The mean age was 34.7 years (range 24 - 46, and the mean admission CD4 count was 20.8 (range 1 - 68 cells/μl and median 18.5 cells/μl. All specimens demonstrated typical PcP histopathology; in addition, 9 showed significant interstitial fibrosis. Three had co-infection with cytomegalovirus (CMV, two of which had fibrosis present. There was no evidence of TB or other fungal infections. Conclusion. The high mortality seen in this cohort of PcP patients was due to intractable respiratory failure from interstitial lung fibrosis. whereas the differential includes ventilator induced lung injury, drug resistance or co-infections, we suggest that this is part of the disease progression in certain individuals. Further studies are required to identify interventions that could modify this process and improve outcomes in patients with PcP who require mechanical ventilation. S Afr J HIV Med 2012;13(2:64-67.

  5. Volúmenes pulmonares normales en pacientes con fibrosis pulmonar idiopática y enfisema Normal lung volumes in patients with idiopathic pulmonary fibrosis and emphysema

    Directory of Open Access Journals (Sweden)

    Juan Pablo Casas

    2008-08-01

    pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. Previous reports suggest that when both diseases coexist, pulmonary volumes are compensated and a smaller than expected reduction or even normal lung volumes can be found. We report 4 male patients of 64, 60, 73 and 70 years, all with heavy cigarette smoking history and progressive breathlessness. Three of them had severe limitation in their quality of life. All four showed advanced lung interstitial involvement, at high resolution CT scan, fibrotic changes predominantly in the subpleural areas of lower lung fields and concomitant emphysema in the upper lobes. Emphysema and pulmonary fibrosis was confirmed by open lung biopsy in one patient. The four patients showed normal spirometry and lung volumes with severe compromise of gas exchange and poor exercise tolerance evaluated by 6 minute walk test. Severe pulmonary arterial hypertension was also confirmed in three patients. Normal lung volumes does not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  6. High-dose ibuprofen therapy associated with esophageal ulceration after pneumonectomy in a patient with cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Anbar Ran D

    2004-09-01

    Full Text Available Abstract Background Lung disease in patients with cystic fibrosis is thought to develop as a result of airway inflammation, infection, and obstruction. Pulmonary therapies for cystic fibrosis that reduce airway inflammation include corticosteroids, rhDNase, antibiotics, and high-dose ibuprofen. Despite evidence that high-dose ibuprofen slows the progression of lung disease in patients with cystic fibrosis, many clinicians have chosen not to use this therapy because of concerns regarding potential side effects, especially gastrointestinal bleeding. However, studies have shown a low incidence of gastrointestinal ulceration and bleeding in patients with cystic fibrosis who have been treated with high-dose ibuprofen. Case presentation The described case illustrates a life-threatening upper gastrointestinal bleed that may have resulted from high-dose ibuprofen therapy in a patient with CF who had undergone a pneumonectomy. Mediastinal shift post-pneumonectomy distorted the patient's esophageal anatomy and may have caused decreased esophageal motility, which led to prolonged contact of the ibuprofen with the esophagus. The concentrated effect of the ibuprofen, as well as its systemic effects, probably contributed to the occurrence of the bleed in this patient. Conclusions This report demonstrates that gastrointestinal tract anatomical abnormalities or dysmotility may be contraindications for therapy with high-dose ibuprofen in patients with cystic fibrosis.

  7. When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome?

    Science.gov (United States)

    Van Saen, D; Vloeberghs, V; Gies, I; Mateizel, I; Sermon, K; De Schepper, Jean; Tournaye, H; Goossens, E

    2018-06-01

    When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome (KS)? In KS, germ cell loss is not observed in testicular tissue from fetuses in the second semester of pregnancy but present at a prepubertal age when the testicular architecture is still normal, while fibrosis is highly present at an adolescent age. Most KS patients are azoospermic at adult age because of a massive germ cell loss. However, the timing when this germ cell loss starts is not known. It is assumed that germ cell loss increases at puberty. Therefore, testicular sperm extraction (TESE) at an adolescent age has been suggested to increase the chances of sperm retrieval at onset of spermatogenesis. However, recent data indicate that testicular biopsies from peripubertal KS patients contain only a few germ cells. In this study, we give an update on fertility preservation in adolescent KS patients and evaluate whether fertility preservation would be beneficial at prepubertal age. The possibility of retrieving testicular spermatozoa by TESE was evaluated in adolescent and adult KS men. The presence of spermatogonia and the degree of fibrosis were also analysed in testicular biopsies from KS patients at different ages. The patients were divided into four age groups: foetal (n = 5), prepubertal (aged 4-7 years; n = 4), peripubertal (aged 12-16 years; n = 20) and adult (aged 18-41 years; n = 27) KS patients. In peripubertal and adult KS patients, retrieval of spermatozoa was attempted by semen analysis after masturbation, vibrostimulation, electroejaculation or by TESE. MAGE-A4 immunohistochemistry was performed to evaluate the presence of germ cells in testicular biopsies from foetal, prepubertal, peripubertal and adult KS patients. Tissue morphology was evaluated by haematoxylin-periodic acid Schiff (H/PAS) staining. Testicular spermatozoa were collected by TESE in 48.1% of the adult KS patients, while spermatozoa were recovered after TESE in only one peripubertal patient (5

  8. Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis.

    Science.gov (United States)

    Calabrese, C; Tosco, A; Abete, P; Carnovale, V; Basile, C; Magliocca, A; Quattrucci, S; De Sanctis, S; Alatri, F; Mazzarella, G; De Pietro, L; Turino, C; Melillo, E; Buonpensiero, P; Di Pasqua, A; Raia, V

    2015-03-01

    In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  9. Is there an association between vitamin D and liver fibrosis in patients with chronic hepatitis C?

    Directory of Open Access Journals (Sweden)

    Kalinca da Silva OLIVEIRA

    Full Text Available ABSTRACT BACKGROUND Vitamin D is known for its immunomodulatory, anti-inflammatory and antifibrotic properties, which are quite relevant in the pathogenesis and treatment of many causes of chronic liver disease. OBJECTIVE This study aimed to evaluate the association between serum vitamin D levels and the histopathological findings in patients with chronic hepatitis C virus infection. METHODS Cross-sectional study composed of patients with chronic hepatitis C. All patients underwent vitamin D 25 dosage and anthropometric data analysis. Liver biopsy was performed in a maximum 36-month period before inclusion in the study. RESULTS Of the 74 patients included in the study, 45 (60.8% were women, mean age was 57.03±9.24 years, and 63 (85.1% were white. No association was observed between the serum levels of vitamin D and inflammatory activity (P=0.699 nor with the degree of liver fibrosis (P=0.269. CONCLUSION In this study, no association was observed between vitamin D and inflammatory activity, as well as the degree of liver fibrosis, in patients with chronic hepatitis C.

  10. Oral glucose tolerance test and continuous glucose monitoring to assess diabetes development in cystic fibrosis patients.

    Science.gov (United States)

    Clemente León, María; Bilbao Gassó, Laura; Moreno-Galdó, Antonio; Campos Martorrell, Ariadna; Gartner Tizzano, Silvia; Yeste Fernández, Diego; Carrascosa Lezcano, Antonio

    2018-01-01

    Patients with cystic fibrosis (CF) undergo a slow and progressive process toward diabetes. Oral glucose tolerance test (OGTT) is recommended to diagnose impaired glucose levels in these patients. Continuous glucose monitoring (CGM) measures glucose profiles under real-life conditions. To compare OGTT and CGM results in CF patients. Paired OGTT and 6-day CGM profiles (146.2±9.1h/patient) were performed in 30 CF patients aged 10-18 years. According to OGTT, 14 patients had normal glucose tolerance (NGT), 14 abnormal glucose tolerance (AGT), and two cystic fibrosis-related diabetes (CFRD). In 27 patients (13 NGT, 13 AGT, 1 CFRD), CGM showed glucose values ranging from 140 to 200mg/dL during similar monitoring times (2%-14% with NGT, 1%-16.9% with AGT, and 3% with CFRD). Glucose peak levels ≥200mg/dL were seen in seven patients (3 NGT, 3 AGT, 1 CFRD). According to CGM, two patients had all glucose values under 140mg/dL (1 NGT, 1 AGT). Seventeen patients had glucose levels ranging from 140 to 200mg/dL (10 NGT, 6 AGT, 1 CFRD). Ten patients (3 NGT, 7 AGT) had glucose values ≥200mg/dL for ≤1% of the monitoring time and one (CFRD) for >1% of the monitoring time. OGTT results did not agree with those of the CGM. CGM allows for diagnosis of glucose changes not detected by OGTT. Such changes may contribute to optimize pre-diabetes management in CF patients. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Acoustic Radiation Force Impulse Elastography for fibrosis evaluation in patients with chronic hepatitis C: An international multicenter study

    Energy Technology Data Exchange (ETDEWEB)

    Sporea, Ioan, E-mail: isporea@umft.ro [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Bota, Simona, E-mail: bota_simona1982@yahoo.com [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Peck-Radosavljevic, Markus, E-mail: markus.peck@meduniwien.ac.at [Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna (Austria); Sirli, Roxana, E-mail: roxanasirli@gmail.com [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Tanaka, Hironori, E-mail: hironori@hyo-med.ac.jp [Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Iijima, Hiroko, E-mail: hiroko.iijima@nifty.com [Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Badea, Radu, E-mail: rbadea2003@yahoo.com [3rd Medical Clinic, University of Medicine, Cluj Napoca (Romania); Lupsor, Monica, E-mail: monica.lupsor@umfcluj.ro [3rd Medical Clinic, University of Medicine, Cluj Napoca (Romania); Fierbinteanu-Braticevici, Carmen, E-mail: cfierbinteanu@yahoo.com [2nd Medical Clinic and Gastroenterology, University Hospital, Bucharest (Romania); Petrisor, Ana, E-mail: ana1petrisor@yahoo.com [2nd Medical Clinic and Gastroenterology, University Hospital, Bucharest (Romania); Saito, Hidetsugu, E-mail: hidetsugusaito@gmail.com [Department of Internal Medicine, School of Medicine, Keio University, Tokyo (Japan); Ebinuma, Hirotoshi, E-mail: ebinuma@a5.keio.jp [Department of Internal Medicine, School of Medicine, Keio University, Tokyo (Japan); Friedrich-Rust, Mireen, E-mail: Mireen.Friedrich-Rust@kgu.de [Department of Internal Medicine, J.W. Goethe University, Frankfurt/Main (Germany); Sarrazin, Christoph, E-mail: sarrazin@em.uni-frankfurt.de [Department of Internal Medicine, J.W. Goethe University, Frankfurt/Main (Germany); and others

    2012-12-15

    Aim: The aim of this international multicenter study was to evaluate the reliability of Acoustic Radiation Force Impulse (ARFI) elastography for predicting fibrosis severity, in patients with chronic hepatitis C. Patients and methods: We compared ARFI to liver biopsy (LB) in 914 patients (10 centers, 5 countries) with chronic hepatitis C. In each patient LB (evaluated according to the METAVIR score) and ARFI measurements were performed (median of 5–10 valid measurements, expressed in meters/second – m/s). In 400 from the 914 patients, transient elastography (TE) was also performed (median of 6–10 valid measurements, expressed in kiloPascals – kPa). Results: Valid ARFI measurements were obtained in 911 (99.6%) of 914 cases. On LB 61 cases (6.7%) had F0, 241 (26.4%) had F1, 202 (22.1%) had F2, 187 (20.4%) had F3, and 223 (24.4%) had F4 fibrosis. A highly significant correlation (r = 0.654) was found between ARFI measurements and fibrosis (p < 0.0001). The predictive values of ARFI for various stages of fibrosis were: F ≥ 1 – cut-off > 1.19 m/s (AUROC = 0.779), F ≥ 2 – cut-off > 1.33 m/s (AUROC = 0.792), F ≥ 3 – cut-off > 1.43 m/s (AUROC = 0.829), F = 4 – cut-off > 1.55 m/s (AUROC = 0.842). The correlation with histological fibrosis was not significantly different for TE in comparison with ARFI elastography: r = 0.728 vs. 0.689, p = 0.28. TE was better than ARFI for predicting the presence of liver cirrhosis (p = 0.01) and fibrosis (F ≥ 1, METAVIR) (p = 0.01). Conclusion: ARFI elastography is a reliable method for predicting fibrosis severity in chronic hepatitis C patients.

  12. Prevalence and Severity of Dysphonia in Patients with Cystic Fibrosis: A Pilot Study.

    Science.gov (United States)

    Willis, John; Michael, Deirdre D; Boyer, Holly; Misono, Stephanie

    2015-07-01

    To assess the prevalence and severity of dysphonia in patients with cystic fibrosis sinusitis. We hypothesized that patients with CF sinusitis, compared with 2 control groups, would have higher self-reported prevalence of dysphonia and greater severity of dysphonia, according to patient-reported outcome measures as well as auditory-perceptual evaluation by expert listeners. Cross-sectional comparative pilot study. Academic tertiary care clinic. Analysis included 37 study participants: 17 patients with CF sinusitis, 10 healthy individuals, and 10 patients with non-CF sinusitis. All participants completed the 10-item Voice Handicap Index (VHI-10) questionnaire and provided voice samples. On all samples, 6 blinded speech-language pathologists independently performed auditory-perceptual evaluation, using Consensus Auditory-Perceptual Evaluation of Voice. To assess severity of sinonasal symptoms, we used the 20-item Sinonasal Outcome Test (SNOT-20). Standard parametric and nonparametric statistical analysis was performed. The differences between the 3 groups in prevalence of abnormal VHI-10 scores were not statistically significant. SNOT-20 scores were similar in the 2 sinusitis patient groups. VHI-10 scores were highest in patients with CF sinusitis, intermediate in patients with non-CF sinusitis, and lowest in healthy individuals (P = .005). Auditory-perceptual evaluation demonstrated greater overall severity of dysphonia in patients with CF sinusitis compared with the 2 control groups (P = .0005). Cystic fibrosis sinusitis appeared to be associated with worse vocal function as measured by patient self-report as well as auditory-perceptual evaluation of voice compared with patients with non-CF sinusitis and healthy controls. Further investigation in this area is warranted. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  13. Suggestions for the optimization of the initial tobramycin dose in adolescent and adult patients with cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J; Vinks, A A; Heijerman, H G; Hermans, J; Bakker, W

    Clinical pharmacokinetic data of intravenously administered tobramycin in 34 patients with cystic fibrosis (CF) were correlated with patient parameters. Patients began tobramycin therapy with 10 mg/kg/day in three divided doses. Peak and trough serum concentrations were measured. Tobramycin dose was

  14. Expression of cytokine signaling genes in morbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis.

    Science.gov (United States)

    Estep, J Michael; Baranova, Ancha; Hossain, Noreen; Elariny, Hazem; Ankrah, Kathy; Afendy, Arian; Chandhoke, Vikas; Younossi, Zobair M

    2009-05-01

    White adipose tissue (WAT) from visceral adiposity plays an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Development of NASH and its progression to fibrosis is partially due to cytokines and adipokines produced by WAT. The aim of this study was to assess the association of hepatic fibrosis and NASH by evaluating the intrinsic differences in the inflammatory cytokine signaling in the visceral adipose tissue obtained from morbidly obese patients. We used targeted microarrays representing human genes involved in the inflammatory and fibrogenic reactions to profile visceral adipose samples of 15 well-matched NASH patients with and without fibrosis. Additionally, visceral adipose samples were subjected to real-time polymerase chain reaction profiling of 84 inflammations related genes. Eight genes (CCL2, CCL4, CCL18, CCR1, IL10RB, IL15RA, and LTB) were differentially expressed in NASH with fibrosis. Additionally, an overlapping but distinct list of the differentially expressed genes were found in NASH with type II diabetes (DM; IL8, BLR1, IL2RA, CD40LG, IL1RN, IL15RA, and CCL4) as compared to NASH without DM. Inflammatory cytokines are differentially expressed in the adipose tissue of NASH with fibrosis, as well in NASH with DM. These findings point at the interaction of adipose inflammatory cytokines, DM, hepatic fibrosis in NASH, and its progression to cirrhosis and end-stage liver disease.

  15. Evaluation of a bovine antibody test for diagnosing Mycobacterium avium complex in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Qvist, Tavs; Pressler, Tacjana; Katzenstein, Terese L.

    2017-01-01

    Introduction: The aim of this study was to test a commercial bovine enzyme-linked immunosorbent assay for investigating antibody activity against Mycobacterium avium complex. Methods: All patients at the Copenhagen Cystic Fibrosis (CF) Center who had culture for nontuberculous mycobacteria...... before and after culture conversion was performed in case patients. Results: Out of 286 included subjects, six had clinical M. avium complex pulmonary disease at the time of sera sampling. These patients presented with higher antibody test values (P-value ... at ruling out pulmonary disease. Screening sera from patients with CF could guide clinicians to focus attention on patients at higher risk of M. avium complex pulmonary disease. Pediatr Pulmonol. 2017;52:34–40....

  16. Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD.

    Science.gov (United States)

    Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A; Kleiner, David; Brunt, Elizabeth M; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James; Loomba, Rohit

    2015-07-01

    Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m(2), respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with

  17. Value of FibroScan in diagnosis of hepatic fibrosis in patients with HBeAg-negative chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    LUO Junhua

    2014-07-01

    Full Text Available ObjectiveTo evaluate the value of transient elastography (FibroScan, FS in predicting hepatic fibrosis in patients with HBeAg-negative chronic hepatitis B (CHB. MethodsOne hundred and four patients with HBeAg-negative CHB, who were diagnosed and treated in Hubei Hospital of Traditional Chinese Medicine from June 2011 to May 2013, were enrolled in this study. All patients underwent FS for liver stiffness measurement before liver biopsy. Statistical analysis was applied to compare liver stiffness (kPa with fibrosis stage (determined by liver biopsy. The receiver operating characteristic (ROC curve of FS was constructed, and the area under the ROC curve (AUROC was calculated to analyze the accuracy of live stiffness in predicting significant fibrosis and cirrhosis. Comparison between groups was made by Kruskal-Wallis H test, followed by Mann-Whitney U test for multiple comparisons. The correlation between two variables was analyzed by Spearman rank and Pearson correlation test. ResultsLiver stiffness gradually rose as the degree of hepatic fibrosis increased, with significant differences between groups (P<0.01 or P<0.05. Liver stiffness was positively correlated with the stage of hepatic fibrosis (r=0.810, P<0.01. The AUROC of liver stiffness for detecting liver cirrhosis was 0.956; the cut-off value for diagnosing liver cirrhosis was 13.1 kPa; the sensitivity was 92.7%, and the specificity was 80%. ConclusionFS is a promising noninvasive method for the assessment of hepatic fibrosis in patients with HBeAg-negative CHB; particularly, it has high accuracy in the diagnosis of liver cirrhosis. FS combined with direct or indirect markers may play an important role in differential diagnosis and efficacy evaluation in patients with hepatic fibrosis.

  18. Patient considerations and drug selection in the treatment of idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Trawinska MA

    2016-04-01

    Full Text Available Maria A Trawinska,1 Ruwani D Rupesinghe,1 Simon P Hart1,2 1Hull and East Yorkshire Hospitals NHS Trust, 2Hull York Medical School, Academic Respiratory Medicine, Castle Hill Hospital, Cottingham, East Yorkshire, UK Abstract: Idiopathic pulmonary fibrosis (IPF is a progressive interstitial lung disease of unknown cause. Approximately 5,000 people are diagnosed with IPF in the UK every year. People with IPF suffer significant morbidity and, without any curative treatment at present, survival rates remain poor with a median survival of 3 years. While treatment remains largely supportive, many drug therapies have been trialed in IPF over the years. Pirfenidone and nintedanib are newly licensed treatments for IPF and the first drugs to have shown convincing evidence of slowing disease progression. In addition to evaluating clinical evidence, we also discuss elements affecting drug choice from the viewpoint of patients and health care professionals. We discuss pharmacological and nonpharmacological aspects of providing best supportive care for patients with IPF. However, few good quality studies exist focusing on controlling symptoms specifically in patients with IPF, and recommendations are often extrapolated from evidence in other chronic diseases. In covering these topics, we hope to provide readers with a comprehensive review of the available evidence pertaining to all aspects of care for patients suffering with IPF. Keywords: interstitial lung disease, high-resolution computed tomography, forced vital capacity, usual interstitial pneumonia, clinical trials, decision making, idiopathic pulmonary fibrosis

  19. Comparison of AI techniques for prediction of liver fibrosis in hepatitis patients.

    Science.gov (United States)

    Keltch, Brian; Lin, Yuan; Bayrak, Coskun

    2014-08-01

    Globally one in twelve people have the Hepatitis B or Hepatitis C virus. Diagnosis and treatment of this disease is guided by liver biopsies where a small amount of tissue is removed by a surgeon and examined by a pathologist to determine the fibrosis stage from F(0) (no damage) to F(4) (cirrhosis). Biopsies are costly and carry some risk for the patient. Non-invasive techniques for determining fibrosis stage have been developed and evaluated since 2003. Non-invasive methods have utilized serum markers, imaging test, and genetic studies. The accuracy of these non-invasive techniques has not achieved sufficient acceptance and so the invasive biopsy is still considered the gold standard.Clinical decision support systems (CDSS) use decision support system theory and technology to assist clinicians in the evaluation and treatment process. Using historical clinical data and the relationship processed by Artificial Intelligence (AI) techniques to aid physicians in their decision making process is the goal of CDSS. The CDSS provides a large number of medical support functions to help clinicians make the most reasonable diagnosis and choose the best treatment measures.This paper applies four artificial intelligence predictive techniques to publicly available data on 424 Hepatitis B and Hepatitis C patients. Demographic and standard serum markers are utilized to predict fibrosis stage and compare these predictions to known biopsy results. A final decision tree evaluation is applied to make a final prediction. We have also developed a publically available web application that can be used as a prototype for presenting AI predictive results in a CDSS environment based on these models. This technique along with others could mitigate the need for some liver biopsies in the more than 500 million Hepatitis B and C patients worldwide with additional validation and verification.

  20. Lung Abscess: An Early Complication of Lung Transplantation in a Patient with Cystic Fibrosis.

    Science.gov (United States)

    Markelić, I; Jakopović, M; Klepetko, W; Džubur, F; Hećimović, A; Makek, M J; Samaržija, M; Dugac, A V

    2017-01-01

    A 22-year-old woman with cystic fibrosis (CF) developed lung abscess, as a rare complication caused by multidrug-resistant (MDR) Acinetobacter baumannii infection, after lung transplantation (LT). After 6 months of long-term antibiotic therapy, the abscess was successfully eliminated. In reviewed published literature, no previous report was found describing this kind of complication caused by MDR A. baumannii in post-LT patient with CF. In our experience, lung abscess in LT recipients with CF can be successfully treated with prolonged antibiotic therapy.

  1. Idiopathic retroperitoneal fibrosis associated with Hashimoto's thyroiditis in a patient with a single functioning kidney

    Directory of Open Access Journals (Sweden)

    Byung Sun Kim

    2013-12-01

    Full Text Available Retroperitoneal fibrosis (RPF is a rare disease characterized by the presence of fibroinflammatory tissue around the abdominal aorta and ureteral entrapment in most cases. Idiopathic RPF is frequently reported in association with autoimmune diseases; however, there have been few reports of idiopathic RPF associated with Hashimoto's thyroiditis. Here, we report a case of idiopathic RPF with Hashimoto's thyroiditis in a patient with a single functioning kidney, which was successfully treated by corticosteroid therapy and transient intraureteral stent insertion with a double-J catheter.

  2. Cedecea davisae’s Role in a Polymicrobial Lung Infection in a Cystic Fibrosis Patient

    Directory of Open Access Journals (Sweden)

    Thayer G. Ismaael

    2012-01-01

    Full Text Available Chronic airway colonization and infection are the hallmark of cystic fibrosis (CF. Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cepacia are well-documented bacterial culprits in this chronic suppurative airway disease. Advanced molecular diagnostics have uncovered a possible role of a larger group of microorganisms in CF. Cedecea is a member of the family Enterobacteriaceae and is an emerging pathogen. We present a case of a polymicrobial healthcare-associated pneumonia in a CF patient caused by Cedecea davisae, among other bacteria.

  3. Changes of liver function and serum hepatic fibrosis markers levels in patients with trichloroethylene induced drugrash-like dermatitis

    International Nuclear Information System (INIS)

    Li Senhua; Xie Guoqiang; Zeng Zeming

    2004-01-01

    Objective: To investigate the liver function damage and serum hepatic fibrosis markers levels changes in patients suffering from trichloroethylene induced drugrash-like dermatitis. Methods: Serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC III), type IV collagen ( IV C) levels (with RIA), mono-amine oxidase (MAO) activity (with chemo-colorimetry) and liver function tests (including ALT, AGT, total protein, albumin, total bile acid, with automated biochemical analysis system) were determined in 30 controls and 30 patients with trichloroethylene induced drugrash-like dermatitis. Results: Severe liver function damage was demonstrated in all the patients. The serum hepatic fibrosis markers levels were significantly increased (vs controls, P<0.01) and correlated well with the degree of hepatic damage. Conclusion: Liver damage occurred early in patients with trichloroethylene induced dermatitis, accompanied with laboratory evidence of hepatic fibrosis. (authors)

  4. Bronchial artery embolization for therapy of pulmonary bleeding in patients with cystic fibrosis

    International Nuclear Information System (INIS)

    Thalhammer, A.; Jacobi, V.; Balzer, J.; Straub, R.; Vogl, T.J.

    2002-01-01

    Introduction: Acute pulmonary emergencies in patient with cystic fibrosis (CF) can be found in cases of pneumothorax as well as hemoptysis. If the bleeding cannot be stopped by conservative methods, an embolization of the bronchial arteries should be done. Materials and Method: 11 patients were embolized using a combination of PVA particles and microcoils. Results: From January 1996 to June 2001 17 bronchial arteries in 11 patients were embolized. 7 patients suffered from chronical hemoptysis, 4 patients had an acute hemoptysis. In 4 patients both sides were embolized, in 3 patients only one side. The remaining 4 patients needed a second intervention, embolizing the other side. The primary embolizated bronchial artery was still closed in all 4 patients. In 1 patient the selective catheterization of a bronchial artery was not successful, thus the embolization could not be carried out. 1 patient died 5 days after the intervention due to a fulminant pneumonia (Pseudomonas aeruginosa) without recurrent bleeding. In two patients atypical branches from intercostal arteries feeding the bronchial arteries were detected and successfully embolized. All patients profited from the therapy, as bleeding could be stopped or at least be reduced. 3 patients suffered from back pain during or after intervention. There were no severe complications like neurological deficiencies or necroses. (orig.) [de

  5. An exploration of partnership through interactions between young 'expert' patients with cystic fibrosis and healthcare professionals.

    Science.gov (United States)

    MacDonald, Kath; Irvine, Lindesay; Smith, Margaret Coulter

    2015-12-01

    To explore how young 'expert patients' living with Cystic Fibrosis and the healthcare professionals with whom they interact perceive partnership and negotiate care. Modern healthcare policy encourages partnership, engagement and self-management of long-term conditions. This philosophy is congruent with the model adopted in the care of those with Cystic Fibrosis, where self-management, trust and mutual respect are perceived to be integral to the development of the ongoing patient/professional relationship. Self-management is associated with the term; 'expert patient'; an individual with a long-term condition whose knowledge and skills are valued and used in partnership with healthcare professionals. However, the term 'expert patient' is debated in the literature as are the motivation for its use and the assumptions implicit in the term. A qualitative exploratory design informed by Interpretivism and Symbolic Interactionism was conducted. Thirty-four consultations were observed and 23 semi-structured interviews conducted between 10 patients, 2 carers and 12 healthcare professionals. Data were analysed thematically using the five stages of 'Framework' a matrix-based qualitative data analysis approach and were subject to peer review and respondent validation. The study received full ethical approval. Three main themes emerged; experiences of partnership, attributes of the expert patient and constructions of illness. Sub-themes of the 'ceremonial order of the clinic', negotiation and trust in relationships and perceptions of the expert patient are presented. The model of consultation may be a barrier to person-centred care. Healthcare professionals show leniency in negotiations, but do not always trust patients' accounts. The term 'expert patient' is unpopular and remains contested. Gaining insight into structures and processes that enable or inhibit partnership can lead to a collaborative approach to service redesign and a revision of the consultation model. © 2015

  6. Pathomorphology of liver fibrosis in trepanobioptates of patients with steatohepatitis: main types, sources of development, features of progression

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2017-12-01

    Full Text Available Until recently, among the pathologists, hepatologists and gastroenterologists, a discussion continues on the morphogenesis and gradation of liver fibrosis in non-alcoholic patients (NASH and alcoholic steatohepatitis (ASH. Purpose of the study. Studying the main types and sources of liver fibrosis in patients with nonalcoholic and alcoholic steatohepatitis, justifying the gradation of its severity, taking into account the quantitative dynamics of fibrogenic producer cells, the relative area of fibrosis and the deposition of type I, III and IV collagen in the liver. Material and methods. Histological and histochemical examination of liver fibrosis was performed in 198 patients with NASH of 18-79 years and in 79 patients with ASH of 47-63 years. Immunohistochemical study with measurement of the area of expression of activated αSMA + perisinusoidal stellate cells and αSMA + portal myofibroblasts with F1 (mild, F2 (moderate, F3 (severe fibrosis and F4 fibrosis / cirrhosis was performed in 80 trepanobioptates of patients with NASH (20 cases in each group, electron microscopic examination of the liver – in 10 deceased patients suffering from NASH. Results. In patients with NASH and ASH, there are two major types of liver fibrosis progress: the perisinusoidal pericellular and portal-Z3 perisinusoidal fibrosis, the development of which is the new generation of αSMA + star cells and αSMA + portal myofibroblasts of the fibrogenic immunophenotype, with co-expression of fascin and vimentin and absence of desmine expression. As the perisinusoidal pericellular fibrosis progresses from the mild F1 degree, to the severe F3 fibrosis and to the extremely severe F4 fibrosis / cirrhosis of the pericellular type, the area of the Masson-positive extracellular molecular-fibrous matrix (H = 88,70 р = 0,05 and the area of αSMA + collagen-producing stellate cells of perisinusoidal-pericellular localization (H = 45,12, p = 0,05. According to the data of

  7. Celiac Disease in Patients with Cystic Fibrosis-Related Bone Disease

    Directory of Open Access Journals (Sweden)

    Melissa S. Putman

    2017-01-01

    Full Text Available Both cystic fibrosis (CF and celiac disease can cause low bone mineral density (BMD and fractures. Celiac disease may occur at a higher frequency in patients with CF than the general population, and symptoms of these conditions may overlap. We report on two patients presenting with CF-related bone disease in the past year who were subsequently found to have concurrent celiac disease. Because adherence to a gluten-free diet may improve BMD in patients with celiac disease, this could have important implications for treatment. Clinicians should consider screening for celiac disease in patients with CF who have low BMD, worsening BMD in the absence of other risk factors, and/or difficult to treat vitamin D deficiency.

  8. SERS detection of the biomarker hydrogen cyanide from Pseudomonas aeruginosa cultures isolated from cystic fibrosis patients

    DEFF Research Database (Denmark)

    Lauridsen, Rikke Kragh; Madsen Sommer, Lea Mette; Johansen, Helle Krogh

    2017-01-01

    Pseudomonas aeruginosa is the primary cause of chronic airway infections in cystic fibrosis (CF) patients. Persistent infections are seen from the first P. aeruginosa culture in about 75% of young CF patients, and it is important to discover new ways to detect P. aeruginosa at an earlier stage...... long-term infection, a mutation in the patho-adaptive lasR gene can alter the expression of HCN, which is why it is sometimes not possible to detect HCN in the breath of chronically infected patients. Four P. aeruginosa reference strains and 12 clinical P. aeruginosa strains isolated from CF children...... were evaluated, and HCN was clearly detected from overnight cultures of all wild type-like isolates and half of the later isolates from the same patients. The clinical impact could be that P. aeruginosa infections could be detected at an earlier stage, because daily breath sampling with an immediate...

  9. Listening to motivational music while walking elicits more positive affective response in patients with cystic fibrosis.

    Science.gov (United States)

    Calik-Kutukcu, Ebru; Saglam, Melda; Vardar-Yagli, Naciye; Cakmak, Aslihan; Inal-Ince, Deniz; Bozdemir-Ozel, Cemile; Sonbahar-Ulu, Hazal; Arikan, Hulya; Yalcin, Ebru; Karakaya, Jale

    2016-05-01

    The purpose of this study was to investigate the effects of motivational and relaxation music on affective responses during exercise in patients with cystic fibrosis (CF). Thirty-seven patients with CF performed the 6-min walk test (6MWT) under three experimental conditions: listening to no music, relaxation music, and motivational music. 6-min distance × body weight product (6MWORK) was calculated for each trial. Patients' affective responses during exercise was evaluated with Feeling Scale (FS). The motivational qualities of music were evaluated with the Brunel Music Rating Inventory-2 (BMRI-2). 6MWORK was significantly lower while listening to relaxation music compared to 6MWORK without music (p motivational music than 6MWT with relaxation music (p motivational music can lead to positive affective response during exercise and increase the enjoyment of patients from exercises in CF. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. CT analysis of the effect of pirfenidone in patients with idiopathic pulmonary fibrosis

    International Nuclear Information System (INIS)

    Iwasawa, Tae; Ogura, Takashi; Sakai, Fumikazu; Kanauchi, Tetsu; Komagata, Takanobu; Baba, Tomohisa; Gotoh, Toshiyuki; Morita, Satoshi; Yazawa, Takuya; Inoue, Tomio

    2014-01-01

    Purpose: Pirfenidone is a new, anti-fibrotic drug used for the treatment of idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the utility of computed tomography (CT) in the imaging assessment of the response to pirfenidone therapy. Materials and methods: Subjects were 78 patients with IPF who underwent CT on two occasions with one-year interval (38 consecutive patients treated with pirfenidone and 40 age-matched control). Changes in the fibrous lesion on sequential CTs were assessed as visual score by two radiologists. We measured the volume and change per year of fibrous pattern (F-pattern) quantitatively using a computer-aided system on sequential CTs. Results: The baseline vital capacity (%pred VC) was 74.0 ± 14.0% in the pirfenidone group and 74.6 ± 16.6% in controls (p = NS). Deterioration of respiratory status was defined as 10% or greater decline in %pred VC value after 12-month treatment. A significantly larger proportion of pirfenidone-treated patients showed stable respiratory status (21 of 38, 65.6%) than the control (15 of 40, 37.5%). The change in fibrous lesion was significantly smaller in the pirfenidone group than the control in both of visual score (p = 0.006) and computer analysis (p < 0.001). The decline in VC correlated significantly with the increase in fibrotic lesion (p < 0.001). Conclusion: CT can be used to assess pirfenidone-induced slowing of progression of pulmonary fibrosis.

  11. Sinus biofilms in patients with cystic fibrosis: is adjusted eradication therapy needed?

    DEFF Research Database (Denmark)

    Aanaes, Kasper; Eickhardt, Steffen; Johansen, Helle Krogh

    2015-01-01

    The paranasal sinuses can be a focus for colonisation of the cystic fibrosis (CF) lungs with pathogens. In the sinuses, bacteria can adapt to the lung environment and enhance their antibiotic resistance, with biofilm formation thought to be the most important adaptive mechanism, causing recalcitr......The paranasal sinuses can be a focus for colonisation of the cystic fibrosis (CF) lungs with pathogens. In the sinuses, bacteria can adapt to the lung environment and enhance their antibiotic resistance, with biofilm formation thought to be the most important adaptive mechanism, causing...... recalcitrant disease. The presence of biofilms in CF sinuses is sparsely described. In this descriptive cross-sectional study, the sinus mucosa from 16 CF patients were analysed by fluorescence in situ hybridization using specific peptide nucleic acid (PNA-FISH) probes for Pseudomonas aeruginosa...... and Staphylococcus aureus to demonstrate the presence of biofilms. Small clusters of biofilm were visualised lining the sinus mucosa of CF patients. Biofilms were found in 10 out of 18 cases; 7 with intermittent lung colonisation, 2 chronically infected, and one lung transplanted patient. Finding P. aeruginosa...

  12. Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection

    Science.gov (United States)

    Parikh, Pathik; Ryan, John D.

    2017-01-01

    Chronic hepatitis B virus (HBV) infection is a major cause of liver morbidity and mortality worldwide. While a proportion of the 250 million individuals chronically infected with HBV will not come to significant harm or require therapy, many others risk developing complications of the end-stage liver disease such as decompensated cirrhosis and hepatocellular carcinoma (HCC), without intervention. Due to the complex natural history of HBV infection, patients require an expert assessment to interpret biochemistry, viral serology and appropriately stage the disease, and to initiate monitoring and/or therapy where indicated. The detection and quantification of liver fibrosis is a key factor for disease management and prognostication for an individual with HBV. The reliance on invasive liver biopsy to stage disease is diminishing with the advent of robust non-invasive blood- and imaging-based algorithms which can reliably stage disease in many cases. These tests are now incorporated into International guidelines for HBV management and relied upon daily to inform clinical judgement. Both blood- and imaging-based approaches have advantages over liver biopsy, including minimal risks, lower cost, better patient acceptance and speed of results, while disadvantages include lower diagnostic accuracy in intermediate disease stages and variability with co-existing hepatic inflammation or steatosis. This review outlines the methods of fibrosis assessment in chronic HBV infection and focuses on the most commonly used blood- and imaging-based non-invasive tests, reviewing their diagnostic performance and applicability to patient care. PMID:28251119

  13. CT analysis of the effect of pirfenidone in patients with idiopathic pulmonary fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Iwasawa, Tae, E-mail: tae_i_md@wb3.so-net.ne.jp [Department of Radiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama (Japan); Ogura, Takashi [Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama (Japan); Sakai, Fumikazu [Department of Diagnostic Radiology, International Medical Center of Saitama Medical University, Saitama (Japan); Kanauchi, Tetsu [Department of Radiology, Saitama Cardiovascular and Respiratory Center, Saitama (Japan); Komagata, Takanobu [Department of Radiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama (Japan); Baba, Tomohisa [Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama (Japan); Gotoh, Toshiyuki [Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama (Japan); Morita, Satoshi [Department of Biostatistics and Epidemiology, Yokohama City University Medical Center (Japan); Yazawa, Takuya [Department of Pathology, Kyorin University School of Medicine, Tokyo (Japan); Inoue, Tomio [Department of Radiology Yokohama City University, School of Medicine, Yokohama (Japan)

    2014-01-15

    Purpose: Pirfenidone is a new, anti-fibrotic drug used for the treatment of idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the utility of computed tomography (CT) in the imaging assessment of the response to pirfenidone therapy. Materials and methods: Subjects were 78 patients with IPF who underwent CT on two occasions with one-year interval (38 consecutive patients treated with pirfenidone and 40 age-matched control). Changes in the fibrous lesion on sequential CTs were assessed as visual score by two radiologists. We measured the volume and change per year of fibrous pattern (F-pattern) quantitatively using a computer-aided system on sequential CTs. Results: The baseline vital capacity (%pred VC) was 74.0 ± 14.0% in the pirfenidone group and 74.6 ± 16.6% in controls (p = NS). Deterioration of respiratory status was defined as 10% or greater decline in %pred VC value after 12-month treatment. A significantly larger proportion of pirfenidone-treated patients showed stable respiratory status (21 of 38, 65.6%) than the control (15 of 40, 37.5%). The change in fibrous lesion was significantly smaller in the pirfenidone group than the control in both of visual score (p = 0.006) and computer analysis (p < 0.001). The decline in VC correlated significantly with the increase in fibrotic lesion (p < 0.001). Conclusion: CT can be used to assess pirfenidone-induced slowing of progression of pulmonary fibrosis.

  14. Lung fibrosis quantified by HRCT in scleroderma patients with different disease forms and ANA specificities

    Directory of Open Access Journals (Sweden)

    S. Mancin

    2011-09-01

    Full Text Available Objective: to define the prevalence of interstitial lung fibrosis in systemic sclerosis (SSc and its relationship with the different clinical forms of disease and ANA specificities. Methods: fifty patients with SSc were submitted to pulmonary high resolution computed tomography (HRCT. Lung abnormalities were evaluated according to Warrick’s score that considers both the severity and the extent of fibrotic lesions. Results: pulmonary HRCT abnormalities were observed in 84% of SSc patients. Ground glass aspects (60%, irregular pleural margins (56% and septal/subpleural lines (68% were the most common lesions. The distribution of these abnormalities favoured the posterior basilar segments of both lungs. HRCT findings were significantly more frequent in males and in patients with the cutaneous diffuse form of SSc and with the specific antibody anti-Scl70. Conclusions: HRCT is a very useful method for the diagnosis of interstitial lung fibrosis in SSc. Warrick’s score permits to quantify the HRCT findings and to evaluate their relationship with the disease clinical forms and ANA specificities.

  15. Increase in interleukin-8 production from circulating neutrophils upon antibiotic therapy in cystic fibrosis patients.

    Science.gov (United States)

    Montemurro, Pasqualina; Mariggiò, Maria A; Barbuti, Giovanna; Cassano, Amalia; Vincenti, Alessandra; Serio, Gabriella; Guerra, Lorenzo; Diana, Anna; Santostasi, Teresa; Polizzi, Angela; Fumarulo, Ruggiero; Casavola, Valeria; Manca, Antonio; Conese, Massimo

    2012-12-01

    It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis. Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry. ROS and interleukin (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs under basal conditions. IL-8 levels further increased after therapy. Early apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and this pattern did not change after antibiotic treatment. Circulating PMNs are primed in CF acute patients. Further studies are needed to consider PMN-produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF patients. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  16. [Relation between gene mutations and pancreatic exocrine function in patients with cystic fibrosis].

    Science.gov (United States)

    Radivojević, D; Guć-Sćekić, M; Djurisić, M; Lalić, T; Minić, P; Kanavakis, E

    2001-01-01

    Cystic fibrosis (CF), is the most common autosomal-recessive disease in Caucasians, with an incidence of approximately 1:2500 live births and a carrier frequency of approximately 4-5%. Causes of the disease are mutations in the CF gene which is located on chromosome 7 (region 7q31). Although a single mutation, a deletion of phenylalanine at position 508 (DF508) in exon 10, accounts for almost 70% of all CF chromosomes, over 900 other mutations have been identified in this large gene. CF gene encodes a membrane protein, which functions as aion channel- CFTR (cystic fibrosis transmembrane regulator protein). The exocrine pancreas is a gland that secretes water, enzymes and electrolytes into the intestinal lumen. These enzymes are needed for the normal digestion of food, and their reduced secretion in cystic fibrosis will cause malabsortion and malnutrition in CF patients. Pancreatic dysfunction in CF begins in uteri. Most patients with CF typically present insufficient pancreatic exocrine function (PI phenotype) and 10-15% of CF patients are pancreatic sufficient (PS phenotype). It has been shown elsewhere that the pancreatic function status in CF could be correlated to mutations in the CFTR gene. To determine the relation between genotype and pancreatic status, we analyzed 32 CF patients in whom both CF gene mutant alleles were identified (Table 1). Patients included in this study attended the Paediatric Department of Mother and Child Health Institute in Belgrade. The diagnosis was based on typical clinical manifestations and high levels of sweat chloride concentration (higher than 60 mmol/L). Of the 32 patients studied, only one (3.12%) was PS and the rest (96.88%) had PI phenotype. For each CF genotype the number of patients who were PI or PS is given in Table 1. The most striking observation was that all given genotypes correlated with either PI or PS, but not with both. On the basis of both preceding hypotheses and our present data (Table 2 and Table 3), it was

  17. Diagnosis of chronic rhino sinusitis in patients with cystic fibrosis: correlation between anamnesis, nasal endoscopy and computed tomography

    International Nuclear Information System (INIS)

    Boari, Leticia; Castro Junior, Ney Penteado de

    2005-01-01

    The sinonasal involvement is one of the most common manifestations in cystic fibrosis. Data show a high incidence of chronic rhino sinusitis in these patients. Although it has been found radiographic opacification of the sinus in more than 90% of cases, few are symptomatic. So that, it is difficult to recognize nasossinusal disease in patients with cystic fibrosis. Questionnaire, nasal endoscopy and CT-scan are very important methods in this approach. Aim: to evaluate the diagnosis of chronic rhino sinusitis in patients with cystic fibrosis by anamnesis, nasal endoscopy and CT-scan and compare those results.Study Design: Clinical prospective. Material and method: evaluation of 34 patients - older than 6 years and with a confirmed diagnoses of cystic fibrosis - by anamnesis (questionnaire), nasal endoscopy (score Lund-Kennedy) and CT-scan (score Lund-Mackay). Results: chronic rhino sinusitis was confirmed in: 20,58% of cases by the questionnaire, 73,52% of the cases by the nasal endoscopy and in 93,54% of the cases by the CT-scan. The results showed significant differences. The correlation between nasal endoscopy score (Lund-Kennedy score) and CT-scan score (Lund-Mackay score) was statistically significant. Conclusion: the diagnosis of chronic rhino sinusitis was statistically different between the three methods. It was higher in imaging analysis and lower in questionnaire. The nasal endoscopy is an excellent method to evaluate nasossinusal disease in cystic fibrosis. (author)

  18. Factors affecting nebulised medicine adherence in adult patients with cystic fibrosis: a qualitative study.

    Science.gov (United States)

    Hogan, Alice; Bonney, Mary-Ann; Brien, Jo-Anne; Karamy, Rita; Aslani, Parisa

    2015-02-01

    Nebulised medicines contribute to the high treatment burden experienced by patients with cystic fibrosis (CF). This study explored experiences of adult patients with CF when using nebulised medicines, factors impacting on their adherence to nebulised therapy and strategies they used to facilitate adherence. Community setting, in Sydney, Australia. Ten patients with CF were recruited through a CF patient organisation. Semi-structured face-to-face interviews were conducted, addressing the study objectives. Interviews were audio-recorded, transcribed verbatim and content analysed for anticipated and emergent themes. Experiences with using nebulised medicines; and barriers and facilitators of adherence to nebulised medicines. Participants' age ranged from 22 to 45 years, with half being male. Four broad themes (with more specific sub-themes) were identified from the interviews: experiences with using nebulised medicines (cleaning nebuliser, time taken to use nebuliser medicine, flexibility in use of nebuliser); feelings about using nebulised medicines (necessary/important, dislike, part of life); factors impacting non-adherence (time consuming therapy, side effects/effects of medicine, work/social demands, lack of perceived importance); factors and strategies facilitating adherence (perceived medicine importance, habit/routine, support, health benefits, technology/medicine dose form, timetabling). Nebulised therapy for cystic fibrosis patients takes a substantial amount of time, with patients trying to alter their routine to incorporate nebulising into their daily lives. However there are still many factors that lead to low adherence, including work/social demands and travelling. Patients balance the necessity for nebulised therapy against the barriers, and engage in intentional non-adherence at times. Future strategies and resources should target and address specific factors identified by patients with CF as being important and impacting their adherence to nebulised

  19. Pulmonary function impairment in patients with combined pulmonary fibrosis and emphysema with and without airflow obstruction

    Directory of Open Access Journals (Sweden)

    Kitaguchi Y

    2014-07-01

    Full Text Available Yoshiaki Kitaguchi,1,2 Keisaku Fujimoto,3 Masayuki Hanaoka,1 Takayuki Honda,4 Junichi Hotta,2 Jiro Hirayama2 1First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, 2Department of Internal Medicine, Okaya City Hospital, Okaya, 3Department of Clinical Laboratory Sciences, 4Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan Background: The syndrome of combined pulmonary fibrosis and emphysema (CPFE is a recently described entity associating upper-lobe emphysema and lower-lobe fibrosis. We sought to evaluate differences in pulmonary function between CPFE patients with and without airflow obstruction. Subjects and methods: Thirty-one CPFE patients were divided into two groups according to the presence or absence of irreversible airflow obstruction based on spirometry (forced expiratory volume in 1 second/forced vital capacity <70% following inhalation of a β2-agonist as follows: CPFE patients with airflow obstruction (CPFE OB+ group, n=11, and CPFE patients without airflow obstruction (CPFE OB– group, n=20. Pulmonary function, including respiratory impedance evaluated using impulse oscillometry and dynamic hyperinflation following metronome-paced incremental hyperventilation, was retrospectively analyzed in comparison with that observed in 49 chronic obstructive pulmonary disease (COPD patients (n=49. Results: In imaging findings, low-attenuation-area scores on chest high-resolution computed tomography, representing the degree of emphysema, were significantly lower in the CPFE OB– group than in the CPFE OB+ and COPD groups. In contrast, the severity of pulmonary fibrosis was greater in the CPFE OB– group than in the CPFE OB+ group. In pulmonary function, lung hyperinflation was not apparent in the CPFE OB– group. Impairment of diffusion capacity was severe in both the CPFE OB– and CPFE OB+ groups. Impulse oscillometry showed that respiratory resistance was not

  20. Evaluation of respiratory dynamics by volumetric capnography during submaximal exercise protocol of six minutes on treadmill in cystic fibrosis patients.

    Science.gov (United States)

    Parazzi, Paloma L F; Marson, Fernando A L; Ribeiro, Maria A G O; Schivinski, Camila I S; Ribeiro, José D

    2017-11-29

    Volumetric capnography provides the standard CO 2 elimination by the volume expired per respiratory cycle and is a measure to assess pulmonary involvement. Thus, the objective of this study was to evaluate the respiratory dynamics of healthy control subjects and those with cystic fibrosis in a submaximal exercise protocol for six minutes on the treadmill, using volumetric capnography parameters (slope 3 [Slp3], Slp3/tidal volume [Slp3/TV], and slope 2 [Slp2]). This was a cross-sectional study with 128 subjects (cystic fibrosis, 64 subjects; controls, 64 subjects]. Participants underwent volumetric capnography before, during, and after six minutes on the treadmill. Statistical analysis was performed using the Friedman, Mann-Whitney, and Kruskal-Wallis tests, considering age and sex. An alpha=0.05 was considered. Six minutes on the treadmill evaluation: in cystic fibrosis, volumetric capnography parameters were different before, during, and after six minutes on the treadmill; the same was observed for the controls, except for Slp2. Regarding age, an Slp3 difference was observed in cystic fibrosis patients regardless of age, at all moments, and in controls for age≥12 years; a difference in Slp3/TV was observed in cystic fibrosis and controls, regardless of age; and an Slp2 difference in the cystic fibrosis, regardless of age. Regarding sex, Slp3 and Slp3/TV differences were observed in cystic fibrosis regardless of sex, and in controls in male participants; an Slp2 difference was observed in the cystic fibrosis and female participants. The analysis between groups (cystic fibrosis and controls) indicated that Slp3 and Slp3/TV has identified the CF, regardless of age and sex, while the Slp2 showed the CF considering age. Cystic fibrosis showed greater values of the parameters before, during, and after exercise, even when stratified by age and sex, which may indicate ventilation inhomogeneity in the peripheral pathways in the cystic fibrosis. Copyright © 2017

  1. Analysis of cystic fibrosis gener product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis.

    Science.gov (United States)

    Gelrud, Andres; Sheth, Sunil; Banerjee, Subhas; Weed, Deborah; Shea, Julie; Chuttani, Ram; Howell, Douglas A; Telford, Jennifer J; Carr-Locke, David L; Regan, Meredith M; Ellis, Lynda; Durie, Peter R; Freedman, Steven D

    2004-08-01

    The mechanism by which pancreas divisum may lead to recurrent episodes of acute pancreatitis in a subset of individuals is unknown. Abnormalities of the cystic fibrosis gene product (CFTR) have been implicated in the genesis of idiopathic chronic pancreatitis. The aim of this study was to determine if CFTR function is abnormal in patients with pancreas divisum and recurrent acute pancreatitis (PD/RAP). A total of 69 healthy control subjects, 12 patients with PD/RAP, 16 obligate heterozygotes with a single CFTR mutation, and 95 patients with cystic fibrosis were enrolled. CFTR function was analyzed by nasal transepithelial potential difference testing in vivo. The outcomes of the PD/RAP patients following endoscopic and surgical treatments were concomitantly analyzed. Direct measurement of CFTR function in nasal epithelium in response to isoproterenol demonstrated that the values for PD/RAP were intermediate between those observed for healthy controls and cystic fibrosis patients. The median value was 13 mV for PD/RAP subjects, which was statistically different from healthy controls (22 mV, p= 0.001) and cystic fibrosis pancreatic sufficient (-1 mV, p < 0.0001) and pancreatic insufficient (-3 mV, p < 0.0001) patients. These results suggest a link between CFTR dysfunction and recurrent acute pancreatitis in patients with pancreas divisum and may explain why a subset of patients with pancreas divisum develops recurrent acute pancreatitis. Copyright 2004 American College of Gastroenterology

  2. Nebulized hypertonic saline via positive expiratory pressure versus via jet nebulizer in patients with severe cystic fibrosis.

    LENUS (Irish Health Repository)

    O'Connell, Oisin J

    2011-06-01

    Nebulized hypertonic saline is a highly effective therapy for patients with cystic fibrosis (CF), yet 10% of patients are intolerant of hypertonic saline administered via jet nebulizer. Positive expiratory pressure (PEP) nebulizers splint open the airways and offers a more controlled rate of nebulization.

  3. Clinical Predictors of Liver Fibrosis in Patients With Chronic Hepatitis B Virus Infection From Children to Adults.

    Science.gov (United States)

    Wu, Jia-Feng; Song, Shih-Hsi; Lee, Chee-Seng; Chen, Huey-Ling; Ni, Yen-Hsuan; Hsu, Hong-Yuan; Wu, Tzee-Chung; Chang, Mei-Hwei

    2018-04-11

    This study aimed to elucidate predictors of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection. Transient elastography was performed to define liver stiffness in 533 patients with chronic HBV infection (mean age ± standard deviation, 30.72 ± 0.57 years). Protein array was performed on serum samples and lysates of Huh7 cells transfected with HBV mutants; the results were confirmed by enzyme-linked immunosorbent assay. Single-nucleotide polymorphisms in the gene encoding interleukin 1β (IL-1β) were examined in patients with chronic HBV infection with and without liver fibrosis. Male sex, age ≥18 years, and serum α-fetoprotein level >3.6 ng/mL were independent predictors of a liver stiffness measurement of ≥7 kPa (P = .005, .019, and rs16944 and the CC genotype at rs1143627 in the gene encoding IL-1β were associated with higher serum IL-1β levels and liver fibrosis. Male sex, age ≥18 years, elevated α-fetoprotein level, and HBeAg-negative hepatitis are risk factors for liver fibrosis. IL-1β is involved in the progression of liver fibrosis in subjects with HBeAg-negative hepatitis.

  4. Evaluation of Teriparatide for Treatment of Osteoporosis in Four Patients with Cystic Fibrosis: A Case Series

    Directory of Open Access Journals (Sweden)

    Oranan Siwamogsatham

    2014-01-01

    Full Text Available Introduction. Bone disease is a common complication of cystic fibrosis (CF. To date, there have been no reports on the effectiveness of teriparatide, recombinant human parathyroid hormone, to treat CF-related bone disease. Case Presentation. We report on four patients with CF-related bone disease who were treated with teriparatide. Three patients completed two years of therapy with teriparatide, and all had significant improvements in their bone mineral density (BMD. One patient was unable to tolerate teriparatide and discontinued treatment 1 week into therapy. Conclusion. Teriparatide may be a potential treatment option for CF-related bone disease. This report highlights the need for further investigation into the use of teripartide in the CF population.

  5. Lung transplantation for high-risk patients with idiopathic pulmonary fibrosis.

    Science.gov (United States)

    De Oliveira, Nilto C; Julliard, Walker; Osaki, Satoru; Maloney, James D; Cornwell, Richard D; Sonetti, David A; Meyer, Keith C

    2016-10-07

    Survival for patients with idiopathic pulmonary fibrosis (IPF) and high lung allocation score (LAS) values may be significantly reduced in comparison to those with lower LAS values. To evaluate outcomes for high-risk IPF patients as defined by LAS values ≥46 (N=42) versus recipients with LAS values pulmonary complications was increased for the higher LAS group versus recipients with LAS <46, 30-day mortality and actuarial survival did not differ between the two cohorts. Although lung transplantation in patients with IPF and high LAS values is associated with increased risk of early post-transplant complications, long-term post-transplant survival for our high-LAS cohort was equivalent to that for the lower LAS recipients.

  6. Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Kragh, Kasper Nørskov; Alhede, Morten; Jensen, Peter Østrup

    2014-01-01

    Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the in vivo growth physiology of P. aeruginosa within lungs...... of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF patients and the growth rates of P. aeruginosa in infected lungs...... in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also...

  7. Chest computed tomography scores are predictive of survival in patients with cystic fibrosis awaiting lung transplantation

    DEFF Research Database (Denmark)

    Loeve, Martine; Hop, Wim C. J.; de Bruijne, Marleen

    2012-01-01

    Rationale: Up to a third of cystic fibrosis (CF) patients awaiting lung transplantation (LTX) die while waiting. Inclusion of computed tomography (CT) scores may improve survival prediction models such as the lung allocation score (LAS). Objectives: This study investigated the association between...... CT and survival in CF patients screened for LTX. Methods: Clinical data and chest CTs of 411 CF patients screened for LTX between 1990 and 2005 were collected from 17 centers. CTs were scored with the Severe Advanced Lung Disease (SALD) 4-category scoring system, including the components "infection....../inflammation" (INF), air trapping/hypoperfusion (AT), normal/hyperperfusion (NOR) and bulla/cysts (BUL). The volume of each component was computed using semi-automated software. Survival analysis included Kaplan-Meier curves, and Cox-regression models. Measurements and main results: 366 (186 males) out of 411...

  8. Prevalence and Profile of Fibrosis in Diabetic Patients with Non-alcoholic Fatty Liver Disease and the Associated Factors.

    Science.gov (United States)

    Prasetya, Ignatius Bima; Hasan, Irsan; Wisnu, Wismandari; Rumende, Cleopas Martin

    2017-04-01

    the risk of Non-Alcoholic Fatty Liver Disease (NAFLD) is increasing in patients with type-2 diabetes. Prevalence and factors related to the increased risk of NAFLD in diabetic patients in Indonesia has never been studied before. Data regarding the profile of fibrosis in the population has also been unknown. This study aimed to identify the difference on the profile of diabetic patients with and without NAFLD as well as the degree of fibrosis. the study was conducted using a cross-sectional method in type-2 diabetic patients who were treated at the outpatient clinic of endocrinology and metabolic division in Cipto Mangunkusumo Hospital. Sampling was done consecutively. Collected data comprised of age, duration of diabetes, body mass index (BMI), waist circumference, HDL, triglyceride, and HbA1C levels. Abdominal ultrasonography was conducted for all patients to determine the presence of NAFLD. Patients with NAFLD were subsequently underwent transient elastography in order to assess their degree of liver fibrosis. Chi-square or Fisher's-Exact tests were used for bivariate analysis and logistic regression was used for multivariate analysis. as many as 186 patients were analyzed in the study and 84 patients (45.2%) were demonstrated to have NAFLD. Transient elastography examinations were carried out in 68 patients and 17 patients (25.0%) were found with severe fibrosis. Univariate analysis showed significant differences on BMI (PR=1.878; 95%CI= 1.296-2.721; pdiabetic patients in Cipto Mangunkusumo Hospital has reached 45.2% and 25.0% among them had severe fibrosis. BMI is the only factor found to be associated with the occurrence of NAFLD.

  9. Arteriovenous fistula stenosis in hemodialysis patients is characterized by an increased adventitial fibrosis.

    Science.gov (United States)

    Simone, Simona; Loverre, Antonia; Cariello, Marica; Divella, Chiara; Castellano, Giuseppe; Gesualdo, Loreto; Pertosa, Giovanni; Grandaliano, Giuseppe

    2014-10-01

    Arteriovenous fistula (AVF) stenosis is the major cause of vascular access failure in hemodialysis. Adventitial remodeling has been suggested to play a role in the pathogenesis of AVF stenosis. This study aimed to evaluate adventitial fibrosis in stenotic AVF and investigate the underlying molecular mechanisms. Forty-four patients undergoing surgery for AVF creation were examined; ten presented AVF failure, with histological-proven AVF stenosis. In stenotic AVF we observed a significant increase of adventitia extracellular matrix deposition and alpha-smooth muscle actin (α-SMA)(+) cell numbers; most of these cells were myofibroblast (α-SMA(+)/vimentin(+)). Phosphorylated platelet-derived growth factor β receptor (p-PDGFRβ) was significantly increased within the adventitia of stenotic compared to native AVF, along with a marked increase in the phosphorylation of Akt and ERK, two key kinases in PDGFRβ signalling. Myofibroblasts were the main cell type associated with the activation of p-PDGFRβ. At the same time, we observed a significant adventitial vessels rarefaction in stenotic AVF, as demonstrated by a reduced CD34 expression. This event was associated with a marked reduction in the expression of KDR/fetal liver kinase-1, the main vascular endothelial growth factor receptor. The degree of adventitial fibrosis was directly correlated with the extent of adventitial α-SMA and inversely associated with adventitial CD34 expression. Finally, we observed an increase in CD34(+)/α-SMA(+) cells within the adventitia of failed AVF. This study suggests that AVF failure is associated with an increased adventitial fibrosis, myofibroblast activation and capillary rarefaction, potentially linked with endothelial-to-mesenchymal transition. In this scenario, our data suggest that PDGF may play a pathogenic role.

  10. Clinical impact of depression and anxiety in patients with idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Ye Jin Lee

    Full Text Available Although depression and anxiety represent significant yet treatable comorbidities in patients with idiopathic pulmonary fibrosis (IPF, their impact on the clinical course and prognosis of IPF remain unclear.We investigated the prevalence and clinical significance of depression and anxiety in patients with IPF.The present study included a prospective cohort comprising 112 Korean patients with IPF who had completed the Hospital Anxiety and Depression Scale (HADS questionnaire.Symptoms of depression and anxiety were present in 25.9% and 21.4% of patients with IPF, respectively (HADS scores ≥8. No significant differences in demographic data, age, sex, smoking status, Modified Medical Research Council Dyspnea Scale (MMRC scores, pulmonary function tests, or Gender-Age-Physiology Index for IPF were observed between patients with depression or anxiety and those without. However, in patients with anxiety, St. George's Respiratory Questionnaire (SGRQ scores were significantly higher than those of patients without anxiety (40.5 versus 23.5; p = 0.003. The survival rate and total number of hospital admissions did not significantly differ between patients with depression/anxiety and those without.Our findings indicate that depression and anxiety are relatively common in patients with IPF. Although no significant differences were noted with regard to survival rate and hospitalization, the present study suggests that depression and anxiety significantly influence quality of life in patients with IPF.

  11. Experience with perioperative pirfenidone for lung cancer surgery in patients with idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Iwata, Takekazu; Yoshida, Shigetoshi; Nagato, Kaoru; Nakajima, Takahiro; Suzuki, Hidemi; Tagawa, Tetsuzo; Mizobuchi, Teruaki; Ota, Satoshi; Nakatani, Yukio; Yoshino, Ichiro

    2015-10-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse lung disease associated with an increased risk of lung cancer. Patients with IPF sometimes develop a life-threatening acute exacerbation of IPF (AE-IPF) after lung cancer surgery. In this retrospective study, pirfenidone, an antifibrotic agent, was perioperatively administered to IPF patients with lung cancer with the aim of preventing postoperative AE-IPF, and the feasibility and clinical outcomes were investigated. Twelve IPF patients with concomitant lung cancer who received perioperative pirfenidone treatment (PPT) for lung cancer surgery were retrospectively investigated. Sixteen IPF patients undergoing lung cancer surgery without PPT were analyzed as historical controls. Compared to the controls, the PPT patients had a more severely impaired preoperative pulmonary function and a larger number of limited pulmonary resections. There was a significant preoperative decrease in the serum KL-6 levels of the PPT patients. No severe pirfenidone-related complications or IPF-related events occurred in the PPT patients, while six control patients developed AE-IPF (P = 0.0167). A quantitative histopathological evaluation of resected lung specimens found that tissue changes associated with IPF were significantly fewer in the PPT patients (P = 0.021). PPT is a feasible perioperative treatment for IPF patients with lung cancer. Its effectiveness in preventing postoperative AE-IPF thus warrants prospective verification.

  12. Predictive factors for the severity of liver fibrosis in patients with chronic hepatitis C and moderate alcohol consumption.

    Science.gov (United States)

    Vădan, Roxana; Gheorghe, Liana; Becheanu, Gabriel; Iacob, Răzvan; Iacob, Speranţa; Gheorghe, Cristian

    2003-09-01

    Among the histological lesions seen in chronic hepatitis C (CHC), the presence of steatosis, bile duct lesions and lymphoid aggregates are characteristic. Recent reports suggest that steatosis is an independent risk factor for liver fibrosis in CHC. The aim of our study was to determine the relative contribution of steatosis and moderate alcohol consumption to the severity of liver fibrosis in patients infected with genotype 1 hepatitis C virus. We evaluated the patients with biopsy proven CHC and no or only moderate alcohol intake (<40 g/day). The demographical parameters of the study population, the indices of alcohol consumption: erythrocyte median corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), the histological characteristics were noted and a statistical analysis was performed in order to determine the factors independently associated with severe fibrosis and with severe steatosis. From the 200 patients included in the study, 82 were males and 118 females, with a mean age of 47.75+/-10.42 years. At univariate analysis, advanced (grade 2, 3) fibrosis correlated with: the age at the time of biopsy, increased inflammatory activity (HAI), moderate/severe steatosis, alcohol intake, elevated GGT and MCV values. After multivariate logistic regression only age, HAI and steatosis were independently associated with advanced fibrosis stage. Regarding hepatic steatosis, from the factors found to correlate with severe steatosis at univariate analysis (alcohol intake, elevated GGT and MCV levels, severe fibrosis), after multivariate logistic regression only the elevated level of GGT was an independent prognostic factor for severe steatosis. Steatosis is an important risk factor for the severity of liver disease in CHC patients. Among patients with genotype 1 hepatitis C virus infection and moderate alcohol intake, those with serum levels of GGT over two times the normal value are at high risk for severe steatosis.

  13. Value of five noninvasive diagnostic techniques and their combinations in diagnosis of liver fibrosis in patients with chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    ZHANG Xu

    2016-10-01

    Full Text Available Objective To investigate the correlation of aspartate aminotransferase to platelet ratio index (APRI, FIB-4, Forns index, S index, and FibroScan with the degree of liver fibrosis, the diagnostic value of these techniques used alone or in combination, and the clinical value of these noninvasive techniques in the assessment of the degree of liver fibrosis in patients with chronic hepatitis B (CHB. Methods A retrospective analysis was performed for the clinical data of 91 patients with pathologically confirmed CHB who visited General Hospital of Ningxia Medical University and underwent liver biopsy from January 2009 to April 2015. According to the Scheuer pathological stage and liver fibrosis stage (S, the patients were divided into non-liver fibrosis group (a liver fibrosis stage of S0, 32 patients, mild liver fibrosis group (a liver fibrosis stage of <S2, 30 patients, and marked liver fibrosis group (a liver fibrosis stage of ≥S2, 29 patients. The APRI, FIB-4, Forns index, and S index were calculated, and liver stiffness was measured by FibroScan. An analysis of variance was used for the comparison of normally distributed continuous data between three groups, and the Dunnett t-test was used for further comparison between any two groups. The Spearman correlation analysis was also performed. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC were used to evaluate the value of these noninvasive techniques in the diagnosis of liver fibrosis. Results There were significant differences in age, albumin, aspartate aminotransferase, alanine aminotransferase, and platelet count between the three groups (F=3.552, 4.035, 4.374, and 5.992, all P<0.05, and there were significant differences in these parameters between the non-liver fibrosis group and the mild and marked liver fibrosis groups (P<0.05. There were significant differences in APRI, FIB-4, Forns index, S index, and FibroScan between the three groups (F

  14. Web-based symptom screening in cystic fibrosis patients: A feasibility study.

    Science.gov (United States)

    Balzano, Julie; Fresenius, Ashley; Walker, Patricia; Berdella, Maria; Portenoy, Russell K; Bookbinder, Marilyn; Glajchen, Myra; Plachta, Amy; Langfelder-Schwind, Elinor; Chen, Jack; Dhingra, Lara

    2016-01-01

    Cystic fibrosis (CF) causes high illness burden. Screening may identify patients who could potentially benefit from interventions for symptoms or other sources of distress. We evaluated the feasibility of a web-based system for routine monitoring. Adult CF patients enrolled in a study of palliative care service delivery completed web-based assessments every 30 days on global distress, physical and psychological symptom distress, and the perceived benefits of discussing advance care planning (ACP) with CF clinicians. Feasibility was assessed by the rate of survey completion, survey reminders, and missed surveys during a 9-month rolling enrollment period. Of 74 participants (47.3% women, 94.4% white), 36.7% had comorbid diabetes, and 56.9% had an FEV1% predicted score of 40-69. In total, patients completed 456 (80.6%) of 566 surveys every 30 days over the assessment period. Sixty-five (87.8%) completed 405 (79.7%) of 508 surveys online and 9 (12.2%) completed 51 (88.0%) of 58 surveys using a combination of online, telephone, and mail-based methods. Many surveys were completed without reminders (online: 261 [64.4%] of 405; combined methods: 29 [56.9%] of 51), with 166 (36.4%) surveys requiring 1 or more reminders. Further, 23.0% (17) of patients noted elevated global distress; 20.3% (15) endorsed physical symptom distress, 12.2% (9) had psychological distress, and 58.1% (43) reported that discussing ACP would be beneficial. Repeated web-based screening for symptom distress and ACP preferences is feasible in adult CF patients. Future studies should assess the system's generalizability and staff resources when implementing reminders and non-web methods of completion. Copyright © 2015 European Cystic Fibrosis Society. All rights reserved.

  15. Assessment of Correlation between Sweat Chloride Levels and Clinical Features of Cystic Fibrosis Patients.

    Science.gov (United States)

    Raina, Manzoor A; Khan, Mosin S; Malik, Showkat A; Raina, Ab Hameed; Makhdoomi, Mudassir J; Bhat, Javed I; Mudassar, Syed

    2016-12-01

    Cystic Fibrosis (CF) is an autosomal recessive disorder and the incidence of this disease is undermined in Northern India. The distinguishable salty character of the sweat belonging to individuals suffering from CF makes sweat chloride estimation essential for diagnosis of CF disease. The aim of this prospective study was to elucidate the relationship of sweat chloride levels with clinical features and pattern of CF. A total of 182 patients, with clinical features of CF were included in this study for quantitative measurement of sweat chloride. Sweat stimulation and collection involved pilocarpine iontophoresis based on the Gibson and Cooks methodology. The quantitative estimation of chloride was done by Schales and Schales method with some modifications. Cystic Fibrosis Trans Membrane Conductance Regulator (CFTR) mutation status was recorded in case of patients with borderline sweat chloride levels to correlate the results and for follow-up. Out of 182 patients having clinical features consistent with CF, borderline and elevated sweat chloride levels were present in 9 (5%) and 41 (22.5%) subjects respectively. Elevated sweat chloride levels were significantly associated with wheeze, Failure To Thrive (FTT), history of CF in Siblings, product of Consanguineous Marriage (CM), digital clubbing and steatorrhoea on univariate analysis. On multivariate analysis only wheeze, FTT and steatorrhoea were found to be significantly associated with elevated sweat chloride levels (p<0.05). Among the nine borderline cases six cases were positive for at least two CFTR mutations and rest of the three cases were not having any mutation in CFTR gene. The diagnosis is often delayed and the disease is advanced in most patients at the time of diagnosis. Sweat testing is a gold standard for diagnosis of CF patients as genetic mutation profile being heterozygous and unlikely to become diagnostic test.

  16. Evaluation of Medication-related Self-care Skills in Patients With Cystic Fibrosis.

    Science.gov (United States)

    Lewis, Kelsey Lackey; John, Barnabas; Condren, Michelle; Carter, Sandra M

    2016-01-01

    BACKGROUND: As the life expectancy of patients with cystic fibrosis (CF) increases, the focus on ensuring success with medication therapies is increasingly important. The ability of patients to autonomously manage medications and related therapies is poorly described in the literature. OBJECTIVE: The goal of this project was to assess the level of medication-related knowledge and self-care skills in patients with CF. METHODS: This project took place in a Cystic Fibrosis Foundation accredited affiliate center. Eighty-nine patients between the ages of 6 and 60 were eligible to participate based on inclusion and exclusion criteria. Pharmacists administered a 16-item questionnaire and detailed medication history during clinic visits from January through May 2014. RESULTS: Forty-five patients 6 to 41 years old participated in the study. The skills most often performed independently were preparing nebulizer treatments (85%) and telling someone if they feel their medicines are causing a problem (89%). Skills least often performed were carrying a medication list (82%) and bringing a medication list to appointments (76%). In respondents 21 years of age and older, less than 75% of respondents were involved with obtaining financial resources, maintaining equipment, carrying a medication list, or rinsing their mouth after using inhaled medicines. Participants were able to provide drug name, dose, and frequency of use for pancreatic enzymes and azithromycin 37% and 24% of the time, respectively. CONCLUSIONS: In the population surveyed, many medication-related skills had not been acquired by early adulthood. Assessing and providing education for medication-related self-care skills at all ages are needed.

  17. Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients

    DEFF Research Database (Denmark)

    Bracht, Thilo; Mölleken, Christian; Ahrens, Maike

    2016-01-01

    in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without......). CONCLUSIONS: We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic...... fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals....

  18. Molecular profiling of early stage liver fibrosis in patients with chronic hepatitis C virus infection

    International Nuclear Information System (INIS)

    Bieche, Ivan; Asselah, Tarik; Laurendeau, Ingrid; Vidaud, Dominique; Degot, Claude; Paradis, Valerie; Bedossa, Pierre; Valla, Dominique-Charles; Marcellin, Patrick; Vidaud, Michel

    2005-01-01

    The molecular mechanisms of acute hepatitis C virus (HCV) infection, end-stage hepatitis (cirrhosis), and hepatocellular carcinoma have been extensively studied, but little is known of the changes in liver gene expression during the early stages of liver fibrosis associated with chronic HCV infection, that is, the transition from normal liver (NL) of uninfected patients to the first stage of liver fibrosis (F1-CH-C). To obtain insight into the molecular pathogenesis of F1-CH-C, we used real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to study the mRNA expression of 240 selected genes in liver tissue with F1-CH-C, in comparison with NL. The expression of 54 (22.5%) of the 240 genes was significantly different between F1-CH-C and NL; 46 genes were upregulated and 8 were downregulated in F1-CH-C. The most noteworthy changes in gene expression mainly affected the transcriptional network regulated by interferons (IFNs), including both IFN-α/β-inducible genes (STAT1, STAT2, ISGF3G/IRF9, IFI27, G1P3, G1P2, OAS2, MX1) and IFN-γ-inducible genes (CXCL9, CXCL10, CXCL11). Interesting, upregulation of IFN-α/β-inducible genes (but not IFN-γ-inducible genes) was independent of histological scores (grade and stage of fibrosis) and HCV characteristics (hepatic HCV mRNA levels and the HCV genotype), and was specific to HCV (as compared to hepatitis B virus (HBV)). Other genes dysregulated in F1-CH-C, albeit less markedly than IFN-α/β- and IFN-γ-inducible genes, were mainly involved in the activation of lymphocytes infiltrating the liver (IFNG, TNF, CXCL6, IL6, CCL8, CXCR3, CXCR4, CCR2), cell proliferation (p16/CDKN2A, MKI67, p14/ARF), extracellular matrix remodeling (MMP9, ITGA2), lymphangiogenesis (XLKD1/LYVE), oxidative stress (CYP2E1), and cytoskeleton microtubule organization (STMN2/SCG10). Thus, a limited number of signaling pathways, and particularly the transcriptional network regulated by interferons, are dysregulated in the first

  19. The relation between bevacizumab injection and the formation of subretinal fibrosis in diabetic patients with panretinal photocoagulation.

    Science.gov (United States)

    Batman, Cosar; Ozdamar, Yasemin

    2010-01-01

    To report the development of subretinal fibrosis after the injection of intravitreal bevacizumab in eyes with proliferative diabetic retinopathy (PDR) refractory to panretinal laser photocoagulation (PRP). Twenty-one eyes of 15 patients treated with PRP and intravitreal injection of bevacizumab were included in this study. The clinical outcomes of 21 eyes having subretinal fibrosis after intravitreal bevacizumab injection were reviewed. There were 9 men and 6 women with a mean age of 51.3 +/- 8.9 years. All eyes had PDR refractory to panretinal photocoagulation and were treated with at least one intravitreal injection of 1.25 mg of bevacizumab (mean number of injections: 1.8). Before injection, there was subretinal fibrosis in 5 eyes and vitreoretinal traction in 19 eyes. After a mean follow-up period of 7 months, the development or progression of subretinal fibrosis was detected in all eyes. Intravitreal injection of bevacizumab may cause formation or progression of subretinal fibrosis in patients with PDR refractory to PRP. Copyright 2010, SLACK Incorporated.

  20. Prediction of liver-related events using fibroscan in chronic hepatitis B patients showing advanced liver fibrosis.

    Directory of Open Access Journals (Sweden)

    Seung Up Kim

    Full Text Available Liver stiffness measurement (LSM using transient elastography (FibroScan® can assess liver fibrosis noninvasively. This study investigated whether LSM can predict the development of liver-related events (LREs in chronic hepatitis B (CHB patients showing histologically advanced liver fibrosis.Between March 2006 and April 2010, 128 CHB patients with who underwent LSM and liver biopsy (LB before starting nucleot(side analogues and showed histologically advanced fibrosis (≥F3 with a high viral loads [HBV DNA ≥2,000 IU/mL] were enrolled. All patients were followed regularly to detect LRE development, including hepatic decompensation (variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome and hepatocellular carcinoma (HCC.The mean age of the patient (72 men, 56 women was 52.2 years. During the median follow-up period [median 27.8 (12.6-61.6 months], LREs developed in 19 (14.8% patients (five with hepatic decompensation, 13 with HCC, one with both. Together with age, multivariate analysis identified LSM as an independent predictor of LRE development [P19 kPa were at significantly greater risk than those with LSM≤19 kPa for LRE development (HR, 7.176; 95% CI, 2.257-22.812; P = 0.001.LSM can be a useful predictor of LRE development in CHB patients showing histologically advanced liver fibrosis.

  1. Respiratory infections by Achromobacter xylosoxidans in a cohort of Cystic Fibrosis patients: identification, antimicrobial susceptibility and molecular epidemiology

    Directory of Open Access Journals (Sweden)

    Antonietta Lambiase

    2010-03-01

    Full Text Available Pulmonary infections by Gram-negative bacteria such as Achromobacter xylosoxidans are recovered frequently in patients with Cystic Fibrosis. Aims of this study were to value the isolation frequency of A.xylosoxidans strains in a cohort of Cystic Fibrosis patients, to investigate their antimicrobial sensitivity and to establish possible clonal likeness among strains.A retrospective study was undertaken between January 2004 and December 2008 on 300 patients receiving care at the Regional Cystic Fibrosis Centre of “Federico II” University, Naples. Sputum samples were collected and selective media as well as commercial systems for bacterial identification were used. The activity of antimicrobial agents was determined using diffusion and micro-dilution methods. For DNA-fingerprinting, a genomic DNA macrorestriction followed by pulsed-field gel electrophoresis was carried out. A total of 238 strains from 51 patients were isolated. Strains were resistant to aztreonam, about half of these were resistant to gentamicin and trimethoprim-sulphamethoxazole. They were sensitive to piperacillin, piperacillin/tazobactam, and also to carbapenems, quinolones, cephalosporines. Macrorestriction analysis applied on some isolates showed substantial heterogeneity among strains.Actually, the prognostic role of A. xylosoxidans in Cystic Fibrosis is unclear, but this finding must imply difficulties on therapeutic approach. So, it is need to be on the look out regard such microorganisms. Preliminary results of DNA-fingerprinting indicate no evidence of clonal likeness and then of patient-to-patient spread.

  2. Caracterización epidemiológica de pacientes pediátricos con fibrosis quística Epidemiological characterization of pediatric patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Félix O. Dickinson

    2005-06-01

    Full Text Available La fibrosis quística constituye un importante problema pediátrico por la elevada y prematura mortalidad que lo caracteriza, la deficiente calidad de vida que genera en los enfermos y la ausencia de un tratamiento curativo. Métodos: Se describieron algunas características de 15 pacientes con fibrosis quística ingresados en el Hospital Pediátrico “William Soler” entre 1998 y 2002. Se calcularon porcentajes según grupos de edad, sexo, síntomas y signos más frecuentes, motivo de ingreso, estadía hospitalaria, antibióticos aplicados, y otros. Resultados: No hubo fallecidos durante el período estudiado, predominaron las edades pediátricas (86,6 %, el sexo masculino (67 % y el color de la piel blanco (80 %. Los síntomas más frecuentes fueron las infecciones respiratorias (67 %, el bajo peso corporal (48 % y los trastornos digestivos (25 %, los cuales comenzaron como promedio a los 20,6 meses de edad. La caracterización genética fue mayormente delta F 508 (66 %. Entre las causas de los ingresos se encontraron, fundamentalmente, recibir antibiótico-terapia (45 %, para tratamiento por infecciones respiratorias bajas (22 % y por fibrosis quística (15 %. Hubo un total de 72 ingresos y se acumularon 1 088 días de estadía hospitalaria, con un promedio de 15 días. En casi todos los casos se aplicó antibiótico-terapia debido a los aislamientos de Psedomona aeruginosa como causa de infección respiratoria. Se utilizaron 11 antibióticos diferentes, de los cuales los más frecuentes fueron amikacina, ceftazidima, gentamicina, tobramicina y ciprofloxacina. La combinación más frecuente, pero no la única, fue la de un beta-lactámico y un aminoglucósidoCystic fibrosis is an important pediatric problem due to its high and premature mortality, to the deficient quality of life it generates in the patients and to the absence of a curative treatment. Methods: some characteristics of 15 patients with cystic fibrosis admitted in

  3. Retroperitoneal Fibrosis: A Retrospective Clinical Data Analysis of 30 Patients in a 10-year Period

    Directory of Open Access Journals (Sweden)

    Hai-Jiang Zhou

    2015-01-01

    Full Text Available Background: Retroperitoneal fibrosis (RPF is an uncommon disease that is characterized by development of fibrosclerotic tissues involving retroperitoneal structures. This study aimed to investigate the clinical features of 30 patients with RPF in a single center in Beijing in a 10-year period. Methods: We retrospectively analyzed clinical data on demographic characteristics, clinical manifestations, laboratory findings, radiological findings, modalities of treatments, outcomes and prognosis of 30 patients with RPF. Patients were treated in Beijing Chao-Yang Hospital between January 2003 and December 2013. Results: The mean age of patients with RPF was 56.7 ± 14.4 years. Twenty-three patients were men and seven patients were women. Acute phase reactants were elevated in most patients. Rheumatic factor was positive in 4/25 (16.0% patients, and antinuclear antibody was positive in 6/22 (27.3% patients. Elevation of IgG4 was observed in 9/22 (40.9% patients. The most common type was I + III (n = 13, followed by I + II + III (n = 12. Five patients undertook an 18 F-fluoro-deoxy-D-glucose positron emission tomography examination and increased uptake was detected in four patients. Eight patients received combination therapy with glucocorticoids and tamoxifen. Surgical intervention treatments included intraureteral double-J stent implantation (n = 26, percutaneous nephrostomy (n = 2, open ureterolysis and intraperitonealization of the ureters (n = 5 and laparoscopic ureterolysis and intraperitonealization of the ureters (n = 5. Three patients underwent hemodialysis because of renal failure. Conclusions: Clinical characteristics of RPF patients in our study are similar to those previously reported. Steroids and immunosuppressive therapy combined with ureterolysis could be a viable choice of treatment for RPF. More prospective, multi-center studies with a longer follow-up are warranted.

  4. [Nocardia farcinica lung infection in a patient with cystic fibrosis and a lung transplant].

    Science.gov (United States)

    Chacón, C F; Vicente, R; Ramos, F; Porta, J; Lopez Maldonado, A; Ansotegui, E

    2015-03-01

    Patients with cystic fibrosis have a higher risk of developing chronic respiratory infectious diseases. The Nocardia farcinica lung infection is rare in this group of patients, and there are limited publications about this topic. Its diagnosis is complex, due to the clinical and the radiology signs being non-specific. Identification of the agent responsible in the sputum culture is occasionally negative. It is a slow growing organism and for this reason treatment is delayed, which can lead to an increase in complications, hospitable stays, and mortality. A case is reported on a 26 year-old woman with cystic fibrosis and chronic lung colonization by Nocardia farcinica and Aspergillus fumigatus, on long-term treatment with ciprofloxacin, trimethoprim-sulfamethoxazole, and posaconazole, who was admitted to ICU after bilateral lung transplantation. The initial post-operative progress was satisfactory. After discharge, the patient showed a gradual respiratory insufficiency with new chest X-ray showing diffuse infiltrates. Initially, the agent was not seen in the sputum culture. Prompt and aggressive measures were taken, due to the high clinical suspicion of a Nocardia farcinica lung infection. Treatment with a combination of amikacin and meropenem, and later combined with linezolid, led to the disappearance of the lung infiltrates and a clinical improvement. In our case, we confirm the rapid introduction of Nocardia farcinica in the new lungs. The complex identification and the delay in treatment increased the morbimortality. There is a special need for its eradication in patients with lung transplant, due to the strong immunosuppressive treatment. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Breathing pattern and chest wall volumes during exercise in patients with cystic fibrosis, pulmonary fibrosis and COPD before and after lung transplantation.

    Science.gov (United States)

    Wilkens, H; Weingard, B; Lo Mauro, A; Schena, E; Pedotti, A; Sybrecht, G W; Aliverti, A

    2010-09-01

    Pulmonary fibrosis (PF), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often cause chronic respiratory failure (CRF). In order to investigate if there are different patterns of adaptation of the ventilatory pump in CRF, in three groups of lung transplant candidates with PF (n=9, forced expiratory volume in 1 s (FEV(1))=37+/-3% predicted, forced vital capacity (FVC)=32+/-2% predicted), CF (n=9, FEV(1)=22+/-3% predicted, FVC=30+/-3% predicted) and COPD (n=21, FEV(1)=21+/-1% predicted, FVC=46+/-2% predicted), 10 healthy controls and 16 transplanted patients, total and compartmental chest wall volumes were measured by opto-electronic plethysmography during rest and exercise. Three different breathing patterns were found during CRF in PF, CF and COPD. Patients with COPD were characterised by a reduced duty cycle at rest and maximal exercise (34+/-1%, pvolume (0.75+/-0.10 and 0.79+/-0.07 litres) (pvolumes increased significantly in patients with COPD and CF but not in those with PF. End-inspiratory volumes did not increase in CF and PF. The breathing pattern of transplanted patients was similar to that of healthy controls. There are three distinct patterns of CRF in patients with PF, CF and COPD adopted by the ventilatory pump to cope with the underlying lung disease that may explain why patients with PF and CF are prone to respiratory failure earlier than patients with COPD. After lung transplantation the chronic adaptations of the ventilatory pattern to advanced lung diseases are reversible and indicate that the main contributing factor is the lung itself rather than systemic effects of the disease.

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

    Directory of Open Access Journals (Sweden)

    M. P. M. Graham-Brown

    2017-01-01

    Full Text Available 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.

  7. Lung Ultrasonography in Patients With Idiopathic Pulmonary Fibrosis: Evaluation of a Simplified Protocol With High-Resolution Computed Tomographic Correlation.

    Science.gov (United States)

    Vassalou, Evangelia E; Raissaki, Maria; Magkanas, Eleftherios; Antoniou, Katerina M; Karantanas, Apostolos H

    2018-03-01

    To compare a simplified ultrasonographic (US) protocol in 2 patient positions with the same-positioned comprehensive US assessments and high-resolution computed tomographic (CT) findings in patients with idiopathic pulmonary fibrosis. Twenty-five consecutive patients with idiopathic pulmonary fibrosis were prospectively enrolled and examined in 2 sessions. During session 1, patients were examined with a US protocol including 56 lung intercostal spaces in supine/sitting (supine/sitting comprehensive protocol) and lateral decubitus (decubitus comprehensive protocol) positions. During session 2, patients were evaluated with a 16-intercostal space US protocol in sitting (sitting simplified protocol) and left/right decubitus (decubitus simplified protocol) positions. The 16 intercostal spaces were chosen according to the prevalence of idiopathic pulmonary fibrosis-related changes on high-resolution CT. The sum of B-lines counted in each intercostal space formed the US scores for all 4 US protocols: supine/sitting and decubitus comprehensive US scores and sitting and decubitus simplified US scores. High-resolution CT-related Warrick scores (J Rheumatol 1991; 18:1520-1528) were compared to US scores. The duration of each protocol was recorded. A significant correlation was found between all US scores and Warrick scores and between simplified and corresponding comprehensive scores (P idiopathic pulmonary fibrosis. The 16-intercostal space simplified protocol in the lateral decubitus position correlated better with high-resolution CT findings and was less time-consuming compared to the sitting position. © 2017 by the American Institute of Ultrasound in Medicine.

  8. NIKEI: a new inexpensive and non-invasive scoring system to exclude advanced fibrosis in patients with NAFLD.

    Directory of Open Access Journals (Sweden)

    Münevver Demir

    Full Text Available AIMS: To develop, validate and compare a non-invasive fibrosis scoring system for non-alcoholic fatty liver disease (NAFLD derived from routinely obtained clinical and biochemical parameters. METHODS: 267 consecutive patients with biopsy proven fatty liver or non-alcoholic steatohepatitis were randomly assigned to the estimation (2/3 or validation (1/3 group to develop a model for the prediction of advanced fibrosis. Univariate statistics were performed to compare patients with and without advanced fibrosis, and following a multivariate logistic regression analysis a new scoring system was constructed. This non-invasive Koeln-Essen-index (NIKEI was validated and compared to the FIB-4 index by calculating the area under the receiver operating characteristic curve (AUC. We evaluated a stepwise combination of both scoring systems for the precise prediction of advanced fibrosis. To set in contrast, we additionally tested the diagnostic accuracy of the AST/ALT ratio, BARD score and the NAFLD fibrosis score in our cohort. RESULTS: Age, AST, AST/ALT ratio, and total bilirubin were identified as significant predictors of advanced fibrosis and used to construct the NIKEI with an AUC of 0.968 [0.937; 0.998] compared to 0.929 [0.869; 0.989] for the FIB-4 index. The absence of advanced fibrosis could be confirmed with excellent accuracy (99-100%. The positive predictive value of the FIB-4 index was higher (100% vs. 60%, however, the false negative rate was also high (33%. With a stepwise combination of both indices 82%-84% of biopsies would have been avoidable without a single misclassification. The AUROC for AST/ALT ratio, the NAFLD fibrosis score, and the BARD score were 0.81 (95% CI, 0.72-0.90, 0.96 (95% CI 0.92-0.99, and 0.67 (95% CI 0.55-0.78, respectively. CONCLUSION: The NIKEI can reliably exclude advanced fibrosis in subjects with NAFLD. In combination with the FIB-4 index misclassification with inadequate clinical management can be avoided while

  9. Ten-Year Survival in Patients with Idiopathic Pulmonary Fibrosis After Lung Transplantation.

    Science.gov (United States)

    ten Klooster, Liesbeth; Nossent, George D; Kwakkel-van Erp, Johanna M; van Kessel, Diana A; Oudijk, Erik J; van de Graaf, Ed A; Luijk, Bart; Hoek, Rogier A; van den Blink, Bernt; van Hal, Peter Th; Verschuuren, Erik A; van der Bij, Wim; van Moorsel, Coline H; Grutters, Jan C

    2015-12-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrosing lung disease with a median survival of approximately 3 years after diagnosis. The only medical option to improve survival in IPF is lung transplantation (LTX). The purpose of this study was to evaluate trajectory data of IPF patients listed for LTX and to investigate the survival after LTX. Data were retrospectively collected from September 1989 until July 2011 of all IPF patients registered for LTX in the Netherlands. Patients were included after revision of the diagnosis based on the criteria set by the ATS/ERS/JRS/ALAT. Trajectory data, clinical data at time of screening, and donor data were collected. In total, 98 IPF patients were listed for LTX. During the waiting list period, 30 % of the patients died. Mean pulmonary artery pressure, 6-min walking distance, and the use of supplemental oxygen were significant predictors of mortality on the waiting list. Fifty-two patients received LTX with a median overall survival after transplantation of 10 years. This study demonstrated a 10-year survival time after LTX in IPF. Furthermore, our study demonstrated a significantly better survival after bilateral LTX in IPF compared to single LTX although bilateral LTX patients were significantly younger.

  10. in pediAtriC CystiC FiBrosis pAtients

    Directory of Open Access Journals (Sweden)

    Zuzanna Gorski

    2016-12-01

    Full Text Available Introduction. Cystic fibrosis (CF is an autosomal recessive disease affecting the epithelial lining of the respiratory tract andexocrine glands (1-5. many children suffering from CF are often diagnosed and treated for various co-morbidities, includingchronic rhinosinusitis (Crs and nasal polyposis (np (3, 4, 6, 7, which will remain the focus of this article.Aim. the aim of this study was to examine the characteristic of patients with cystic fibrosis (CF admitted to the pediatricotolaryngology department due to coexisting chronic rhinosinusitis (Crs or nasal polyposis (np. the study focused on thedemographics, symptoms and management of children with CF with coexisting Crs and/or np. the data was then compared tothe results that had been presented in the literature.Material and methods. A retrospective study of 26 pediatric patients previously diagnosed with CF that were admitted to thedepartment of pediatric otolaryngology of the medical University of Warsaw between 2010 and 2015 was conducted. patients’medical histories were carefully reviewed. data on patients’ age, gender, symptoms and CF comorbidities were collected. thenumber and type of procedures performed on each patient were documented. Further assessment of the localization of polypswas performed in all np-positive patients.Results. the study included 26 patients (15 males and 11 females. mean age was 9 years. Crs and np was present in 100% and88.5% of the patients, respectively. 23 children underwent a total of 35 sinus surgeries due to Crs and/or np. 6 patients requiredone or more revision surgeries, with a total revision rate of 54.1%. Adenoidectomy (At and/or adenotonsillectomy (Att wasperformed in 10 patients. 5 children were disqualified from the surgery, due to various reasons. the most common localizationof np was maxillary sinus, followed by ethmoid sinus, sphenoid sinus, frontal sinus, and nasal cavity.Conclusions. due to a wide range of clinical findings in many organs

  11. Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C.

    Science.gov (United States)

    Vergniol, Julien; Boursier, Jérôme; Coutzac, Clélia; Bertrais, Sandrine; Foucher, Juliette; Angel, Camille; Chermak, Faiza; Hubert, Isabelle Fouchard; Merrouche, Wassil; Oberti, Frédéric; de Lédinghen, Victor; Calès, Paul

    2014-07-01

    No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM 0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis. Three-year evolution of noninvasive tests of liver fibrosis has a strong prognostic value in CHC patients. These tests should be repeated to monitor patients and predict their outcome. © 2014 by the American Association for the Study of Liver Diseases.

  12. Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir.

    Science.gov (United States)

    Younossi, Zobair M; Stepanova, Maria; Afdhal, Nezam; Kowdley, Kris V; Zeuzem, Stefan; Henry, Linda; Hunt, Sharon L; Marcellin, Patrick

    2015-08-01

    New interferon-free anti-HCV regimens are highly efficacious with a favorable safety profile. We assessed health-related quality of life (HRQL) and work productivity in patients with different stages of hepatic fibrosis treated with sofosbuvir+ledipasvir. Four questionnaires [Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index:Specific Health Problem (WPAI:SHP)] were administered at baseline, during, and after treatment with sofosbuvir+ledipasvir+ribavirin or sofosbuvir+ledipasvir (ION-1,2,3 clinical trials). Metavir fibrosis stage was determined from pre-treatment liver biopsies. There were 1005 patients included (stage F0: n=94; F1: n=311; F2: n=301; F3: n=197; F4: n=102). At baseline, patients with more advanced fibrosis had more HRQL impairments, predominantly related to physical functioning (stage 0 vs. stage 4 by up to 0.126 on a normalized 0-1 scale p0.05 across fibrosis stages). In multivariate analysis, advanced fibrosis was independently associated with impairment of HRQL and work productivity (beta up to -0.056 in comparison with none-to-mild fibrosis, pwork productivity after viral clearance was not related to the stage of fibrosis (all p>0.05). Although advanced hepatic fibrosis is associated with HRQL and work productivity impairment, viral eradication with sofosbuvir+ledipasvir leads to HRQL improvement regardless of fibrosis stage. HCV patients with early fibrosis experience similar improvement of patient reported outcomes as those with advanced fibrosis. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  13. The effect of sinus surgery with intensive follow-up on pathogenic sinus bacteria in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Aanaes, Kasper; von Buchwald, Christian; Hjuler, Thomas

    2013-01-01

    Most patients with cystic fibrosis (CF) have chronic rhinosinusitis; their sinuses are often colonized with bacteria that can initiate and maintain deleterious pulmonary infections. Theoretically, eradication of the sinus bacteria should reduce the frequency of lung infections and thereby reduce...... pulmonary morbidity. This article addressed whether bacteria in CF sinuses are eligible for eradication by sinus surgery and postoperative treatment....

  14. Comparing the harmful effects of nontuberculous mycobacteria and Gram negative bacteria on lung function in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Qvist, Tavs; Taylor-Robinson, David; Waldmann, Elisabeth

    2015-01-01

    BACKGROUND: To better understand the relative effects of infection with nontuberculous mycobacteria and Gram negative bacteria on lung function decline in cystic fibrosis, we assessed the impact of each infection in a Danish setting. METHODS: Longitudinal registry study of 432 patients with cystic...

  15. Tubulointerstitial fibrosis in patients with IgG4-related kidney disease: pathological findings on repeat renal biopsy

    NARCIS (Netherlands)

    Arai, Haruna; Hayashi, Hiroki; Takahashi, Kazuo; Koide, Shigehisa; Sato, Waichi; Hasegawa, Midori; Yamaguchi, Yutaka; Aten, Jan; Ito, Yasuhiko; Yuzawa, Yukio

    2015-01-01

    Renal parenchymal lesions in patients with IgG4-related kidney disease (IgG4-RKD) are characterized by tubulointerstitial nephritis with storiform fibrosis and infiltration by high numbers of IgG4-positive plasma cells. The aim of this study was to evaluate the clinical and pathological effects of

  16. Clinical effects of sinus surgery and adjuvant therapy in cystic fibrosis patients - can chronic lung infections be postponed?

    DEFF Research Database (Denmark)

    Aanaes, K; Johansen, H K; Skov, M

    2013-01-01

    The paranasal sinuses can be a bacterial reservoir for pulmonary infections in patients with cystic fibrosis (CF) METHODOLOGY: In this prospective, non-randomised, uncontrolled, intervention cohort study, the clinical effect of sinus surgery followed by two weeks` intravenous antibiotics, 6 month...

  17. Unusual distribution of Burkholderia cepacia complex species in Danish cystic fibrosis clinics may stem from restricted transmission between patients

    DEFF Research Database (Denmark)

    Nørskov-Lauritsen, Niels; Johansen, Helle Krogh; Fenger, Mette G

    2010-01-01

    Forty-four of 48 Burkholderia cepacia complex strains cultured from Danish cystic fibrosis patients were Burkholderia multivorans, a distribution of species that has not been reported before. Although cases of cross infections were demonstrated, no major epidemic clone was found. The species...

  18. Dynamic in vivo mutations within the ica operon during persistence of Staphylococcus aureus in the airways of cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Bianca Schwartbeck

    2016-11-01

    Full Text Available Cystic fibrosis (CF is associated with chronic bacterial airway infections leading to lung insufficiency and decreased life expectancy. Staphylococcus aureus is one of the most prevalent pathogens isolated from the airways of CF patients. Mucoid colony morphology has been described for Pseudomonas aeruginosa, the most common pathogen in CF, but not for S. aureus. From the airways of 8 of 313 CF patients (2.5% mucoid S. aureus isolates (n = 115 were cultured with a mean persistence of 29 months (range 1 month, 126 months. In contrast to non-mucoid S. aureus, mucoid isolates were strong biofilm formers. The upstream region of the ica operon, which encodes the proteins responsible for the synthesis of the polysaccharide intercellular adhesin (PIA, of mucoid isolates was sequenced. Spa-types of mucoid and non-mucoid strains were identical, but differed between patients. Mucoid isolates carried a 5 bp deletion in the intergenic region between icaR and icaA. During long-term persistence, from two patients subsequent non-mucoid isolates (n = 12 with 5 bp deletions were cultured, which did not produce biofilm. Sequencing of the entire ica operon identified compensatory mutations in various ica-genes including icaA (n = 7, icaD (n = 3 and icaC (n = 2. Six sequential isolates of each of these two patients with non-mucoid and mucoid phenotypes were subjected to whole genome sequencing revealing a very close relationship of the individual patient's isolates. Transformation of strains with vectors expressing the respective wild-type genes restored mucoidy. In contrast to the non-mucoid phenotype, mucoid strains were protected against neutrophilic killing and survived better under starvation conditions. In conclusion, the special conditions present in CF airways seem to facilitate ongoing mutations in the ica operon during S. aureus persistence.

  19. The development of diabetes among Danish cystic fibrosis patients over the last two decades

    DEFF Research Database (Denmark)

    Knudsen, Karin B; Mathiesen, Elisabeth R; Eriksen, Vibeke

    2015-01-01

    OBJECTIVE: Cystic fibrosis (CF)-related diabetes (CFRD) is correlated with age and has been associated with a decline in body mass index (BMI), pulmonary function, and survival. Over the last two decades, the focus has been on the early diagnosis and treatment of diabetes; therefore, in this study...... of a birth cohort consisting of 161 CF patients born between 1975 and 1994 and followed until 2011. RESULTS: Over two decades, the incidence of CFRD among 11- to 16-year-old children remained unchanged at 12-14%, while the proportion of children with chronic pulmonary infection at age 10 declined from 31...... to 8% (p pulmonary function, BMI or survival was identified when comparing CFRD...

  20. Molecular typing of Burkholderia cepacia complex isolated from patients attending an Italian Cystic Fibrosis Centre.

    Science.gov (United States)

    Teri, Antonio; Sottotetti, Samantha; Biffi, Arianna; Girelli, Daniela; D'Accico, Monica; Arghittu, Milena; Colombo, Carla; Corti, Fabiola; Pizzamiglio, Giovanna; Cariani, Lisa

    2018-04-01

    Bacteria from the Burkholderia cepacia complex (Bcc) are capable of causing severe infections in patients with cystic fibrosis (CF). Bcc infection is often extremely difficult to treat due to its intrinsic resistance to multiple antibiotics. In addition, it seems to speed up the decline of lung function and is considered a contraindication for lung transplantation in CF. This study investigates the species of the Bcc strains recovered from chronically infected CF subjects by means of: isolation, identification methods and complete recA nucleotide sequences of 151 samples. Molecular typing showed that B. cenocepacia III is the dominant strain found in the group of subjects being treated at the Milan CF Centre (Italy) and that the infection is chronically maintained by the same species. Defining species by means of molecular analysis yields important information for the clinician in order to establish the most appropriate therapy and implement correct measures for prevention of transmission among CF subjects.

  1. Pancreatic changes in cystic fibrosis: CT and sonographic appearances

    International Nuclear Information System (INIS)

    Daneman, A.; Gaskin, K.; Martin, D.J.; Cutz, E.

    1983-01-01

    The computed tomographic (CT) and sonographic appearances of the late stages of pancreatic damage in three patients with cystic fibrosis are illustrated. All three had severe exocrine pancreatic insufficiency with steatorrhea. In two patients CT revealed complete fatty replacement of the entire pancreas. In the third, increased echogenicity of the pancreas on sonography and the inhomogeneous attenuation on CT were interpreted as being the result of a combination of fibrosis, fatty replacement, calcification, and probable cyst formation

  2. Change in fibrosis score as a predictor of mortality among HIV-infected patients with viral hepatitis.

    Science.gov (United States)

    Jain, Mamta K; Seremba, Emmanuel; Bhore, Rafia; Dao, Doan; Joshi, Reeti; Attar, Nahid; Yuan, He-Jun; Lee, William M

    2012-02-01

    Noninvasive markers of liver fibrosis, measured at baseline, have been shown to predict liver-related mortality. It remains unknown if a change in the value of the scores over time predicts mortality in patients with HIV and viral hepatitis. In this retrospective study, survival in HIV/hepatitis B virus (HBV; n = 67), HIV/hepatitis C virus (HCV; n = 43), and HIV/HBV/HCV (n = 41) patients was examined using Kaplan-Meier life table analysis. Aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and FIB-4 scores, two noninvasive markers of liver fibrosis, were calculated at baseline and at last available clinical follow-up to determine the change in fibrosis score. Factors associated with mortality were assessed by Cox proportional hazards, including the change in the noninvasive marker score between the two time points. All-cause mortality was determined by Social Security Death Index and chart review. Sixty-seven were coinfected with HIV/HBV, 43 with HIV/HCV, and 41 were triply infected (HIV/HBV/HCV). Kaplan-Meier analysis showed similar survival for the three groups at 7 years of follow-up (p = 0.10). However, median length of follow-up was lower in HIV/HCV (60.5; range 0-102) compared to HIV/HBV (75.7; 12.3-126.5) and HIV/HBV/HCV (80.0; 2.7-123) months, respectively, p = 0.02. Baseline fibrosis score (p = 0.002), an increase in the value for noninvasive measurements for fibrosis (p < 0.001), and the presence of HIV/HCV coinfection (p = 0.041) were each associated with higher risk for mortality. Baseline fibrosis score (p = 0.03) and an increase in FIB-4 score (p = 0.05) were independent predictors of all-cause mortality, but liver-related mortality was not evaluated. In this study, baseline fibrosis score was predictive of 7-year all-cause mortality. Further studies are needed in a prospective cohort to evaluate the predictive value of monitoring changes in fibrosis scores over time to predict mortality in patients with viral hepatitis.

  3. Case series of omalizumab for allergic bronchopulmonary aspergillosis in cystic fibrosis patients.

    Science.gov (United States)

    Nové-Josserand, Raphaële; Grard, Soazic; Auzou, Lila; Reix, Philippe; Murris-Espin, Marlène; Brémont, François; Mammar, Benyebka; Mely, Laurent; Hubert, Dominique; Durieu, Isabelle; Burgel, Pierre-Régis

    2017-02-01

    Allergic bronchopulmonary aspergillosis (ABPA) affects up to 15% of patients with cystic fibrosis (CF). Corticosteroids are used as first-line therapy, but relapse and adverse effects commonly occur. Case reports have suggested the efficacy of the anti-IgE recombinant humanized monoclonal antibody omalizumab. A retrospective multicenter observational French study retrieved 32 CF patients (11 children and 21 adults) who have received omalizumab for more than 3 months in the context of ABPA. Clinical characteristics, concomitant medications (inhaled and oral corticosteroids, antifungal drugs), lung function, body mass index (BMI), and serum IgE were compared at the start and during the first year of omalizumab therapy. Omalizumab-related adverse effects and costs were also evaluated. No significant difference with omalizumab could be demonstrated with regard to lung function, BMI, or the number of patients receiving oral corticosteroids. At the time of initiation of omalizumab, 56% of patients were receiving oral corticosteroids. Five patients were able to discontinue corticosteroids during follow-up and nine patients were able to reduce their daily dose. A total of 78% of the patients had received antifungal therapy at the time of the initiation of omalizumab. Treatment tolerance was good (12.5% of patients experienced side effects). The median cost of omalizumab treatment was €3,620 per patient per month. Omalizumab may represent a steroid-sparing therapy in CF patients with ABPA. A randomized-controlled trial is urgently required to provide higher level of evidence regarding the efficacy and cost-effectiveness of omalizumab in CF patients with ABPA. Pediatr Pulmonol. 2017;52:190-197. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Association of MICA gene polymorphisms with liver fibrosis in schistosomiasis patients in the Dongting Lake region

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Zheng; Luo, Qi-Zhi; Lin, Lin [Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, Hunan Province (China); Su, Yu-Ping; Peng, Hai-Bo [Central Blood Bank in Yueyang, Yueyang, Hunan Province (China); Du, Kun; Yu, Ping [Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, Hunan Province (China); Wang, Shi-Ping [Key Laboratory of Schistosomiasis in Hunan, Department of Parasitology, College of Basic Medical Sciences, Central South University, Changsha, Hunan Province (China)

    2012-03-02

    Major histocompatibility complex class I chain-related A (MICA) is a highly polymorphic gene located within the MHC class I region of the human genome. Expressed as a cell surface glycoprotein, MICA modulates immune surveillance by binding to its cognate receptor on natural killer cells, NKG2D, and its genetic polymorphisms have been recently associated with susceptibility to some infectious diseases. We determined whether MICA polymorphisms were associated with the high rate of Schistosoma parasitic worm infection or severity of disease outcome in the Dongting Lake region of Hunan Province, China. Polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (SBT) were applied for high-resolution allele typing of schistosomiasis cases (N = 103, age range = 36.2-80.5 years, 64 males and 39 females) and healthy controls (N = 141, age range = 28.6-73.3 years, 73 males and 68 females). Fourteen MICA alleles and five short-tandem repeat (STR) alleles were identified among the two populations. Three (MICA*012:01/02, MICA*017 and MICA*027) showed a higher frequency in healthy controls than in schistosomiasis patients, but the difference was not significantly correlated with susceptibility to S. japonicum infection (Pc > 0.05). In contrast, higher MICA*A5 allele frequency was significantly correlated with advanced liver fibrosis (Pc < 0.05). Furthermore, the distribution profile of MICA alleles in this Hunan Han population was significantly different from those published for Korean, Thai, American-Caucasian, and Afro-American populations (P < 0.01), but similar to other Han populations within China (P > 0.05). This study provides the initial evidence that MICA genetic polymorphisms may underlie the severity of liver fibrosis occurring in schistosomiasis patients from the Dongting Lake region.

  5. Association Study for 26 Candidate Loci in Idiopathic Pulmonary Fibrosis Patients from Four European Populations

    Directory of Open Access Journals (Sweden)

    Amit Kishore

    2016-07-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF affects lung parenchyma with progressing fibrosis. In this study, we aimed to replicate MUC5B rs35705950 variants and determine new plausible candidate variants for IPF among four different European populations. We genotyped 26 IPF candidate loci in 165 IPF patients from four European countries: Czech Republic (n = 41, Germany (n = 33, Greece (n = 40, France (n = 51 and performed association study comparing observed variant distribution with this obtained in a genetically similar Czech healthy control population (n = 96 described in our earlier data report. A highly significant association for a promoter variant (rs35705950 of mucin encoding MUC5B gene was observed in all IPF populations, individually and combined [OR (95% CI; p-value as 5.23 (8.94-3.06; 1.80x10-11. Another non-coding variant, rs7934606 in MUC2 was significant among German patients [2.85 (5.05-1.60; 4.03x10-4] and combined European IPF cases [2.18 (3.16-1.50; 3.73x10-5]. The network analysis for these variants indicated gene-gene and gene-phenotype interactions in IPF and lung biology. With replication of MUC5B rs35705950 previously reported in U.S. populations of European descent and indicating other plausible polymorphic variants relevant for IPF, we provide additional reference information for future extended functional and population studies aimed, ideally with inclusion of clinical parameters, at identification of IPF genetic markers.

  6. Association of MICA gene polymorphisms with liver fibrosis in schistosomiasis patients in the Dongting Lake region

    International Nuclear Information System (INIS)

    Gong, Zheng; Luo, Qi-Zhi; Lin, Lin; Su, Yu-Ping; Peng, Hai-Bo; Du, Kun; Yu, Ping; Wang, Shi-Ping

    2012-01-01

    Major histocompatibility complex class I chain-related A (MICA) is a highly polymorphic gene located within the MHC class I region of the human genome. Expressed as a cell surface glycoprotein, MICA modulates immune surveillance by binding to its cognate receptor on natural killer cells, NKG2D, and its genetic polymorphisms have been recently associated with susceptibility to some infectious diseases. We determined whether MICA polymorphisms were associated with the high rate of Schistosoma parasitic worm infection or severity of disease outcome in the Dongting Lake region of Hunan Province, China. Polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (SBT) were applied for high-resolution allele typing of schistosomiasis cases (N = 103, age range = 36.2-80.5 years, 64 males and 39 females) and healthy controls (N = 141, age range = 28.6-73.3 years, 73 males and 68 females). Fourteen MICA alleles and five short-tandem repeat (STR) alleles were identified among the two populations. Three (MICA*012:01/02, MICA*017 and MICA*027) showed a higher frequency in healthy controls than in schistosomiasis patients, but the difference was not significantly correlated with susceptibility to S. japonicum infection (Pc > 0.05). In contrast, higher MICA*A5 allele frequency was significantly correlated with advanced liver fibrosis (Pc < 0.05). Furthermore, the distribution profile of MICA alleles in this Hunan Han population was significantly different from those published for Korean, Thai, American-Caucasian, and Afro-American populations (P < 0.01), but similar to other Han populations within China (P > 0.05). This study provides the initial evidence that MICA genetic polymorphisms may underlie the severity of liver fibrosis occurring in schistosomiasis patients from the Dongting Lake region

  7. Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Young Eun Chon

    Full Text Available Transient elastography (TE, a non-invasive tool that measures liver stiffness, has been evaluated in meta-analyses for effectiveness in assessing liver fibrosis in European populations with chronic hepatitis C (CHC. However, these data cannot be extrapolated to populations in Asian countries, where chronic hepatitis B (CHB is more prevalent. In this study, we performed a meta-analysis to assess the overall performance of TE for assessing liver fibrosis in patients with CHB.Studies from the literature and international conference abstracts which enrolled only patients with CHB or performed a subgroup analysis of such patients were enrolled. Combined effects were calculated using area under the receiver operating characteristic curves (AUROC and diagnostic accuracy values of each study.A total of 18 studies comprising 2,772 patients were analyzed. The mean AUROCs for the diagnosis of significant fibrosis (F2, severe fibrosis (F3, and cirrhosis (F4 were 0.859 (95% confidence interval [CI], 0.857-0.860, 0.887 (95% CI, 0.886-0.887, and 0.929 (95% CI, 0.928-0.929, respectively. The estimated cutoff for F2 was 7.9 (range, 6.1-11.8 kPa, with a sensitivity of 74.3% and specificity of 78.3%. For F3, the cutoff value was determined to be 8.8 (range, 8.1-9.7 kPa, with a sensitivity of 74.0% and specificity of 63.8%. The cutoff value for F4 was 11.7 (range, 7.3-17.5 kPa, with a sensitivity of 84.6% and specificity of 81.5%.TE can be performed with good diagnostic accuracy for quantifying liver fibrosis in patients with CHB.

  8. Clinical effects of diet supplementation with DHA in pediatric patients suffering from cystic fibrosis.

    Science.gov (United States)

    Leggieri, E; De Biase, R V; Savi, D; Zullo, S; Halili, I; Quattrucci, S

    2013-08-01

    Cystic fibrosis (CF) patients present an altered fatty acid (FA) metabolism characterized by imbalance in the arachidonic/docosohexasenoic acid (AA/DHA) ratio in favour of the former which can contribute to the increase in pulmonary inflammation. The present study aims to assess respiratory, nutritional, clinical and laboratory parameters, and inflammatory markers after six months of DHA supplementation in paediatric patients suffering from CF. A dose of 1 g/10 kg/die was administered to ten CF patients of paediatric age for the first month and 250 mg/10 kg/die for the remaining 5 months. We carried out follow-ups at T0 (baseline), T6 (after six months of the diet) and T12 (six months after supplementation was interrupted) during which respiratory, nutritional, clinical and laboratory parameters were assessed. After six months of DHA supplementation inflammatory marker levels had diminished: interleukin 8 (IL-8) and Tumour Necrosis Factor Alfa (TNF-α) in serum, and calprotectin in stools. In addition, auxometric parameters were improved as was the clinical condition of patients, who tolerated DHA well. Dietetic integration with DHA seems to improve clinical condition and the inflammatory pulmonary and intestinal state of pediatric patients suffering from CF.

  9. MR Differentiation of Lung Cancer from Progressive Massive Fibrosis in Patients with Coal Worker's Pneumoconiosis

    International Nuclear Information System (INIS)

    Kim, Young Jin; Jung, Jung Im; Park, Seog Hee; Lim, Young; Koo, Jung Wan

    2010-01-01

    To analyze the potential of MR to distinguish lung cancer from progressive massive fibrosis (PMF) in patients with coal worker's pneumoconiosis. The study consisted of 9 patients with pathologically proven lung cancer and 26 PMFs in 17 patients. All the patients had radiologic evidence of pneumoconiosis. T1-weighted FLASH images were obtained before and 0.5, 1, 2, 3, 4, 5, 7.5, 10, 12.5, and 15 minutes after injection of Gd-DTPA. T2-weighted fast spin-echo images were obtained. The imaging findings were evaluated for enhancement time curve, contrast uptake equivalent (CE), and enhancement factor (EF). On T1WI, there was no significant signal intensity difference between lung cancer and PMF. On T2WI, all lung cancer showed high signal intensity, as opposed to all PMFs which showed low signal intensity except for one PMF. Only one PMF showed high signal intensity on T2WI. For the dynamic contrast study, lung cancer showed faster and slightly stronger enhancement than PMFs. For a delayed image, most of the lung cancers (78%) showed washout, as opposed to a plateau in most of PMFs (73%) (p=0.0153). However, no difference was detected between the EFmax of lung cancer and PMFs (p=0.349). MR is potentially a useful tool in distinguishing lung cancer from PMFs in patients with coal worker's pneumoconiosis

  10. Comparison of CPI and GAP models in patients with idiopathic pulmonary fibrosis: a nationwide cohort study.

    Science.gov (United States)

    Lee, Sang Hoon; Park, Jong Sun; Kim, Song Yee; Kim, Dong Soon; Kim, Young Whan; Chung, Man Pyo; Uh, Soo Taek; Park, Choon Sik; Park, Sung Woo; Jeong, Sung Hwan; Park, Yong Bum; Lee, Hong Lyeol; Shin, Jong Wook; Lee, Eun Joo; Lee, Jin Hwa; Jegal, Yangin; Lee, Hyun Kyung; Kim, Yong Hyun; Song, Jin Woo; Park, Moo Suk

    2018-03-19

    The clinical course of idiopathic pulmonary fibrosis (IPF) is difficult to predict, partly owing to its heterogeneity. Composite physiologic index (CPI) and gender-age-physiology (GAP) models are easy-to-use predictors of IPF progression. This study aimed to compare the predictive values of these two models. From 2003 to 2007, the Korean Interstitial Lung Disease (ILD) Study Group surveyed ILD patients using the 2002 ATS/ERS criteria. A total of 832 patients with IPF were enrolled in this study. CPI was calculated as follows: 91.0 - (0.65 × %DL CO ) - [0.53 × %FVC + [0.34 × %FEV 1 . GAP stage was calculated based on gender (0-1 points), age (0-2 points), and two physiologic lung function parameters (0-5 points). The two models had similar significant predictive values for patients with IPF (p GAP for prediction of 1-, 2-, and 3-year mortality in this study. The AUC was higher for surgically diagnosed IPF patients than for clinically diagnosed patients. However, neither CPI nor GAP yielded good predictions of outcomes; the AUC was approximately 0.61~0.65. Although both CPI and GAP stage are significantly useful predictors for IPF, they have limited capability to accurately predict outcomes.

  11. Burkholderia species infections in patients with cystic fibrosis in British Columbia, Canada. 30 years' experience.

    Science.gov (United States)

    Zlosnik, James E A; Zhou, Guohai; Brant, Rollin; Henry, Deborah A; Hird, Trevor J; Mahenthiralingam, Eshwar; Chilvers, Mark A; Wilcox, Pearce; Speert, David P

    2015-01-01

    We have been collecting Burkholderia species bacteria from patients with cystic fibrosis (CF) for the last 30 years. During this time, our understanding of their multispecies taxonomy and infection control has evolved substantially. To evaluate the long-term (30 year) epidemiology and clinical outcome of Burkholderia infection in CF, and fully define the risks associated with infection by each species. Isolates from Burkholderia-positive patients (n=107) were speciated and typed annually for each infected patient. Microbiological and clinical data were evaluated by thorough review of patient charts, and statistical analyses performed to define significant epidemiological factors. Before 1995, the majority of new Burkholderia infections were caused by epidemic clones of Burkholderia cenocepacia. After implementation of new infection control measures in 1995, Burkholderia multivorans became the most prevalent species. Survival analysis showed that patients with CF infected with B. cenocepacia had a significantly worse outcome than those with B. multivorans, and a novel finding was that, after Burkholderia infection, the prognosis for females was significantly worse than for males. B. multivorans and B. cenocepacia have been the predominant Burkholderia species infecting people with CF in Vancouver. The implementation of infection control measures were successful in preventing new acquisition of epidemic strains of B. cenocepacia, leaving nonclonal B. multivorans as the most prevalent species. Historically, survival after infection with B. cenocepacia has been significantly worse than B. multivorans infection, and, of new significance, we show that females tend toward worse clinical outcomes.

  12. [Structured care in an ISO certified centre for patients with cystic fibrosis and their families].

    Science.gov (United States)

    Ellemunter, H; Eder, J; Steinkamp, G

    2011-10-01

    Cystic fibrosis (CF) is a chronic, life-shortening disease of multiple organ systems. Guidelines recommend that patients should be treated in specialised CF centres with multi-professional teams. We describe the organisation of medical care at the CF centre of Innsbruck University as well as results of treatment. Procedures and delivery of multi-professional care have been elaborated and structured. Since 2006 the Centre has been repeatedly certified according to DIN ISO 9001:2000. The patient database is being used during the doctor's consultation and for the continuous monitoring of treatment results. In 2010, 71 of the 148 patients (48%) were between 18 and 56 years old. The total number of patients has doubled and the proportion of adults tripled since 1995. Nevertheless, median FEV1 remained stable (>80% of predicted) during the last 15 years. Compared with 18 CF centres of the German Benchmarking Group, patients treated in Innsbruck had favourable FEV1 values: 52% of adults had a normal FEV1 (>80% pred.) and only 23% an FEV1 <50% of predicted. A structured programme of multi-professional care was associated with favourable treatment results, both longitudinally and in comparison to other CF centres. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to a potential antifibrotic therapy

    DEFF Research Database (Denmark)

    Karsdal, Morten A; Henriksen, Kim; Nielsen, Mette Juul

    2016-01-01

    There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic t...

  14. Factors Associated with Worse Lung Function in Cystic Fibrosis Patients with Persistent Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Sibylle Junge

    Full Text Available Staphylococcus aureus is an important pathogen in cystic fibrosis (CF. However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures. Our main hypothesis was that patients with high S. aureus density in their respiratory specimens would more likely experience worsening of their lung disease than patients with low bacterial loads.Therefore, we conducted an observational prospective longitudinal multi-center study and assessed the association between lung function and S. aureus bacterial density in respiratory samples, co-infection with other CF-pathogens, nasal S. aureus carriage, clinical status, antibiotic therapy, IL-6- and IgG-levels against S. aureus virulence factors.195 patients from 17 centers were followed; each patient had an average of 7 visits. Data were analyzed using descriptive statistics and generalized linear mixed models. Our main hypothesis was only supported for patients providing throat specimens indicating that patients with higher density experienced a steeper lung function decline (p<0.001. Patients with exacerbations (n = 60, S. aureus small-colony variants (SCVs, n = 84 and co-infection with Stenotrophomonas maltophilia (n = 44 had worse lung function (p = 0.0068; p = 0.0011; p = 0.0103. Patients with SCVs were older (p = 0.0066 and more often treated with trimethoprim/sulfamethoxazole (p = 0.0078. IL-6 levels positively correlated with decreased lung function (p<0.001, S. aureus density in sputa (p = 0.0016, SCVs (p = 0.0209, exacerbations (p = 0.0041 and co-infections with S. maltophilia (p = 0.0195 or A. fumigatus (p = 0.0496.In CF-patients with chronic S. aureus cultures, independent risk factors for worse lung function are high bacterial density in throat cultures, exacerbations, elevated IL-6 levels, presence of S. aureus SCVs and co-infection with S. maltophilia.ClinicalTrials.gov NCT00669760.

  15. [18F]-Fluorodeoxyglucose Positron Emission Tomography in the Diagnosis, Treatment Stratification, and Monitoring of Patients with Retroperitoneal Fibrosis: A Prospective Clinical Study.

    Science.gov (United States)

    Fernando, Archie; Pattison, James; Horsfield, Catherine; D'Cruz, David; Cook, Gary; O'Brien, Tim

    2017-06-01

    The ability to distinguish malignant from benign retroperitoneal fibrosis (RPF) and to select patients who are likely to respond to steroid treatment using a noninvasive test would be a major step forward in the management of patients with RPF. To prospectively evaluate the potential of [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET) to improve clinical decision-making and management of RPF. A total of 122 RPF patients were assessed and managed by a multidisciplinary RPF service between January 2012 and December 2015. Of these, 78 patients underwent 101 FDG-PET scans, as well as computed tomography and blood tests. Management was based on the findings from these investigations. Median follow-up was 16 mo. Of the 24 patients with negative [ 18 F]-FDG-PET, none (0%) had malignancy on biopsy (negative predictive value 100%). [ 18 F]-FDG-PET identified malignancy in 4/4 patients (100%) before biopsy. All four patients had highly avid PET (maximum standardised uptake value ≥4) with atypical avidity distribution. [ 18 F]-FDG-PET revealed avidity in 19/38 patients (50%) with normal inflammatory markers and no avidity in 10/63 patients (16%) with raised marker levels. Patients with highly avid PET were significantly more likely to respond to steroids compared to those with low avidity (9/11 [82%] vs 3/24 [12%]; ppositron emission tomography scans could reduce the need for biopsy in patients with retroperitoneal fibrosis (RPF). This technique can distinguish cancer from noncancerous RPF, and may be better than blood tests in assessing and monitoring RPF. It also appears to predict a patient's response to steroids, which should allow more individualised treatment. Copyright © 2017 European Association of Urology. All rights reserved.

  16. Presence of anxiety and depression in patients with bronchiectasis unrelated to cystic fibrosis.

    Science.gov (United States)

    Girón Moreno, Rosa María; Fernandes Vasconcelos, Gilda; Cisneros, Carolina; Gómez-Punter, Rosa Mar; Segrelles Calvo, Gonzalo; Ancochea, Julio

    2013-10-01

    Patients with chronic bronchiectasis (BQ) may suffer from psychological disorders. The objective of this study was to assess the presence of anxiety and depression in patients from a specialised BQ Unit, using validated questionnaires. We included patients consecutively diagnosed with BQ (unrelated to cystic fibrosis) by high resolution computed tomography in the study. Patients were clinically stable in the previous three weeks and voluntarily completed the Beck Depression Inventory, State-Trait Anxiety Inventory and St. George's Respiratory Questionnaire, after signing the informed consent. They were classified according to their scores on the psychological screening questionnaires, and their results were compared with the clinical, radiological and functional parameters and Quality of Life. Seventy patients were included, 48 women and 22 men, with a mean age of 64.19years. Thirty-four percent (34%) of patients showed symptoms of depression, and around 55% had scores above the 50th percentile in trait and state anxiety. The amount of sputum was associated with trait anxiety. Bacterial colonization was related to anxiety (trait and state), especially Pseudomonas aeruginosa colonization. Female patients showed a higher risk of depression. There was no relationship between the Quality of Life scores and the established classifications of anxiety and depression. A high percentage of patients with BQ presented anxiety (trait and state) and depression. The daily sputum production and bacterial colonization (especially with P. aeruginosa) were the variables most related to anxiety; depression was more common in women. We believe that the presence of psychological disorders should be evaluated, especially in patients with this profile. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

  17. Serum γ-glutamyl transferase levels, insulin resistance and liver fibrosis in patients with chronic liver diseases.

    Directory of Open Access Journals (Sweden)

    Salvatore Petta

    Full Text Available BACKGROUND AND AIMS: Serum levels of γ-glutamyl-transpeptidase(γ-GT were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD, genotype 1 chronic hepatitis C (G1CHC and chronic hepatitis B (CHB, we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR and severity of liver fibrosis. METHODS: 843 consecutive patients with chronic liver disease (CLD(193 NAFLD, 481 G1CHC, 169 CHB were evaluated by liver biopsy (Kleiner and Scheuer scores and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT. RESULTS: By multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120-6.564,p = 0.02, G1CHC (OR3.461,CI2.138-5.603,p80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079-15.970,p = 0.03 for NAFLD; OR2.250,CI1.211-4.181,p = 0.01 for G1CHC; OR3.096,CI2.050-34.220,p = 0.01 for CHB. CONCLUSIONS: In patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD.

  18. The effect of fibrosis in the upper neck on radiation-related cranial nerve palsy in patients with nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Kong Lin; Zhang Youwang; Hu Chaosu; Wu Yongru; Guo Xiaomao

    2007-01-01

    Objective: To analyse the effect of fibrosis in the upper neck on the development of radiation-induced cranial nerve palsy (CNP) in nasopharyngeal carcinoma (NPC) patients after radiation treatment. Methods: Between Feb. 2000 and Feb. 2002, 317 consecutive patients with NPC who survival at least 5 years came to our radiotherapy center for follow-up, who were analyzed in this study. Patients who received re-irradiation were excluded. All patients received definitive external beam radiotherapy (EBRT) with either Cobalt-60 or megavoltage linear accelerators. The median radiotherapy dose was 71 Gy (range 55-86 Gy) to the primary disease, 61 Gy (range 34-72 Gy) to the upper neck. High-dose-rate brachytherapy with Ir-192 source was used in 24 patients either as part of definitive treatment or as a boost for residual disease in the nasopharynx. Forty-five patients also received chemotherapy with various regimens. Results: The median follow-up was 11.4 years (range 5.1-38.0 years). A total of 81 patients (25.5%) developed radiation-induced posterior CN group (CN IX-XII) palsy with an average annual rate of 1.8%. The cumulative incidence of CNP was 5.7%, 17.4% and 37.3% at 5-, 10- and 20-year respectively. Fifty-four (17%) patients showed severe fibrosis (G3-4) in the upper neck. Univariate and multivariate analysis showed that the total dose of radiation to the nasopharynx and upper neck fibrosis were independent risk factors for developing CNP after RT for NPC. Neck severe fibrosis was associated with approximately two-fold risk of developing CNP (RR=1.936, 95% CI: 1.521-2.466, P 70 Gy to the nasopharynx were associated with increased risk of developing CNP. Other factors, including gender, age, N classifications, chemotherapy, unconventional fractionation radiation, total radiation dose to the upper neck, and brachytherapy did not influence the risk of CNP. Conclusions: Patients who had severe fibrosis in the upper neck may be at increased risk of radiation

  19. Impact of Comorbidities on Mortality in Patients with Idiopathic Pulmonary Fibrosis.

    Directory of Open Access Journals (Sweden)

    Michael Kreuter

    Full Text Available Comorbidities significantly influence the clinical course of idiopathic pulmonary fibrosis (IPF. However, their prognostic impact is not fully understood. We therefore aimed to determine the impact of comorbidities, as individual and as whole, on survival in IPF.The database of a tertiary referral centre for interstitial lung diseases was reviewed for comorbidities, their treatments, their frequency and survival in IPF patients.272 patients were identified of which 12% had no, 58% 1-3 and 30% 4-7 comorbidities, mainly cardiovascular, pulmonary and oncologic comorbidities. Median survival according to the frequency of comorbidities differed significantly with 66 months for patients without comorbidities, 48 months when 1-3 comorbidities were reported and 35 months when 4-7 comorbidities were prevalent (p = 0.004. A multivariate Cox proportional hazard analyses identified other cardiac diseases and lung cancer as significant predictors of death, gastro-oesophageal reflux disease (GERD and diastolic dysfunction had a significant positive impact on survival. A significant impact of comorbidities associated therapies on survival was not discovered. This included the use of proton pump inhibitors at baseline, which was not associated with a survival benefit (p = 0.718. We also established a predictive tool for highly prevalent comorbidities, termed IPF comorbidome which demonstrates a new relationship of IPF and comorbidities.Comorbidities are frequent in IPF patients. Some comorbidities, especially lung cancer, mainly influence survival in IPF, while others such as GERD may inherit a more favourable effect. Moreover, their cumulative incidence impacts survival.

  20. Correlation of tomographic findings with pulmonary function parameters in nonsmoking patients with idiopathic pulmonary fibrosis

    International Nuclear Information System (INIS)

    Lopes, Agnaldo Jose; Capone, Domenico; Mogami, Roberto; Jansen, Jose Manoel .E mail: phel.lop@uol.com.br; Cunha, Daniel Leme da; Melo, Pedro Lopes de

    2007-01-01

    Objective: To correlate tomographic findings with pulmonary function parameters in patients with idiopathic pulmonary fibrosis (IPF). Methods: A cross-sectional study was carried out, in which 30 nonsmoking patients with IPF were evaluated. Using a semiquantitative scoring system, the following high-resolution computerized tomography findings were quantified: total interstitial disease (TID), reticular abnormality/honeycombing, and ground-glass opacity (GGO). The functional variables were measured by spirometry, forced oscillation technique (FOT), helium dilution method, as well as the single-breath method of measuring diffusion capacity of the lung for carbon monoxide (DLCO). Results: Of the 30 patients studied, 18 were female, and 12 were male, with a mean age of 70.9 years. We found that TID and reticular abnormality and honeycombing correlated significantly (negative correlations) with the measurements of forced vital capacity (FVC), total lung capacity (TLC), DLCO, and dynamic respiratory compliance were found, as well as that GGO correlated significantly (and positively) with residual volume/TLC. The ratio of forced expiratory flow between 25 and 75% of FVC to FVC (FEF25-75%/FVC) correlated positively with TID, reticular abnormality/honeycombing, and GGO. Conclusion: In IPF patients, the measurements of volume, diffusion, and dynamic compliance are the physiological variables which best reflect the extent of the interstitial disease on HRCT scans. (author)

  1. Costs of treatment of adult patients with cystic fibrosis in Poland and internationally.

    Science.gov (United States)

    Kopciuch, Dorota; Zaprutko, Tomasz; Paczkowska, Anna; Nowakowska, Elżbieta

    2017-07-01

    Despite its low prevalence, cystic fibrosis (CF) may have a considerable impact on healthcare system expenditures in terms of direct healthcare costs and lost productivity. This study was aimed at calculation of costs associated with CF treatment in Poland, as well as at comparison of average costs of treatment of CF patients in selected countries, taking into account the purchasing power parity. Retrospective study. The researchers undertook a retrospective study of adult patients with CF taking into account the broadest social perspective possible. Medical and non-medical direct costs as well as indirect costs were calculated. CF costs estimated by researchers from other countries over the last 15 years were also compared. Total annual treatment cost per one CF patient in Poland was on average EUR 19,581.08. Costs of treatment of CF patients over the last 15 years varied between the countries and ranged from EUR 23,330.82 in Bulgaria to EUR 68,696.42 in the United States. CF is an international problem. The data in this study could be the baseline for integrated and harmonised approaches for periodical assessment of the future impact of new public policies and interventions for rare diseases at the national and international levels. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  2. SERS detection of the biomarker hydrogen cyanide from Pseudomonas aeruginosa cultures isolated from cystic fibrosis patients

    Science.gov (United States)

    Lauridsen, Rikke Kragh; Sommer, Lea M.; Johansen, Helle Krogh; Rindzevicius, Tomas; Molin, Søren; Jelsbak, Lars; Engelsen, Søren Balling; Boisen, Anja

    2017-03-01

    Pseudomonas aeruginosa is the primary cause of chronic airway infections in cystic fibrosis (CF) patients. Persistent infections are seen from the first P. aeruginosa culture in about 75% of young CF patients, and it is important to discover new ways to detect P. aeruginosa at an earlier stage. The P. aeruginosa biomarker hydrogen cyanide (HCN) contains a triple bond, which is utilized in this study because of the resulting characteristic C≡N peak at 2135 cm-1 in a Raman spectrum. The Raman signal was enhanced by surface-enhanced Raman spectroscopy (SERS) on a Au-coated SERS substrate. After long-term infection, a mutation in the patho-adaptive lasR gene can alter the expression of HCN, which is why it is sometimes not possible to detect HCN in the breath of chronically infected patients. Four P. aeruginosa reference strains and 12 clinical P. aeruginosa strains isolated from CF children were evaluated, and HCN was clearly detected from overnight cultures of all wild type-like isolates and half of the later isolates from the same patients. The clinical impact could be that P. aeruginosa infections could be detected at an earlier stage, because daily breath sampling with an immediate output could be possible with a point-of-care SERS device.

  3. Altered Sputum Microstructure as a Marker of Airway Obstruction in Cystic Fibrosis Patients

    Science.gov (United States)

    Duncan, Gregg; Jung, James; West, Natalie; Boyle, Michael; Suk, Jung Soo; Hanes, Justin

    In the lungs of cystic fibrosis (CF) patients, highly viscoelastic mucus remains stagnant in the lung leading to obstructed airways prone to recurrent infections. Bulk-fluid rheological measurement is primarily used to assess the pathological features of mucus. However, this approach is limited in detecting microscopic properties on the length scale of pathogens and immune cells. We have shown in prior work based on the transport of muco-inert nanoparticles (MIP) in CF sputum that patients can carry significantly different microstructural properties. In this study, we aimed to determine the factors leading to variations between patients in sputum microstructure and their clinical implications. The microrheological properties of CF sputum were measured using multi-particle tracking experiments of MIP. MIP were made by grafting polyethylene glycol onto the surface of polystyrene nanoparticles which prior work has shown prevents adhesion to CF sputum. Biochemical analyses show that sputum microstructure was significantly altered by elevated mucin and DNA content. Reduction in sputum pore size is characteristic of patients with obstructed airways as indicated by measured pulmonary function tests. Our microstructural read-out may serve as a novel biomarker for CF.

  4. [Anesthetic complications in sequential bipulmonary transplantation in patients with cystic fibrosis. Apropos of 6 cases].

    Science.gov (United States)

    López, L M; Vicente, R; Ramos, F; Palacios, L; Calvo, A; Hernández, S; Borro, J M; Morales, P; Montero, R

    1996-03-01

    Cystic fibrosis (CF) is a disease characterized mainly by altered exocrine gland function that eventually produces irreversible dysfunction of the pancreas and lungs. The respiratory insufficiency that develops in CF patients in the advanced stages of disease can only be corrected at this time by lung or heart-lung transplantation. We describe our experience with 6 terminal phase CF patients who underwent sequential double lung transplantation (SDLT). Anesthesia was intravenous, with exhaustive hemodynamic and respiratory monitoring. During surgery the most frequently encountered hemodynamic complications were low minute volume, arterial hypotension and irregular heart rate. The main respiratory complications were hypoxemia, hypercapnia and pulmonary edema of the implanted lung, which developed in all cases to varying degrees related to the organ's state of preservation and duration of ischemia. Other complications were the need for extracorporeal circulation in 1 case, oliguria and blood loss requiring multiple transfusions. The most critical moments were at the time of clamping the pulmonary artery, the period after revascularization of the donated lung, and at the start of patient ventilation through the first implanted lung so that the second could be implanted. Although our series is small, it is of interest given the limited Spanish experience with lung transplantation in CF patients, and the good early results obtained, which are similar to those reported for other diseases.

  5. Correlation of tomographic findings with pulmonary function parameters in nonsmoking patients with idiopathic pulmonary fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, Agnaldo Jose; Capone, Domenico; Mogami, Roberto; Jansen, Jose Manoel [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). School of Medical Sciences].E mail: phel.lop@uol.com.br; Cunha, Daniel Leme da [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Pedro Ernesto University Hospital. Dept. of Radiology and Diagnostic Imaging; Melo, Pedro Lopes de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. of Biology

    2007-11-15

    Objective: To correlate tomographic findings with pulmonary function parameters in patients with idiopathic pulmonary fibrosis (IPF). Methods: A cross-sectional study was carried out, in which 30 nonsmoking patients with IPF were evaluated. Using a semiquantitative scoring system, the following high-resolution computerized tomography findings were quantified: total interstitial disease (TID), reticular abnormality/honeycombing, and ground-glass opacity (GGO). The functional variables were measured by spirometry, forced oscillation technique (FOT), helium dilution method, as well as the single-breath method of measuring diffusion capacity of the lung for carbon monoxide (DLCO). Results: Of the 30 patients studied, 18 were female, and 12 were male, with a mean age of 70.9 years. We found that TID and reticular abnormality and honeycombing correlated significantly (negative correlations) with the measurements of forced vital capacity (FVC), total lung capacity (TLC), DLCO, and dynamic respiratory compliance were found, as well as that GGO correlated significantly (and positively) with residual volume/TLC. The ratio of forced expiratory flow between 25 and 75% of FVC to FVC (FEF25-75%/FVC) correlated positively with TID, reticular abnormality/honeycombing, and GGO. Conclusion: In IPF patients, the measurements of volume, diffusion, and dynamic compliance are the physiological variables which best reflect the extent of the interstitial disease on HRCT scans. (author)

  6. MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Yasmina Bauer

    2017-03-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease. Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7, Fas death receptor ligand, osteopontin and procollagen type I C-peptide, to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF. In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4. MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression.

  7. Non-organ-specific autoantibodies in chronic hepatitis C patients: association with histological activity and fibrosis.

    Science.gov (United States)

    Chrétien, P; Chousterman, M; Abd Alsamad, I; Ozenne, V; Rosa, I; Barrault, C; Lons, T; Hagège, H

    2009-01-01

    Non-organ-specific autoantibodies (NOSAs) are frequently found in the sera of patients with Hepatitis C Virus (HCV) infection. However, no conclusive answers have been produced concerning the clinical relevance of these antibodies. To determine whether a relationship might exist between the presence of NOSA and the severity of liver disease in chronic hepatitis C. 186 treatment-naïve chronic hepatitis C patients were studied consecutively for autoantibodies. Liver biopsies were analyzed according to the Metavir score. NOSAs were present in 75 patients (40%). Anti-nuclear antibodies were found in 32% of patients (speckled pattern), anti-smooth muscle in 15% without F-actin specificity, anti-mitochondria in 0.5%, and anti-LKM1 in 0.5%, respectively. No liver-cytosol1 or soluble liver antigen antibodies were detected. There was a highly significant correlation between the positivity of NOSA and the degree of inflammation and hepatocellular injury (p = 0.001) and also with the degree of fibrosis (p < 0.0001). The presence of NOSA was associated with higher aspartate aminotransferase, gamma-glutamyl-transpeptidase, gamma-globulin and immunoglobulin G levels. By contrast, no differences were observed regarding age, gender, route of infection, duration of disease, HCV genotypes or viral load. NOSAs were associated with the most severe forms of chronic HCV infections.

  8. Oxandrolone Improves Height Velocity and BMI in Patients with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Seffrood ErinE

    2009-01-01

    Full Text Available Objective. To evaluate the effectiveness of oxandrolone in improving the nutritional status and linear growth of pediatric patients with cystic fibrosis (CF. Methods. Medical records of patients with CF treated with oxandrolone were reviewed for height z score, height velocity (HV, BMI z score, weight velocity (WV, Tanner stage, pulmonary function, liver enzyme levels, and any reported adverse events. Data were compared before (pre-Ox and after (Ox oxandrolone using a paired t-test. Results. 5 subjects (ages 8.5–14.5 years were treated with oxandrolone 2.5 mg daily for 8–38 months. After 8–12 months of treatment, there was a statistically significant improvement in HV (  cm/yr,  cm/yr, and BMI z score ( , , . Both height z score ( , , and WV (  kg/yr, Ox  kg/yr, showed beneficial trends that did not reach statistical significance. No adverse events were reported. Conclusions. In this brief clinical report, oxandrolone improved the HV and BMI z score in patients with CF. Larger studies are needed to determine if oxandrolone is an effective, safe, and affordable option to stimulate appetite, improve weight gain, and promote linear growth in patients with CF.

  9. Changes of contents of serum markers of hepatic fibrosis after matrine treatment in patients with chronic B hepatitis

    International Nuclear Information System (INIS)

    Zhang Guifen; Ma yunbao; Zhang Xiaoyi

    2005-01-01

    Objective: To explore the effect of matrine on reversal of hepatic fibrosis. Methods: Serum hyaluronic acid ( HA), laminin (LN) and type III procollagen (PC III) levels were measured with RIA in 40 patients with chronic B hepatitis treated with matrine and 40 other patients treated without matrine both before and 3, 6 months after treatment as well as in 32 controls. Results: Before treatment, the serum contents of all the three markers in both groups of patients were significantly higher than those in the controls (P 0.05) and increased further at 6 months (vs before treatment, P 0.05), but the levels in the matrine group were significantly lower than those in the group without matrine at 6 months (P < 0.01). Conclusion: Matrine exerts marked anti-fibrosis effect in patients with chronic B hepatitis. (authors)

  10. Significance of measurement of serum fibrosis markers (HA, LN, P III P, IV C) in patients with pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Zhou Mingxian

    2006-01-01

    Objective: To study the clinical significance of determination of serum fibrosis markers in patients with pulmonary tuberculosis. Methods: Serum hyaluronic acid (HA), laminin (LN), procollagen III peptide (P III P) and Type IV collagen (IV C) contents were determined with RIA in 128 patients with pulmonary tuberculosis both before and after treatment as well as in 40 controls. Results: Before treatment, the serum contents of the four markers in the patients were significantly higher than those in the controls (P 0.05). Decreases of the levels in treatment failures were not significant and the levels remained significantly higher than those in controls (P<0.01 or P<0.05). Conclusion: Determination of serum fibrosis markers levels in patients with pulmonary tuberculosis is valuable for early diagnosis as well as for evaluation of the effect of chemotherapy. (authors)

  11. The Role of Ultrasound Imaging in the Definition of the Stage of Liver Fibrosis in Patients with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Dmitry Konstantinov

    2014-09-01

    Full Text Available The aim of this research was to develop a method for noninvasive staging of liver fibrosis (LF in patients with chronic hepatitis C (CHC based on ultrasound imaging (UI of the abdominal cavity. We examined 124 patients with CHC. The diagnosis was verified on the basis of clinical and epidemiological, serological and molecular biological data. Direct ultrasonic parameters of the structure and hemodynamics of liver and spleen were supplemented with estimated indicators: square of the expected cross-section of the lobes of the liver and spleen, as well as their ratio. On the basis of the discriminant analysis of the survey data of 82 patients, we developed an analytical model (with predictive value of 95.2% for interval estimation of the fibrosis degree in CHC patients. We have concluded that UI performed on modern equipment, including Doppler, is able to determine the degree of LF without resorting to histological verification.

  12. CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Ewa Ziętkiewicz

    Full Text Available Cystic fibrosis (CF is caused by mutations in the cystic fibrosis transmembrane regulator gene (CFTR. In light of the strong allelic heterogeneity and regional specificity of the mutation spectrum, the strategy of molecular diagnostics and counseling in CF requires genetic tests to reflect the frequency profile characteristic for a given population. The goal of the study was to provide an updated comprehensive estimation of the distribution of CFTR mutations in Polish CF patients and to assess the effectiveness of INNOLiPA_CFTR tests in Polish population. The analyzed cohort consisted of 738 patients with the clinically confirmed CF diagnosis, prescreened for molecular defects using INNOLiPA_CFTR panels from Innogenetics. A combined efficiency of INNOLiPA CFTR_19 and CFTR_17_TnUpdate tests was 75.5%; both mutations were detected in 68.2%, and one mutation in 14.8% of the affected individuals. The group composed of all the patients with only one or with no mutation detected (109 and 126 individuals, respectively was analyzed further using a mutation screening approach, i.e. SSCP/HD (single strand conformational polymorphism/heteroduplex analysis of PCR products followed by sequencing of the coding sequence. As a result, 53 more mutations were found in 97 patients. The overall efficiency of the CF allele detection was 82.5% (7.0% increase compared to INNOLiPA tests alone. The distribution of the most frequent mutations in Poland was assessed. Most of the mutations repetitively found in Polish patients had been previously described in other European populations. The most frequent mutated allele, F508del, represented 54.5% of Polish CF chromosomes. Another eight mutations had frequencies over 1%, 24 had frequencies between 1 and 0.1%; c.2052-2053insA and c.3468+2_3468+3insT were the most frequent non-INNOLiPA mutations. Mutation distribution described herein is also relevant to the Polish diaspora. Our study also demonstrates that the reported

  13. Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles.

    Science.gov (United States)

    Terlizzi, Vito; Castaldo, Giuseppe; Salvatore, Donatello; Lucarelli, Marco; Raia, Valeria; Angioni, Adriano; Carnovale, Vincenzo; Cirilli, Natalia; Casciaro, Rosaria; Colombo, Carla; Di Lullo, Antonella Miriam; Elce, Ausilia; Iacotucci, Paola; Comegna, Marika; Scorza, Manuela; Lucidi, Vincenzina; Perfetti, Anna; Cimino, Roberta; Quattrucci, Serena; Seia, Manuela; Sofia, Valentina Maria; Zarrilli, Federica; Amato, Felice

    2017-04-01

    The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator ( CFTR ) complex alleles. We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans , or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (pT] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). The effect of complex alleles partially depends on the mutation in trans . Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. MALDI imaging reveals NCOA7 as a potential biomarker in oral squamous cell carcinoma arising from oral submucous fibrosis.

    Science.gov (United States)

    Xie, Xiaoyan; Jiang, Yuchen; Yuan, Yao; Wang, Peiqi; Li, Xinyi; Chen, Fangman; Sun, Chongkui; Zhao, Hang; Zeng, Xin; Jiang, Lu; Zhou, Yu; Dan, Hongxia; Feng, Mingye; Liu, Rui; Chen, Qianming

    2016-09-13

    Oral squamous cell carcinoma (OSCC) ranks among the most common cancer worldwide, and is associated with severe morbidity and high mortality. Oral submucous fibrosis (OSF), characterized by fibrosis of the mucosa of the upper digestive tract, is a pre-malignant lesion, but the molecular mechanisms underlying this malignant transformation remains to be elucidated. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was employed to profile the differentially expressed peptides/proteins between OSCC tissues and the corresponding adjacent non-cancerous OSF tissues. Sixty-five unique peptide peaks and nine proteins were identified with altered expression levels. Of them, expression of NCOA7 was found to be up-regulated in OSCC tissues by immunohistochemistry staining and western blotting, and correlated with a pan of clinicopathologic parameters, including lesion site, tumor differentiation status and lymph node metastasis. Further, we show that overexpression of NCOA7 promotes OSCC cell proliferation in either in vitro or in vivo models. Mechanistic study demonstrates that NCOA7 induces OSCC cell proliferation probably by activating aryl hydrocarbon receptor (AHR). The present study suggests that NCOA7 is a potential biomarker for early diagnosis of OSF malignant transformation, and leads to a better understanding of the molecular mechanisms responsible for OSCC development.

  15. Aerobic exercise and respiratory muscle strength in patients with cystic fibrosis.

    Science.gov (United States)

    Dassios, Theodore; Katelari, Anna; Doudounakis, Stavros; Dimitriou, Gabriel

    2013-05-01

    The beneficial role of exercise in maintaining health in patients with cystic fibrosis (CF) is well described. Few data exist on the effect of exercise on respiratory muscle function in patients with CF. Our objective was to compare respiratory muscle function indices in CF patients that regularly exercise with those CF patients that do not. This cross-sectional study assessed nutrition, pulmonary function and respiratory muscle function in 37 CF patients that undertook regular aerobic exercise and in a control group matched for age and gender which consisted of 44 CF patients that did not undertake regular exercise. Respiratory muscle function in CF was assessed by maximal inspiratory pressure (Pimax), maximal expiratory pressure (Pemax) and pressure-time index of the respiratory muscles (PTImus). Median Pimax and Pemax were significantly higher in the exercise group compared to the control group (92 vs. 63 cm H2O and 94 vs. 64 cm H2O respectively). PTImus was significantly lower in the exercise group compared to the control group (0.089 vs. 0.121). Upper arm muscle area (UAMA) and mid-arm muscle circumference were significantly increased in the exercise group compared to the control group (2608 vs. 2178 mm2 and 23 vs. 21 cm respectively). UAMA was significantly related to Pimax in the exercising group. These results suggest that CF patients that undertake regular aerobic exercise maintain higher indices of respiratory muscle strength and lower PTImus values, while increased UAMA values in exercising patients highlight the importance of muscular competence in respiratory muscle function in this population. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Increased levels of anti-glycan antibodies in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Hirche TO

    2011-09-01

    Full Text Available Abstract Background The prevalence of Crohn's disease (CD is increased in patients with cystic fibrosis (CF. Anti-Saccharomyces cerevisiae antibodies (ASCA have been suggested as a screening tool to detect CD in CF. Recently, several new anti-glycan antibodies have been reported in CD. Materials and methods The sera of 119 CF patients of various age groups were prospectively screened for ASCA type IgG (gASCA, anti-laminaribioside carbohydrate IgG antibodies (ALCA, anti-chitobioside carbohydrate IgA antibodies (ACCA, and anti-mannobioside carbohydrate IgG antibodies (AMCA. The frequency of these anti-glycan antibodies was then compared in patients with CD, ulcerative colitis, rheumatoid arthritis and healthy volunteers. Results A significant number of CF patients were positive for gASCA (51.3% [41.6-60.6] and up to three other anti-glycan antibodies concurrently. Serum levels of anti-glycan antibodies in CF and CD were not related to parameters of inflammation. Despite the well-documented difference in clinical course between male and female CF patients no gender difference of anti-glycan antibodies was found. In contrast, there was a significant positive correlation between anti-glycan markers and age in CF patients. Conclusions Our findings demonstrate for the first time the increased frequency of a panel of anti-glycan antibodies in CF and provide a link between the presence of these serological biomarkers and patient's age. Anti-glycan antibody profiling may therefore become a valuable tool in the care of patients with CF.

  17. CYFRA 21.1 in bronchoalveolar lavage of idiopathic pulmonary fibrosis patients.

    Science.gov (United States)

    Vercauteren, Inge M; Verleden, Stijn E; McDonough, John E; Vandermeulen, Elly; Ruttens, David; Lammertyn, Elise J; Bellon, Hannelore; De Dycker, Els; Dooms, Christophe; Yserbyt, Jonas; Verleden, Geert M; Vanaudenaerde, Bart M; Wuyts, Wim A

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of interstitial lung diseases, however, clinically relevant biomarkers of diagnosis or prognosis are lacking. In this study, we investigated the levels of a fragment of Cytokeratin 19 (CYFRA 21.1) in bronchoalveolar lavage (BAL) of IPF patients at time of diagnosis. We further evaluated associations between CYFRA 21.1, pulmonary function evolution, mortality, and BAL cell count. Using the Lumipulse® G1200, CYFRA 21.1 was measured in BAL samples of 81 IPF patients and 9 controls. Based upon the median detected level (1.2 ng/mL) of CYFRA 21.1 in IPF patients, they were subdivided into an IPF CYFRA 21.1 low group (≤ 1.2 ng/mL) and IPF CYFRA 21.1 high group (> 1.2 ng/mL). The CYFRA 21.1 levels were significantly higher in BAL of IPF patients compared to controls (P = .0015).Worse survival was observed, but no changes in pulmonary function, for IPF patients with high CYFRA 21.1 levels versus patients with low CYFRA 21.1 levels [P = .030, HR: 0.41, (0.18-0.92)[. The CYFRA 21.1 level correlated with both neutrophils (%: R = 0.60, P < .0001; #: R = 0.47, P < .0001) and eosinophils (%: R = 0.38, P = .0005; #: R = 0.30, P < .0072). CYFRA 21.1 is increased in BAL of IPF patients. IPF patients with a high CYFRA 21.1 concentration have a worse survival. CYFRA 21.1 levels correlate with eosinophils and neutrophils. Further studies are warranted in using CYFRA 21.1 as a biomarker for IPF prognosis.

  18. MRI-based flow measurements in the main pulmonary artery to detect pulmonary arterial hypertension in patients with cystic fibrosis

    International Nuclear Information System (INIS)

    Wolf, T.; Anjorin, A.; Abolmaali, N.; Posselt, H.; Smaczny, C.; Vogl, T.J.

    2009-01-01

    Development of pulmonary arterial hypertension (PH) is a common problem in the course of patients suffering from cystic fibrosis (CF). This study was performed to evaluate MRI based flow measurements (MR venc ; Velocity ENCoding) to detect signs of an evolving PH in patients suffering from CF. 48 patients (median age: 16 years, range: 10 - 40 years, 25 female) suffering from CF of different severity (mean FEV1: 74 % ± 23, mean Shwachman-score: 63 ± 10) were examined using MRI based flow measurements of the main pulmonary artery (MPA). Phase-contrast flash sequences (TR: 9.6 ms, TE: 2.5 ms, bandwidth: 1395 Hertz/Pixel) were utilized. Results were compared to an age- and sex-matched group of 48 healthy subjects. Analyzed flow data where: heart frequency (HF), cardiac output (HZV), acceleration time (AT), proportional acceleration time related to heart rate (ATr), mean systolic blood velocity (MFG), peak velocity (Peak), maximum flow (Fluss max ), mean flow (Fluss mitt ) and distensibility (Dist). The comparison of means revealed significant differences only for MFG, Fluss max and Dist, but overlap was marked. However, using a scatter-plot of AT versus MFG, it was possible to identify five CF-patients demonstrating definite signs of PH: AT = 81 ms ± 14, MFG = 46 ± 11 cm/s, Dist = 41 % ± 7. These CF-patients where the most severely affected in the investigated group, two of them were listed for complete heart and lung transplantation. The comparison of this subgroup and the remaining CF-patients revealed a highly significant difference for the AT (p = 0.000001) without overlap. Screening of CF-patients for the development of PH using MR venc of the MPA is not possible. In later stages of disease, the quantification of AT, MFG and Dist in the MPA may be useful for the detection, follow-up and control of therapy of PH. MR venc of the MPA completes the MRI-based follow-up of lung parenchyma damage in patients suffering from CF. (orig.)

  19. [Value of non-invasive models of liver fibrosis in judgment of treatment timing in chronic hepatitis B patients with ALT < 2×upper limit of normal].

    Science.gov (United States)

    Zhou, Q Q; Hu, Y B; Zhou, K; Zhang, W W; Li, M H; Dong, P; Di, J G; Hong, L; Du, Q W; Xie, Y; Sun, Q F

    2016-09-20

    Objective: To investigate the value of non-invasive liver fibrosis models, FIB-4, S index, aspartate aminotransferase to platelet ratio index(APRI), globulin-platelet(GP)model, aspartate aminotransferase/platelet/gamma-glutamyl transpeptidase/alpha-fetoprotein(APGA), and platelet/age/phosphatase/alpha-fetoprotein/aspartate aminotransferase(PAPAS), in the diagnosis of marked liver fibrosis in chronic hepatitis B(CHB)patients with ALT liver biopsy was performed to obtain pathological results, and routine serological tests were performed, including routine blood test, serum biochemical parameters, hepatitis B virus(HBV)markers, and HBV DNA. According to liver pathology, the patients were divided into non-marked liver fibrosis group(S liver fibrosis group(S≥2)with 65 patients. The non-invasive models for predicting liver fibrosis was established with reference to original articles. SPSS 19.0 software was used for statistical analysis, and the receiver operating characteristic(ROC)curve was used to compare the value of different non-invasive models in predicting marked liver fibrosis in this population. Results: All the non-invasive models had a certain diagnostic value for liver fibrosis degree in these patients, and the areas under the ROC curve for APRI, FIB-4, APGA, S index, PAPAS, and GP model were 0.718, 0.691, 0.758, 0.729, 0.673, and 0.691, respectively. APGA had the largest area under the ROC curve(0.758, 95% CI 0.673-0.844), and gamma-glutamyl transpeptidase was significantly positively correlated with liver fibrosis degree. Conclusion: The non-invasive models of liver fibrosis can identify marked liver fibrosis in CHB patients with ALT liver biopsy to the certain degree.

  20. Clinical and nutritional aspects of cystic fibrosis patients assisted by a home enteral nutrition program in Brazil

    OpenAIRE

    Haack, Adriana; Garbi Novaes, Maria Rita

    2013-01-01

    This study to assessed 47 cystic fibrosis (CF) patients assisted by a program of Home Enteral Nutrition. Anthropometric measurements included weight, height, triceps skinfold thickness, waist circunference and spirometry was also performed. Enzymes, nutritional and fat-soluble vitamin supplementations were recorded. There were no associations with enzymes and vitamin supplements between groups that did or did not have a nutritional deficit. Spirometry of patients without nutritional deficit, ...

  1. 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.

  2. Evaluación nutricional dietética en pacientes afectos de fibrosis quística Dietetic nutritional assessment in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Aida E. Esplugas Montoya

    2008-09-01

    absorption of micronutrients and liposoluble vitamins. To maintain an appropriate nutritional status is a decisive aspect in the treatment of these patients. The aim of this paper was to characterize the dietetic nutritional status of children in nutritional risk situations. METHODS: A descriptive study was conducted in a group of patients with cystic fibrosis. The sample included 17 patients seen in “William Soler” Teaching Children Hospital. RESULTS: In the survey done, it was found that the caloric percentage distribution supplied by foods consumed by patients was 12 % for proteins, 33 % for fats, and 55 % for carbohydrates. Energy supplied by these food increased to 3 400 kcal with a minimal interval of 1 703 kcal, and a maximum of 6 180 kcal. For proteins, consumption was 101 g, with a range from 49 to 207 g; for fats it was 128 g, with a range between 60g and 270g; and for carbohydrates, it was 457 g, with a minimal interval of 243 g, and a maximum interval of 704 g. CONCLUSIONS: Dietetic assessment of a child may predict an alteration in its nutritional status before the biochemical alteration, and long before the clinical signs of defficiency be evident.

  3. Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

    Science.gov (United States)

    Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

    2018-04-18

    Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

  4. Protein turnover in malnourished patients with cystic fibrosis: Effects of elemental and nonelemental nutritional supplements

    International Nuclear Information System (INIS)

    Pelekanos, J.T.; Holt, T.L.; Ward, L.C.; Cleghorn, G.J.; Shepherd, R.W.

    1990-01-01

    To evaluate the relative efficacy of nonelemental versus semielemental enteral supplements for nutritional rehabilitation of cystic fibrosis (CF) patients, whole-body protein turnover using the [ 15 N]glycine method was studied in nine malnourished CF patients during enteral feedings, in a block design study comparing a semielemental formula (Criticare), a higher protein density but nonelemental formula (Traumacal) (T), and a nonelemental formula that had been modified to become isocaloric and isonitrogenous to the semielemental formula (modified Traumacal, MT). No significant differences in rates of protein synthesis or catabolism were observed comparing the three formulas. However, the higher protein density nonelemental formula resulted in higher net protein deposition compared to the other two formulas (T + 0.42 g kg-1 10 h-1 versus 0.33 g kg-1 10 h-1 for Criticare and -0.59 g kg-1 10 h-1 for MT), although this was significant (p less than 0.05) for the MT versus T comparison only. This study lends support to the use of less expensive nonelemental formulas for the nutritional management of malnourished patients with CF

  5. Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients

    DEFF Research Database (Denmark)

    Islam, S; Oh, H; Jalal, S

    2009-01-01

    pump protein MexY was determined by real-time PCR and correlated with susceptibilities to amikacin and tobramycin. The chromosomal genes mexZ, rplY, galU, PA5471 and nuoG, which were found to have a role in the gradual increase in MICs of aminoglycoside antibiotics in laboratory mutants of P....... aeruginosa, were analysed. MexY mRNA overproduction was found in 17/20 isolates collected in 1994 and 1997, and was correlated with decreased susceptibility to aminoglycosides. Alteration of the MexXY-OprM efflux system has been the main mechanism of resistance to aminoglycoside antibiotics in CF P......In total, 40 Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients were included in this study. Twenty of these were collected in 1994 and 1997, from six CF patients, and the rest were collected from different CF patients in 2000 and 2001. The relative expression of mRNA for the efflux...

  6. Iodine deficiency and subclinical hypothyroidism are common in cystic fibrosis patients.

    Science.gov (United States)

    Naehrlich, Lutz; Dörr, Helmuth-Günther; Bagheri-Behrouzi, Azadeh; Rauh, Manfred

    2013-04-01

    Disorders of thyroid function have been inconsistently described in cystic fibrosis (CF) patients and in CF transmembrane regulator protein knockout animals. The literature lacks reports on iodine status of CF individuals. We hypothesize, that iodine deficiency is common in CF and account for abnormal thyroid function in CF patients. We investigated 129 children, adolescents, and adults with CF, who were living in the northern part of Bavaria/Germany. Malnutrition and lung function were analyzed. Urinary iodine excretion, TSH (thyroid-stimulating hormone), and ft4 (free thyroxine) were measured and set in relation to population-based, age-adjusted reference ranges. Subclinical hypothyroidism (normal fT4, elevated TSH) was found in 11.6% of subjects, and iodine deficiency in 83.7%. No correlations were found with age, BMI, status of malnutrition, or lung function. Dramatic iodine deficiency was found in our cohort of CF patients. This condition can cause subclinical hypothyroidism; therefore, an individual iodine supplementation program is necessary and should be started immediately. Crown Copyright © 2012. Published by Elsevier GmbH. All rights reserved.

  7. Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients.

    Science.gov (United States)

    Bracht, Thilo; Mölleken, Christian; Ahrens, Maike; Poschmann, Gereon; Schlosser, Anders; Eisenacher, Martin; Stühler, Kai; Meyer, Helmut E; Schmiegel, Wolff H; Holmskov, Uffe; Sorensen, Grith L; Sitek, Barbara

    2016-07-04

    The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0-F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system). MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80 % sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV) was performed. MFAP4 levels were shown to differ between no to moderate fibrosis stages F0-F2 and severe stages (F3 and F4) with high statistical significance (t test on log scale, p value <2.2·10(-16)). In the LOOCV, the univariate classification resulted in 85.8 % sensitivity and 54.9 % specificity while the multivariate model yielded 81.3 % sensitivity and 61.5 % specificity (restricted approaches). We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals.

  8. Impact of old Schistosomiasis infection on the use of transient elastography (Fibroscan) for staging of fibrosis in chronic HCV patients.

    Science.gov (United States)

    Ramzy, Iman; Elsharkawy, Aisha; Fouad, Rabab; Hafez, Hanan Abdel; El Raziky, Maissa; El Akel, Wafaa; El-Sayed, Mohammad; Khattab, Hany; Shehata, Mohamed; Elsharkawy, Marwa; Radwan, Amr; Esmat, Gamal

    2017-12-01

    In tropical regions, Hepatitis C virus (HCV) - Schistosomiasis coinfection remains one of the health problems. With the new era of HCV treatment and the variety of methods of assessment of liver fibrosis so we aimed to evaluate the effectiveness of FibroScan for staging hepatic fibrosis in HCV-Schistosomiasis coinfected patients. Three groups of patients were enrolled. Group 1: chronic HCV with out antischistosomal antibody (122 patients), Group 2: chronic HCV with positive antischistosomal antibodies and without periportal tract thickening (122 patients), Group 3: chronic HCV with positive antischistosomal antibodies and ultrasonographic picture of periportal tract thickening (108 patients). Routine laboratory workup, serum Antischistosomal antibody, and Schistosomal antigen in serum were performed. Ultrasound guided liver biopsy with histopathological examination; abdominal ultrasound and fibroscan examination were done for all patients. The agreement between results of liver biopsy and results of fibroscan in the staging of fibrosis was the best in group 1 (55.7%), Although the agreement was higher among those with no periportal tract thickening (70.7%) and the disagreement was higher among those with positive schistosomal serology (66.5%), yet this relation was not statistically significant. Multivariate logistic regression analysis showed that disagreement is significantly associated with older age, higher BMI (≥30), and increase in anti Schistosomal antibody titer. Fibroscan is a reliable, non-invasive tool for staging hepatic fibrosis among HCV-schistosomiasis co-infected patients with no effect of the induced periportal tract thickening on the readings. Only higher antischistosomal antibody titres may cause disagreement between liver biopsy and fibroscan. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Prevalence and Profile of Fibrosis in Diabetic Patients with Non-alcoholic Fatty Liver Disease and the Associated Factors

    Directory of Open Access Journals (Sweden)

    Ignatius Bima Prasetya

    2017-04-01

    Full Text Available Background: the risk of Non-Alcoholic Fatty Liver Disease (NAFLD is increasing in patients with type-2 diabetes. Prevalence and factors related to the increased risk of NAFLD in diabetic patients in Indonesia has never been studied before. Data regarding the profile of fibrosis in the population has also been unknown. This study aimed to identify the difference on the profile of diabetic patients with and without NAFLD as well as the degree of fibrosis. Methods: the study was conducted using a cross-sectional method in type-2 diabetic patients who were treated at the outpatient clinic of endocrinology and metabolic division in Cipto Mangunkusumo Hospital. Sampling was done consecutively. Collected data comprised of age, duration of diabetes, body mass index (BMI, waist circumference, HDL, triglyceride, and HbA1C levels. Abdominal ultrasonography was conducted for all patients to determine the presence of NAFLD. Patients with NAFLD were subsequently underwent transient elastography in order to assess their degree of liver fibrosis. Chi-square or Fisher’s-Exact tests were used for bivariate analysis and logistic regression was used for multivariate analysis. Results: as many as 186 patients were analyzed in the study and 84 patients (45.2% were demonstrated to have NAFLD. Transient elastography examinations were carried out in 68 patients and 17 patients (25.0% were found with severe fibrosis. Univariate analysis showed significant differences on BMI (PR=1.878; 95%CI= 1.296-2.721; p<0.001 and waist circumference (PR=2.368; 95%CI= 1.117-5.017; p=0.018 between patients with and without NAFLD. However, the multivariate test showed that BMI was the only factor that had a significance difference between both groups (OR=2.989; 95%CI=1.625-5.499; p<0.001. Conclusion: prevalence of NAFLD among type-2 diabetic patients in Cipto Mangunkusumo Hospital has reached 45.2% and 25.0% among them had severe fibrosis. BMI is the only factor found to be associated

  10. The emergence of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis patients on inhaled antibiotics

    Directory of Open Access Journals (Sweden)

    Atqah AbdulWahab

    2017-01-01

    Full Text Available Introduction: Multidrug-resistant Pseudomonas aeruginosa (MDR-PA is an important and growing issue in the care of patients with cystic fibrosis (CF, and a major cause of morbidity and mortality. Objective: The objective of the study was to describe the frequency of MDR-PA recovered from the lower respiratory samples of pediatric and adult CF patients, and its antibiotic resistance pattern to commonly used antimicrobial agents including β-lactams, aminoglycosides, and fluoroquinolones. Materials and Methods: The lower respiratory isolates of P. aeruginosa were obtained from inpatients and outpatients CF clinics from a tertiary care teaching hospital for the period from October 2014 to September 2015. The identification and antimicrobial susceptibility for all the isolates were performed by using the BD Phoenix™ and E-test in compliance with Clinical and Laboratory Standards Institute (CLSI guidelines. Results: A total of 61 P. aeruginosa samples were isolated from thirty CF patients from twenty families. Twelve sputum samples were positive for MDR-PA (seven nonmucoid and five mucoid isolates from five CF patients (five families with moderate-to-very severe lung disease given MDR-PA frequency of 19.7%. The median age of the study group was 20 (range 10–30 years. Three CF patients were on chronic inhaled tobramycin and two on nebulized colistin. The antimicrobial patterns of isolates MDR-PA showed the highest rate of resistance toward each gentamycin, amikacin, and cefepime (100%, followed by 91.7% to ciprofloxacin, 75% to tobramycin, 58.3% to meropenem, and 50% to piperacillin-tazobactam. None of the isolates were resistant to colistin during the study period. Conclusion: The study results emphasize that the emergence of a significant problem in the clinical isolates of P. aeruginosa in CF patients that dictate appropriate attention to the antibiotic management after proper surveillance.

  11. Disease specific knowledge about cystic fibrosis, patient education and counselling in Poland

    Directory of Open Access Journals (Sweden)

    Sławomir Chomik

    2014-06-01

    Full Text Available introduction and objective. The presented study assesses levels of specific knowledge of the disease among cystic fibrosis (CF patients and their families, and evaluates the effectiveness of a targeted, disease specific education programme. materials and methods. A cross-sectional survey among 462 families with a CF child evaluated their knowledge of the disease. A one year follow up survey among 200 families assessed the effectiveness of an educational programme developed to correct gaps, errors and misconceptions identified in the previously administered survey. Self-administered, comprehensive, 5-domains, 45-item multiple-choice CF Disease Knowledge Questionnaire (CFDKQ was anonymously completed by 462 subjects. results. 228 respondents were male (49%, 234 female (51%. The level of disease-specific knowledge in the age groups 0–6 and 7–10 years, was significantly higher than in 11–14 and 15–18 years of age groups (p<0.005. General medical and Genetics/Reproduction knowledge was low in all patients. Significant predictors of patient and parental knowledge were age and domicile. Patients and parents rely heavily on doctors for information about CF (77%. The follow-up survey (CFDKQ emphasized that special education programmes significantly improved levels of disease specific knowledge (p<0.0001. conclusions. If left uncorrected, the misconceptions, gaps and errors in CF knowledge identified in the presented study could result in inadvertent non-adherence to treatment, and impact on the progression and outcome of the disease. Secondly, the results demonstrate the effectiveness of targeted, disease specific information in improving disease knowledge of CF patients and their families, and highlights the value and need for the development of educational programmes for chronically ill patients and their families.

  12. Elevated IgG4 serum levels in patients with cystic fibrosis.

    Science.gov (United States)

    Clerc, Axelle; Reynaud, Quitterie; Durupt, Stéphane; Chapuis-Cellier, Colette; Nové-Josserand, Raphaële; Durieu, Isabelle; Lega, Jean Christophe

    2017-01-01

    Serum immunoglobulin (Ig) G4 elevation has been associated with several pathological conditions other than IgG4-related disease (IgG4-RD). In cystic fibrosis (CF), an elevation of specific IgG4 has been associated with colonization and infection by Pseudomonas aeruginosa. IgG4 elevation may be a marker of chronic infection or inflammatory stimulation. The aim of this study was to explore the prevalence of elevated IgG4 levels in CF and its correlation with the major clinical and microbiological features found in CF patients. In a cross-sectional study, we analyzed data from a large cohort of adult CF patients attending the CF center of Lyon University Hospital. An elevated IgG4 level was defined as being above the cut-off value of 135 mg/dL. One hundred and sixty-five CF patients were analyzed. An IgG4 elevation was detected in 43 patients (26%). Compared with the control group (≤ 135 mg/dL), high IgG4 patients exhibited a greater prevalence of Staphylococcus aureus colonization and higher IgG, IgG1, IgG2 and IgE levels. No significant differences were observed in terms of pulmonary function, colonization with Pseudomonas aeruginosa, or the annual rate of bronchial exacerbations. An elevated IgG4 serum level was frequently detected in adult CF patients and did not appear to be associated with poor lung function. We suggest that IgG4 elevation is a marker of the activation of tolerance. Its clinical significance remains to be demonstrated.

  13. Reduced incidence of lung cancer in patients with idiopathic pulmonary fibrosis treated with pirfenidone.

    Science.gov (United States)

    Miura, Yukiko; Saito, Takefumi; Tanaka, Toru; Takoi, Hiroyuki; Yatagai, Yohei; Inomata, Minoru; Nei, Takahito; Saito, Yoshinobu; Gemma, Akihiko; Azuma, Arata

    2018-01-01

    Idiopathic pulmonary fibrosis (IPF) is a disease with a worse prognosis than some types of cancer. In patients with IPF, lung cancer is critical because of the associated high mortality rate from its progression and fatal complications from anticancer treatments. Therefore, preventing lung cancer in patients with IPF is primordial. Pirfenidone is an anti-fibrotic agent that reduces the decline in forced vital capacity. This study aimed to assess the effect of pirfenidone in the development of lung cancer in patients with IPF. Data from 261 patients with IPF with and without pirfenidone were retrospectively reviewed, and the incidence of lung cancer was analyzed. In the pirfenidone group, the incidence of lung cancer was significantly lower than in the non-pirfenidone group (2.4% vs. 22.0%, P < 0.0001). Multivariate Cox proportional hazards regression analysis demonstrated that pirfenidone decreased the risk of lung cancer (hazard ratio, 0.11; 95% confidence interval, 0.03 to 0.46; P = 0.003), whereas coexisting emphysema increased the incidence of lung cancer (hazard ratio, 3.22; 95% confidence interval, 1.35 to 7.70; P = 0.009). Pirfenidone might correlate with a decreased risk of lung cancer in patients with IPF. However, no definite conclusion can be drawn from this retrospective study, and a multicenter, prospective cohort study is still warranted to confirm the effect of pirfenidone on lung cancer in patients with IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  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. Evaluating the sinus and Nasal Quality of Life Survey in the pediatric cystic fibrosis patient population.

    Science.gov (United States)

    Xie, Deborah X; Wu, Jeffanie; Kelly, Katherine; Brown, Rebekah F; Shannon, Chevis; Virgin, Frank W

    2017-11-01

    The Sinus and Nasal Quality of Life Survey (SN-5) is a validated quality of life (QOL) questionnaire for chronic rhinosinusitis in patients age 2-12. Its utility in the cystic fibrosis (CF) has been studied, but not yet validated. The purpose of this study is to determine the effectiveness of the SN-5 for evaluation of sinonasal symptoms in the pediatric CF population. This retrospective study analyzed SN-5 surveys completed between 2012 and 2015 by pediatric CF patients and caregivers. Baseline and follow-up overall QOL scores and specific symptom scores were obtained from surveys completed in the three-year span. Non-parametric statistics were conducted to identify differences in survey data. A total of 165 patients completed baseline and follow-up surveys. The overall QOL of the patient cohort did not change over the duration of the study (p = 0.660). Thirty-seven patients indicated higher overall QOL, with all five symptom scores showing significant improvement. Analysis by age group showed that QOL was significantly correlated with all five symptoms for children ages 0-4. In patients 5-12 years, overall QOL was only correlated with sinus infection (r = -0.3090, p = 0.01). QOL was significantly correlated with sinus infection (r = -0.2903, p = 0.04) and allergy symptoms (r = -0.5644, p 12 years of age. There remains a need for a validated CRS QOL tool for children with CF. Though the SN-5 has previously been described as a potential instrument, our data suggest that it may be more valuable in children ages 0-4. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Structure of the cystic fibrosis transmembrane conductance regulator in the inward-facing conformation revealed by single particle electron microscopy

    Directory of Open Access Journals (Sweden)

    Ateeq Al-Zahrani

    2015-05-01

    Full Text Available The most common inherited disease in European populations is cystic fibrosis. Mutations in the gene lead to loss of function of the cystic fibrosis transmembrane conductance regulator protein (CFTR. CFTR is a member of the ATP-binding cassette family of membrane proteins that mostly act as active transporters using ATP to move substances across membranes. These proteins undergo large conformational changes during the transport cycle, consistent with an inward-facing to outward-facing translocation mechanism that was originally proposed by Jardetzky. CFTR is the only member of this family of proteins that functions as an ion channel, and in this case ATP and phosphorylation of a regulatory domain controls the opening of the channel. In this article we describe the inward-facing conformation of the protein and show it can be modulated by the presence of a purified recombinant NHERF1-PDZ1 domain that binds with high affinity to the CFTR C-terminal PDZ motif (-QDTRL. ATP hydrolysis activity of CFTR can also be modulated by glutathione, which we postulate may bind to the inward-facing conformation of the protein. A homology model for CFTR, based on a mitochondrial ABC transporter of glutathione in the inward-facing configuration has been generated. The map and the model are discussed with respect to the biology of the channel and the specific relationship between glutathione levels in the cell and CFTR. Finally, disease-causing mutations are mapped within the model and discussed in terms of their likely physiological effects.

  17. Diagnostic Accuracy of Platelet Count and Platelet Indices in Noninvasive Assessment of Fibrosis in Nonalcoholic Fatty Liver Disease Patients

    Directory of Open Access Journals (Sweden)

    Tamara Milovanovic Alempijevic

    2017-01-01

    Full Text Available Objective. Keeping in mind the rising prevalence of nonalcoholic fatty liver disease (NAFLD and the need to establish noninvasive tests for its detection, the aim of our study was to investigate whether platelet count (PC, mean platelet volume (MPV, and platelet distribution width (PDW can predict the presence of liver fibrosis in this group of patients. Methods. In 98 patients with NAFLD and 60 healthy volunteers, complete blood counts with automated differential counts were performed and values of PC, PDW, MPV, and PCT were analyzed. Results. Patients with NAFLD had lower PC and higher MPV, PCT, and PDW compared to the controls (P < 0.05. When NAFLD group was stratified according to severity of liver fibrosis, there was a statistically significant difference in the average values of PDW and PC between the groups (P < 0.05. Conclusion. Patients with NAFLD have significantly higher values of PCT, PDW, and MPV when compared to the healthy controls. Further studies are needed to establish their potential use for prediction of the degree of liver steatosis and fibrosis in NAFLD patients.

  18. Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Q.; Li, T. [Department of Respirology, Qilu Hospital of Shandong University, Jinan, Shandong Province (China); Li, J.C. [Neurosurgical Intensive Care Unit, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province (China); Li, Y. [Department of Respirology, Qilu Hospital of Shandong University, Jinan, Shandong Province (China)

    2015-07-10

    The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m{sup 2}), normal weight (18.5≤BMI<25.0 kg/m{sup 2}), overweight (25.0≤BMI<30.0 kg/m{sup 2}), and obese (BMI≥30.0 kg/m{sup 2}). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m{sup 2}. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ{sup 2}=35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis.

  19. Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis

    International Nuclear Information System (INIS)

    Qi, Q.; Li, T.; Li, J.C.; Li, Y.

    2015-01-01

    The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m 2 ), normal weight (18.5≤BMI<25.0 kg/m 2 ), overweight (25.0≤BMI<30.0 kg/m 2 ), and obese (BMI≥30.0 kg/m 2 ). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m 2 . The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ 2 =35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis

  20. Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease Than Transient Elastography.

    Science.gov (United States)

    Imajo, Kento; Kessoku, Takaomi; Honda, Yasushi; Tomeno, Wataru; Ogawa, Yuji; Mawatari, Hironori; Fujita, Koji; Yoneda, Masato; Taguri, Masataka; Hyogo, Hideyuki; Sumida, Yoshio; Ono, Masafumi; Eguchi, Yuichiro; Inoue, Tomio; Yamanaka, Takeharu; Wada, Koichiro; Saito, Satoru; Nakajima, Atsushi

    2016-03-01

    Noninvasive methods have been evaluated for the assessment of liver fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We compared the ability of transient elastography (TE) with the M-probe, and magnetic resonance elastography (MRE) to assess liver fibrosis. Findings from magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF) measurements were compared with those from TE-based controlled attenuation parameter (CAP) measurements to assess steatosis. We performed a cross-sectional study of 142 patients with NAFLD (identified by liver biopsy; mean body mass index, 28.1 kg/m(2)) in Japan from July 2013 through April 2015. Our study also included 10 comparable subjects without NAFLD (controls). All study subjects were evaluated by TE (including CAP measurements), MRI using the MRE and PDFF techniques. TE identified patients with fibrosis stage ≥2 with an area under the receiver operating characteristic (AUROC) curve value of 0.82 (95% confidence interval [CI]: 0.74-0.89), whereas MRE identified these patients with an AUROC curve value of 0.91 (95% CI: 0.86-0.96; P = .001). TE-based CAP measurements identified patients with hepatic steatosis grade ≥2 with an AUROC curve value of 0.73 (95% CI: 0.64-0.81) and PDFF methods identified them with an AUROC curve value of 0.90 (95% CI: 0.82-0.97; P steatosis in patients with NAFLD than TE and CAP methods. MRI-based noninvasive assessment of liver fibrosis and steatosis is a potential alternative to liver biopsy in clinical practice. UMIN Clinical Trials Registry No. UMIN000012757. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis

    Directory of Open Access Journals (Sweden)

    Q. Qi

    2015-08-01

    Full Text Available The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m2, normal weight (18.5≤BMI<25.0 kg/m2, overweight (25.0≤BMI<30.0 kg/m2, and obese (BMI≥30.0 kg/m2. Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m2. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ2=35.16, P<0.001. The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis.

  2. The need for patient-centred clinical research in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Russell, Anne-Marie; Sprangers, Mirjam A G; Wibberley, Steven; Snell, Noel; Rose, Daniel M; Swigris, Jeff J

    2015-09-24

    Patient-centredness is an accepted term and is perceived by healthcare professionals to be morally and ethically desirable. We are motivated by the belief that this approach will improve the patient-professional experience of the decision-making process and improve health outcomes. We acknowledge that patients, either as participants or as co-investigators, have positive contributions to make to research. As the idiopathic pulmonary fibrosis (IPF) community enters a new era of clinical research activity we consider that there is greater capacity for patient involvement and partnership.Patient involvement in research can be optimised through collaborations in the research design, study conduct, and dissemination. There is increasing interest in using patient- reported outcomes (PROs), such as health-related quality of life, and symptoms measures to inform decision-making and ensure patient perspectives are taken into account. PROs are an essential component of specialist IPF services, to monitor and improve care delivery and to measure and benchmark performance. In clinical trials, PROs can additionally be used to define entry criteria, evaluate efficacy of an intervention, and evaluate adverse events. We suggest that there is a much wider scope for including patient-centred PROs in clinical research and for creative thought in developing patient co-investigator roles.Participation in research activity requires highly refined decision-making processes, particularly in a condition such as IPF, which has an often unpredictable trajectory. The IPF research landscape has changed and the design and conduct of clinical trials in IPF requires some radical rethinking. It is accepted that involving patients in the role of co-investigators will impact the research questions we ask and result in study designs that are patient-centred. IPF clinical trials have been hindered by the lack of availability of validated, disease-specific questionnaires. A conservative approach

  3. Peptide microarray analysis of substrate specificity of the transmembrane Ser/Thr kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance regulator and phosphorylase.

    Science.gov (United States)

    Wang, Hong; Brautigan, David L

    2006-11-01

    Human lemur (Lmr) kinases are predicted to be Tyr kinases based on sequences and are related to neurotrophin receptor Trk kinases. This study used homogeneous recombinant KPI-2 (Lmr2, LMTK2, Cprk, brain-enriched protein kinase) kinase domain and a library of 1,154 peptides on a microarray to analyze substrate specificity. We found that KPI-2 is strictly a Ser/Thr kinase that reacts with Ser either preceded by or followed by Pro residues but unlike other Pro-directed kinases does not strictly require an adjacent Pro residue. The most reactive peptide in the library corresponds to Ser-737 of cystic fibrosis transmembrane conductance regulator, and the recombinant R domain of cystic fibrosis transmembrane conductance regulator was a preferred substrate. Furthermore the KPI-2 kinase phosphorylated peptides corresponding to the single site in phosphorylase and purified phosphorylase b, making this only the second known phosphorylase b kinase. Phosphorylase was used as a specific substrate to show that KPI-2 is inhibited in living cells by addition of nerve growth factor or serum. The results demonstrate the utility of the peptide library to probe specificity and discover kinase substrates and offer a specific assay that reveals hormonal regulation of the activity of this unusual transmembrane kinase.

  4. The reliability of lung crackle characteristics in cystic fibrosis and bronchiectasis patients in a clinical setting

    International Nuclear Information System (INIS)

    Marques, Alda; Bruton, Anne; Barney, Anna

    2009-01-01

    Lung sounds provide useful information for assessing and monitoring respiratory patients, but standard auscultation is subjective. Computer aided lung sound analysis (CALSA) enables the quantification and characterisation of added lung sounds (e.g. crackles). At present, little is known about the reliability of these sound characteristics. Therefore, the aim of this study was to explore the reliability of crackle initial deflection width (IDW) and two-cycle deflection (2CD) in a clinical population. Fifty-four subjects (37 bronchiectasis, 17 cystic fibrosis) were recruited from out-patient clinics. Three repeated lung sound recordings were taken at seven anatomical sites with a digital stethoscope connected to a laptop computer. The intra-subject reliability of crackle IDW and 2CD was found to be 'good' to 'excellent', estimated by the analysis of variance, intraclass correlation coefficient (IDW 0.76;0.85, 2CD 0.83;0.94), Bland and Altman 95% limits of agreement (IDW −0.50;0.47 ms, 2CD −2.12;1.87 ms) and smallest real difference (IDW 0.30;0.66 ms, 2CD 1.57;2.42 ms). Crackle 2CD was found to be more reliable than IDW. It is concluded that crackle IDW and 2CD characterized by CALSA have good test–retest reliability. This technique requires further evaluation since CALSA has potential to diagnose or monitor respiratory conditions, and provide an objective physiological measure for respiratory interventions

  5. Genetic Adaptation of Achromobacter sp. during Persistence in the Lungs of Cystic Fibrosis Patients.

    Directory of Open Access Journals (Sweden)

    Winnie Ridderberg

    Full Text Available Achromobacter species are increasingly isolated from the respiratory tract of cystic fibrosis patients and often a chronic infection is established. How Achromobacter sp. adapts to the human host remains uncharacterised. By comparing longitudinally collected isolates of Achromobacter sp. isolated from five CF patients, we have investigated the within-host evolution of clonal lineages. The majority of identified mutations were isolate-specific suggesting co-evolution of several subpopulations from the original infecting isolate. The largest proportion of mutated genes were involved in the general metabolism of the bacterium, but genes involved in virulence and antimicrobial resistance were also affected. A number of virulence genes required for initiation of acute infection were selected against, e.g. genes of the type I and type III secretion systems and genes related to pilus and flagellum formation or function. Six antimicrobial resistance genes or their regulatory genes were mutated, including large deletions affecting the repressor genes of an RND-family efflux pump and a beta-lactamase. Convergent evolution was observed for five genes that were all implicated in bacterial virulence. Characterisation of genes involved in adaptation of Achromobacter to the human host is required for understanding the pathogen-host interaction and facilitate design of future therapeutic interventions.

  6. Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient

    DEFF Research Database (Denmark)

    Main, K M; Skov, M; Sillesen, Ida Blok

    2002-01-01

    and 1,600 microg budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total...

  7. Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Li, Fu Jun; Surolia, Ranu; Li, Huashi; Wang, Zheng; Kulkarni, Tejaswini; Liu, Gang; de Andrade, Joao A; Kass, Daniel J; Thannickal, Victor J; Duncan, Steven R; Antony, Veena B

    2017-09-01

    Autoimmunity has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, the repertoire of autoantigens involved in this disease and the clinical relevance of these autoimmune responses are still being explored. Our initial discovery assays demonstrated that circulating and intrapulmonary vimentin levels are increased in IPF patients. Subsequent studies showed native vimentin induced HLA-DR-dependent in vitro proliferation of CD4 T cells from IPF patients and enhanced the production of IL-4, IL-17, and TGF-β1 by these lymphocytes in contrast to normal control specimens. Vimentin supplementation of IPF PBMC cultures also resulted in HLA-DR-dependent production of IgG with anti-vimentin specificities. Circulating anti-vimentin IgG autoantibody levels were much greater in IPF subjects from the University of Alabama at Birmingham ( n = 102) and the University of Pittsburgh (U. Pitt., n = 70) than in normal controls. Anti-vimentin autoantibody levels in IPF patients were HLA biased and inversely correlated with physiological measurements of lung function (i.e., forced expiratory volumes and diffusing capacities). Despite considerable intergroup differences in transplant-free survival between these two independent IPF cohorts, serious adverse outcomes were most frequent among the patients within each population that had the highest anti-vimentin autoantibody levels (University of Alabama at Birmingham: hazard ratio 2.5, 95% confidence interval 1.2-5.3, p = 0.012; University of Pittsburgh: hazard ratio 2.7, 95% confidence interval 1.3-5.5, p = 0.006). These data show that anti-vimentin autoreactivity is prevalent in IPF patients and is strongly associated with disease manifestations. These findings have implications with regard to the pathogenesis of this enigmatic disease and raise the possibility that therapies specifically directed at these autoimmune processes could have therapeutic efficacy. Copyright © 2017 by The American Association

  8. Long term follow-up of a tobacco prevention and cessation program in cystic fibrosis patients.

    Science.gov (United States)

    Ortega-García, Juan Antonio; Perales, Joseph E; Cárceles-Álvarez, Alberto; Sánchez-Sauco, Miguel Felipe; Villalona, Seiichi; Mondejar-López, Pedro; Pastor-Vivero, María Dolores; Mira Escolano, Pilar; James-Vega, Diana Carolina; Sánchez-Solís, Manuel

    2016-03-02

    This study evaluates the impact over time of a telephone-based intervention in tobacco cessation and prevention targeting patients with cystic fibrosis (CF) in the Mediterranean region of Murcia, Spain. We conducted an experimental prospective study with a cohort of CF patients using an integrative smoking cessation programme, between 2008 and 2013. The target population included family members and patients from the Regional CF unit. The study included an initial tobacco exposure questionnaire, measurement of lung function, urinary cotinine levels, anthropomorphic measures and the administered intervention at specific time intervals. Of the 88 patients tracked through follow-up, active smoking rates were reduced from 10.23% to 4.55% (p = 0.06). Environmental tobacco exposure was reduced in non-smoker patients from 62.03% to 36.90% (p < 0.01) during the five year follow-up. Significant reductions in the gradient of household tobacco smoke exposure were also observed with a decrease of 12.60%, from 31.65% (n = 25/79) to 19.05% (n = 16/84) in 2013 (p = <0.01). Cotinine was significantly correlated with both active and passive exposure (p<0.01) with a significant reduction of cotinine levels from 63.13 (28.58-97.69) to 20.56 (0.86-40.27) ng/ml (p<0.01). The intervention to significantly increase the likelihood of family quitting (smoke-free home) was 1.26 (1.05-1.54). Telephone based interventions for tobacco cessation and prevention is a useful tool when applied over time. Trained intervention professionals in this area are needed in the environmental health approach for the treatment of CF.

  9. Antibiotic-resistant obligate anaerobes during exacerbations of cystic fibrosis patients.

    Science.gov (United States)

    Worlitzsch, D; Rintelen, C; Böhm, K; Wollschläger, B; Merkel, N; Borneff-Lipp, M; Döring, G

    2009-05-01

    Pseudomonas aeruginosa and Staphylococcus aureus are thought to cause the majority of lung infections in patients with cystic fibrosis (CF). However, other bacterial pathogens may contribute to the pathophysiology of lung disease. Here, obligate anaerobes were identified in a cross-sectional study, and cell numbers and antibiotic susceptibilities of facultative and obligate anaerobes from 114 sputum samples from nine children and 36 adults with CF were determined. Furthermore, in 12 CF patients, we investigated whether conventional intravenous antibiotic therapy, administered during acute exacerbations, would affect the numbers of obligate anaerobes. Fifteen genera of obligate anaerobes were identified in 91% of the CF patients. Cell numbers (mean: 2.2 x 10(7) +/- standard deviation 6.9 x 10(7) CFU/mL of sputum sample) were comparable to those of P. aeruginosa and S. aureus. Staphylococcus saccharolyticus and Peptostreptococcus prevotii were most prevalent. Infection with P. aeruginosa did not increase the likelihood that obligate anaerobes are present in sputum specimens. Single obligate anaerobic species persisted for up to 11 months in sputum plugs in vivo. Patients with and without obligate anaerobes in sputum specimens did not differ in lung function. Intravenous therapy directed against P. aeruginosa during acute exacerbations increased lung function, but did not reduce the numbers of obligate anaerobes. Obligate anaerobic species differed widely in their patterns of resistance against meropenem, piperacillin-tazobactam, clindamycin, metronidazole and ceftazidime. In 58% of patients with acute exacerbations, obligate anaerobes were detected that were resistant to the antibiotics used for treatment. Antibiotic therapy, optimized to target anaerobes in addition to P. aeruginosa, may improve the management of CF lung disease.

  10. Patients' experiences of coping with Idiopathic Pulmonary Fibrosis and their recommendations for its clinical management.

    Science.gov (United States)

    Senanayake, Sameera; Harrison, Kim; Lewis, Michael; McNarry, Melitta; Hudson, Joanne

    2018-01-01

    Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive and life-limiting condition. From a healthcare perspective it is vital to establish effective methods of improving the quality of remaining life in these patients. This requires a detailed understanding of the multiple impacts of an IPF diagnosis on the individual. We sought to understand how patients coped with their initial diagnosis, how they live with the disease day-to-day, and their experiences and opinions of the professional support they receive. A patient-centred approach was used to explore the social, psychological and physical impacts of IPF. Semi-structured interviews were conducted by an experienced academic. Interview questions were written by the researchers but guided by informal conversations with patients and clinicians. An inductive thematic approach was used to analyse the data, allowing us to identify common themes in the patients' experiences. Of fifty invited participants, ten took part in the study (aged 53-81 years; 9 male). Inductive analysis of interviews identified seven second-order themes and eleven first-order themes, represented by two General Dimensions: 'Patient experience with the condition' and 'Patient-led recommendations for practice'. The key message on 'coping' in these patients was that acceptance of their condition led to a sense of optimism. Participants reported using appraisal-focused coping strategies to change their perspectives (thinking positively) and emotion-focused strategies to overcome depression (the main opportunity for emotional expression being an IPF support group). The support group also facilitated problem-focused coping: individuals exchanged knowledge and experience and gave one another tips on how to live with their condition. Health professionals should provide patients with information that focuses on living with IPF, encouraging them to make lifestyle changes and adaptations to improve quality of life. Family members should receive

  11. Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Petta, S; Amato, M C; Di Marco, V; Cammà, C; Pizzolanti, G; Barcellona, M R; Cabibi, D; Galluzzo, A; Sinagra, D; Giordano, C; Craxì, A

    2012-01-01

    Metabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD). To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. One hundred and forty-two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. Serum levels of TNFα, IL-6, adiponectin and leptin were also assessed. All biopsies were scored for NAFLD activity score (NAS) and its components, and for staging (Kleiner). By multiple linear regression analysis, VAI was independently associated with higher HOMA (P = 0.04), and fibrosis (P = 0.04). In addition, an independent association was found between higher VAI and lower adiponectin levels (P = 0.002). Higher HOMA (OR 1.149, 95% CI 1.003-1.316, P = 0.04), higher VAI (OR 1.446, 95% CI 1.023-2.043, P = 0.03), lobular inflammation (OR 3.777, 95% CI 1.771-8.051, P = 0.001), and ballooning (OR 2.884, 95% CI 1.231-6.757, P = 0.01) were correlated with significant fibrosis (F2-F4) on multiple logistic regression analysis. In particular, the prevalence of significant fibrosis progressively increased from patients with a VAI ≤ 2.1 and HOMA ≤ 3.4 (26%) to those with a VAI > 2.1 and HOMA > 3.4 (83%). In NAFLD patients, visceral adiposity index is an expression of both qualitative and quantitative adipose tissue dysfunction and, together with insulin resistance, is independently correlated with significant fibrosis. © 2011 Blackwell Publishing Ltd.

  12. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Kowdley, Kris V; Belt, Patricia; Wilson, Laura A; Yeh, Matthew M; Neuschwander-Tetri, Brent A; Chalasani, Naga; Sanyal, Arun J; Nelson, James E

    2012-01-01

    Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P 1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P 1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis. Copyright © 2011 American Association for the Study of Liver Diseases.

  13. LEFT ATRIAL FIBROSIS IN PATIENTS WITH ATRIAL FIBRILLATION ACCORDING TO MAGNETIC RESONANCE IMAGING WITH LATE GADOLINIUM ENHANCEMENT

    Directory of Open Access Journals (Sweden)

    O. V. Stukalova

    2015-01-01

    Full Text Available Rationale: Atrial fibrillation (AF is the most common type of arrhythmia. Left atrial abnormalities in AF require further investigation.Aim: To evaluate characteristics of myocardial structure of the left atrium by magnetic resonance imaging (MRI with delayed contrast enhancement in patients with AF associated with essential hypertension (EH, in those without any cardiovascular disorders, and in patients with AF after cryoablation of the pulmonary artery orifice.Materials and methods: The study enrolled 53 patients with AF (mean age 56 years. Twenty eight of them had AF without any associated cardiovascular disorders (lone AF, or LAF group, 25 patients had AF related to EH (AF + EH group. Three patients had undergone anti-arrhythmic intervention. Cardiac MRI was performed in all patients with high resolution late gadolinium enhancement (LGE at 15–20 min after i.v. gadoversetamide (0.15 mmol/kg. For LGE MRI, we used a novel high resolution inversion recovery (inversion times 290–340 ms magnetic resonance pulse sequence with isotropic voxel (size 1.25 . 1.25 .2.5 mm and fat saturation. Left atrium walls were segmented semi-automatically on the LGE images. Left atrium fibrosis quantification was performed with the original software LGE Heart Analyzer, developed in Russian Cardiology Research and Production Complex (Moscow.Results: Left atrium fibrosis (mean, 9 [1.7; 18] % was found both in patients with AF + EH and with lone AF. There was a trend towards more significant left atrial fibrosis in the group of AF + EH, compared to that in the lone AF group (10.972 [6.98; 19.366] % vs 4.37 [0.893; 18.575] %, respectively, p = 0.1. The extent of left atrium fibrosis correlated with left atrium dilatation (r = 0.37, p < 0.001 and with the decreased ejection fraction (r = -0.4, р < 0.001. The patients who had undergone an antiarrhythmic intervention, demonstrated formation of intensive LGE zones in the ablation areas.Conclusion: Quantification of

  14. Clinical efficacy and safety of ICS/LABA in patients with combined idiopathic pulmonary fibrosis and emphysema.

    Science.gov (United States)

    Dong, Fushi; Zhang, Yimei; Chi, Fangzhou; Song, Qi; Zhang, Lijuan; Wang, Yupeng; Che, Chunli

    2015-01-01

    The study aim was to explore the clinical efficacy and safety of inhaled corticosteroids (ICS)/long-acting beta2-agonists (LABA) in combined with idiopathic pulmonary fibrosis and emphysema. 45 patients with combined idiopathic pulmonary fibrosis and emphysema (CPFE) who were treated with ICS/LABA (Group A), 24 patients with CPFE who were treated without ICS/LABA (Group B) and 35 patients with idiopathic pulmonary fibrosis (IPF) (Group C) were enrolled into this study. Then, clinical efficacy and safety of ICS/LABA was analyzed through lung function scores and lung high-resolution computed tomography (HRCT) scans. Compared with baseline levels, the FEV1%, FVC% and DLCO% levels were increased 11.2%, 13.53% and 12.8% respectively in group A, but declined 14.21%, 16.8% and 21.25% respectively in group B, meanwhile, lung HRCT score was declined 9.31 in group A but increased 14.87 in group B, and there was significant difference between group A and group B (P0.05). The incidence of adverse reaction was higher in group A than that in group B during this study, but there was no significant difference (P>0.05). ICS/LABA therapy could improve lung function condition in patients with CPFE and declined acute out-break frequency and severity of diseases during acute episode period.

  15. Role of the Aspartate Transaminase and Platelet Ratio Index in Assessing Hepatic Fibrosis and Liver Inflammation in Adolescent Patients with HBeAg-Positive Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Yu Zhijian

    2015-01-01

    Full Text Available This study described an index of aspartate aminotransferase-to-platelet ratio index (APRI to assess hepatic fibrosis with limited expense and widespread availability compared to the liver biopsy in adolescent patients with CHB.

  16. Azithromycin maintenance therapy in patients with cystic fibrosis : A dose advice based on a review of pharmacokinetics, efficacy, and side effects

    NARCIS (Netherlands)

    Wilms, Erik B.; Touw, Daniel J.; Heijerman, Harry G.M.; Van Der Ent, Cornelis K.

    Azithromycin maintenance therapy results in improvement of respiratory function in patients with cystic fibrosis (CF). In azithromycin maintenance therapy, several dosing schemes are applied. In this review, we combine current knowledge about azithromycin pharmacokinetics with the dosing schedules

  17. Cellular responses of A549 alveolar epithelial cells to serially collected Pseudomonas aeruginosa from cystic fibrosis patients at different stages of pulmonary infection

    DEFF Research Database (Denmark)

    Hawdon, Nicole A; Aval, Pouya Sadeghi; Barnes, Rebecca J

    2010-01-01

    Pseudomonas aeruginosa is the major cause of chronic pulmonary disease in cystic fibrosis (CF) patients. During chronic infection, P. aeruginosa lose certain virulence factors, transform into a mucoid phenotype, and develop antibiotic resistance. We hypothesized that these genetic and phenotypic ...

  18. Oxandrolone Improves Height Velocity and BMI in Patients with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Todd Varness

    2009-01-01

    Full Text Available Objective. To evaluate the effectiveness of oxandrolone in improving the nutritional status and linear growth of pediatric patients with cystic fibrosis (CF. Methods. Medical records of patients with CF treated with oxandrolone were reviewed for height z score, height velocity (HV, BMI z score, weight velocity (WV, Tanner stage, pulmonary function, liver enzyme levels, and any reported adverse events. Data were compared before (pre-Ox and after (Ox oxandrolone using a paired t-test. Results. 5 subjects (ages 8.5–14.5 years were treated with oxandrolone 2.5 mg daily for 8–38 months. After 8–12 months of treatment, there was a statistically significant improvement in HV (pre-Ox=5.3±1.4 cm/yr, Ox=8.3±1.2 cm/yr, P<.01 and BMI z score (pre-Ox=−0.61±1.04, Ox=−0.30±0.86, P=.02. Both height z score (pre-Ox=−1.64±0.63, Ox=−1.30±0.49, P=.057 and WV (pre-Ox=4.2±3.7 kg/yr, Ox =6.8±1.0 kg/yr, P=.072 showed beneficial trends that did not reach statistical significance. No adverse events were reported. Conclusions. In this brief clinical report, oxandrolone improved the HV and BMI z score in patients with CF. Larger studies are needed to determine if oxandrolone is an effective, safe, and affordable option to stimulate appetite, improve weight gain, and promote linear growth in patients with CF.

  19. Iron accumulates in the lavage and explanted lungs of cystic fibrosis patients.

    Science.gov (United States)

    Abstract Oxidative stress participates in the pathophysiology of cystic fibrosis (CF). An underlying disruption in iron homeostasis can frequently be demonstrated in injuries and diseases associated with an oxidative stress. We tested the hypothesis that iron accumulation and ...

  20. Serial quantitative CT evaluation for patients with idiopathic pulmonary fibrosis (IPF) using Gaussian Histogram Normalized Correlation (GHNC)

    International Nuclear Information System (INIS)

    Iwasawa, Tae; Ogura, Takashi; Nishimura, Junichi; Asakura, Akira; Gotoh, Toshiyuki; Yazawa, Takuya; Inoue, Tomio

    2006-01-01

    We assessed serial changes in high-resolution CT findings quantitatively using originally developed software Gaussian Histogram Normalized Correlation (GHNC) in 15 patients with idiopathic pulmonary fibrosis (IPF). Mean follow-up period was 1.4 years. The volume of honeycombing increased with 0.8±0.9%TLC (predicted Total lung capacity) per year, the normal lung volume reduced by 4.1±7.3%TLC per year. GHNC is useful for the quantitative evaluation. (author)

  1. Emphysema Is Common in Lungs of Cystic Fibrosis Lung Transplantation Patients: A Histopathological and Computed Tomography Study

    OpenAIRE

    Mets, Onno M.; Roothaan, Suzan M.; Bronsveld, Inez; Luijk, Bart; van de Graaf, Ed A.; Vink, Aryan; de Jong, Pim A.

    2015-01-01

    Background Lung disease in cystic fibrosis (CF) involves excessive inflammation, repetitive infections and development of bronchiectasis. Recently, literature on emphysema in CF has emerged, which might become an increasingly important disease component due to the increased life expectancy. The purpose of this study was to assess the presence and extent of emphysema in endstage CF lungs. Methods In explanted lungs of 20 CF patients emphysema was semi-quantitatively assessed on histology speci...

  2. Introduction to Pulmonary Fibrosis

    Science.gov (United States)

    ... page: Introduction to Pulmonary Fibrosis What Is Pulmonary Fibrosis? Pulmonary fibrosis is a disease where there is scarring ... of pulmonary fibrosis. Learn more How Is Pulmonary Fibrosis Diagnosed? Pulmonary fibrosis can be difficult to diagnose, so it ...

  3. Effectiveness of a Home-Based Active Video Game Programme in Young Cystic Fibrosis Patients.

    Science.gov (United States)

    Del Corral, Tamara; Cebrià I Iranzo, Maria Àngels; López-de-Uralde-Villanueva, Ibai; Martínez-Alejos, Roberto; Blanco, Isabel; Vilaró, Jordi

    2018-01-01

    Exercise-based rehabilitation is already a part of cystic fibrosis (CF) treatment; however, patient adherence is low. To assess the effectiveness of a home exercise programme using active video games (AVGs) as a training modality for children and adolescents with CF. Thirty-nine children with CF were randomised to a control group (CG, n = 20, age 11 ± 6 years; FEV1 86.2 ± 20.5% of predicted) or a training group (AVGG, n = 19, age 13 ± 3 years; FEV1 82.7 ± 21.7% of predicted). The home training protocol consisted of 30- to 60-min sessions, 5 days/week, for 6 weeks using a Nintendo Wii™ platform. Exercise capacity was measured by the 6-min walk test (6MWT) and modified shuttle walk test (MSWT); muscular strength was estimated using the horizontal jump test (HJT), medicine ball throw (MBT), and hand grip strength (right [RHG]; left [LHG]); and quality of life was rated using the Cystic Fibrosis Questionnaire-Revised (CFQ-R). All the children were measured at baseline, after rehabilitation, and at 12 months. For the group × time interaction ANOVAs, the AVGG showed significant between-group differences in exercise capacity: 6MWT farthest walking distance, 38.4 m (p < 0.01); MSWT farthest walking distance, 78.4 m (p < 0.05); and muscular strength: HJT 9.8 cm, MBT 30.8 cm, RHG 7 kg, and LHG 6.5 kg (p < 0.01), before versus after intervention. The CFQ-R reported significantly higher scores on respiratory symptoms after the intervention and favoured the AVGG, and there was an improvement in other domains after 12 months. Adherence to the home exercise programme was 95% during the 6- week intervention period. A home-based programme using AVGs can effectively improve exercise capacity, muscular strength and quality of life in the short-term in children and adolescents with CF. The effects of training on muscle performance and quality of life were sustained over 12 months. © 2017 S. Karger AG, Basel.

  4. Mathematical model reveals role of nucleotide signaling in airway surface liquid homeostasis and its dysregulation in cystic fibrosis.

    Science.gov (United States)

    Sandefur, Conner I; Boucher, Richard C; Elston, Timothy C

    2017-08-29

    Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease. A systems-level description of airway surface liquid (ASL) homeostasis could accelerate development of such therapies. Accordingly, we developed a mathematical model to describe the dynamic coupling of ion and water transport to extracellular purinergic signaling. We trained our model from steady-state and time-dependent experimental measurements made using normal and cystic fibrosis (CF) cultured human airway epithelium. To reproduce CF conditions, reduced chloride secretion, increased potassium secretion, and increased sodium absorption were required. The model accurately predicted ASL height under basal normal and CF conditions and the collapse of surface hydration due to the accelerated nucleotide metabolism associated with CF exacerbations. Finally, the model predicted a therapeutic strategy to deliver nucleotide receptor agonists to effectively rehydrate the ASL of CF airways.

  5. Strategies to optimize treatment adherence in adolescent patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Bishay LC

    2016-10-01

    Full Text Available Lara C Bishay, Gregory S Sawicki Division of Respiratory Diseases, Boston Children’s Hospital, Boston, MA, USA Abstract: While development of new treatments for cystic fibrosis (CF has led to a significant improvement in survival age, routine daily treatment for CF is complex, burdensome, and time intensive. Adolescence is a period of decline in pulmonary function in CF, and is also a time when adherence to prescribed treatment plans for CF tends to decrease. Challenges to adherence in adolescents with CF include decreased parental involvement, time management and significant treatment burden, and adolescent perceptions of the necessity and value of the treatments prescribed. Studies of interventions to improve adherence are limited and focus on education, without significant evidence of success. Smaller studies on behavioral techniques do not focus on adolescents. Other challenges for improving adherence in adolescents with CF include infection control practices limiting in-person interactions. This review focuses on the existing evidence base on adherence intervention in adolescents with CF. Future directions for efforts to optimize treatment adherence in adolescents with CF include reducing treatment burden, developing patient-driven technology to improve tracking, communication, and online support, and rethinking the CF health services model to include assessment of individualized adherence barriers. Keywords: compliance, adolescence, medication, self management, intervention

  6. Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2012-02-01

    RATIONALE: Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking. OBJECTIVES: To investigate the antiinflammatory effect of hypertonic saline (HTS) treatment within the CF lung by focusing on IL-8. METHODS: Degradation of IL-8 in CF lung secretions after treatment with glycosaminoglycan lyases and HTS was analyzed by Western blot analysis and ELISA. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post nebulization of HTS (7% saline). MEASUREMENTS AND MAIN RESULTS: In vivo CF bronchoalveolar lavage fluid (BALF) IL-8 levels were significantly higher than the control group (P < 0.05). Digesting glycosaminoglycans in CF BALF displaced IL-8 from glycosaminoglycan matrices, rendering the chemokine susceptible to proteolytic cleavage. High sodium concentrations also liberate IL-8 in CF BALF in vitro, and in vivo in CF sputum from patients receiving aerosolized HTS, resulting in degradation of IL-8 and decreased neutrophil chemotactic efficiency. CONCLUSIONS: Glycosaminoglycans possess the ability to influence the chemokine profile of the CF lung by binding and stabilizing IL-8, which promotes neutrophil chemotaxis and activation. Nebulized hypertonic saline treatment disrupts the interaction between glycosaminoglycans and IL-8, rendering IL-8 susceptible to proteolytic degradation with subsequent decrease in neutrophil chemotaxis, thereby facilitating resolution of inflammation.

  7. Postoperative outcomes and quality of life in patients with cystic fibrosis undergoing laparoscopic cholecystectomy: a retrospective study.

    Science.gov (United States)

    Cogliandolo, Andrea; Patania, Mariangela; Currò, Giuseppe; Chillè, Giovanni; Magazzù, Giuseppe; Navarra, Giuseppe

    2011-06-01

    Approximately 28% of the patients with cystic fibrosis are affected by cholelythiasis. More than 40% of them have a symptomatic disease, which would mandate cholecystectomy. The aim of this study was to review surgical and respiratory outcomes and quality of life scores of cystic fibrosis patients undergoing laparoscopic cholecystectomy for symptomatic cholelythiasis to verify the hypothesis that cholecystectomy is a low-risk operation by laparoscopy, not affecting unfavorably respiratory function and quality of life. Study group was consisted of 9 patients with a mean age of 24.8±8.1 years (range, 15 to 38 y), 2 male and 7 female patients, with cystic fibrosis and symptomatic cholelithiasis. Three patients also presented common bile duct stones. All the patients underwent perioperative Positive End-Expiratory Pressure mask sessions and aggressive antibiotic regimens. At the middle of the antibiotics regimen period, a standard laparoscopic cholecystectomy was performed. In the 3 cases with common duct lithiasis, the so-called "rendezvous" technique was carried out. Preoperatively, intraoperatively, and postoperatively, respiratory function was strictly monitored by the evaluation of SO2 and of the forced expiratory volume in 1 second (FEV1). Preoperatively and 6 months after laparoscopic cholecystectomy the Gastro Intestinal Quality of Life Index was evaluated on all patients. All the operations were completed laparoscopically. No mortality was observed. The intraoperative mean SO2 was 89.0%±5.6% (range, 80% to 95%), versus 82.8%±8.5% (range, 66% to 91%) at the extubation (P=0.006). Intraoperative respiratory functions were stable in 6 patients. In 3 patients, a severe bronchospasm occurred determining marked desaturation. Preoperative mean FEV1 was 70.5%±7.0% (range, 55% to 75%) versus 61.8%±13.2% (range, 39% to 80%) 48 hours after the operation (P=0.132). The 3 patients, who experienced intraoperatively severe bronchospasm, reported a 48 hours postoperative

  8. Advances toward the elucidation of hypertonic saline effects on Pseudomonas aeruginosa from cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Anne-Laure Michon

    Full Text Available OBJECTIVES: Nebulized hypertonic saline (HTS has beneficial effects including reducing pulmonary exacerbations in Cystic Fibrosis (CF patients. Several mechanisms may explain these effects but antimicrobial activity of NaCl remains largely unexplored. We aimed to measure the antimicrobial effect of NaCl on Pseudomonas aeruginosa isolated from the respiratory tract in CF patients. METHODS: NaCl minimal inhibitory concentration (MIC and minimal bactericidal concentration (MBC were determined for strains characterized for mucoidy, antimicrobial resistance, and ability to form biofilm using 0,9% to 15% NaCl solutions. NaCl effects on biofilm formation, preformed biofilm, and mobility were evaluated. Kinetics of antimicrobial effects was studied. RESULTS: The growth of all isolates (n = 85 from 34 patients was inhibited by 6% NaCl solution. A 10% concentration had a bactericidal activity on 90% of the isolates. Mucoid and multidrug resistant (MDR isolates displayed lower MICs compared to non-mucoid and to non-MDR isolates, respectively. Time-kill kinetics showed that NaCl exhibited a rapid, dose and growth phase dependent bactericidal effect. Three percent or more of NaCl inhibited biofilm formation for 69% of strongly adherent isolates. A dose-dependent decrease of preformed biofilm viability and an inhibitory activity on bacterial motility were observed. CONCLUSIONS: NaCl inhibited the growth of all isolates and killed 38% of tested isolates within concentration range currently used in therapeutics. Our results suggest that anti-pseudomonal activity is another mechanism of action of HTS to add to those already established. Clinical trials are needed to compare diverse HTS conditions of use (rhythm, dose and mode of delivery to obtain efficient and optimized anti-P. aeruginosa effects. More generally, NaCl effect on other opportunistic pathogens as well as on global microbiotae recovered during polymicrobial diseases warrants further investigations.

  9. Progressive massive fibrosis in patients with pneumoconiosis: utility of MRI in differentiating from lung cancer.

    Science.gov (United States)

    Ogihara, Yukihiro; Ashizawa, Kazuto; Hayashi, Hideyuki; Nagayasu, Takeshi; Hayashi, Tomayoshi; Honda, Sumihisa; Uetani, Masataka

    2018-01-01

    Background It is occasionally difficult to distinguish progressive massive fibrosis (PMF) from lung cancer on computed tomography (CT) in patients with pneumoconiosis. Purpose To evaluate the magnetic resonance imaging (MRI) features of PMF and to assess its ability to differentiate PMF from lung cancer. Material and Methods Between 2000 and 2014, 40 pulmonary lesions suspected to be lung cancer on the basis of CT in 28 patients with known pneumoconiosis were evaluated. Twenty-four of the 40 lesions were pathologically or clinically diagnosed as PMF. The signal pattern on T2-weighted (T2W) images, post-contrast enhancement pattern on T1-weighted (T1W) images, and the pattern of the time intensity curve (TIC) on contrast-enhanced dynamic studies were evaluated. All images were analyzed independently by two chest radiologists. Results All 24 PMF lesions showed low signal intensity (SI) on T2W images (sensitivity, 100%), while 15 of 16 lung cancer lesions showed intermediate or high SI on T2W images (specificity, 94%) when PMF was regarded as a positive result. Six of 17 PMF lesions showed a homogeneous enhancement pattern (sensitivity, 35%), and 4/9 lung cancer lesions showed an inhomogeneous or a ring-like enhancement pattern (specificity, 44%). Six of 16 PMF lesions showed a gradually increasing enhancement pattern (sensitivity, 38%), and 7/9 lung cancer lesions showed rapid enhancement pattern (specificity, 78%). Conclusion When differentiation between PMF and lung cancer in patients with pneumoconiosis is difficult on CT, an additional MRI study, particularly the T2W imaging sequence, may help differentiate between the two.

  10. Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.

    Directory of Open Access Journals (Sweden)

    Mette Kolpen

    Full Text Available Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS. We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O, an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO3(- and NO2(- in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 µM N2O (range 1.4-157.9 µM N2O. The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3(- decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention.

  11. Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.

    Science.gov (United States)

    Kolpen, Mette; Kühl, Michael; Bjarnsholt, Thomas; Moser, Claus; Hansen, Christine Rønne; Liengaard, Lars; Kharazmi, Arsalan; Pressler, Tanja; Høiby, Niels; Jensen, Peter Østrup

    2014-01-01

    Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF) patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs) surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS). We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O), an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO3(-) and NO2(-) in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 µM N2O (range 1.4-157.9 µM N2O). The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3(-) decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention.

  12. Patients' perspectives on how idiopathic pulmonary fibrosis affects the quality of their lives

    Directory of Open Access Journals (Sweden)

    Gould Michael K

    2005-10-01

    Full Text Available Abstract Background Idiopathic pulmonary fibrosis (IPF is a debilitating lung disease with a survival of only three to five years from the time of diagnosis. Due to a paucity of studies, large gaps remain in our understanding of how IPF affects the quality of patients' lives. In only one other study did investigators ask patients directly for their perspectives on this topic. Further, currently there is no disease-specific instrument to measure health-related quality of life (HRQL in patients with IPF. A carefully constructed measurement instrument, sensitive to underlying change, is needed for use in clinical trials and longitudinal studies of patients with IPF. Before developing such an instrument, researchers must improve their understanding of the relevant effects of IPF on patients' lives. On a broader scale, to provide the best care for people with IPF, clinicians must appreciate – from patients' perspectives – how this disease affects various aspects of their lives. Methods We used focus groups and individual in-depth interviews with 20 IPF patients to collect their perspectives on how IPF affects their lives (with a focus on the quality of their lives. We then analyzed these perspectives and organized them into a conceptual framework for describing HRQL in patients with IPF. Next, we examined how well certain existing measurement instruments – which have been administered to IPF patients in prior studies – covered the domains and topics our patients identified. Results In our framework, we identified 12 primary domains: symptoms, IPF therapy, sleep, exhaustion, forethought, employment and finances, dependence, family, sexual relations, social participation, mental and spiritual well-being, mortality. Each domain is composed of several topics, which describe how IPF affects patients' lives. When we compared the content of our conceptual framework with the existing instruments, we found the coverage of the existing instruments to

  13. Liver fibrosis in treatment-naïve HIV-infected and HIV/HBV co-infected patients: Zambia and Switzerland compared.

    Science.gov (United States)

    Wandeler, Gilles; Mulenga, Lloyd; Vinikoor, Michael J; Kovari, Helen; Battegay, Manuel; Calmy, Alexandra; Cavassini, Matthias; Bernasconi, Enos; Schmid, Patrick; Bolton-Moore, Carolyn; Sinkala, Edford; Chi, Benjamin H; Egger, Matthias; Rauch, Andri

    2016-10-01

    To examine the association between hepatitis B virus (HBV) infection and liver fibrosis in HIV-infected patients in Zambia and Switzerland. HIV-infected adults starting antiretroviral therapy in two clinics in Zambia and Switzerland were included. Liver fibrosis was evaluated using the aspartate aminotransferase-to-platelet-ratio index (APRI), with a ratio >1.5 defining significant fibrosis and a ratio >2.0 indicating cirrhosis. The association between hepatitis B surface antigen (HBsAg) positivity, HBV replication, and liver fibrosis was examined using logistic regression. In Zambia, 96 (13.0%) of 739 patients were HBsAg-positive compared to 93 (4.5%) of 2058 in Switzerland. HBsAg-positive patients were more likely to have significant liver fibrosis than HBsAg-negative ones: the adjusted odds ratio (aOR) was 3.25 (95% confidence interval (CI) 1.44-7.33) in Zambia and 2.50 (95% CI 1.19-5.25) in Switzerland. Patients with a high HBV viral load (≥20000 IU/ml) were more likely to have significant liver fibrosis compared to HBsAg-negative patients or patients with an undetectable viral load: aOR 3.85 (95% CI 1.29-11.44) in Zambia and 4.20 (95% CI 1.64-10.76) in Switzerland. In both settings, male sex was a strong risk factor for significant liver fibrosis. Despite the differences in HBV natural history between Sub-Saharan Africa and Europe, the degree of liver fibrosis and the association with important risk factors were similar. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  14. PROGRESSION OF LIVER FIBROSIS IN MONOINFECTED PATIENTS BY HEPATITIS C VIRUS AND COINFECTED BY HCV AND HUMAN IMMUNODEFICIENCY VIRUS

    Directory of Open Access Journals (Sweden)

    Cristiane Valle TOVO

    2013-03-01

    Full Text Available Context The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. Objective To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected Methods Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. Conclusion The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations. Contexto A progressão da fibrose hepática em pacientes coinfectados pelos vírus da hepatite C (VHC e da imunodeficiência humana (VHC/HIV tem sido mais estudada na última década. Estudos realizados antes da terapia antiretroviral de alta potência (HAART sugerem que o HIV pode mudar a história natural da infecção pelo VHC, levando a uma progressão mais rápida da fibrose hepática. Objetivo Avaliar e comparar a progressão de fibrose em duas populações de pacientes (coinfectados VHC/HIV e monoinfectados VHC. Métodos Foram avaliados retrospectivamente 70 pacientes monoinfectados VHC e 26 coinfectados VHC/HIV nunca tratados para o VHC e que haviam realizado duas biopsias hepáticas seriadas. Não houve diferença na progressão de fibrose entre os dois grupos. Conclusão A evolução do grau de fibrose não foi pior nos pacientes coinfectados. A ausência de imunodepressão e o menor intervalo de tempo entre as biopsias no grupo de coinfectados são poss

  15. Genotypic Diversity within a Single Pseudomonas aeruginosa Strain Commonly Shared by Australian Patients with Cystic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Anna Sze Tai

    Full Text Available In cystic fibrosis (CF, Pseudomonas aeruginosa undergoes intra-strain genotypic and phenotypic diversification while establishing and maintaining chronic lung infections. As the clinical significance of these changes is uncertain, we investigated intra-strain diversity in commonly shared strains from CF patients to determine if specific gene mutations were associated with increased antibiotic resistance and worse clinical outcomes. Two-hundred-and-one P. aeruginosa isolates (163 represented a dominant Australian shared strain, AUST-02 from two Queensland CF centres over two distinct time-periods (2001-2002 and 2007-2009 underwent mexZ and lasR sequencing. Broth microdilution antibiotic susceptibility testing in a subset of isolates was also performed. We identified a novel AUST-02 subtype (M3L7 in adults attending a single Queensland CF centre. This M3L7 subtype was multi-drug resistant and had significantly higher antibiotic minimum inhibitory concentrations than other AUST-02 subtypes. Prospective molecular surveillance using polymerase chain reaction assays determined the prevalence of the 'M3L7' subtype at this centre during 2007-2009 (170 patients and 2011 (173 patients. Three-year clinical outcomes of patients harbouring different strains and subtypes were compared. MexZ and LasR sequences from AUST-02 isolates were more likely in 2007-2009 than 2001-2002 to exhibit mutations (mexZ: odds ratio (OR = 3.8; 95% confidence interval (CI: 1.1-13.5 and LasR: OR = 2.5; 95%CI: 1.3-5.0. Surveillance at the adult centre in 2007-2009 identified M3L7 in 28/509 (5.5% P. aeruginosa isolates from 13/170 (7.6% patients. A repeat survey in 2011 identified M3L7 in 21/519 (4.0% P. aeruginosa isolates from 11/173 (6.4% patients. The M3L7 subtype was associated with greater intravenous antibiotic and hospitalisation requirements, and a higher 3-year risk of death/lung transplantation, than other AUST-02 subtypes (adjusted hazard ratio [HR] = 9.4; 95%CI: 2

  16. Liver fibrosis alleviation after co-transplantation of hematopoietic stem cells with mesenchymal stem cells in patients with thalassemia major.

    Science.gov (United States)

    Ghavamzadeh, Ardeshir; Sotoudeh, Masoud; Hashemi Taheri, Amir Pejman; Alimoghaddam, Kamran; Pashaiefar, Hossein; Jalili, Mahdi; Shahi, Farhad; Jahani, Mohammad; Yaghmaie, Marjan

    2018-02-01

    The aims of this study are to determine the replacement rate of damaged hepatocytes by donor-derived cells in sex-mismatched recipient patients with thalassemia major and to determine whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells (HSCs) can alleviate liver fibrosis. Ten sex-mismatched donor-recipient pairs who received co-transplantation of HSCs with mesenchymal stem cells were included in our study. Liver biopsy was performed before transplantation. Two other liver biopsies were performed between 2 and 5 years after transplantation. The specimens were studied for the presence of donor-derived epithelial cells or hepatocytes using fluorescence in situ hybridization by X- and Y-centromeric probes and immunohistochemical staining for pancytokeratin, CD45, and a hepatocyte-specific antigen. All sex-mismatched tissue samples demonstrated donor-derived hepatocyte independent of donor gender. XY-positive epithelial cells or hepatocytes accounted for 11 to 25% of the cells in histologic sections of female recipients in the first follow-up. It rose to 47-95% in the second follow-up. Although not statistically significant, four out of ten patients showed signs of improvement in liver fibrosis. Our results showed that co-transplantation of HSC with mesenchymal stem cells increases the rate of replacement of recipient hepatocytes by donor-derived cells and may improve liver fibrosis.

  17. [Clinical value of angiogenin in predicting the prognosis of patients with idiopathic pulmonary fibrosis].

    Science.gov (United States)

    Bai, Yanling; Zhu, Haiyan; Sun, Qiyu; Gu, Guozhong; Zhang, Lingyu; Li, Ying; Yang, Baofeng

    2017-09-01

    To explore the relationship between angiogenin-1/2 (Ang-1/2) and clinical parameters of idiopathic pulmonary fibrosis (IPF), and to assess the value of Ang-1/2 in predicting the prognosis of patients with IPF. A retrospective analysis was conducted. Ninety-one patients diagnosed as IPF by high resolution CT (HRCT) and lung biopsy admitted to Daqing Oil Field General Hospital from March 2014 to January 2015 were enrolled. The general data, serum parameters and pulmonary function parameters of all patients were collected. After treatment, all of the 91 patients were followed-up to 2 years. The patients were divided into favorable prognosis group and unfavorable prognosis group according to follow-up results. The differences in all parameters between the two groups were compared. The relationship between Ang-1, Ang-2 and lung function parameters was analyzed by Pearson correlation analysis. Cox proportional hazard regression model was used to evaluate the effect of clinical parameters on the prognosis of patients with IPF. The effect of Ang-2 in predicting prognosis of patients with IPF was analyzed by receiver operating characteristic (ROC) curve. During the 2-year follow-up period, 30 of 91 patients showed a favorable prognosis, and 55 showed an unfavorable prognosis with a poor prognosis rate of 64.71%, and 6 patients withdrew from the study due to loss of follow-up and death. Compared with the favorable prognosis group, Ang-2 level in the unfavorable prognosis group was significantly increased (μg/L: 2.88±1.63 vs. 1.89±1.22, t = 2.909, P = 0.005), but Ang-1 only showed a slight increase (μg/L: 28.70±14.26 vs. 25.62±11.95, t = 1.005, P = 0.318). The results of Pearson correlation analysis showed that Ang-2 level was negatively correlated with forced expiratory volume in 1 second (FVC1) and the percentage of carbon monoxide diffusing capacity accounting for the expected value (DLCO%: r value was -0.227 and -0.206, and P value was 0.147 and 0.253, respectively

  18. Do patient-reported outcomes (PROs have a role in the management of patients with cystic fibrosis?

    Directory of Open Access Journals (Sweden)

    Sam eSalek

    2012-03-01

    Full Text Available Background: Health-related quality of life (HRQoL is a rapidly growing area of expertise and the most commonly used patient-reported outcome (PRO. The impact of CF on HRQoL is liable to be great, making CF patients ideal candidates for the application of HRQoL instruments. The aims of this study were to assess the affect of CF on HRQoL, to ascertain the reliability and validity of the UKSIP and the CFQoL in the adult CF population, and to examine their role in the management of patients. Methods: Seventy participants were recruited from the All Wales Adult Cystic Fibrosis Centre at Llandough Hospital, UK. There were two stages to the study; self-report of the UKSIP and CFQoL in the first stage, and completion of the same two questionnaires seven to ten days later for the second stage. Results: The areas of HRQoL most impaired by CF were employment and concerns regarding the future. The UKSIP and CFQoL showed high internal consistency (rα=0.89-0.93 and test-retest reliability (rs=0.57-0.94, p<0.005 in the CF population. Validity was variable; with the UKSIP showing discrimination across socio-demographic factors, whilst the CFQoL showed increased sensitivity to clinical variables. Many parameters influenced patient-reported HRQoL, with the greatest correlations seen with the Borg score (p<0.005. The use of a HRQoL instrument in CF annual reviews is recommended to provide holistic patient care. The results of this study underpin the value of HRQoL as a patient-reported outcome measure in the management of adult CF.

  19. ARFI cut-off values and significance of standard deviation for liver fibrosis staging in patients with chronic liver disease.

    Science.gov (United States)

    Goertz, Ruediger S; Sturm, Joerg; Pfeifer, Lukas; Wildner, Dane; Wachter, David L; Neurath, Markus F; Strobel, Deike

    2013-01-01

    Acoustic radiation force impulse (ARFI) elastometry quantifies hepatic stiffness, and thus degree of fibrosis, non-invasively. Our aim was to analyse the diagnostic accuracy of ARFI cut-off values, and the significance of a defined limit of standard deviation (SD) as a potential quality parameter for liver fibrosis staging in patients with chronic liver diseases (CLD). 153 patients with CLD (various aetiologies) undergoing liver biopsy, and an additional 25 patients with known liver cirrhosis, were investigated. ARFI measurements were performed in the right hepatic lobe, and correlated with the histopathological Ludwig fibrosis score (inclusion criteria: at least 6 portal tracts). The diagnostic accuracy of cut-off values was analysed with respect to an SD limit of 30% of the mean ARFI value. The mean ARFI elastometry showed 1.95 ± 0.87 m/s (range 0.79-4.40) in 178 patients (80 female, 98 male, mean age: 52 years). The cut-offs were 1.25 m/s for F ≥ 2, 1.72 m/s for F ≥ 3 and 1.75 m/s for F = 4, and the corresponding AUROC 80.7%, 86.2% and 88.7%, respectively. Exclusion of 31 patients (17.4%) with an SD higher than 30% of the mean ARFI improved the diagnostic accuracy: The AUROC for F ≥ 2, F ≥ 3 and F = 4 were 86.1%, 91.2% and 91.5%, respectively. The diagnostic accuracy of ARFI can be improved by applying a maximum SD of 30% of the mean ARFI as a quality parameter--which however leads to an exclusion of a relevant number of patients. ARFI results with a high SD should be interpreted with caution.

  20. Correlation between serum levels of PC III and the degree of hepatic fibrosis in patients with chronic liver diseases

    International Nuclear Information System (INIS)

    Wang Xue; Xu Yu; Li Wenjie; Zhang Jun; Yu Ying; Wang Kun

    2007-01-01

    Objective: To study the correlation between serum level of PC III and the degree of liver fibrosis in patients with chronic liver diseases. Methods: Serum level of PC III was assayed with RIA and other markers of liver function (including ALT, AST, STB, SDB, TP, ALB, TBA) were assayed with automatic biochemical analyzer in 188 patients with various chronic liver diseases. PC III only were examined in 70 controls. Results: (1) The serum levels of PC III were in this order: chronic severe hepatitis (n=27, 501.17 ± 191.09) > liver cirrhosis from chronic hepatitis (n=27,334.52 ± 139.14) > chronic moderate hepatitis ( n = 32,298.02 ± 151.02) > primary liver cancer (n=39,281.42 ± 143.48) > normal controls (n=70,122.56 ± 92.94). (2) The serum levels of PC III were positively correlated with STB and SDB levels (P<0.05) in patients with chronic severe hepatitis and was significantly positively correlated with ALP levels (P<0.01). (3) The serum level of PC III were significantly positively correlated with STB, SDB, TBA and ALP in patients with cirrhosis from chronic hepatitis (P<0.01). (4) The serum levels of PC III were significantly positively correlated with AST and ALP levels in patients with chronic moderate hepatitis (P<0.01). (5) The serum levels of PC III were significantly positively correlated with STB, SDB, TBA, AST and ALP in patients with primary liver cancer (P<0.01). Conclusion: Serum level of PC III might adequately reflect the activity of the process of hepatic fibrosis, but did not necessarily reflect the degree of fibrosis already attained. (authors)

  1. Improved noninvasive prediction of liver fibrosis by liver stiffness measurement in patients with nonalcoholic fatty liver disease accounting for controlled attenuation parameter values.

    Science.gov (United States)

    Petta, Salvatore; Wong, Vincent Wai-Sun; Cammà, Calogero; Hiriart, Jean-Baptiste; Wong, Grace Lai-Hung; Marra, Fabio; Vergniol, Julien; Chan, Anthony Wing-Hung; Di Marco, Vito; Merrouche, Wassil; Chan, Henry Lik-Yuen; Barbara, Marco; Le-Bail, Brigitte; Arena, Umberto; Craxì, Antonio; de Ledinghen, Victor

    2017-04-01

    Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). Controlled attenuation parameter (CAP) is a new parameter provided by the same machine used for LSM and associated with both steatosis and body mass index, the two factors mostly affecting LSM performance in NAFLD. We aimed to determine whether prediction of liver fibrosis by LSM in NAFLD patients is affected by CAP values. Patients (n = 324) were assessed by clinical and histological (Kleiner score) features. LSM and CAP were performed using the M probe. CAP values were grouped by tertiles (lower 132-298, middle 299-338, higher 339-400 dB/m). Among patients with F0-F2 fibrosis, mean LSM values, expressed in kilopascals, increased according to CAP tertiles (6.8 versus 8.6 versus 9.4, P = 0.001), and along this line the area under the curve of LSM for the diagnosis of F3-F4 fibrosis was progressively reduced from lower to middle and further to higher CAP tertiles (0.915, 0.848-0.982; 0.830, 0.753-0.908; 0.806, 0.723-0.890). As a consequence, in subjects with F0-F2 fibrosis, the rates of false-positive LSM results for F3-F4 fibrosis increased according to CAP tertiles (7.2% in lower versus 16.6% in middle versus 18.1% in higher). Consistent with this, a decisional flowchart for predicting fibrosis was suggested by combining both LSM and CAP values. In patients with NAFLD, CAP values should always be taken into account in order to avoid overestimations of liver fibrosis assessed by transient elastography. (Hepatology 2017;65:1145-1155). © 2016 by the American Association for the Study of Liver Diseases.

  2. Non-invasive assessment of liver fibrosis progression in hepatitis C patients retreated for 96 weeks with antiviral therapy: a randomized study.

    Science.gov (United States)

    Zarski, Jean-Pierre; Sturm, Nathalie; Desmorat, Hervé; Melin, Pascal; Raabe, Jean-Jacques; Bonny, Corinne; Sogni, Philippe; Pinta, Alexandrina; Rouanet, Stéphanie; Babany, Gérard; Cheveau, Alice; Chevallier, Michèle

    2010-08-01

    The efficacy of a maintenance therapy in non-responder patients with chronic hepatitis C has been essentially evaluated by histological semiquantitative scores. The aim was to evaluate the efficiency of 2 years of treatment with peginterferon alpha-2a vs alpha-tocopherol in these patients by histology, morphometry and blood markers of fibrosis. Hundred and five HCV patients with a Metavir fibrosis score > or = 2 were randomized to receive peginterferon alpha-2a 180 microg/week (PEG) (n=55) or alpha-tocopherol (TOCO) 1000 mg/day (n=50) for 96 weeks. The primary endpoint was improvement or stabilization of the Metavir fibrosis score by biopsy performed at week 96. Secondary endpoints included a quantitative assessment of fibrosis by morphometry and changes in blood markers of fibrosis. There was no difference at baseline between PEG and TOCO according to the metavir (83.3 vs 86.8%, P=0.751) stage. The median fibrosis rate, measured with morphometry was 2.72 and 2.86% at day 0, and 3.66 and 2.82% at week 96, in the PEG and TOCO groups (P=0.90) respectively. However, the percentage of patients with metavir activity grade improvement was significantly higher in the PEG group vs the TOCO group (52.8 vs 23.7%, P=0.016). Non-invasive markers analysis did not show any significant change in both groups. Long-term therapy with peginterferon alpha-2a did not reduce liver fibrosis degree assessed by morphometry and blood tests as compared with alpha-tocopherol. Blood tests could be useful to assess liver fibrosis changes in clinical trials.

  3. Heart Rate Recovery After 6-Min Walk Test Predicts Survival in Patients With Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Swigris, Jeffrey J.; Swick, Jeff; Wamboldt, Frederick S.; Sprunger, David; du Bois, Roland; Fischer, Aryeh; Cosgrove, Gregory P.; Frankel, Stephen K.; Fernandez-Perez, Evans R.; Kervitsky, Dolly; Brown, Kevin K.

    2009-01-01

    Background: In patients with idiopathic pulmonary fibrosis (IPF), our objectives were to identify predictors of abnormal heart rate recovery (HRR) at 1 min after completion of a 6-min walk test (6MWT) [HRR1] and 2 min after completion of a 6MWT (HRR2), and to determine whether abnormal HRR predicts mortality. Methods: From 2003 to 2008, we identified IPF patients who had been evaluated at our center (n = 76) with a pulmonary physiologic examination and the 6MWT. We used logistic regression to identify predictors of abnormal HRR, the product-limit method to compare survival in the sample stratified on HRR, and Cox proportional hazards analysis to estimate the prognostic capability of abnormal HRR. Results: Cutoff values were 13 beats for abnormal HRR1 and 22 beats for HRR2. In a multivariable model, predictors of abnormal HRR1 were diffusing capacity of the lung for carbon monoxide (odds ratio [OR], 0.4 per 10% predicted; 95% confidence interval [CI], 0.2 to 0.7; p = 0.003), change in heart rate from baseline to maximum (OR, 0.9; 95% CI, 0.8 to 0.97; p = 0.01), and having a right ventricular systolic pressure > 35 mm Hg as determined by transthoracic echocardiogram (OR, 12.7; 95% CI, 2.0 to 79.7; p = 0.01). Subjects with an abnormal HRR had significantly worse survival than subjects with a normal HRR (for HRR1, p = 0.0007 [log-rank test]; for HRR2, p = 0.03 [log-rank test]); these results held for the subgroup of 30 subjects without resting pulmonary hypertension (HRR1, p = 0.04 [log-rank test]). Among several candidate variables, abnormal HRR1 appeared to be the most potent predictor of mortality (hazard ratio, 5.2; 95% CI, 1.8 to 15.2; p = 0.004). Conclusion: Abnormal HRR after 6MWT predicts mortality in IPF patients. Research is needed to confirm these findings prospectively and to examine the mechanisms of HRR in IPF patients. PMID:19395579

  4. Reduced nasal nitric oxide production in cystic fibrosis patients with elevated systemic inflammation markers.

    Directory of Open Access Journals (Sweden)

    Ruth K Michl

    Full Text Available BACKGROUND: Nitric oxide (NO is produced within the respiratory tract and can be detected in exhaled bronchial and nasal air. The concentration varies in specific diseases, being elevated in patients with asthma and bronchiectasis, but decreased in primary ciliary dyskinesia. In cystic fibrosis (CF, conflicting data exist on NO levels, which are reported unexplained as either decreased or normal. Functionally, NO production in the paranasal sinuses is considered as a location-specific first-line defence mechanism. The aim of this study was to investigate the correlation between upper and lower airway NO levels and blood inflammatory parameters, CF-pathogen colonisation, and clinical data. METHODS AND FINDINGS: Nasal and bronchial NO concentrations from 57 CF patients were determined using an electrochemical analyser and correlated to pathogen colonisation of the upper and lower airways which were microbiologically assessed from nasal lavage and sputum samples. Statistical analyses were performed with respect to clinical parameters (lung function, BMI, laboratory findings (CRP, leucocytes, total-IgG, fibrinogen, and anti-inflammatory and antibiotic therapy. There were significant correlations between nasal and bronchial NO levels (rho = 0.48, p<0.001, but no correlation between NO levels and specific pathogen colonisation. In patients receiving azithromycin, significantly reduced bronchial NO and a tendency to reduced nasal NO could be found. Interestingly, a significant inverse correlation of nasal NO to CRP (rho = -0.28, p = 0.04 and to leucocytes (rho = -0.41, p = 0.003 was observed. In contrast, bronchial NO levels showed no correlation to clinical or inflammatory parameters. CONCLUSION: Given that NO in the paranasal sinuses is part of the first-line defence mechanism against pathogens, our finding of reduced nasal NO in CF patients with elevated systemic inflammatory markers indicates impaired upper airway defence. This

  5. Monitoring methotrexate-induced liver fibrosis in patients with psoriasis: utility of transient elastography

    Directory of Open Access Journals (Sweden)

    Cheng HS

    2018-05-01

    Full Text Available Harriet S Cheng,1 Marius Rademaker2 1Dermatology Service, Auckland City Hospital, Auckland, New Zealand; 2Waikato Clinical Campus, Auckland University Medical School, Hamilton, New Zealand Abstract: Increasingly, existing evidence indicates that methotrexate-associated liver injury is related to comorbid risk factors such as diabetes, alcoholism, and obesity, rather than to methotrexate itself. Despite this fact, significant effort continues to be expended in the monitoring of low-dose methotrexate in patients with psoriasis. The gold standard investigation has been liver biopsy, but this is associated with significant morbidity and mortality. As methotrexate-induced liver injury is uncommon, the risk/benefit ratio of liver biopsy has been questioned. Fortunately, a number of new technologies have been developed for the diagnosis of chronic liver disease, including transient elastography (TE. TE is a type of shear wave ultrasound elastography, which measures the speed of shear waves used to estimate hepatic tissue stiffness. Several meta-analyses show very high pooled sensitivity and specificity for the diagnosis of hepatic cirrhosis (87% and 91%, respectively in a variety of chronic liver disorders. It has a negative predictive value for cirrhosis of >90% and a positive predictive value of 75%. Recent European guidelines now advocate the use of TE as the first-line test for the assessment of fibrosis in alcohol- or hepatitis-related liver disease, including nonalcoholic fatty liver disease (NAFLD. As the prevalence of obesity and metabolic syndrome, including NAFLD, is significantly elevated in patients with psoriasis, TE may be worth considering as a routine investigation for any patient with psoriasis. Although high-quality studies comparing TE with standard liver biopsy in the monitoring of psoriatics on low-dose methotrexate are lacking, the evidence from multiple small cohort studies and case series demonstrates its effectiveness. A recent

  6. Diagnosis and Treatment of Endocrine Co-Morbidities in Patients with Cystic Fibrosis

    Science.gov (United States)

    Siwamogsatham, Oranan; Alvarez, Jessica

    2015-01-01

    Purpose of review The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis (CF). Recent findings As life expectancy in CF has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes (CFRD), cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. Summary Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with CF. This review summarizes the updated screening and management of endocrine diseases in the CF population. PMID:25105995

  7. The molecular analysis of mutations in exons 4, 11 and 21 of the cystic fibrosis transmembrane conductance regulator (CFTR gene in cystic fibrosis patients in Kermanshah, Iran

    Directory of Open Access Journals (Sweden)

    Nasibe Karimi

    2017-03-01

    Full Text Available Introduction: Cystic fibrosis (CF is a common genetic disorder in white populations with an autosomal recessive pattern, caused by mutations in the CFTR gene. The frequency of more than 1950 various mutations reported in the CFTR gene significantly varies in different populations. ∆F508 is a common mutation in exon 10, which is first addressed in the molecular analysis of the disease. Other exons are required to be investigated owing to failing to identify mutations in the patients. The present study was conducted to investigate mutations in exons 4, 11 and 21 of the CFTR gene using the sequencing method in CF patients in Kermanshah province, Iran. Methods: The present descriptive study was conducted on all patients with CF presenting to the medical genetics center in Kermanshah in 2010-2011. After taking blood samples and extracting DNA using saturated NaCl solution, sequences of exons were amplified using PCR and sequenced for identifying mutations. Results: The frequency of mutations was found to be respectively 0, 0 and 5.5% in exon 11, 21 and 4. The D110H mutation was found to be homozygous in one subject and heterozygous in another. Moreover, the 4029A>G polymorphism (12.9% was found to be homozygous in two subjects and heterozygous in three others. Conclusion: The D110H mutation is recommended to be included in the screening programs of the study population. The results obtained support the effects of ethnic and geographical factors on the distribution of CF mutations.

  8. Bone mineral and body composition alterations in paediatric cystic fibrosis patients

    Energy Technology Data Exchange (ETDEWEB)

    Reix, Philippe; Bellon, Gabriel [Hopital Femme Mere Enfant, Service de Pediatrie, Pneumologie, Allergologie, Mucoviscidose, Bron (France); Braillon, Pierre [Hospices Civils de Lyon, Service d' Imagerie Foetale et Pediatrique, Bron (France)

    2010-03-15

    With the increased life span of cystic fibrosis (CF) patients, CF-related bone diseases could have an increased prevalence and morbidity in this group. In children, previous retrospective and prospective studies have yielded conflicting results on bone mineralization. To monitor body composition and bone mineral status of children with CF. We reviewed the dual-energy X-ray absorptiometry (DXA) data of 161 children with CF (age 10 {+-} 4.8 years). Total body bone mineral content (BMCt), total lean tissue mass (LTMt) and total fat mass (FMt) were measured and compared to expected data calculated from ideal weight for height (Wi; e.g. BMCti, LTMti, FMti). The bt (BMCt/BMCti), lt (LTMt/LTMti) and ft (FMt/FMti) ratios were used as quantitative variables. Low bt ratio was found at all ages (mean bt ratio 0.94{+-}0.10; P<0.001), even in children <6 years of age. However, the children's BMCt was satisfactorily adapted to their weight. lt and ft ratios were not constant across age groups. Children <10 years had 8% reduction of their lt ratio, maintaining normal levels thereafter. The opposite trend was found for ft ratio. Poor clinical, nutritional status and vitamin A levels were correlated with bt and lt ratios. Our results indicate that children with CF could have early alterations in their bone status and that lt and ft ratios did not have constant values across ages. Interpreting DXA data using this approach is suitable in children with CF. (orig.)

  9. Bone mineral and body composition alterations in paediatric cystic fibrosis patients

    International Nuclear Information System (INIS)

    Reix, Philippe; Bellon, Gabriel; Braillon, Pierre

    2010-01-01

    With the increased life span of cystic fibrosis (CF) patients, CF-related bone diseases could have an increased prevalence and morbidity in this group. In children, previous retrospective and prospective studies have yielded conflicting results on bone mineralization. To monitor body composition and bone mineral status of children with CF. We reviewed the dual-energy X-ray absorptiometry (DXA) data of 161 children with CF (age 10 ± 4.8 years). Total body bone mineral content (BMCt), total lean tissue mass (LTMt) and total fat mass (FMt) were measured and compared to expected data calculated from ideal weight for height (Wi; e.g. BMCti, LTMti, FMti). The bt (BMCt/BMCti), lt (LTMt/LTMti) and ft (FMt/FMti) ratios were used as quantitative variables. Low bt ratio was found at all ages (mean bt ratio 0.94±0.10; P<0.001), even in children <6 years of age. However, the children's BMCt was satisfactorily adapted to their weight. lt and ft ratios were not constant across age groups. Children <10 years had 8% reduction of their lt ratio, maintaining normal levels thereafter. The opposite trend was found for ft ratio. Poor clinical, nutritional status and vitamin A levels were correlated with bt and lt ratios. Our results indicate that children with CF could have early alterations in their bone status and that lt and ft ratios did not have constant values across ages. Interpreting DXA data using this approach is suitable in children with CF. (orig.)

  10. Clearance of technetium-99m-DTPA and HRCT findings in the evaluation of patients with Idiopathic Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Karkavitsas Nikolaos

    2006-02-01

    Full Text Available Abstract Background Clearance of inhaled technetium-labeled diethylenetriamine pentaacetate (99mTc-DTPA is a marker of epithelial damage and an index of lung epithelial permeability. The aim of this study was to investigate the role of 99mTc-DTPA scan in patients with Idiopathic Pulmonary Fibrosis (IPF. Our hypothesis is that the rate of pulmonary 99mTc-DTPA clearance could be associated with extent of High Resolution Computed Tomography (HRCT abnormalities, cell differential of bronchoalveolar lavage fluid (BALF and pulmonary function tests (PFTs in patients with IPF. Methods We studied prospectively 18 patients (14 male, 4 female of median age 67yr (range 55–81 with histologically proven IPF. HRCT scoring included the mean values of extent of disease. Mean values of these percentages represented the Total Interstitial Disease Score (TID. DTPA clearance was analyzed according to a dynamic study using a Venticis II radioaerosol delivery system. Results The mean (SD TID score was 36 ± 12%, 3 patients had mild, 11 moderate and 4 severe TID. Abnormal DTPA clearance half-time (t1/2 Conclusion Our data suggest that 99mTc-DTPA lung scan is not well associated with HRCT abnormalities, PFTs, and BALF cellularity in patients with IPF. Further studies in large scale of patients are needed to define the role of this technique in pulmonary fibrosis.

  11. 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

  12. Diagnostic Usefulness of APRI and FIB-4 for the Prediction of Liver Fibrosis After Liver Transplantation in Patients Infected with Hepatitis C Virus.

    Science.gov (United States)

    Imai, H; Kamei, H; Onishi, Y; Ishizu, Y; Ishigami, M; Goto, H; Ogura, Y

    2018-06-01

    Aspartate transaminase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) are well known as representative indirect serum biomarkers related to liver fibrosis. The usefulness of these markers for the diagnosis of liver fibrosis after liver transplantation (LT) in hepatitis C virus (HCV)-infected patients and the influence of splenectomy were investigated. From June 2003 to May 2014, 31 HCV-infected patients who underwent LT and postoperative follow-up liver biopsies were included in this study. The association between liver fibrosis and serum biomarkers and the influence of splenectomy on APRI and FIB-4 were also investigated. A total of 195 biopsy specimens were collected, and liver fibrosis was identified as: F0, 59.7%; F1, 34.1%; and F2, 6.3%. Both APRI and FIB-4 were significantly higher in patients who showed F1 and F2 in liver biopsy specimen than F0 (P values, .009 and .022, respectively); sensitivity and specificity of APRI were, respectively, 63.4% and 66.7%, and those of FIB-4 were 57.7% and 69.6%. In 11 patients (35.5%) who underwent splenectomy at the time of LT, the cutoff values for APRI and FIB-4 were 0.61 and 1.41, which were significantly lower than the corresponding values (1.00 and 3.64) of patients without splenectomy. APRI and FIB-4 could effectively estimate liver fibrosis after LT for HCV-related liver disease. For LT patients with splenectomy, APRI and FIB-4 were also useful to estimate liver fibrosis, but the standard values should be adjusted lower than those for patients without splenectomy. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Quantitative measurement of hepatic fibrosis with gadoxetic acid-enhanced magnetic resonance imaging in patients with chronic hepatitis B infection: A comparative study on aspartate aminotransferase to platelet ratio index and fibrosis-4 index

    International Nuclear Information System (INIS)

    Lee, Guy Mok; Kim, Youe Ree; Cho, Eun Young; Lee, Young Hwan; Yoon, Kwon Ha; Ryu, Jong Hyun; Kim, Tae Hoon

    2017-01-01

    To quantitatively measure hepatic fibrosis on gadoxetic acid-enhanced magnetic resonance (MR) in chronic hepatitis B (CHB) patients and identify the correlations with aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) values. This study on gadoxetic acid-enhanced 3T MR imaging included 81 patients with CHB infection. To quantitatively measure hepatic fibrosis, MR images were analyzed with an aim to identify inhomogeneous signal intensities calculated from a coefficient of variation (CV) map in the liver parenchyma. We also carried out a comparative analysis between APRI and FIB-4 based on metaregression results. The diagnostic performance of the CV map was evaluated using a receiver-operating characteristic (ROC) curve. In the MR images, the mean CV values in control, groups I, II, and III based on APRI were 4.08 ± 0.92, 4.24 ± 0.80, 5.64 ± 1.11, and 5.73 ± 1.28, respectively (p < 0.001). In CHB patients grouped by FIB-4, the mean CV values of groups A, B, and C were 4.22 ± 0.95, 5.40 ± 1.19, and 5.71 ± 1.17, respectively (p < 0.001). The mean CV values correlated well with APRI (r = 0.392, p < 0.001) and FIB-4 (r = 0.294, p < 0.001). In significant fibrosis group, ROC curve analysis yielded an area under the curve of 0.875 using APRI and 0.831 using FIB-4 in HB, respectively. Gadoxetic acid-enhanced MR imaging for calculating a CV map showed moderate correlation with APRI and FIB-4 values and could be employed to quantitatively measure hepatic fibrosis in patients with CHB

  14. Quantitative measurement of hepatic fibrosis with gadoxetic acid-enhanced magnetic resonance imaging in patients with chronic hepatitis B infection: A comparative study on aspartate aminotransferase to platelet ratio index and fibrosis-4 index

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Guy Mok; Kim, Youe Ree; Cho, Eun Young; Lee, Young Hwan; Yoon, Kwon Ha [Wonkwang University School of Medicine, Iksan (Korea, Republic of); Ryu, Jong Hyun; Kim, Tae Hoon [Imaging Science Research Center, Wonkwang University, Iksan (Korea, Republic of)

    2017-06-15

    To quantitatively measure hepatic fibrosis on gadoxetic acid-enhanced magnetic resonance (MR) in chronic hepatitis B (CHB) patients and identify the correlations with aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) values. This study on gadoxetic acid-enhanced 3T MR imaging included 81 patients with CHB infection. To quantitatively measure hepatic fibrosis, MR images were analyzed with an aim to identify inhomogeneous signal intensities calculated from a coefficient of variation (CV) map in the liver parenchyma. We also carried out a comparative analysis between APRI and FIB-4 based on metaregression results. The diagnostic performance of the CV map was evaluated using a receiver-operating characteristic (ROC) curve. In the MR images, the mean CV values in control, groups I, II, and III based on APRI were 4.08 ± 0.92, 4.24 ± 0.80, 5.64 ± 1.11, and 5.73 ± 1.28, respectively (p < 0.001). In CHB patients grouped by FIB-4, the mean CV values of groups A, B, and C were 4.22 ± 0.95, 5.40 ± 1.19, and 5.71 ± 1.17, respectively (p < 0.001). The mean CV values correlated well with APRI (r = 0.392, p < 0.001) and FIB-4 (r = 0.294, p < 0.001). In significant fibrosis group, ROC curve analysis yielded an area under the curve of 0.875 using APRI and 0.831 using FIB-4 in HB, respectively. Gadoxetic acid-enhanced MR imaging for calculating a CV map showed moderate correlation with APRI and FIB-4 values and could be employed to quantitatively measure hepatic fibrosis in patients with CHB.

  15. Sputum biomarkers and the prediction of clinical outcomes in patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Theodore G Liou

    Full Text Available Lung function, acute pulmonary exacerbations (APE, and weight are the best clinical predictors of survival in cystic fibrosis (CF; however, underlying mechanisms are incompletely understood. Biomarkers of current disease state predictive of future outcomes might identify mechanisms and provide treatment targets, trial endpoints and objective clinical monitoring tools. Such CF-specific biomarkers have previously been elusive. Using observational and validation cohorts comprising 97 non-transplanted consecutively-recruited adult CF patients at the Intermountain Adult CF Center, University of Utah, we identified biomarkers informative of current disease and predictive of future clinical outcomes. Patients represented the majority of sputum producers. They were recruited March 2004-April 2007 and followed through May 2011. Sputum biomarker concentrations were measured and clinical outcomes meticulously recorded for a median 5.9 (interquartile range 5.0 to 6.6 years to study associations between biomarkers and future APE and time-to-lung transplantation or death. After multivariate modeling, only high mobility group box-1 protein (HMGB-1, mean=5.84 [log ng/ml], standard deviation [SD] =1.75 predicted time-to-first APE (hazard ratio [HR] per log-unit HMGB-1=1.56, p-value=0.005, number of future APE within 5 years (0.338 APE per log-unit HMGB-1, p<0.001 by quasi-Poisson regression and time-to-lung transplantation or death (HR=1.59, p=0.02. At APE onset, sputum granulocyte macrophage colony stimulating factor (GM-CSF, mean 4.8 [log pg/ml], SD=1.26 was significantly associated with APE-associated declines in lung function (-10.8 FEV(1% points per log-unit GM-CSF, p<0.001 by linear regression. Evaluation of validation cohorts produced similar results that passed tests of mutual consistency. In CF sputum, high HMGB-1 predicts incidence and recurrence of APE and survival, plausibly because it mediates long-term airway inflammation. High APE-associated GM

  16. Comparative evaluation of chest radiography, low-field MRI, the Shwachman-Kulczycki score and pulmonary function tests in patients with cystic fibrosis

    International Nuclear Information System (INIS)

    Anjorin, Angela; Vogl, Thomas J.; Schmidt, Helga; Posselt, Hans-Georg; Smaczny, Christina; Ackermann, Hanns; Deimling, Michael; Abolmaali, Nasreddin

    2008-01-01

    The aim of this study was to investigate whether the parenchymal lung damage in patients suffering from cystic fibrosis (CF) can be equivalently quantified by the Chrispin-Norman (CN) scores determined with low-field magnetic resonance imaging (MRI) and conventional chest radiography (CXR). Both scores were correlated with pulmonary function tests (PFT) and the Shwachman-Kulczycki method (SKM). To evaluate the comparability of MRI and CXR for different states of the disease, all scores were applied to patients divided into three age groups. Seventy-three CF patients (mean SKM score: 62 ± 8) with a median age (range) of 14 years (7-32) were included. The mean CN scores determined with both imaging methods were comparable (CXR: 12.1 ± 4.7; MRI: 12.0 ± 4.5) and showed high correlation (P < 0.05, R = 0.97). Only weak correlations were found between imaging, PFT, and SKM. Both imaging modalities revealed significantly more severe disease expression with age, while PFT and SKM failed to detect early signs of disease. We conclude that imaging of the lung in CF patients is capable of detecting subtle and early parenchymal destruction before lung function or clinical scoring is affected. Furthermore, low-field MRI revealed high consistency with chest radiography and may be used for a thorough follow-up while avoiding radiation exposure. (orig.)

  17. Assessment of hepatic fibrosis by fibroscan in egyptian chronic hemodialysis patients with chronic Hepatitis C (genotype 4: A single-center study

    Directory of Open Access Journals (Sweden)

    Bahaa El-Din Moustafa Zayed

    2017-01-01

    Full Text Available Assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC can help to evaluate the long-term prognosis, complications of hepatitis C virus (HCV as well as eligibility for renal transplantation,. Our aim was to assess liver fibrosis in Egyptian hemodialysis (HD patients infected with CHC genotype 4 using a fibroscan. This cross-sectional observational study was conducted over two years on a cohort of 134 Egyptian patients on prevalent HD at Kasr Al Ainy Hospital. All patients were subjected to routine laboratory evaluation including, hepatitis B surface antigen, hepatitis B core antibody, hepatitis Be antigen, hepatitis C antibody (HCVAb and human immunodeficiency virus antibody, quantitative polymerase chain reaction (PCR for both HCV and hepatitis B virus (HBV, serum hyaluronic acid level, and alpha-fetoprotein (AFP. Fibroscan was performed on all HCV-positive patients. The mean age was 47.43 ± 12.65 years, 50.7% were male, and 49.3% were female. The most common causes of end-stage renal disease were hypertensive nephropathy (32.1% and diabetic nephropathy (18.7%. HCVAb was positive in 57.5% of the patients and HBV was positive in 3%. Forty HCV-positive patients (57.1% who underwent fibroscan had mild to significant fibrosis, and thirty patients (42.9% had advanced fibrosis. There was significant correlation between HCV PCR and duration on HD, number of blood transfusions, and hyaluronic acid (HA level. In addition, there was a significant correlation between serum HA and HD duration as well as liver fibrosis. No significant correlation was found between duration on HD and fibrosis stage (P = 0.619; also, no significant correlation was noted between the age of the patients and HA level or stage of fibrosis (P = 0.970. Fibro-scan is a simple noninvasive test that can be used to assess liver fibrosis in HD patients with CHC. Most of the study patients had mild to significant fibrosis.

  18. Prosthetic rehabilitation of oral submucous fibrosis patients: A systematic review of published case reports and case series.

    Directory of Open Access Journals (Sweden)

    Shankargouda Patil

    Full Text Available Oral submucous fibrosis (OSF is an insidious chronic condition characterized by restricted mouth opening. Prosthetic rehabilitation is challenging for OSF patients as obtaining a good impression requires adequate mouth opening. The aim of the present review is to systematically present the data from case reports published in the English-language literature.A comprehensive search of the literature databases (PubMed, Medline, SCOPUS, Web of Science and Google Scholar along with the references of published articles on prosthetic rehabilitation in OSF patients published to date was conducted. Keywords included a combination of 'Oral submucous fibrosis', 'prosthesis', 'dentures' and/or 'restricted mouth opening'. Citations from selected references and bibliographic linkages taken from similar cases were included in this review. The inclusion criteria selected for case reports on prosthetic rehabilitation in OSF patients, and cases of restricted mouth opening due to causes other than OSF were excluded from the study.A total of 21 cases were identified and analysed from 17 papers published in the English-language literature. Of these, 9 cases employed the sectional denture technique, 4 cases emphasized the need-based treatment approach in which conventional methods were modified, and 4 cases used mouth exercising devices. Finally, 1 case each involved, flexible denture, oral screen prosthes