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Sample records for human disease cystic

  1. Neonatal renal cystic diseases.

    Science.gov (United States)

    Khare, Anshika; Krishnappa, Vinod; Kumar, Deepak; Raina, Rupesh

    2017-08-02

    Neonatal renal cystic diseases have a great impact on the morbidity and mortality of the affected neonates and infants. A good insight into the pathophysiology, diagnosis and treatment options of various neonatal renal cystic diseases aid in early diagnosis and intervention, thereby preventing complications. PubMed search was done for articles on "neonatal renal cystic diseases" and relevant publications including reviews were considered for our article. Both hereditary and nonhereditary causes of cystic kidney diseases can result in severe morbidity and mortality. The main diagnostic modality is ultrasound imaging and most of the neonatal renal cystic diseases are detected during prenatal ultrasound screening. Commonly encountered neonatal renal cystic diseases are autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease and multicystic dysplastic kidney. A thorough knowledge of various renal cystic diseases can be of extreme prognostic value. Physicians should be aware of the impact of early diagnosis and intervention on the lives of those affected. Further research about treatment of these diseases is ongoing and can result in breakthrough therapies for these patients.

  2. Multiple cystic lung disease.

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    Ferreira Francisco, Flavia Angélica; Soares Souza, Arthur; Zanetti, Gláucia; Marchiori, Edson

    2015-12-01

    Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt-Hogg-Dubé); other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management. Copyright ©ERS 2015.

  3. Human gross cyst breast disease and cystic fluid: bio-molecular, morphological, and clinical studies.

    Science.gov (United States)

    Mannello, Ferdinando; Tonti, Gaetana Anna Maria; Papa, Stefano

    2006-05-01

    For more than one and a half century the cystic disease of the breast has been recognized as the most frequent female benign breast lesion. Although some conundrums and controversies exist about the relation between gross cysts and breast cancer, recent evidence suggests that the multidisciplinary study of gross cystic breast disease (GCBD) may be a powerful tool for predicting the natural history of the multifaceted gross cyst pathology. A lot of papers have been published on breast cyst fluids (BCF) concerning biochemical, hormonal and morphological aspects, demonstrating that the intracystic fluid contains a wide variety of components (such as ions, lipids, proteins, enzymes, growth factors and antigens) and suggesting that their profile provides additional knowledge on both physiopathology and etiologic pathways of human gross cystic breast disease. The aim of this overview is the critical evaluation of all data accumulated in the last thirty years, in order to highlight the utility of biochemical and epidemiological studies to identify gross cysts, if any, at higher breast cancer risk.

  4. Cystic and nodular lung disease.

    Science.gov (United States)

    Richards, J Caleb; Lynch, David A; Chung, Jonathan H

    2015-06-01

    Diffuse cystic and nodular lung diseases have characteristic imaging findings. The most common causes of cystic lung disease are lymphangioleiomyomatosis and Langerhans cell histiocytosis. Other less common cystic lung diseases include Birt-Hogg-Dube syndrome, lymphocytic interstitial pneumonitis, and light chain deposition disease. Computed tomography is used to differentiate cystic lung disease from emphysema, honeycombing, cavities, and bronchiectasis, which mimic cystic lung disease. Diffuse nodular lung disease are categorized as centrilobular, perilymphatic, and random types. In diffuse nodular lung disease, a specific diagnosis is achieved through a combination of history, physical examination, and imaging findings. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Acquired cystic kidney disease

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    Choyke, P.L. [National Institutes of Health, Bethesda, MD (United States). Dept. of Diagnostic Radiology

    2000-11-01

    Acquired cystic kidney disease (ACKD), also known as acquired renal cystic disease (ARCD,) occurs in patients who are on dialysis for end-stage renal disease. It is generally accepted that ACKD develops as a consequence of sustained uremia and can first manifest even before dialysis is initiated while the patient is still in chronic renal failure. The role of immune suppression, particularly in transplant recipients, in the development of ACKD, is still under investigation. The prevalence of ACKD is directly related to the duration of dialysis and the risk of cancer is directly related to the presence of cysts. Herein we review the current understanding of the pathophysiology and imaging implications of ACKD. (orig.)

  6. Adventitial Cystic Disease

    Directory of Open Access Journals (Sweden)

    Chii-Hong Lee

    2006-01-01

    Full Text Available Adventitial cystic disease (ACD is an unusual cystic tumor of blood vessels characterized by the accumulation of mucinous substance in the adventitia of the non-axial blood vessels adjacent to joints. Patients with ACD often suffer from intermittent claudication and/or limb pain, mostly involving the popliteal artery. We report a 30-year-old male who presented with intermittent claudication in his left leg. Angiography showed an obstructive lesion in the left popliteal artery. The lesion was treated successfully by surgical excision followed by graft vessel replacement. ACD involving the popliteal artery was diagnosed by pathologic findings of multiple cysts of the adventitia with external compression and focal narrowing of the vascular lumen. The cysts contained acid mucin and were partially lined by multiple rows of cytologically bland, synovium-like cells with positive immunoreactivity to vimentin and CD68 but negative immunoreactivity to cytokeratin. The histopathologic findings in this case suggest that it was caused by the developmental rests of mucin-secreting mesenchymal cells derived from the knee joint.

  7. Cystic kidney disease: a primer.

    Science.gov (United States)

    Cramer, Monica T; Guay-Woodford, Lisa M

    2015-07-01

    Renal cystic diseases encompass a broad group of disorders with variable phenotypic expression. Cystic disorders can present during infancy, childhood, or adulthood. Often, but not always, they can be distinguished by the clinical features including age at presentation, renal imaging characteristics, including cyst distribution, and the presence/distribution of extrarenal manifestations. It is important to take the clinical context into consideration when assessing renal cystic disease in children and adults. For example, solitary kidney cysts may be completely benign when they develop during adulthood but may represent early polycystic kidney disease when observed during childhood. In this review, we have categorized renal cystic disease according to inherited single-gene disorders, for example, autosomal recessive polycystic kidney disease; syndromic disorders associated with kidney cysts, for example, tuberous sclerosis complex; and nongenetic forms of renal cystic disease, for example, simple kidney cysts. We present an overview of the clinical characteristics, genetics (when appropriate), and molecular pathogenesis and the diagnostic evaluation and management of each renal cystic disease. We also provide an algorithm that distinguishes kidney cysts based on their clinical features and may serve as a helpful diagnostic tool for practitioners. A review of Autosomal Dominant Polycystic Disease was excluded as this disorder was reviewed in this journal in March 2010, volume 17, issue 2. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  8. The disease burden of human cystic echinococcosis based on HDRs from 2001 to 2014 in Italy.

    Directory of Open Access Journals (Sweden)

    Toni Piseddu

    2017-07-01

    Full Text Available Cystic echinococcosis (CE is an important neglected zoonotic parasitic infection belonging to the subgroup of seven Neglected Zoonotic Disease (NZDs included in the World Health Organization's official list of 18 Neglected Tropical Diseases (NTDs. CE causes serious global human health concerns and leads to significant economic losses arising from the costs of medical treatment, morbidity, life impairments and fatality rates in human cases. Moreover, CE is endemic in several Italian Regions. The aim of this study is to perform a detailed analysis of the economic burden of hospitalization and treatment costs and to estimate the Disability Adjusted Life Years (DALYs of CE in Italy.In the period from 2001 to 2014, the direct costs of 21,050 Hospital Discharge Records (HDRs belonging to 12,619 patients with at least one CE-related diagnosis codes were analyzed in order to quantify the economic burden of CE. CE cases average per annum are 901 (min-max = 480-1,583. Direct costs include expenses for hospitalizations, medical and surgical treatment incurred by public and private hospitals and were computed on an individual basis according to Italian Health Ministry legislation. Moreover, we estimated the DALYs for each patient. The Italian financial burden of CE is around € 53 million; the national average economic burden per annum is around € 4 million; the DALYs of the population from 2001 to 2014 are 223.35 annually and 5.26 DALYs per 105 inhabitants.In Italy, human CE is responsible for significant economic losses in the public health sector. In humans, costs associated with CE have been shown to have a great impact on affected individuals, their families and the community as a whole. This study could be used as a tool to prioritize and make decisions with regard to a surveillance system for this largely preventable yet neglected disease. It demonstrates the need of implementing a CE control program aimed at preventing the considerable economic

  9. Human cystic echinococcosis in South Africa

    NARCIS (Netherlands)

    Mogoye, Benjamin; Menezes, Colin N.; Grobusch, Martin P.; Wahlers, Kerstin; Frean, John

    2012-01-01

    Cystic echinococcosis (CE) is caused by the tapeworm, Echinococcus granulosus. The tapeworms resides in the small intestines of canids and the lifecycle involves both intermediate and definitive hosts. Humans are accidental intermediate hosts. Cystic echinococcosis is an economically important

  10. Acquired Cystic Kidney Disease

    Science.gov (United States)

    ... Diabetes Inspidus Glomerular Diseases Goodpasture Syndrome Henoch-Schönlein Purpura IgA Nephropathy Kidney Disease in Children Childhood Nephrotic ... will treat infections with antibiotics—medications that kill bacteria. If large cysts are causing pain, a health ...

  11. Acquired Cystic Kidney Disease

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    ... always be reported to a doctor. Although doctors debate the exact per centage, somewhere between 10 and ... diseases. This publication is not copyrighted. The Clearing house encourages users of this fact sheet to duplicate ...

  12. Biomarkers in Paediatric Cystic Fibrosis Lung Disease.

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    Ramsey, Kathryn A; Schultz, André; Stick, Stephen M

    2015-09-01

    Biomarkers in cystic fibrosis are used i. for the measurement of cystic fibrosis transmembrane regulator function in order to diagnose cystic fibrosis, and ii. to assess aspects of lung disease severity (e.g. inflammation, infection). Effective biomarkers can aid disease monitoring and contribute to the development of new therapies. The tests of cystic fibrosis transmembrane regulator function each have unique strengths and weaknesses, and biomarkers of inflammation, infection and tissue destruction have the potential to enhance the management of cystic fibrosis through the early detection of disease processes. The development of biomarkers of cystic fibrosis lung disease, in particular airway inflammation and infection, is influenced by the challenges of obtaining relevant samples from infants and children for whom early detection and treatment of disease might have the greatest long term benefits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Prenatal ultrasonographic findings of renal cystic diseases of the fetus

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    Cho, Jeong Yeon; Song, Mi Jin; Lee, Young Ho; Cho, Byung Jae; Hong, Sung Ran [Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-03-15

    The renal cystic diseases of the fetus consist of variable types of multicystic dysplastic kidney, autosomal recessive polycystic kidney, autosomal dominant polycystic kidney, obstructive cystic renal dysplasia, simple renal cyst, medullary cystic disease, and various syndromes with associated cystic renal diseases. Prenatal US findings of renal cystic diseases were compared and analyzed with the pathologic and postnatal US findings to establish the differential points of renal cystic diseases.

  14. Outcome in cystic fibrosis liver disease.

    LENUS (Irish Health Repository)

    Rowland, Marion

    2011-01-01

    Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD.

  15. Renal cystic disease and associated ciliopathies.

    Science.gov (United States)

    Kagan, Karl O; Dufke, Andreas; Gembruch, Ulrich

    2017-04-01

    To review disorders that are associated with renal cystic disease during prenatal life and to highlight the strong association between renal cystic disease and ciliopathies. There are numerous causative genes for ciliopathies that can present with cystic kidney disease. In the group of single gene ciliopathies, autosomal dominant polycystic kidney disease is by far the most prevalent one. Other examples are autosomal recessive polycystic kidney disease, nephronophthisis, Bardet-Biedl syndrome, Meckel-Gruber syndrome, Joubert syndrome and related disorders as well as X-linked orofaciodigital syndrome type 1, respectively. The prevalence of these inherited disorders sums up to about in 1 : 2000 people. These disorders with their hepatorenal fibrocystic character should be classified as multisystem diseases. Understanding of the origin of renal cystic disease and associated disorders is important to make the appropriate prenatal diagnosis and for counseling affected parents. In the future, understanding of the pathophysiology may help to develop new treatment strategies.

  16. Primary Cilia in Cystic Kidney Disease.

    Science.gov (United States)

    Avasthi, Prachee; Maser, Robin L; Tran, Pamela V

    Primary cilia are small, antenna-like structures that detect mechanical and chemical cues and transduce extracellular signals. While mammalian primary cilia were first reported in the late 1800s, scientific interest in these sensory organelles has burgeoned since the beginning of the twenty-first century with recognition that primary cilia are essential to human health. Among the most common clinical manifestations of ciliary dysfunction are renal cysts. The molecular mechanisms underlying renal cystogenesis are complex, involving multiple aberrant cellular processes and signaling pathways, while initiating molecular events remain undefined. Autosomal Dominant Polycystic Kidney Disease is the most common renal cystic disease, caused by disruption of polycystin-1 and polycystin-2 transmembrane proteins, which evidence suggests must localize to primary cilia for proper function. To understand how the absence of these proteins in primary cilia may be remediated, we review intracellular trafficking of polycystins to the primary cilium. We also examine the controversial mechanisms by which primary cilia transduce flow-mediated mechanical stress into intracellular calcium. Further, to better understand ciliary function in the kidney, we highlight the LKB1/AMPK, Wnt, and Hedgehog developmental signaling pathways mediated by primary cilia and misregulated in renal cystic disease.

  17. Cystic fibrosis-related bone disease.

    Science.gov (United States)

    Paccou, Julien; Fardellone, Patrice; Cortet, Bernard

    2013-11-01

    This review highlights recently published data on the pathophysiology, guidelines and treatment of cystic fibrosis (CF)-related bone disease. The exact role of the cystic fibrosis transmembrane conductance regulator (CFTR), specifically the ΔF508 allele, has been investigated in F508del-CFTR homozygous mice and the F508del-CFTR mutation may contribute to CF-related bone disease by slowing new bone formation. The European Cystic Fibrosis Society has issued guidelines for bone mineral density assessment, management of low-trauma fractures and bisphosphonate therapy. A systematic review based on meta-analyses reports that oral and intravenous bisphosphonates both improve bone mineral density in CF patients, but no data are available concerning the reduction of low-trauma fractures. European Cystic Fibrosis Society guidelines may help physicians to improve the management of CF-related bone disease.

  18. Renal cystic diseases in children: new concepts

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    Avni, Fred E. [University Clinics of Brussels - Erasme Hospital, Departments of Medical Imaging and Pediatric Nephrology, Brussels (Belgium); Hall, Michelle [Pediatric Nephrology Erasme Hospital, Brussels (Belgium)

    2010-06-15

    This review highlights the changes that have occurred in the general approach to cystic renal diseases in children. For instance, genetic mutations at the level of the primary cilia are considered as the origin of many renal cystic diseases. Furthermore, these diseases are now included in the spectrum of the hepato-renal fibrocystic diseases. Imaging plays an important role as it helps to detect and characterize many of the cystic diseases based on a detailed sonographic analysis. The diagnosis can be achieved during fetal life or after birth. Hyperechoic kidneys and/or renal cysts are the main sonographic signs leading to such diagnosis. US is able to differentiate between recessive and dominant polycystic kidney diseases, hepatocyte nuclear factor 1 Beta mutation, glomerulocystic kidneys and nephronophtisis. MR imaging can, in selected cases, provide additional information including the progressive associated hepatic changes. (orig.)

  19. Localized cystic disease of the kidney: distinction from cystic neoplasms and hereditary polycystic diseases.

    Science.gov (United States)

    Ding, Yi; Chen, Longwen; Deng, Fang-Ming; Melamed, Jonathan; Fan, Rong; Bonsib, Stephen; Zhou, Ming

    2013-04-01

    Cystic changes are common in both neoplastic and non-neoplastic kidney diseases. The most important diagnostic consideration is to rule out cystic neoplasms and hereditary polycystic kidney disease for patient management. Localized cystic disease of the kidney is a rare, nongenetic and nonprogressive cystic disease that may mimic cystic neoplasms or hereditary polycystic disease. However, reports in the literature on its pathologic characteristics are scarce, and most surgical pathologists are unfamiliar with this entity. We report the clinicopathologic characteristics of 9 such cases that mimicked renal neoplasms and were treated surgically. Nine patients, including 5 men and 4 women, had a mean age of 33.3 years (range, 18 to 56 y) at diagnosis. Two patients presented with gross hematuria. In the remaining 7 patients, localized cystic disease was discovered incidentally. None had a personal history of cystic disease of the kidney or other organs or a family history of cystic renal disease. On imaging studies, solitary multilocular cystic lesions were identified in all patients with a mean size of 2.9 cm (range, 0.8 to 6 cm). Of 7 patients with documented Bosniak classification, 4 lesions were class III, and 3 lesions were class II. Follow-up was available in 5 patients, with a mean follow-up time of 14.6 months (range, 5 to 31 mo). No cysts were observed in the ipsilateral and contralateral kidneys during follow-up. Partial and total nephrectomy was performed in 8 and 1 patient, respectively. Grossly, the cystic lesions were not discrete and merged imperceptibly with the adjacent renal parenchyma without a discrete margin or capsule. Microscopically, cystic lesions involved renal papillae in all cases, and the cystic space was continuous with dilated collecting ducts. Cysts were lined with cuboidal or flat epithelial cells identical to those lining the collecting ducts. Significant inflammation was absent. The surrounding renal parenchyma was normal. With this

  20. Liver Disease in Cystic Fibrosis: an Update

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    Parisi, Giuseppe Fabio; Di Dio, Giovanna; Franzonello, Chiara; Gennaro, Alessia; Rotolo, Novella; Lionetti, Elena; Leonardi, Salvatore

    2013-01-01

    Context Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. Evidence Acquisition A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. Results CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease. Conclusions Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of

  1. Liver disease in cystic fibrosis: an update.

    Science.gov (United States)

    Parisi, Giuseppe Fabio; Di Dio, Giovanna; Franzonello, Chiara; Gennaro, Alessia; Rotolo, Novella; Lionetti, Elena; Leonardi, Salvatore

    2013-08-14

    Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emerged especially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause of mortality in CF (the third after pulmonary disease and transplant complications), only about the 33%of CF patients presents clinically significant hepatobiliary disease. Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed at delaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of fibrosis prevention and to avoid its

  2. Amyloid-associated Cystic Lung Disease.

    Science.gov (United States)

    Zamora, Ana C; White, Darin B; Sykes, Anne-Marie G; Hoskote, Sumedh S; Moua, Teng; Yi, Eunhee S; Ryu, Jay H

    2016-05-01

    Amyloid-associated cystic lung disease is rare. It can be associated with collagen vascular disease (CVD). We aimed to describe the clinical, radiology, and pathology findings of this entity. We reviewed the records of subjects having biopsy-proven pulmonary amyloidosis with cystic lung disease demonstrated at high-resolution computed tomography (HRCT). Demographic characteristics, association with CVD and lymphoproliferative disorders, pulmonary function, and pathology results were reviewed. HRCT appearance was analyzed for number, size, distribution, and morphology of cysts and nodules. Twenty-one subjects (13 female, eight male; median age, 61 years) with cystic pulmonary amyloidosis were identified. The most common pulmonary function patterns were normal (42%) and obstructive (32%). The most common associated CVD was Sjögren syndrome (10 of 12). Nine subjects had no CVD. Cysts tended to be multiple (≥ 10 in 14 of 21, 67%), round (21 of 21, 100%), or lobulated (20 of 21, 95%); thin-walled (cystic lung disease can occur with or without underlying CVD. Cystic lesions in the lung are commonly numerous, often are peribronchovascular or subpleural, and are frequently associated with nodular lesions that are often calcified. MALToma was a relatively frequent association. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  3. Early lung disease in cystic fibrosis.

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    Grasemann, Hartmut; Ratjen, Felix

    2013-04-01

    Lung disease in patients with cystic fibrosis is characterised by inflammation and recurrent and chronic infections leading to progressive loss in pulmonary function and respiratory failure. Early management of disease results in substantially improved pulmonary function at first testing (at roughly 6 years of age), but the annual decline in pulmonary function tests in older patients has remained unchanged showing how important the early years are in the disease process. Treatment regimens for patients with cystic fibrosis have changed from predominantly symptomatic treatment to preventive or causal (ie, treatments that address the underlying mechanisms of disease) therapeutic interventions. The infant and preschool age (2-5 years) could represent a unique period of opportunity to postpone or even prevent the onset of cystic fibrosis lung disease. We summarise the current knowledge and the methods used to characterise and quantify early lung disease. We discuss treatment strategies including new drugs that are being developed and their potential role in the treatment of early lung disease in patients with cystic fibrosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Human cystic echinococcosis in South Africa

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    Benjamin Mogoye

    2012-06-01

    Full Text Available Cystic echinococcosis (CE is caused by the tapeworm, Echinococcus granulosus. The tapeworms resides in the small intestines of canids and the lifecycle involves both intermediate and definitive hosts. Humans are accidental intermediate hosts. Cystic echinococcosis is an economically important infection constituting a threat to public health, and is considered an emerging disease around the world. There are at least 10 Echinococcus strain types (G1 – G10, each exhibiting diversity of morphology, development and host range. The epidemiology of CE is poorly understood in South Africa. A retrospective data analysis of the National Health Laboratory Service (NHLS laboratory information system on echinococcosis serology, microscopy and histopathology results in eight provinces (excluding KwaZula-Natal showed an overall positivity rate in submitted diagnostic samples of 17.0% (1056/6211, with the Eastern Cape (30.4%, North West (19.0% and Northern Cape (18.0% provinces showing highest rates. The data showed considerable variability between provinces. The review also showed that most proven cases were negative on serology, implying that the actual number of patients could be underestimated. To our knowledge, no data exist about the prevalent strains of E. granulosus and this prospective study will attempt to fill that gap. The aim is to genotype strains causing the disease in South Africa. Two different polymerase chain reaction (PCR methods will be used to respectively target the 12S rRNA and nad 1 genes. To date, three samples have been genotyped as G1, G5 and G6; suggesting diversity of strains prevalent in the country, but more data is needed for a clearer picture.

  5. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease

    National Research Council Canada - National Science Library

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-01-01

    ... understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control...

  6. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

    Science.gov (United States)

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-08-01

    Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease. Copyright ©ERS 2015.

  7. Cystic lung disease: Achieving a radiologic diagnosis

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    Trotman-Dickenson, Beatrice, E-mail: btrotmandickenson@partners.org

    2014-01-15

    Diffuse cystic lung disease represents a diverse group of uncommon disorders with characteristic appearance on high resolution CT imaging. The combination of imaging appearance with clinical features and genetic testing where appropriate permits a confident and accurate diagnosis in the majority of the diseases without recourse for open lung biopsy. The mechanism of cyst development disease is unclear but in some disorders appears to be related to small airways obstruction. These diseases are incurable, with the exception of Langerhans cell histiocytosis which may spontaneously remit or resolve on smoking cessation. Disease progression is unpredictable; in general older patients have a more benign disease, while young patients may progress rapidly to respiratory failure. An understanding of the complications of cystic lung disease and the appearance of disease progression is essential for the management of these patients. A number of these disorders are associated with malignancy, recognition of the potential tumors permits appropriate imaging surveillance. Due to the widespread use of CT, pulmonary cysts are increasingly discovered incidentally in an asymptomatic individual. The diagnostic challenge is to determine whether these cysts represent an early feature of a progressive disease or have no clinical significance. In the elderly population the cysts are unlikely to represent a progressive disease. In individuals <50 years further evaluation is recommended.

  8. Group B streptococcus (GBS) is an important pathogen in human disease- but what about in cystic fibrosis?

    Science.gov (United States)

    Skolnik, Kate; Nguyen, Austin; Thornton, Christina S; Waddell, Barbara; Williamson, Tyler; Rabin, Harvey R; Parkins, Michael D

    2017-10-02

    Group B Streptococcus (GBS) is a common commensal capable of causing severe invasive infections. Most GBS infections occur in neonates (often as pneumonia). GBS can also cause infection in adults with diabetes and other immunological impairments but rarely leads to pneumonia in adults. GBS has occasionally been found in the sputum of Cystic Fibrosis (CF) patients, an inherited condition known for progressive lung disease. However, the epidemiology and clinical significance of GBS in CF are not understood. We retrospectively reviewed a large single-centre adult CF population with an associated comprehensive, prospectively collected bacterial biobank beginning in 1978. We identified all individuals with GBS isolated from their sputum on at least one occasion. The primary outcome was risk of pulmonary exacerbation (PEx) at the time of the first GBS isolate compared to the preceding visit. Secondary outcomes included determining: prevalence of GBS infection in a CF population, whether GBS infections where transient or persistent, whether GBS strains were shared among patients, change in % predicted FEV 1 at the time of GBS isolate compared to the preceding visit, PEx frequency after the first GBS isolate, change in % predicted FEV 1 after the first GBS isolate, and complications of GBS infection. GBS was uncommon, infecting 3.5% (11/318) adults within our cohort. Only three individuals developed persistent GBS infection, all lasting > 12 months. There were no shared GBS strains among patients. PEx risk was not increased at initial GBS isolation (RR 5.0, CI 0.69-36.1, p=0.10). In the two years preceding initial GBS isolation compared to the two following years, there was no difference in PEx frequency (median 2, range 0-4 vs 1, range 0 to 5, respectively, p=0.42) or lung function decline, as measured by % predicted FEV 1 , (median -1.0%, range -19 to 7% vs median -6.0%, range -18 to 22%, p=0.86). There were no invasive GBS infections. In adults with CF, GBS is uncommon

  9. Integrin α6β4 identifies human distal lung epithelial progenitor cells with potential as a cell-based therapy for cystic fibrosis lung disease.

    Directory of Open Access Journals (Sweden)

    Xiaopeng Li

    Full Text Available To develop stem/progenitor cell-based therapy for cystic fibrosis (CF lung disease, it is first necessary to identify markers of human lung epithelial progenitor/stem cells and to better understand the potential for differentiation into distinct lineages. Here we investigated integrin α6β4 as an epithelial progenitor cell marker in the human distal lung. We identified a subpopulation of α6β4(+ cells that localized in distal small airways and alveolar walls and were devoid of pro-surfactant protein C expression. The α6β4(+ epithelial cells demonstrated key properties of stem cells ex vivo as compared to α6β4(- epithelial cells, including higher colony forming efficiency, expression of stem cell-specific transcription factor Nanog, and the potential to differentiate into multiple distinct lineages including basal and Clara cells. Co-culture of α6β4(+ epithelial cells with endothelial cells enhanced proliferation. We identified a subset of adeno-associated virus (AAVs serotypes, AAV2 and AAV8, capable of transducing α6β4(+ cells. In addition, reconstitution of bronchi epithelial cells from CF patients with only 5% normal α6β4(+ epithelial cells significantly rescued defects in Cl(- transport. Therefore, targeting the α6β4(+ epithelial population via either gene delivery or progenitor cell-based reconstitution represents a potential new strategy to treat CF lung disease.

  10. Human Cystic Echinococcosis: Old Problems and New Perspectives

    Directory of Open Access Journals (Sweden)

    Alessandra Siracusano

    2009-01-01

    Full Text Available Cystic echinococcosis (CE is a widespread chronic endemic helminthic disease caused by infection with metacestodes of the tapeworm Echinococcus granulosus. CE affects humans and has a worldwide prevalence of approximately six million. In this review, we discuss current findings in diagnosis and clinical management of CE and new concepts relating to E. granulosus molecules that directly modulate the host immune responses favouring a strong anti-inflammatory response and perpetuating parasite survival in the host. New insights into the molecular biology of E. granulosus will improve considerably our knowledge of the disease and will provide new potential therapeutic applications to treat or prevent inflammatory immune-mediated disease.

  11. Prevalence and pattern of cystic kidney diseases in Ilorin, Nigeria

    Directory of Open Access Journals (Sweden)

    Chijioke Adindu

    2010-01-01

    Full Text Available Cystic kidney disease is an important cause of chronic renal failure. Since the utili-zation of imaging techniques in the diagnosis of diseases has become widespread, cystic kidney disease is now being increasingly diagnosed. This study is designed to determine the prevalence and pattern of cystic kidney disease at the Nephrology Unit of University of Ilorin Teaching Hospital (UITH, Ilorin. All consecutive adult patients seen in the Nephrology Unit of UITH during a ten-year period (January 1999-December 2008 were studied for the presence of cystic kidney disease. The results were analyzed with specific reference to age, gender, annual inci-dence, type of cystic disease, location of cyst, mode of presentation, complications and prognosis. A total of 67 out of 436 renal patients (15.4% studied had cystic kidney disease. A progressive annual increase in the number of cases was noticed. The age-range was 20-83 years with a mean of 47.4 +/- 16.2 years and the peak incidence was in the third and sixth decades with male to female ratio of 1.3:1. The types of cystic kidney disease identified in the study were: 26 simple cysts (38.8%, 35 polycystic kidney disease (53.3% and six multicystic kidney disease (8.9%. The most common mode of presentation was abdominal pain followed by hypertension, urinary tract infection, chronic renal failure and palpable abdominal mass, in decreasing order. Our study indicates that cystic kidney disease is not an uncommon problem among our renal patients and the incidence is on the increase. Although, routine screening of family members with cystic kidney disease still remains a contentious issue because the knowledge may evoke anxiety in terms of employment and insurance, screening of symptomatic cases or those that develop hypertension, hematuria and proteinuria is strongly recommended.

  12. Computed Tomography in the Evaluation of Cystic Fibrosis Lung Disease

    National Research Council Canada - National Science Library

    Brody, Alan S; Tiddens, Harm A. W. M; Castile, Robert G; Coxson, Harvey O; de Jong, Pim A; Goldin, Jonathan; Huda, Walter; Long, Frederick R; McNitt-Gray, Michael; Rock, Michael; Robinson, Terry E; Sagel, Scott D; CT Scanning in Cystic Fibrosis Special Interest Group

    2005-01-01

    ... of this article is to present the current status of CT scanning in CF. Keywords: computed tomography X-ray; cystic fibrosis; radiation effects; research design The first report of computed tomography (CT) scanning to monitor cystic fibrosis (CF)-related lung disease was published in 1986 (1). Further publications followed, but in general there was little i...

  13. Segmental cystic disease of the kidney: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Han, Soo Bong; Chung, Sung Hwa; Cho, Jae Ho [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

    2008-06-15

    Segmental cystic disease of the kidney is a rare form of cystic disease of the kidney that manifests as variable sized, numerous cysts that are localized in a segment of one kidney. Morphologically and pathologically, it is indistinguishable from autosomal dominant polycystic kidney disease except for its unilateral localization, the lack of an autosomal dominant genetic background and the progressive deterioration of the renal function. We experienced a case of surgically confirmed segmental cystic disease of the kidney in a 49-year-old patient and we report on its ultrasonographic and CT findings, along with a brief review of the relevant literature.

  14. Diffuse cystic lung diseases: differential diagnosis.

    Science.gov (United States)

    Baldi, Bruno Guedes; Carvalho, Carlos Roberto Ribeiro; Dias, Olívia Meira; Marchiori, Edson; Hochhegger, Bruno

    2017-01-01

    Diffuse cystic lung diseases are characterized by cysts in more than one lung lobe, the cysts originating from various mechanisms, including the expansion of the distal airspaces due to airway obstruction, necrosis of the airway walls, and parenchymal destruction. The progression of these diseases is variable. One essential tool in the evaluation of these diseases is HRCT, because it improves the characterization of pulmonary cysts (including their distribution, size, and length) and the evaluation of the regularity of the cyst wall, as well as the identification of associated pulmonary and extrapulmonary lesions. When combined with clinical and laboratory findings, HRCT is often sufficient for the etiological definition of diffuse lung cysts, avoiding the need for lung biopsy. The differential diagnoses of diffuse cystic lung diseases are myriad, including neoplastic, inflammatory, and infectious etiologies. Pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, lymphocytic interstitial pneumonia, and follicular bronchiolitis are the most common diseases that produce this CT pattern. However, new diseases have been included as potential determinants of this pattern. RESUMO As doenças pulmonares císticas difusas se caracterizam pela presença de cistos envolvendo mais de um lobo pulmonar, que se originam por diversos mecanismos, incluindo dilatação dos espaços aéreos distais por obstrução, necrose das paredes das vias aéreas e destruição do parênquima. Essas doenças apresentam evolução variável. A TCAR é fundamental na avaliação dessas doenças uma vez que permite uma melhor caracterização dos cistos pulmonares, incluindo sua distribuição, tamanho, extensão e regularidade das paredes, assim como a determinação de outras lesões pulmonares e extrapulmonares associadas. Frequentemente a TCAR é suficiente para a definição etiológica dos cistos pulmonares difusos, associada a achados clínicos e laboratoriais, sem a necessidade

  15. Sclerotherapy for Benign Cystic Diseases in the Neck

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hoon; Sohn, Chul Ho; Choi, Seung Hong; Yun, Tae Jin [Dept. of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2012-08-15

    Surgery has been the classic treatment of choice for benign cystic diseases, including lymphatic malformation, ranula, branchial cleft cyst, thyroglossal duct cyst, thyroid cyst, parathyroid cyst, and lymphocele. However, surgery is associated with a tendency toward recurrence and may be accompanied by various complications, such as nerve injuries, vascular injuries, and scar formation. Therefore, sclerotherapy using various agents has been applied successfully to treatment of benign cystic diseases in the neck. This editorial reviews the use of various sclerotic agents and application of sclerotherapy to benign cystic diseases in the neck.

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

    Science.gov (United States)

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

    2015-08-12

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

  17. Localized cystic disease of the kidney: a rare entity.

    Science.gov (United States)

    Neyaz, Zafar; Kumar, Sunil; Lal, Hira; Kapoor, Rakesh

    2012-07-01

    Localized cystic disease of the kidney is a benign nonsurgical entity and presents with multiple cystic lesions in just one portion of the kidney or involves the entire one kidney. We report a case of localized cystic disease of the kidney in a 16 year-old-male. This patient underwent an ultrasound examination and incidentally found to have multiple cysts in the right kidney whereas the left kidney was normal. Diagnosis was confirmed by typical MRI findings, absence of any family history, normal results of urine analysis and renal function tests.

  18. [Cystic fibrosis: a new disease in adults].

    Science.gov (United States)

    Asensio de la Cruz, O; Bosque García, M; Marco Valls, M T

    1997-01-01

    Cystic fibrosis (CF) has undergone substantial epidemiological changes. The life expectancy of CF patients and the proportion of affected adults are rising because of advances in diagnosis and treatment. In order to find out more about our current situation, we sent an anonymous questionnaire to all affected members of the Catalonian Association of CF. The questionnaire was sent to 180 patients and their parents asking for information about demographical aspects, diagnosis, pulmonary function, microbiological data, complications, treatment, number of medical visits to CF centers, personal, social and professional development, and the degree of satisfaction with the medical care received. The questionnaire was correctly completed by 75 patients. Of these, 20% were older than 18 years of age. The mean age at diagnosis was 3.25 years. The initial symptoms were: meconium ileus (8%), growth retardation (24%), respiratory problems (34%) and gastrointestinal problems (36%). Sixty percent of the patients showed positive sputum cultures. The most frequently isolated microorganism was P. aeruginosa. Apart form the usual therapy with antibiotics, enzyme replacement and vitamin supplements, other therapeutic measures employed included: alimentary supplements (54%), mucolitics (27%), bronchodilators (45%) and inhaled anti-inflammatories (20%). Complications were present in 56% of the patients and these included hemoptysis, polyps, rectal prolapse, hepatic disease, diabetes, psychological changes, biliary litiasis, pneumothorax, infertility or pancreatitis. The proportion of positive sputum cultures, the type of germ identified and the complications observed changed according to the patient's age. National registers can be very useful tools to make public health plans. They are also good instruments to evaluate the progress made in the treatment of diseases such as CF.

  19. Wnt and planar cell polarity signaling in cystic renal disease.

    Science.gov (United States)

    Goggolidou, Paraskevi

    2014-01-01

    Cystic kidney diseases can cause end stage renal disease, affecting millions of individuals worldwide. They may arise early or later in life, are characterized by a spectrum of symptoms and can be caused by diverse genetic defects. The primary cilium, a microtubule-based organelle that can serve as a signaling antenna, has been demonstrated to have a significant role in ensuring correct kidney development and function. In the kidney, one of the signaling pathways that requires the cilium for normal development is Wnt signaling. In this review, the roles of primary cilia in relation to canonical and non-canonical Wnt/PCP signaling in cystic renal disease are described. The evidence of the associations between cilia, Wnt signaling and cystic renal disease is discussed and the significance of planar cell polarity-related mechanisms in cystic kidney disease is presented. Although defective Wnt signaling is not the only cause of renal disease, research is increasingly highlighting its importance, encouraging the development of Wnt-associated diagnostic and prognostic tools for cystic renal disease.

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

    DEFF Research Database (Denmark)

    Fluge, G; Olesen, Hanne Vebert; 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...

  1. 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...

  2. MicroRNAs in the pathogenesis of cystic kidney disease.

    Science.gov (United States)

    Phua, Yu Leng; Ho, Jacqueline

    2015-04-01

    Cystic kidney diseases are common renal disorders characterized by the formation of fluid-filled epithelial cysts in the kidneys. The progressive growth and expansion of the renal cysts replace existing renal tissue within the renal parenchyma, leading to reduced renal function. While several genes have been identified in association with inherited causes of cystic kidney disease, the molecular mechanisms that regulate these genes in the context of post-transcriptional regulation are still poorly understood. There is increasing evidence that microRNA (miRNA) dysregulation is associated with the pathogenesis of cystic kidney disease. In this review, recent studies that implicate dysregulation of miRNA expression in cystogenesis will be discussed. The relationship of specific miRNAs, such as the miR-17∼92 cluster and cystic kidney disease, miR-92a and von Hippel-Lindau syndrome, and alterations in LIN28-LET7 expression in Wilms tumor will be explored. At present, there are no specific treatments available for patients with cystic kidney disease. Understanding and identifying specific miRNAs involved in the pathogenesis of these disorders may have the potential to lead to the development of novel therapies and biomarkers.

  3. [Epidemiology and systematics of cystic and alveolar hydatid disease].

    Science.gov (United States)

    Gottstein, B

    2000-01-01

    Echinococcus multilocularis, a small tapeworm in foxes, has gained considerable public attention owing to its wide distribution in central Europe. Conversely, diagnosis and treatment of the disease have been significantly improved in recent years. Consequently, the incidence among human populations has remained stable and relatively low for many decades. In southern Germany, France (Franche Comté and Doubs), Austria and Switzerland, the annual incidence ranges between 0.02 and 1.4 new cases per 100,000 inhabitants. The relevance of human AE refers to the high lethality of the untreated disease. Therapy consists predominantly of radical surgery followed by continuous, long-term chemotherapy using albendazole (or mebendazole). The action of chemotherapy alone is parasitostatic rather than parasitocidal; nevertheless, clinical improvement is observed in > 80 % of such cases, including a significantly improved prognosis. Diagnosis relies predominantly on imaging procedures and serology. Immunodiagnosis must be performed early, especially when a preclinical diagnosis is desired upon exposure to infection. Thus, in the framework of seroepidemiological studies, first-time evidence was obtained about the phenomenon of natural resistance in non-diseased persons. This raised the question of a potential immunogenetic predisposition in certain infected persons. E. granulosus (cystic hydatid disease) is practically non-existent as autochthonous infection in central Europe now. Most clinical cases of E. granulosus infections are thus observed among persons who have immigrated from - predominantly - the mediterranean basin.

  4. Congenital cystic disease of the liver in seven dogs

    NARCIS (Netherlands)

    Ingh, T.S.G.A.M. van den; Rothuizen, J.

    1985-01-01

    Seven canine cases of cystic disease of the liver are described. They included 3 cases with solitary cysts, 3 with the adult type of polycystic disease of the liver and one with congenital dilatation of the bile ducts type V, i.e. fusiform dilatation of the intrahepatic and extrahepatic bile ducts.

  5. Lung function imaging methods in Cystic Fibrosis pulmonary disease.

    Science.gov (United States)

    Kołodziej, Magdalena; de Veer, Michael J; Cholewa, Marian; Egan, Gary F; Thompson, Bruce R

    2017-05-17

    Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

  6. Hepatobiliary disease in children and adolescents with cystic fibrosis.

    Science.gov (United States)

    Nascimento, Fernanda de S; Sena, Nelson A; Ferreira, Tatiane da A; Marques, Cibele D F; Silva, Luciana R; Souza, Edna Lúcia

    2017-09-07

    The aims of the study were to determine the frequency of hepatobiliary disease in patients with cystic fibrosis and to describe the sociodemographic, clinical, and laboratory profile of these patients. This was a retrospective, descriptive, and analytical study of 55 patients diagnosed with cystic fibrosis, aged between 3 months and 21 years, followed-up from January 2008 to June 2016 in a referral center. Medical records were consulted and sociodemographic, clinical and laboratory data, including hepatobiliary alterations, imaging studies, genetic studies, liver biopsies, and upper digestive endoscopies were registered. Hepatobiliary disease was diagnosed in 16.4% of the patients and occurred as an initial manifestation of cystic fibrosis in 55.6% of these cases. The diagnosis of hepatopathy occurred before or concomitantly with the diagnosis of cystic fibrosis in 88.9% of the children. All patients with hepatobiliary disease were considered non-white, with a predominance of females (77.8%) and median (IQR) of 54 (27-91) months. Compared with the group without hepatobiliary disease, children with liver disease had a higher frequency of severe mutations identified in the CFTR gene (77.8% vs. 39.6%, p=0.033) and severe pancreatic insufficiency (88.9% vs. 31.6%, p=0.007). The frequency of hepatobiliary disease was high, with a very early diagnosis of the disease and its complications in the studied series. A statistical association was observed between the occurrence of hepatobiliary disease and the presence of pancreatic insufficiency and severe mutations in the CFTR gene. It is emphasized that cystic fibrosis is an important differential diagnosis of liver diseases in childhood. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  7. Renal cystic diseases and renal neoplasms: a mini-review.

    Science.gov (United States)

    Bonsib, Stephen M

    2009-12-01

    The past two decades have witnessed recognition of several new types of renal cell carcinoma, each with distinct cytogenetic abnormalities. Included are several genetic and acquired cystic kidney diseases associated with development of renal cell carcinoma, the topic of this review. The risk in patients with autosomal dominant polycystic kidney disease is not accurately known but may be slightly increased. The risk for patients with von Hippel-Lindau disease is substantial, and death from renal cancer is common. For patients with tuberous sclerosis complex, the challenge is recognition of the occasional malignancy arising in a field of many benign tumors. Patients with end-stage kidney disease and acquired cystic kidney disease may develop a variety of renal cell carcinoma types. Progress in understanding the molecular basis of renal cyst formation and neoplastic disease has fostered development of targeted therapies that now hold promise for a group of neoplasms whose cure was traditionally dependent on surgical approaches.

  8. Hypertonic Saline in Treatment of Pulmonary Disease in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Emer P. Reeves

    2012-01-01

    Full Text Available The pathogenesis of lung disease in cystic fibrosis is characterised by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. Mucus within the cystic fibrosis airways is enriched in negatively charged matrices composed of DNA released from colonizing bacteria or inflammatory cells, as well as F-actin and elevated concentrations of anionic glycosaminoglycans. Therapies acting against airway mucus in cystic fibrosis include aerosolized hypertonic saline. It has been shown that hypertonic saline possesses mucolytic properties and aids mucociliary clearance by restoring the liquid layer lining the airways. However, recent clinical and bench-top studies are beginning to broaden our view on the beneficial effects of hypertonic saline, which now extend to include anti-infective as well as anti-inflammatory properties. This review aims to discuss the described therapeutic benefits of hypertonic saline and specifically to identify novel models of hypertonic saline action independent of airway hydration.

  9. Hypertonic saline in treatment of pulmonary disease in cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2012-01-01

    The pathogenesis of lung disease in cystic fibrosis is characterised by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. Mucus within the cystic fibrosis airways is enriched in negatively charged matrices composed of DNA released from colonizing bacteria or inflammatory cells, as well as F-actin and elevated concentrations of anionic glycosaminoglycans. Therapies acting against airway mucus in cystic fibrosis include aerosolized hypertonic saline. It has been shown that hypertonic saline possesses mucolytic properties and aids mucociliary clearance by restoring the liquid layer lining the airways. However, recent clinical and bench-top studies are beginning to broaden our view on the beneficial effects of hypertonic saline, which now extend to include anti-infective as well as anti-inflammatory properties. This review aims to discuss the described therapeutic benefits of hypertonic saline and specifically to identify novel models of hypertonic saline action independent of airway hydration.

  10. Cystic fibrosis liver disease - from diagnosis to risk factors.

    Science.gov (United States)

    Ciucă, Ioana Mihaiela; Pop, Liviu; Tămaş, Liviu; Tăban, Sorina

    2014-01-01

    Cystic fibrosis (CF) is the most frequent monogenic genetic disease, autosomal recessive transmitted, characterized by an impressive clinical polymorphism and appreciative fatal prospective. Liver disease is the second non-pulmonary cause of death in cystic fibrosis, which, with increasing life expectancy, became an important management problem. Predisposing factors like male gender, pancreatic insufficiency, meconium ileus and severe mutation are incriminated to influence the occurrence of cystic fibrosis associated liver disease (CFLD). Our study included 174 patients with CF, monitored in the National Cystic Fibrosis Centre, Timisoara, Romania. They were routinely followed-up by clinical assessment, liver biochemical tests, ultrasound examinations and other methods like transient elastography, biopsy, in selected cases. Sixty-six patients, with median age at diagnosis 4.33 years, diagnosed with CFLD, without significant gender gap. CFLD was frequent in patients aged over eight years, with meconium ileus history, carriers of severe mutations (p=0.002). Pancreatic insufficiency, although present in 75% of patients with CFLD was not confirmed as risk factor, not male gender, in our study. CF children older than eight years, carriers of a severe genotype, with a positive history of meconium ileus, were more likely predisposed to CFLD.

  11. Gastroesophageal Reflux Disease in Children with Cystic Fibrosis.

    Science.gov (United States)

    Dziekiewicz, Marcin A; Banaszkiewicz, Aleksandra; Urzykowska, Agnieszka; Lisowska, Aleksandra; Rachel, Marta; Sands, Dorota; Walkowiak, Jaroslaw; Radzikowski, Andrzej; Albrecht, Piotr

    2015-01-01

    Previously published studies have indicated that gastroesophageal reflux (GER) disease is common in pediatric patients with cystic fibrosis. The aim of the present study was to get insight into the incidence of GER and to characterize the nature of reflux episodes in children with cystic fibrosis. This was a multicenter, prospective study of children with cystic fibrosis older than 18 months. Forty four consecutive patients (22 boys, mean age 10.4 ± 3.6, range 3.0-17.8 years) were enrolled into the study. All patients underwent 24 h pH-impedance monitoring. GER were classified according to the widely recognized criteria as an acid, weakly acid, weakly alkaline, or proximal. The pH-impedance trace was considered abnormal when acid exposure was >6 %. GER was diagnosed in 24/44 (54.5 %) children. A total of 1585 (median 35, range 7-128) reflux episodes were detected; 1199 (75.6 %) were acidic, 382 (24.1 %) weakly acidic, and 4 (0.3 %) weakly alkaline. Six hundred and ninety-one (43.6 %) reflux episodes reached the proximal esophagus. In 14/44 patients typical GER symptoms were present. We conclude that the incidence of GER in children with cystic fibrosis is very high. In the majority of patients typical GER symptoms are absent. Therefore, diagnostic procedures should be considered, regardless of lacking symptoms. Although acid reflux episodes predominate in children with cystic fibrosis, classical pH-metry may not constitute a sufficient diagnostic method in this population because of a relatively high number of proximal reflux episodes. Such episodes also indicate an increased risk for aspiration. The pH-impedance diagnostic measurement is advocated when suspecting GER in children with cystic fibrosis.

  12. Genetic Influences on Cystic Fibrosis Lung Disease Severity

    Science.gov (United States)

    Weiler, Colleen A.; Drumm, Mitchell L.

    2013-01-01

    Understanding the causes of variation in clinical manifestations of disease should allow for design of new or improved therapeutic strategies to treat the disease. If variation is caused by genetic differences between individuals, identifying the genes involved should present therapeutic targets, either in the proteins encoded by those genes or the pathways in which they function. The technology to identify and genotype the millions of variants present in the human genome has evolved rapidly over the past two decades. Originally only a small number of polymorphisms in a small number of subjects could be studied realistically, but speed and scope have increased nearly as dramatically as cost has decreased, making it feasible to determine genotypes of hundreds of thousands of polymorphisms in thousands of subjects. The use of such genetic technology has been applied to cystic fibrosis (CF) to identify genetic variation that alters the outcome of this single gene disorder. Candidate gene strategies to identify these variants, referred to as “modifier genes,” has yielded several genes that act in pathways known to be important in CF and for these the clinical implications are relatively clear. More recently, whole-genome surveys that probe hundreds of thousands of variants have been carried out and have identified genes and chromosomal regions for which a role in CF is not at all clear. Identification of these genes is exciting, as it provides the possibility for new areas of therapeutic development. PMID:23630497

  13. Cystic fibrosis gene mutations: evaluation and assessment of disease severity

    Directory of Open Access Journals (Sweden)

    Vallières E

    2014-10-01

    Full Text Available Emilie Vallières, Joseph Stuart ElbornCystic Fibrosis and Airways Microbiology Research Group, Queens University Belfast, Belfast, UKAbstract: The cystic fibrosis transmembrane regulator (CFTR gene encodes an ion channel transporter, the CFTR protein. Since its identification in 1989, more than 1,900 sequence variants have been reported, resulting in a wide spectrum of clinical phenotypes. Cystic fibrosis (CF is associated with many CFTR mutants and there is a continuum of disease severity observed. Recent advances in fundamental research have increased our understanding of the consequent molecular defect arising from CF mutations. This knowledge has resulted in the development of CF-specific therapies, targeting either the genetic or the molecular defect. CF care, previously focused on symptom control, is therefore moving toward a "stratified" or "precision" therapeutic approach. This review outlines normal CFTR physiology, the proposed pathologic mechanism underlying CF associated-lung injury, classification of CF mutations, and the CF-specific therapies recently approved or in clinical trials.Keywords: cystic fibrosis, gene mutations, disease severity, evaluation, assessment

  14. Assessment of disease aggression in cystic pancreatic neuroendocrine tumors: A CT and pathology correlation study.

    Science.gov (United States)

    Yano, Motoyo; Misra, Sunil; Salter, Amber; Carpenter, Danielle H

    There are inconsistencies in the literature regarding the clinical significance of cystic components in pancreatic neuroendocrine tumors (NET). This may be related to differences in the identification of cystic NET through imaging and/or pathology. Tumors may also be microscopically or macroscopically cystic. Our primary objective is to determine radiology-pathology correlation for the identification of cystic components. Our secondary objective is to determine if cystic components are associated with indices of tumor aggression. 60 tumors with correlative surgical pathology were assessed retrospectively for cystic components on CT and pathology. Tumor was categorized as solid or cystic on CT and pathology. If cystic on pathology, cystic components were categorized as macroscopic or microscopic. Cystic components were estimated as disease aggression. Associations were tested with Chi square/Fisher's exact test and differences were tested with t-test/Wilcoxon rank sums test. There is moderate agreement between CT and histology for presence of cystic components. Discrepancies were mostly attributable to the presence of microscopic cystic components in tumors appearing solid on CT. There was no difference in size between cystic and solid tumors on CT or pathology. No association between CT-determined cystic components and tumor grade was found. Tumors with cystic components (cystic by CT, and macroscopically cystic by pathology) demonstrated less association with metastases than solid tumors. Cystic components, comprising ≥50% of the tumor by CT and observed macroscopically on pathology, are associated with less aggressive disease. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  15. Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy.

    Science.gov (United States)

    Cantin, André M; Hartl, Dominik; Konstan, Michael W; Chmiel, James F

    2015-07-01

    Lung disease is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Although CF lung disease is primarily an infectious disorder, the associated inflammation is both intense and ineffective at clearing pathogens. Persistent high-intensity inflammation leads to permanent structural damage of the CF airways and impaired lung function that eventually results in respiratory failure and death. Several defective inflammatory responses have been linked to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency including innate and acquired immunity dysregulation, cell membrane lipid abnormalities, various transcription factor signaling defects, as well as altered kinase and toll-like receptor responses. The inflammation of the CF lung is dominated by neutrophils that release oxidants and proteases, particularly elastase. Neutrophil elastase in the CF airway secretions precedes the appearance of bronchiectasis, and correlates with lung function deterioration and respiratory exacerbations. Anti-inflammatory therapies are therefore of particular interest for CF lung disease but must be carefully studied to avoid suppressing critical elements of the inflammatory response and thus worsening infection. This review examines the role of inflammation in the pathogenesis of CF lung disease, summarizes the results of past clinical trials and explores promising new anti-inflammatory options. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  16. State of progress in treating cystic fibrosis respiratory disease

    Directory of Open Access Journals (Sweden)

    Flume Patrick A

    2012-08-01

    Full Text Available Abstract Since the discovery of the gene associated with cystic fibrosis (CF, there has been tremendous progress in the care of patients with this disease. New therapies have entered the market and are part of the standard treatment of patients with CF, and have been associated with marked improvement in survival. Now there are even more promising therapies directed at different components of the pathophysiology of this disease. In this review, our current knowledge of the pathophysiology of lung disease in patients with CF is described, along with the current treatment of CF lung disease, and the therapies in development that offer great promise to our patients.

  17. Modeling Cystic Fibrosis Using Pluripotent Stem Cell-Derived Human Pancreatic Ductal Epithelial Cells.

    Science.gov (United States)

    Simsek, Senem; Zhou, Ting; Robinson, Christopher L; Tsai, Su-Yi; Crespo, Miguel; Amin, Sadaf; Lin, Xiangyi; Hon, Jane; Evans, Todd; Chen, Shuibing

    2016-05-01

    We established an efficient strategy to direct human pluripotent stem cells, including human embryonic stem cells (hESCs) and an induced pluripotent stem cell (iPSC) line derived from patients with cystic fibrosis, to differentiate into pancreatic ductal epithelial cells (PDECs). After purification, more than 98% of hESC-derived PDECs expressed functional cystic fibrosis transmembrane conductance regulator (CFTR) protein. In addition, iPSC lines were derived from a patient with CF carrying compound frameshift and mRNA splicing mutations and were differentiated to PDECs. PDECs derived from Weill Cornell cystic fibrosis (WCCF)-iPSCs showed defective expression of mature CFTR protein and impaired chloride ion channel activity, recapitulating functional defects of patients with CF at the cellular level. These studies provide a new methodology to derive pure PDECs expressing CFTR and establish a "disease in a dish" platform to identify drug candidates to rescue the pancreatic defects of patients with CF. An efficient strategy was established to direct human pluripotent stem cells, including human embryonic stem cells (hESCs) and an induced pluripotent stem cell line derived from patients with cystic fibrosis (CF-iPSCs), to differentiate into pancreatic ductal epithelial cells (PDECs). After purification, more than 98% of hESC-PDECs derived from CF-iPSCs showed defective expression of mature cystic fibrosis transmembrane conductance regulator (CFTR) protein and impaired chloride ion channel activity, recapitulating functional pancreatic defects of patients with CF at the cellular level. These studies provide a new methodology for deriving pure PDECs expressing CFTR, and they establish a "disease-in-a-dish" platform for identifying drug candidates to rescue the pancreatic defects of these patients. ©AlphaMed Press.

  18. Molecular aspects of bovine cystic ovarian disease pathogenesis.

    Science.gov (United States)

    Ortega, Hugo H; Marelli, Belkis E; Rey, Florencia; Amweg, Ayelen N; Díaz, Pablo U; Stangaferro, Matías L; Salvetti, Natalia R

    2015-06-01

    Cystic ovarian disease (COD) is one of the main causes of reproductive failure in cattle and causes severe economic loss to the dairy farm industry because it increases both days open in the post partum period and replacement rates due to infertility. This disease is the consequence of the failure of a mature follicle to ovulate at the time of ovulation in the estrous cycle. This review examines the evidence for the role of altered steroid and gonadotropin signaling systems and the proliferation/apoptosis balance in the ovary with cystic structures. This evidence suggests that changes in the expression of ovarian molecular components associated with these cellular mechanisms could play a fundamental role in the pathogenesis of COD. The evidence also shows that gonadotropin receptor expression in bovine cystic follicles is altered, which suggests that changes in the signaling system of gonadotropins could play a fundamental role in the pathogenesis of conditions characterized by altered ovulation, such as COD. Ovaries from animals with COD exhibit a disrupted steroid receptor pattern with modifications in the expression of coregulatory proteins. These changes in the pathways of endocrine action would trigger the changes in proliferation and apoptosis underlying the aberrant persistence of follicular cysts. Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/6/R251/suppl/DC1. © 2015 Society for Reproduction and Fertility.

  19. The Dynamics of Disease Progression in Cystic Fibrosis.

    Science.gov (United States)

    Adler, Frederick R; Liou, Theodore G

    2016-01-01

    In cystic fibrosis, statistical models have been more successful in predicting mortality than the time course of clinical status. We develop a system of partial differential equations that simultaneously track mortality and patient status, with all model parameters estimated from the extensive and carefully maintained database from the Cystic Fibrosis Foundation. Cystic fibrosis is an autosomal recessive disease that leads to loss of lung function, most commonly assessed using the Forced Expiratory Volume in 1 second (FEV1%). This loss results from inflammation secondary to chronic bacterial infections, particularly Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus (MSSA) and members of the virulent Burkholderia complex. The model tracks FEV1% and carriage of these three bacteria over the course of a patient's life. Analysis of patient state changes from year to year reveals four feedback loops: a damaging positive feedback loop between P. aeruginosa carriage and lower FEV1%, negative feedback loops between P. aeruginosa and MSSA and between P. aeruginosa and Burkholderia, and a protective positive feedback loop between MSSA carriage and higher FEV1%. The partial differential equations built from this data analysis accurately capture the life-long progression of the disease, quantify the key role of high annual FEV1% variability in reducing survivorship, the relative unimportance of short-term bacterial interactions for long-term survival, and the potential benefits of eradicating the most harmful bacteria.

  20. The Dynamics of Disease Progression in Cystic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Frederick R Adler

    Full Text Available In cystic fibrosis, statistical models have been more successful in predicting mortality than the time course of clinical status. We develop a system of partial differential equations that simultaneously track mortality and patient status, with all model parameters estimated from the extensive and carefully maintained database from the Cystic Fibrosis Foundation. Cystic fibrosis is an autosomal recessive disease that leads to loss of lung function, most commonly assessed using the Forced Expiratory Volume in 1 second (FEV1%. This loss results from inflammation secondary to chronic bacterial infections, particularly Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus (MSSA and members of the virulent Burkholderia complex. The model tracks FEV1% and carriage of these three bacteria over the course of a patient's life. Analysis of patient state changes from year to year reveals four feedback loops: a damaging positive feedback loop between P. aeruginosa carriage and lower FEV1%, negative feedback loops between P. aeruginosa and MSSA and between P. aeruginosa and Burkholderia, and a protective positive feedback loop between MSSA carriage and higher FEV1%. The partial differential equations built from this data analysis accurately capture the life-long progression of the disease, quantify the key role of high annual FEV1% variability in reducing survivorship, the relative unimportance of short-term bacterial interactions for long-term survival, and the potential benefits of eradicating the most harmful bacteria.

  1. Prolonged high-frequency oscillatory ventilation in tubercular multifocal cystic lung disease.

    Science.gov (United States)

    Mohari, Nivedita; Raj, Dinesh; Lodha, Rakesh; Kabra, Sushil K

    2012-12-01

    Multifocal cystic lung disease in infants is most commonly congenital, and is managed surgically with perioperative mechanical ventilation. Multifocal cystic lung disease in infants may be due to tuberculosis. We report a young infant with tubercular multifocal cystic lung disease and respiratory failure. The initial chest imaging revealed diffuse nodular infiltrates. Soon after admission he required conventional mechanical ventilation for respiratory failure. The bronchoalveolar lavage fluid grew Mycobacterium tuberculosis in culture. Subsequent chest imaging showed progression to multifocal cystic lung disease. The ventilation mode was changed to high-frequency oscillatory ventilation (HFOV) due to persistent CO(2) retention in the presence of cystic lung disease. The cystic lung disease reversed with antitubercular treatment and prolonged HFOV with slow wean.

  2. Living with Cystic Fibrosis

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  3. What is Cystic Fibrosis?

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  4. What Causes Cystic Fibrosis?

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  5. Ursodeoxycholic acid for cystic fibrosis-related liver disease.

    Science.gov (United States)

    Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L

    2017-09-11

    Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. This is an update of a previous review. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies and searched online trial registries.Date of the most recent search of the Group's trials register: 09 April 2017. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. The authors used GRADE to assess the quality of the evidence. Twelve trials have been identified, of which four trials involving 137 participants were included; data were only available from three of the trials (118 participants) since one cross-over trial did not report appropriate data. The dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30

  6. Hepatocellular carcinoma complicating cystic fibrosis related liver disease.

    LENUS (Irish Health Repository)

    O'Donnell, D H

    2012-02-01

    Early diagnosis and treatment of the respiratory and gastrointestinal complications of cystic fibrosis (CF) have led to improved survival with many patients living beyond the fourth decade. Along with this increased life expectancy is the risk of further disease associated with the chronic manifestations of their condition. We report a patient with documented CF related liver disease for which he was under routine surveillance that presented with histologically proven hepatocellular carcinoma (HCC). It is important that physicians are aware of this association as increased vigilance may lead to earlier diagnosis and perhaps, a better outcome.

  7. Giant cystic degeneration of a uterine leiomyoma in a patient with autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Katrin Arnolds

    2016-04-01

    Capsule: Large uterine leiomyoma with diffuse cystic degeneration in a patient with autosomal dominant polycystic kidney disease, in which step-wise treatments allows successful minimally invasive hysterectomy.

  8. Beyond pancreatic insufficiency and liver disease in cystic fibrosis.

    Science.gov (United States)

    Demeyer, Stephanie; De Boeck, Kris; Witters, Peter; Cosaert, Katrien

    2016-07-01

    Cystic fibrosis is a life shortening hereditary disease, primarily leading to progressive pulmonary infection and exocrine pancreatic dysfunction. Several gastrointestinal complications other than malabsorption can arise during the disease course and with the progressively increasing life span of patients with CF; new and more rare complications are being recognized. We review the literature on gastrointestinal manifestations in CF, excluding the liver and pancreas. We describe the clinical presentation and treatment of more common conditions like gastroesophageal reflux, small intestinal bacterial overgrowth, intussusception, meconium ileus, distal intestinal obstruction syndrome, and constipation, and we also discuss what is known on celiac disease, appendicitis, fibrosing colonopathy, inflammation and inflammatory bowel disease and gastrointestinal cancer. • Gastrointestinal complications arise early in the course of the disease and have a severe impact on the quality of life of the patients. What is New: • This review is a concise summary of the current literature on gastrointestinal complications of cystic fibrosis. • We focused on clinical presentation and diagnostic investigations and provide a comprehensive resume of the current treatment options.

  9. Serological evidence for human cystic echinococcosis in Slovenia

    Directory of Open Access Journals (Sweden)

    Kotar Tadeja

    2008-05-01

    Full Text Available Abstract Background Cystic echinococcosis (CE is caused by the larva of tapeworm Echinococcus granulosus. Dogs and other canids are the primary definitive hosts for this parasite. CE may develop after accidental ingestion of tapeworm eggs, excreted with the feces of these animals. In the intestine, the larvae released from the eggs are nested in the liver, lungs or other organs of livestock as intermediate hosts and humans as aberrant hosts. The aim of this study was to examine serologically whether some of the patients in Slovenia, suspected of CE by imaging findings in the liver or lungs had been infected with the larva of Echinococcus granulosus. Methods Between January 1, 2002 and the end of December 2006, 1323 patients suspected of having echinococcosis were screened serologically by indirect haemagglutination assay (IHA. For confirmation and differentiation of Echinococcus spp. infection, the sera of IHA-positive patients were then retested by western blot (WB. Results Out of 127 IHA-positive sera, 34 sera were confirmed by WB and considered specific for CE. Of 34 sera of CE-positive patients sera, 32 corresponded to the characteristic imaging findings of a liver cysts and 2 to those of lung cysts. The mean age of CE-positive patients was 58.3 years. No significant differences were found between the CE-positive patients in regard to their sex. Conclusion In the study, it was found out that CE was mostly spread in the same area of Slovenia as in the past, but its prevalence decreased from 4.8 per 105 inhabitants in the period 1956–1968 to 1.7 per 105 inhabitants in the period 2002–2006. In spite of the decreased prevalence of CE in the last years, it is suggested that clinicians and public health authorities, especially in the eastern parts of Slovenia where the most CE patients come from, should pay greater attention to this disease in the future.

  10. A Case of Adventitial Cystic Disease of the Popliteal Artery Progressing Rapidly after Percutaneous Ultrasound-guided Aspiration.

    Science.gov (United States)

    Seo, Hiroyuki; Fujii, Hiromichi; Aoyama, Takanobu; Sasako, Yoshikado

    2014-01-01

    Adventitial cystic disease is a rare non-atherosclerotic vascular disease. We report a 36-year-old man with right intermittent claudication by adventitial cystic disease. computed tomography (CT) and magnetic resonance imaging (MRI) revealed an ovoid cystic mass compressing the right popliteal artery and causing severe stenosis of the lumen. Percutaneous aspiration was performed, which improved his symptoms. However, he complained of identical intermittent claudication two weeks later. Radiographic findings revealed that the cystic lesion had progressed rapidly. The cystic lesion was resected and the affected arterial segment was interposed. We consider that conventional surgical intervention remains the favored treatment option in the management of adventitial cystic disease.

  11. [Major complications of acquired renal cystic disease: Wünderlich syndrome and papilar carcinoma.

    Science.gov (United States)

    Rodríguez-Zarco, Enrique; Vallejo-Benítez, Ana; Delgado Cotán, Antonio; Pereira-Gallardo, Sofía

    2017-07-01

    We report a case of acquired renal cystic disease associated with renal dialysis and endstage renal disease. The patient suffered the two major complications related with acquired renal cystic disease; hemorrhage and renal carcinoma. Our case is a patient with acquired renal cystic disease, single kidney after surgery for renal clear cell carcinoma four years earlier, who developed a Wünderlich syndrome (WS). The histological study of the nephrectomy specimen showed a renal papillary carcinoma in the context of acquired renal cystic disease after surgery for a WS. Renal hemorrhage is a serious complication that can lead to a fatal outcome. Patients undergoing dialysis should be monitored actively due to the risk of developing acquired renal cystic disease and associated complications.

  12. Renal diseases in adults with cystic fibrosis: a 40 year single centre experience.

    Science.gov (United States)

    Wilcock, M J; Ruddick, A; Gyi, K M; Hodson, M E

    2015-10-01

    There is a sizable literature describing renal disease in patients with cystic fibrosis. Previous studies have focused on single disease processes alone, most commonly renal stone disease or acute kidney injury. In this study we report for the first time on the prevalence of all forms of renal disease in a cystic fibrosis population. A retrospective review of adult patients with cystic fibrosis attending the Adult Cystic Fibrosis Department at the Royal Brompton Hospital was carried out by searching the department's database to identify patients with renal problems and subsequently retrieving clinical information from medical notes. The prevalence of all renal diseases in our population was 5.1 %. The most commonly identified problem was renal stones. At 2.0 % the prevalence of renal stones in adult patients with cystic fibrosis was comparable to the general population. A range of other renal diseases were identified, the next most common being drug-induced acute kidney injury. A range of cystic fibrosis independent and attributable diseases has been identified but no cystic fibrosis specific disease. In contrast to other cystic fibrosis centres no increased prevalence of renal stones was found.

  13. Epigenetics in Cystic Fibrosis: Epigenetic Targeting of a Genetic Disease.

    Science.gov (United States)

    Sirinupong, Nualpun; Yang, Zhe

    2015-01-01

    Cystic fibrosis (CF) is a deadly genetic disease that affects the lungs and digestive system. A mutation in the CF transmembrane conductance regulator (CFTR) gene is the cause of the disease. How epigenetics contributes to CFTR expression is still poorly understood. Epigenetics is a mechanism that alters gene expression without changing the underlying DNA sequence. Epigenetic mechanisms include DNA methylation and histone modification. Both mechanisms have been implicated in CFTR gene regulation. Here we review epigenetic regulation of CFTR transcription while discussing potential epigenetic targeting strategies including DNA methyltransferase, histone deacetylase, and histone methyltransferase and demethylase inhibition. Because of the reversibility of epigenetics, targeting epigenetic mechanisms has been an attractive therapeutic approach. However, epigenetic targeting of CF disease is still at its infant stage.

  14. Chest CT features of cystic fibrosis in Korea: Comparison with non-cystic fibrosis diseases

    Energy Technology Data Exchange (ETDEWEB)

    Yang, So Yeon; Lee, Kyung Soo; Kim, Tae Jung; Kim, Tae Sung [Dept. of Radiology, and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Cha, Min Jae [Dept. of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul (Korea, Republic of); Yoon, Hyun Jung [Dept. of Radiology, Hanyang University Hospital, Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2017-01-15

    Cystic fibrosis (CF) is a rare congenital disease in Korea, and its clinical and imaging findings are unclear. The objective of our study was to describe the clinical and CT features of CF in Korea and compare its features with those of other diseases mimicking CF. From November 1994 to December 2014, a presumptive diagnosis of CF was made in 23 patients based on clinical or radiological examination. After the exclusion of 10 patients without diagnostic confirmation, 13 patients were included in the study. A diagnosis of CF was made with the CF gene study. CT findings were evaluated for the presence and distribution of parenchymal abnormalities including bronchiectasis, tree-in-bud (TIB) pattern, mucus plugging, consolidation, and mosaic attenuation. Of the 13 patients, 7 (median age, 15 years) were confirmed as CF, 4 (median age, 19 years) had primary ciliary dyskinesia, 1 had bronchiectasis of unknown cause, and 1 had chronic asthma. CT of patients with CF showed bilateral bronchiectasis, TIB pattern, mosaic attenuation, and mucus plugging in all patients, with upper lung predominance (57%). In CT of the non-CF patients, bilateral bronchiectasis, TIB pattern, mosaic attenuation, and mucus plugging were also predominant features, with lower lung predominance (50%). Korean patients with CF showed bilateral bronchiectasis, cellular bronchiolitis, mucus plugging, and mosaic attenuation, which overlapped with those of non-CF patients. CF gene study is recommended for the definitive diagnosis of CF in patients with these clinical and imaging features.

  15. Family Stress with Chronic Childhood Illness: Cystic Fibrosis, Neuromuscular Disease, and Renal Disease.

    Science.gov (United States)

    Holroyd, Jean; Guthrie, Donald

    1986-01-01

    Parents of children with neuromuscular disease, cystic fibrosis, and renal disease were compared with parents of control subjects matched by age to the clinical cases. The three clinical groups exhibited different patterns of stressful response, consistent with the nature of their illnesses and the requirements for care imposed on the families.…

  16. Adventitial cystic disease of the common femoral artery: a case report and literature review.

    Science.gov (United States)

    Kim, Sung Hwan; Lee, Chung Eun; Park, Hyun Oh; Kim, Jong Woo; Choi, Jun Young; Lee, Jeong Hee

    2013-04-01

    Arterial adventitial cystic disease is an uncommon type of non-atherosclerotic peripheral vessel disease. Most cases of arterial adventitial cystic disease occur in the popliteal arteries; however, fewer cases have been reported in the femoral arteries. A 59-year-old male patient visited the hospital with a complaint of a swelling on the lower extremity that had begun two months earlier. Suspecting deep vein thrombosis based on a physical examination and ultrasonography from another hospital, tests were performed. Magnetic resonance imaging (MRI) was performed for exact diagnosis because venous adventitial cystic disease was suspected by computed tomography venography. The MRI indicated venous adventitial cystic disease as well. Thus, a cystic mass excision was performed. In the end, a cystic mass compressing the common femoral vein that originated from the common femoral artery was diagnosed based on the macroscopic findings. This case is reported because blood circulation in the vein was impeded due to arterial adventitial cystic disease, and the symptoms improved after the cystic mass excision and polytetrafluoroethylene roofing angioplasty.

  17. Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes

    OpenAIRE

    Ellsworth, Rachel E.; Jamison, D. Curtis; Touchman, Jeffrey W.; Chissoe, Stephanie L.; Braden Maduro, Valerie V.; Bouffard, Gerard G.; Dietrich, Nicole L.; Beckstrom-Sternberg, Stephen M.; Iyer, Leslie M.; Weintraub, Lauren A.; Cotton, Marc; Courtney, Laura; Edwards, Jennifer; Maupin, Rachel; Ozersky, Philip

    2000-01-01

    The identification of the cystic fibrosis transmembrane conductance regulator gene (CFTR) in 1989 represents a landmark accomplishment in human genetics. Since that time, there have been numerous advances in elucidating the function of the encoded protein and the physiological basis of cystic fibrosis. However, numerous areas of cystic fibrosis biology require additional investigation, some of which would be facilitated by information about the long-range sequence context of the CFTR gene. Fo...

  18. [An unusual cause of cystic lung disease: light chain deposition disease].

    Science.gov (United States)

    Luraine, R; Sohier, L; Kerjouan, M; Desrues, B; Delaval, P; Jouneau, S

    2013-09-01

    Light chain deposition disease is a rare clinical entity characterized by deposition of monoclonal immunoglobulin light chains in organs. The kidneys are almost always affected, while the lung manifestations that have been reported, including nodular or diffuse disease, especially cystic lesions, are unusual. We report the case of a 60-year-old man with a diffuse infiltrative lung disease characterized by numerous apical cysts. The diagnosis of light chain deposition cystic lung disease was obtained by surgical lung biopsy. Light chain deposits in the salivary glands were the only extrapulmonary manifestation. Despite 12 chemotherapy cycles, the patient's lung function and radiological appearances worsened. This is the fourth case describing a cystic lung disease due to light chain deposition in the literature. It highlights the need for comprehensive investigations so as not to miss this rare cause of cystic lung disease, which appears to be related to a primary pulmonary lymphoproliferative disorder. The only treatment that appears to be effective is lung transplantation. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  19. Role of Melatonin in the Prevention of Breast Cancer in Patients With Cystic Breast Disease

    National Research Council Canada - National Science Library

    Wells, Robert

    2000-01-01

    .... The primary objectives of this study are to establish a clinical BCF sample bank among patients with gross cystic breast disease in order to study the relationship between this disease, melatonin...

  20. A contemporary review of venous adventitial cystic disease and three case reports.

    Science.gov (United States)

    Chen, YueXin; Sun, RuiXue; Shao, Jiang; Li, YongJun; Liu, ChangWei

    2015-02-01

    Venous adventitial cystic disease is a rare vascular disease. The objective of the study is to contemporarily review the literature of venous adventitial cystic disease and report three other new cases of adventitial cystic disease in common femoral vein. Articles published between 1947 and April 2013 were searched in OVID and PubMed databases. The search yielded only 38 reported cases of venous adventitial cystic disease. The general characteristics and disease management information of the 41 cases (including our current 3 cases) were analyzed. Venous adventitial cystic disease could develop late in life with an average age of 48.39 years (range, 5 to 77 years). Similar to arterial adventitial cystic disease, venous adventitial cystic disease was also found to have a male predominance (male to female ratio, 1.28:1). The common femoral vein was the most likely vein to be involved (65.9%, 27 cases). Right and left sides were almost equally affected. Extremity swelling (86.8%, 33 cases) was the main symptom of patients presenting with venous adventitial cystic disease. Excision of cyst wall in 30 patients (73.2%) was the main surgical procedure with a recurrence rate of 11.5%. Thirteen involved veins were resected; of which, 10 were reconstructed with prosthetic or autologous graft. No recurrence was reported in these 13 patients. Postoperatively, nine cases received an anticoagulation therapy. In conclusion, the etiology, treatment strategy, and outcomes of venous adventitial cystic disease could not be well understood in the present review due to limited numbers of cases. Studies with careful follow-up for at least up to first several months are recommended. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  1. Imaging of Cystic Fibrosis Lung Disease and Clinical Interpretation.

    Science.gov (United States)

    Wielpütz, M O; Eichinger, M; Biederer, J; Wege, S; Stahl, M; Sommerburg, O; Mall, M A; Kauczor, H U; Puderbach, M

    2016-09-01

    Progressive lung disease in cystic fibrosis (CF) is the life-limiting factor of this autosomal recessive genetic disorder. Increasing implementation of CF newborn screening allows for a diagnosis even in pre-symptomatic stages. Improvements in therapy have led to a significant improvement in survival, the majority now being of adult age. Imaging provides detailed information on the regional distribution of CF lung disease, hence longitudinal imaging is recommended for disease monitoring in the clinical routine. Chest X-ray (CXR), computed tomography (CT) and magnetic resonance imaging (MRI) are now available as routine modalities, each with individual strengths and drawbacks, which need to be considered when choosing the optimal modality adapted to the clinical situation of the patient. CT stands out with the highest morphological detail and has often been a substitute for CXR for regular severity monitoring at specialized centers. Multidetector CT data can be post-processed with dedicated software for a detailed measurement of airway dimensions and bronchiectasis and potentially a more objective and precise grading of disease severity. However, changing to CT was inseparably accompanied by an increase in radiation exposure of CF patients, a young population with high sensitivity to ionizing radiation and lifetime accumulation of dose. MRI as a cross-sectional imaging modality free of ionizing radiation can depict morphological hallmarks of CF lung disease at lower spatial resolution but excels with comprehensive functional lung imaging, with time-resolved perfusion imaging currently being most valuable. • Hallmarks are bronchiectasis, mucus plugging, air trapping, perfusion abnormalities, and emphysema.• Imaging is more sensitive to disease progression than lung function testing.• CT provides the highest morphological detail but is associated with radiation exposure.• MRI shows comparable sensitivity for morphology but excels with additional

  2. Bone disease in cystic fibrosis: new pathogenic insights opening novel therapies.

    Science.gov (United States)

    Jacquot, J; Delion, M; Gangloff, S; Braux, J; Velard, F

    2016-04-01

    Mutations within the gene encoding for the chloride ion channel cystic fibrosis transmembrane conductance regulator (CFTR) results in cystic fibrosis (CF), the most common lethal autosomal recessive genetic disease that causes a number of long-term health problems, as the bone disease. Osteoporosis and increased vertebral fracture risk associated with CF disease are becoming more important as the life expectancy of patients continues to improve. The etiology of low bone density is multifactorial, most probably a combination of inadequate peak bone mass during puberty and increased bone losses in adults. Body mass index, male sex, advanced pulmonary disease, malnutrition and chronic therapies are established additional risk factors for CF-related bone disease (CFBD). Consistently, recent evidence has confirmed that CFTR plays a major role in the osteoprotegerin (OPG) and COX-2 metabolite prostaglandin E2 (PGE2) production, two key regulators in the bone formation and regeneration. Several others mechanisms were also recognized from animal and cell models contributing to malfunctions of osteoblast (cell that form bone) and indirectly of bone-resorpting osteoclasts. Understanding such mechanisms is crucial for the development of therapies in CFBD. Innovative therapeutic approaches using CFTR modulators such as C18 have recently shown in vitro capacity to enhance PGE2 production and normalized the RANKL-to-OPG ratio in human osteoblasts bearing the mutation F508del-CFTR and therefore potential clinical utility in CFBD. This review focuses on the recently identified pathogenic mechanisms leading to CFBD and potential future therapies for treating CFBD.

  3. Progression of Lung Disease in Preschool Patients with Cystic Fibrosis.

    Science.gov (United States)

    Stanojevic, Sanja; Davis, Stephanie D; Retsch-Bogart, George; Webster, Hailey; Davis, Miriam; Johnson, Robin C; Jensen, Renee; Pizarro, Maria Ester; Kane, Mica; Clem, Charles C; Schornick, Leah; Subbarao, Padmaja; Ratjen, Felix A

    2017-05-01

    Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progression in preschool children with CF. Children with CF between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy control subjects were enrolled at three North American CF centers. Multiple breath washout tests were performed at baseline, 1, 3, 6, and 12 months to mimic time points chosen in clinical care and interventional trials; spirometry was also conducted. A generalized linear mixed-effects model was used to distinguish LCI changes associated with normal growth and development (i.e., healthy children) from the progression of CF lung disease. Data were collected on 156 participants with 800 LCI measurements. Although both LCI and spirometry discriminated health from disease, only the LCI identified significant deterioration of lung function in CF over time. The LCI worsened during cough episodes and pulmonary exacerbations, whereas similar symptoms in healthy children were not associated with increased LCI values. LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF.

  4. Imaging of cystic fibrosis lung disease and clinical interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Wielpuetz, M.O.; Eichinger, M.; Kauczor, H.U. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology with Nuclear Medicine; Biederer, J. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Gross-Gerau Community Hospital (Germany). Radiologie Darmstadt; Wege, S. [Heidelberg University Hospital (Germany). Dept. of Pulmonology and Respiratory Medicine; Stahl, M.; Sommerburg, O. [Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Div. of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center; Mall, M.A. [Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Div. of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center; Heidelberg University Hospital (Germany). Dept. of Translational Pulmonology; Puderbach, M. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology with Nuclear Medicine; Hufeland Hospital, Bad Langensalza (Germany). Dept. of Diagnostic and Interventional Radiology

    2016-09-15

    Progressive lung disease in cystic fibrosis (CF) is the life-limiting factor of this autosomal recessive genetic disorder. Increasing implementation of CF newborn screening allows for a diagnosis even in pre-symptomatic stages. Improvements in therapy have led to a significant improvement in survival, the majority now being of adult age. Imaging provides detailed information on the regional distribution of CF lung disease, hence longitudinal imaging is recommended for disease monitoring in the clinical routine. Chest X-ray (CXR), computed tomography (CT) and magnetic resonance imaging (MRI) are now available as routine modalities, each with individual strengths and drawbacks, which need to be considered when choosing the optimal modality adapted to the clinical situation of the patient. CT stands out with the highest morphological detail and has often been a substitute for CXR for regular severity monitoring at specialized centers. Multidetector CT data can be post-processed with dedicated software for a detailed measurement of airway dimensions and bronchiectasis and potentially a more objective and precise grading of disease severity. However, changing to CT was inseparably accompanied by an increase in radiation exposure of CF patients, a young population with high sensitivity to ionizing radiation and lifetime accumulation of dose. MRI as a cross-sectional imaging modality free of ionizing radiation can depict morphological hallmarks of CF lung disease at lower spatial resolution but excels with comprehensive functional lung imaging, with time-resolved perfusion imaging currently being most valuable.

  5. Knockdown of Bicaudal C in Zebrafish (Danio rerio) Causes Cystic Kidneys: A Nonmammalian Model of Polycystic Kidney Disease

    OpenAIRE

    Bouvrette, Denise J; Sittaramane, Vinoth; Heidel, Jerry R.; Chandrasekhar, Anand; Bryda, Elizabeth C.

    2010-01-01

    Polycystic kidney disease (PKD) is one of the leading causes of end-stage renal disease in humans and is characterized by progressive cyst formation, renal enlargement, and abnormal tubular development. Currently, there is no cure for PKD. Although a number of PKD genes have been identified, their precise role in cystogenesis remains unclear. In the jcpk mouse model of PKD, mutations in the bicaudal C gene (Bicc1) are responsible for the cystic phenotype; however, the function of Bicc1 is unk...

  6. 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.

  7. An Approach for Treating the Hepatobiliary Disease of Cystic Fibrosis by Somatic Gene Transfer

    Science.gov (United States)

    Yang, Yiping; Raper, Steven E.; Cohn, Jonathan A.; Engelhardt, John F.; Wilson, James M.

    1993-05-01

    Cystic fibrosis (CF) is an inherited disease of epithelial cell ion transport that is associated with pathology in multiple organ systems, including lung, pancreas, and liver. As treatment of the pulmonary manifestations of CF has improved, management of CF liver disease has become increasingly important in adult patients. This report describes an approach for treating CF liver disease by somatic gene transfer. In situ hybridization and immunocytochemistry analysis of rat liver sections indicated that the endogenous CFTR (cystic fibrosis transmembrane conductance regulator) gene is primarily expressed in the intrahepatic biliary epithelial cells. To specifically target recombinant genes to the biliary epithelium in vivo, recombinant adenoviruses expressing lacZ or human CFTR were infused retrograde into the biliary tract through the common bile duct. Conditions were established for achieving recombinant gene expression in virtually all cells of the intrahepatic bile ducts in vivo. Expression persisted in the smaller bile ducts for the duration of the experiment, which was 21 days. These studies suggest that it may be feasible to prevent CF liver disease by genetically reconstituting CFTR expression in the biliary tract, using an approach that is clinically feasible.

  8. How Is Cystic Fibrosis Treated?

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  9. How Is Cystic Fibrosis Diagnosed?

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  10. Clinical presentation of exclusive cystic fibrosis lung disease

    NARCIS (Netherlands)

    I. Bronsveld (Inez); J. Bijman (Jan); F. Mekus; M. Ballmann; H.J. Veeze; B. Tummler

    1999-01-01

    textabstractThe diagnosis of cystic fibrosis (CF) is based on the occurrence of two mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and on assays that measure the basic defect of abnormal chloride transport in the affected organs.

  11. In silico search for modifier genes associated with pancreatic and liver disease in Cystic Fibrosis.

    Science.gov (United States)

    Trouvé, Pascal; Génin, Emmanuelle; Férec, Claude

    2017-01-01

    Cystic Fibrosis is the most common lethal autosomal recessive disorder in the white population, affecting among other organs, the lung, the pancreas and the liver. Whereas Cystic Fibrosis is a monogenic disease, many studies reveal a very complex relationship between genotype and clinical phenotype. Indeed, the broad phenotypic spectrum observed in Cystic Fibrosis is far from being explained by obvious genotype-phenotype correlations and it is admitted that Cystic Fibrosis disease is the result of multiple factors, including effects of the environment as well as modifier genes. Our objective was to highlight new modifier genes with potential implications in the lung, pancreatic and liver outcomes of the disease. For this purpose we performed a system biology approach which combined, database mining, literature mining, gene expression study and network analysis as well as pathway enrichment analysis and protein-protein interactions. We found that IFI16, CCNE2 and IGFBP2 are potential modifiers in the altered lung function in Cystic Fibrosis. We also found that EPHX1, HLA-DQA1, HLA-DQB1, DSP and SLC33A1, GPNMB, NCF2, RASGRP1, LGALS3 and PTPN13, are potential modifiers in pancreas and liver, respectively. Associated pathways indicate that immune system is likely involved and that Ubiquitin C is probably a central node, linking Cystic Fibrosis to liver and pancreatic disease. We highlight here new modifier genes with potential implications in Cystic Fibrosis. Nevertheless, our in silico analysis requires functional analysis to give our results a physiological relevance.

  12. In silico search for modifier genes associated with pancreatic and liver disease in Cystic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Pascal Trouvé

    Full Text Available Cystic Fibrosis is the most common lethal autosomal recessive disorder in the white population, affecting among other organs, the lung, the pancreas and the liver. Whereas Cystic Fibrosis is a monogenic disease, many studies reveal a very complex relationship between genotype and clinical phenotype. Indeed, the broad phenotypic spectrum observed in Cystic Fibrosis is far from being explained by obvious genotype-phenotype correlations and it is admitted that Cystic Fibrosis disease is the result of multiple factors, including effects of the environment as well as modifier genes. Our objective was to highlight new modifier genes with potential implications in the lung, pancreatic and liver outcomes of the disease. For this purpose we performed a system biology approach which combined, database mining, literature mining, gene expression study and network analysis as well as pathway enrichment analysis and protein-protein interactions. We found that IFI16, CCNE2 and IGFBP2 are potential modifiers in the altered lung function in Cystic Fibrosis. We also found that EPHX1, HLA-DQA1, HLA-DQB1, DSP and SLC33A1, GPNMB, NCF2, RASGRP1, LGALS3 and PTPN13, are potential modifiers in pancreas and liver, respectively. Associated pathways indicate that immune system is likely involved and that Ubiquitin C is probably a central node, linking Cystic Fibrosis to liver and pancreatic disease. We highlight here new modifier genes with potential implications in Cystic Fibrosis. Nevertheless, our in silico analysis requires functional analysis to give our results a physiological relevance.

  13. Disease modifying anti-rheumatic drugs in people with cystic fibrosis-related arthritis.

    Science.gov (United States)

    Thornton, Judith; Rangaraj, Satyapal

    2012-09-12

    Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy and hypertrophic osteoarthropathy. Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its treatment. To review the effectiveness and safety of disease-modifying anti-rheumatic drugs for the management of arthritis related to cystic fibrosis in adults and children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register which comprises references identified from comprehensive electronic database handsearches of relevant journal and abstract books of conference proceedings.Date of most recent search: 10 July 2012. Randomised controlled trials which compared the efficacy and safety of disease-modifying anti-rheumatic drugs (e.g. methotrexate, gold, sulfasalazine, penicillamine, leflunomide, hydroxychloroquine and newer agents such as biologic disease modifying agents and monoclonal antibodies) with each other, with no treatment or with placebo for cystic fibrosis-related arthropathy or hypertrophic osteoarthropathy. No relevant studies were identified. No studies were included in this review. Although it is generally recognised that cystic fibrosis-related arthritis can be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. But when episodic symptoms progress to persistent disease, disease-modifying anti-rheumatic drugs may be needed to limit the course of the disease. It is disappointing that no randomised controlled trials to rigorously evaluate these drugs could be found. This systematic review has identified the need for a well-designed adequately powered randomised controlled trial to assess the efficacy and safety of disease-modifying anti-rheumatic drugs for the

  14. Animal models of gastrointestinal and liver diseases. Animal models of cystic fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and pathophysiology.

    Science.gov (United States)

    Olivier, Alicia K; Gibson-Corley, Katherine N; Meyerholz, David K

    2015-03-15

    Multiple organ systems, including the gastrointestinal tract, pancreas, and hepatobiliary systems, are affected by cystic fibrosis (CF). Many of these changes begin early in life and are difficult to study in young CF patients. Recent development of novel CF animal models has expanded opportunities in the field to better understand CF pathogenesis and evaluate traditional and innovative therapeutics. In this review, we discuss manifestations of CF disease in gastrointestinal, pancreatic, and hepatobiliary systems of humans and animal models. We also compare the similarities and limitations of animal models and discuss future directions for modeling CF. Copyright © 2015 the American Physiological Society.

  15. Microstructural alterations of sputum in cystic fibrosis lung disease

    Science.gov (United States)

    Duncan, Gregg A.; Jung, James; Joseph, Andrea; Thaxton, Abigail L.; West, Natalie E.; Boyle, Michael P.; Hanes, Justin

    2016-01-01

    The stasis of mucus secretions in the lungs of cystic fibrosis (CF) patients leads to recurrent infections and pulmonary exacerbations, resulting in decreased survival. Prior studies have assessed the biochemical and biophysical features of airway mucus in individuals with CF. However, these measurements are unable to probe mucus structure on microscopic length scales relevant to key players in the progression of CF-related lung disease, namely, viruses, bacteria, and neutrophils. In this study, we quantitatively determined sputum microstructure based on the diffusion of muco-inert nanoparticle probes in CF sputum and found that a reduction in sputum mesh pore size is characteristic of CF patients with reduced lung function, as indicated by measured FEV1. We also discovered that the effect of ex vivo treatment of CF sputum with rhDNase I (Pulmozyme) on microstructure is dependent upon the time interval between the most recent inhaled rhDNase I treatment and the sample collection. Microstructure of mucus may serve as a marker for the extent of CF lung disease and as a parameter for assessing the effectiveness of mucus-altering agents. PMID:27812540

  16. [Autosomal recessive polycystic kidney disease and complex nephronophtisis medullary cystic disease].

    Science.gov (United States)

    2008-12-01

    Reseach during the past decade has led to the discovery that defects in some proteins that localize to primary cilia or the basal body are the main contributors to renal cyst development. Autosomal recessive polycystic disease and nephronophthisis- medullary cystic kidney disease are named ciliopathies. The cilium is a microtubule-based organelle that is found on most mammalian cells. Cilia-mediated hypothesis has evolved into the concept of cystogenesis, cilia bend by fluid initiate a calcium influx that prevents cyst formation. Cilia might sense stimuli in the cell enviroment and control cell polarity and mitosis. A new set of pathogenic mechanisms in renal cystic disease defined new therapeutic targets, control of intracellular calcium, inhibition of cAMP and down regulation cannonical Wnt signaling.

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

    NARCIS (Netherlands)

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

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

  18. The use of human mature cystic ovarian teratoma as a model to study the development of human lymphatics

    OpenAIRE

    Al-Jomard, Rashid; Amarin, Zouhair

    2017-01-01

    The angiogenic theory to the development of human lymphatics is not clear. The objective of this study was to investigate the development of human lymphatics. Semi-thin and thin paraffin sections from human mature cystic ovarian teratoma tissues were studied using light and electron microscopy. Lymphatics were formed by the differentiation of mesenchymal cells that gradually acquired morphological features of endothelial cells. It is suggested that in human mature cystic ovarian teratoma the ...

  19. Diverticular disease is associated with benign intra-abdominal cystic disease.

    Science.gov (United States)

    Wrafter, Paula F; Connelly, Tara M; Khan, Jody S A; Lucey, Brian C; Berg, Arthur; Koltun, Walter; Joyce, William P

    2017-05-01

    Diverticular disease (DD) and hepatic and renal cysts have been linked with defects in collagen and dysfunctional matrix metalloproteinases. Consecutive abdominal computed tomography scans between January-July 2015 were prospectively studied to determine a correlation between visceral cysts and DD. Patients with a sigmoid colectomy for pathology other than DD and scans in which DD and/or solid organs were not fully visualized were excluded. A subgroup analysis was performed on youthful DD patients (55, n = 213). 238 DD patients (50.8% male) and 369 controls (40.5% male, p = .02) were included. Incidence of visceral cystic disease in DD patients vs. controls was 71.4% vs. 22.5% (p cystic disease was present in 56.2% of youthful DD patients vs. 29.1% of older controls (p = .004). A significant association between cystic disease and DD was demonstrated overall and in subgroup analysis inclusive of youthful DD patients and older controls. These findings suggest a global defect in connective tissue integrity in DD patients.

  20. 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.

  1. Genetic modifiers of liver disease in cystic fibrosis.

    Science.gov (United States)

    Bartlett, Jaclyn R; Friedman, Kenneth J; Ling, Simon C; Pace, Rhonda G; Bell, Scott C; Bourke, Billy; Castaldo, Giuseppe; Castellani, Carlo; Cipolli, Marco; Colombo, Carla; Colombo, John L; Debray, Dominique; Fernandez, Adriana; Lacaille, Florence; Macek, Milan; Rowland, Marion; Salvatore, Francesco; Taylor, Christopher J; Wainwright, Claire; Wilschanski, Michael; Zemková, Dana; Hannah, William B; Phillips, M James; Corey, Mary; Zielenski, Julian; Dorfman, Ruslan; Wang, Yunfei; Zou, Fei; Silverman, Lawrence M; Drumm, Mitchell L; Wright, Fred A; Lange, Ethan M; Durie, Peter R; Knowles, Michael R

    2009-09-09

    A subset (approximately 3%-5%) of patients with cystic fibrosis (CF) develops severe liver disease with portal hypertension. To assess whether any of 9 polymorphisms in 5 candidate genes (alpha(1)-antitrypsin or alpha(1)-antiprotease [SERPINA1], angiotensin-converting enzyme [ACE], glutathione S-transferase [GSTP1], mannose-binding lectin 2 [MBL2], and transforming growth factor beta1 [TGFB1]) are associated with severe liver disease in patients with CF. Two-stage case-control study enrolling patients with CF and severe liver disease with portal hypertension (CFLD) from 63 CF centers in the United States as well as 32 in Canada and 18 outside of North America, with the University of North Carolina at Chapel Hill as the coordinating site. In the initial study, 124 patients with CFLD (enrolled January 1999-December 2004) and 843 control patients without CFLD were studied by genotyping 9 polymorphisms in 5 genes previously studied as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 patients with CFLD (enrolled January 2005-February 2007) and 1088 with no CFLD. Differences in distribution of genotypes in patients with CFLD vs patients without CFLD. The initial study showed CFLD to be associated with the SERPINA1 Z allele (odds ratio [OR], 4.72; 95% confidence interval [CI], 2.31-9.61; P = 3.3 x 10(-6)) and with TGFB1 codon 10 CC genotype (OR, 1.53; 95% CI, 1.16-2.03; P = 2.8 x 10(-3)). In the replication study, CFLD was associated with the SERPINA1 Z allele (OR, 3.42; 95% CI, 1.54-7.59; P = 1.4 x 10(-3)) but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (OR, 5.04; 95% CI, 2.88-8.83; P = 1.5 x 10(-8)). The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater risk (OR, approximately 5) of developing severe liver disease

  2. Adventitial cystic disease of the common femoral vein presenting as deep vein thrombosis

    Directory of Open Access Journals (Sweden)

    Young-Kyun Kim

    2016-07-01

    Full Text Available Adventitial cystic disease of the common femoral vein is a rare condition. We herein report the case of a 50-year-old woman who presented with painless swelling in her left lower leg that resembled deep vein thrombosis. She underwent femoral exploration and excision of the cystic wall. The presentation, investigation, treatment, and pathology of this condition are discussed with a literature review.

  3. Patient experience in cystic fibrosis care: Development of a disease-specific questionnaire.

    Science.gov (United States)

    Stahl, Katja; Steinkamp, Gratiana; Ullrich, Gerald; Schulz, Wolfgang; van Koningsbruggen-Rietschel, Silke; Heuer, Hans-Eberhard; Ellemunter, Helmut; Schwarz, Carsten

    2015-06-01

    The aim of this study was to develop valid and reliable disease-specific questionnaires for adult patients with cystic fibrosis and for parents of minors with cystic fibrosis for assessing patient experience with cystic fibrosis care. The pilot versions of the questionnaires were developed based on a literature review, interviews with health professionals and focus groups. A postal survey with two reminders was conducted in 56 German cystic fibrosis centres recruiting 2874 participants. Psychometric evaluation was done via exploratory factor analysis and reliability and regression analysis. The questionnaires' ability to differentiate between subgroups and between cystic fibrosis centres was evaluated. Response rates were 74% for both adult patients and parents. Ten factors were extracted for both the adult and the parents' models (Cronbach's alpha between 0.6 and 0.9), explaining 50% and 48% of the variance, respectively. The factors organisation & access and the doctor-patient/parent-interaction had the highest relevance for a good overall care experience. The questionnaires were able to distinguish between different cystic fibrosis centres. The questionnaires are well suited for use in internal and external quality management of cystic fibrosis care due to their good psychometric properties, the ability to differentiate between centres and its practicability. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  4. [Rapid diagnostic tests for the serodiagnosis of human cystic echinococcosis].

    Science.gov (United States)

    Tamarozzi, F; Mariconti, M; Covini, I; Brunetti, E

    2017-02-01

    Cystic echinococcosis (CE) is a parasitic zoonosis especially affecting resource-poor populations in livestock raising areas. Imaging, in particular ultrasound (US), is crucial for the diagnosis, staging, and clinical management of abdominal CE in humans. Serology is a valuable complement to imaging, especially when ultrasound features of CE are absent or unclear. In rural endemic areas, where expertise in US is scant, and conventional serology techniques are unavailable due to lack of laboratory equipment, rapid diagnostic tests (RDTs) may be very useful. Several reports have described the performance of commercial and experimental RDTs in the diagnosis of CE, including a recent study by our group that compared the diagnostic performances of three commercial RDTs for the diagnosis of hepatic CE. To put RDTs for CE in context, we reviewed the available literature in English on this topic. Overall, RDTs appear to be useful in resourcepoor settings where they may replace conventional serodiagnostic tests. However, like other serodiagnostic tests, RDTs lack standardization and show unsatisfactory sensitivity and specificity. An important issue that needs to be addressed is that studies on the diagnostic performance of RDTs fail to take into account the variables known to influence results such as anatomical location and cyst stage.

  5. Cystic Fibrosis: A Risk Condition for Renal Disease.

    Science.gov (United States)

    Santoro, Domenico; Postorino, Adele; Lucanto, Cristina; Costa, Stefano; Cristadoro, Simona; Pellegrino, Salvatore; Conti, Giovanni; Buemi, Michele; Magazzù, Giuseppe; Bellinghieri, Guido

    2017-11-01

    Cystic fibrosis (CF) is the most common autosomal recessive disease affecting the Caucasian population, with a birth incidence ranging between 1:2,500 and 1:1,800. It is caused by mutations in the CF transmembrane regulator gene which is localized on 7 chromosomes. Renal disease is reported as a relatively rare complication in adult patient with CF. We evaluated proteinuria and chronic renal failure (CRF) in a population of patients with CF. A retrospective study was carried out in a referral center for CF at University of Messina in Italy. We identified all patients with renal disease, characterized by proteinuria and/or CRF, during the period 2007 to 2012 and reviewed their medical records to assess influence on renal disease of genotype, number of pulmonary exacerbation, pancreatic insufficiency, pulmonary function, CF-related diabetes, and antibiotics courses. From a population of 77 adult patients with CF, we identified 9 patients with proteinuria (11.7%), and 11 patients (14.28%) with CRF. Mean age was 35.6 (+5.1 standard deviation) years, 55% were female and 33% had diabetes mellitus. Renal biopsy was performed in 3 patients because of nephrotic syndrome in 1 patient and proteinuria with renal failure in the other 2 patients. Renal amyloidosis was disclosed in 2, whereas IgA nephropathy in 1 patient. The ΔF508 mutation in homozygosis was present in 44% of patients with proteinuria (vs. 27% of our CF population, relative risk 2.07), whereas genotype ΔF508/N1303K in 22%. ΔF508 allele mutation was present in 77.7% of proteinuric patients. Our study shows a higher prevalence of renal disease in patients with CF, than was previously described. The main reason may be related to increased life expectancy because of better management. Moreover, patients with ΔF508 homozygosis had higher risk of proteinuria. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  6. Transfer of the Cystic Fibrosis Transmembrane Conductance Regulator to Human Cystic Fibrosis Cells Mediated by Extracellular Vesicles.

    Science.gov (United States)

    Vituret, Cyrielle; Gallay, Kathy; Confort, Marie-Pierre; Ftaich, Najate; Matei, Constantin I; Archer, Fabienne; Ronfort, Corinne; Mornex, Jean-François; Chanson, Marc; Di Pietro, Attilio; Boulanger, Pierre; Hong, Saw See

    2016-02-01

    Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in a deficiency in chloride channel activity. In this study, extracellular vesicles (EVs), microvesicles, and exosomes were used as vehicles to deliver exogenous CFTR glycoprotein and its encoding mRNA (mRNA(GFP-CFTR)) to CF cells to correct the CFTR chloride channel function. We isolated microvesicles and exosomes from the culture medium of CFTR-positive Calu-3 cells, or from A549 cells transduced with an adenoviral vector overexpressing a GFP-tagged CFTR (GFP-CFTR). Both microvesicles and exosomes had the capacity to package and deliver the GFP-CFTR glycoprotein and mRNA(GFP-CFTR) to target cells in a dose-dependent manner. Homologous versus heterologous EV-to-cell transfer was studied, and it appeared that the cellular uptake of EVs was significantly more efficient in homologous transfer. The incubation of CF15 cells, a nasal epithelial cell line homozygous for the ΔF508 CFTR mutation, with microvesicles or exosomes loaded with GFP-CFTR resulted in the correction of the CFTR function in CF cells in a dose-dependent manner. A time-course analysis of EV-transduced CF cells suggested that CFTR transferred as mature glycoprotein was responsible for the CFTR-associated channel activity detected at early times posttransduction, whereas GFP-CFTR translated from exogenous mRNA(GFP-CFTR) was responsible for the CFTR function at later times. Collectively, this study showed the potential application of microvesicles and exosomes as vectors for CFTR transfer and functional correction of the genetic defect in human CF cells.

  7. Adventitial cystic disease of the left external iliac vein: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Hee; Shin, Hyun Woong; Lee, Yil Gi; Koo, Mi Jin [Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2005-10-15

    Adventitial cystic disease (ACD) is a rare, but well-characterized vascular disease. It is most commonly seen in the popliteal artery, but it has also been reported in the venous system. The most commonly involved segment has been the common femoral vein; the disease resulted in luminal compromise and extremity swelling. We report here on a case of adventitial cystic disease of the left external iliac vein that was initially misdiagnosed as deep vein thrombosis in a 68-years-old man who presented with a painless swelling of his left leg.

  8. Interventions for preventing and managing advanced liver disease in cystic fibrosis.

    Science.gov (United States)

    Palaniappan, Senthil K; Than, Nan Nitra; Thein, Aung Win; Moe, Soe; van Mourik, Indra

    2017-08-29

    Cystic fibrosis is an autosomal recessive inherited defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in abnormal regulation of salt and water movement across the membranes. In the liver this leads to focal biliary fibrosis resulting in progressive portal hypertension and end-stage liver disease in some individuals. This can be asymptomatic, but may lead to splenomegaly and hypersplenism, development of varices and variceal bleeding, and ascites; it has negative impact on overall nutritional status and respiratory function in this population. Prognosis is poor once significant portal hypertension is established. The role and outcome of various interventions for managing advanced liver disease (non-malignant end stage disease) in people with cystic fibrosis is currently unidentified. To review and assess the efficacy of currently available treatment options for preventing and managing advanced liver disease in children and adults with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search: 06 April 2017.We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 04 January 2017. Any published and unpublished randomised controlled trials and quasi-randomised controlled trials of advanced liver disease in cystic fibrosis with cirrhosis or liver failure, portal hypertension or variceal bleeding (or both). Authors independently examined titles and abstracts to identify potentially relevant trials, but none were eligible for inclusion in this review. A comprehensive search of the literature did not identify any published eligible randomised controlled trials. In order to develop the best source of evidence, there is a need to undertake randomised controlled trials of interventions for preventing and managing advanced liver disease in

  9. Cystic changes of breast in a family with autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Maleki, Davood; Ghafari, Ali

    2009-10-01

    Autosomal dominant polycystic kidney disease is associated with cysts in many organs including the liver, pancreas, lungs, spleen, ovaries, testes, thyroid, and uterus. However, there is no report, to our knowledge, of cystic changes of the breast along with this disease. We describe 3 members of a family with multiple bilateral breast cysts in association with autosomal dominant polycystic kidney disease.

  10. Cystic adventitial disease of the popliteal artery: an infrequent cause of intermittent claudication

    OpenAIRE

    Kauffman, Paulo; Kuzniec, Sergio; Sacilotto, Roberto; Teivelis, Marcelo Passos; Wolosker, Nelson; Tachibana, Adriano

    2014-01-01

    Intermittent claudication is frequently associated with atherosclerotic disease, but differential diagnosis must be sought in patients with no traditional risk factors. Cystic adventitial disease, of unknown etiology, most frequently affects the popliteal artery, and occasionally presents as intermittent claudication. We report a case of this disease and the surgical treatment, and discuss some aspects related to etiopathogenesis, diagnosis and treatment of this condition.

  11. Treatment of cystic ovarian disease in dairy cattle.

    Science.gov (United States)

    Nakao, T; Numata, Y; Kubo, M; Yamauchi, S

    1978-04-01

    Fourty-four Holstein Friesian cows diagnosed as having ovarian follicular cysts from rectal palpation of the ovaries and observation of estrous behavior were used for the present experiments. Of the 16 cows injected intramuscularly (i.m.) with 110 mg of depot-progestins containing 100 mg of 17alpha-hydroxyprogesterone caproate and 10 mg of progesterone in oil, 8 cows responded with conception with 103 +/- 53 days in average after the treatment. The 8 cows not responding to depot-progestins were injected i.m. with 6,000 MU of HCG on the 10th day after the treatment. As a result, 2 cows of them conceived within 72 days in average after the initial treatment. Of the other 16 cows injected i.m. with 100 mg of progesteron in oil, 3 cows conceived. Interval between the treatment and conception was 36 +/- 9 days in average. In the 11 cows which failed to respond to progesterone treatment, an intramuscular injection of 6,000 MU of HCG on the 5th day after treatment resulted in conception of 7 cows within 42 +/- 10 days in average after the first treatment. Of the remaining 12 cows which received an i.m. injection with 10,000 MU of HCG, 4 cows responded with conception with 64 +/- 51 days in average after treatment. No remarkable rise in serum progesterone levels was observed either 10 days after depot-progestins injection or 5 days after progesterone treatment. Serum progesteron levels increased distinctly after HCG injections. The combined treatment with 100 mg of progesterone and 6,000 MU of HCG at 5 days interval gave the most successful results and this treatment was effective even when performed long after calving. Thus this method of treatment of cystic ovarian disease may be recommended for practical application.

  12. Diffusion weighted imaging in cystic fibrosis disease: beyond morphological imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ciet, Pierluigi [Erasmus Medical Center, Department of Radiology, Rotterdam (Netherlands); Erasmus Medical Center - Sophia Children' s Hospital, Department of Paediatrics, Respiratory Medicine and Allergology, P.O. Box 2060, Rotterdam, Zuid-Holland (Netherlands); Ca' Foncello - General Hospital, Department of Radiology, Treviso (Italy); Serra, Goffredo; Catalano, Carlo [University of Rome ' ' Sapienza' ' , Department of Radiology, Rome (Italy); Andrinopoulou, Eleni Rosalina [Erasmus Medical Center, Department of Biostatistics, Rotterdam (Netherlands); Bertolo, Silvia; Morana, Giovanni [Ca' Foncello - General Hospital, Department of Radiology, Treviso (Italy); Ros, Mirco [Ca' Foncello Hospital, Department of Pediatrics, Treviso (Italy); Colagrande, Stefano [University of Florence - Azienda Ospedaliero-Universitaria Careggi, Department of Experimental and Clinical Biomedical Sciences, Radiodiagnostic Unit n. 2, Florence (Italy); Tiddens, Harm A.W.M. [Erasmus Medical Center, Department of Radiology, Rotterdam (Netherlands); Erasmus Medical Center - Sophia Children' s Hospital, Department of Paediatrics, Respiratory Medicine and Allergology, P.O. Box 2060, Rotterdam, Zuid-Holland (Netherlands)

    2016-11-15

    To explore the feasibility of diffusion-weighted imaging (DWI) to assess inflammatory lung changes in patients with Cystic Fibrosis (CF) CF patients referred for their annual check-up had spirometry, chest-CT and MRI on the same day. MRI was performed in a 1.5 T scanner with BLADE and EPI-DWI sequences (b = 0-600 s/mm{sup 2}). End-inspiratory and end-expiratory scans were acquired in multi-row scanners. DWI was scored with an established semi-quantitative scoring system. DWI score was correlated to CT sub-scores for bronchiectasis (CF-CT{sub BE}), mucus (CF-CT{sub mucus}), total score (CF-CT{sub total-score}), FEV{sub 1}, and BMI. T-test was used to assess differences between patients with and without DWI-hotspots. Thirty-three CF patients were enrolled (mean 21 years, range 6-51, 19 female). 4 % (SD 2.6, range 1.5-12.9) of total CF-CT alterations presented DWI-hotspots. DWI-hotspots coincided with mucus plugging (60 %), consolidation (30 %) and bronchiectasis (10 %). DWI{sub total-score} correlated (all p < 0.0001) positively to CF-CT{sub BE} (r = 0.757), CF-CT{sub mucus} (r = 0.759) and CF-CT{sub total-score} (r = 0.79); and negatively to FEV{sub 1} (r = 0.688). FEV{sub 1} was significantly higher (p < 0.0001) in patients without DWI-hotspots. DWI-hotspots strongly correlated with radiological and clinical parameters of lung disease severity. Future validation studies are needed to establish the exact nature of DWI-hotspots in CF patients. (orig.)

  13. Pioglitazone Attenuates Cystic Burden in the PCK Rodent Model of Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Bonnie L. Blazer-Yost

    2010-01-01

    Full Text Available Polycystic kidney disease (PKD is a genetic disorder characterized by growth of fluid-filled cysts predominately in kidney tubules and liver bile ducts. Currently, the clinical management of PKD is limited to cyst aspiration, surgical resection or organ transplantation. Based on an observation that PPARγ agonists such as pioglitazone and rosiglitazone decrease mRNA levels of a Cl− transport protein, CFTR (cystic fibrosis transmembrane conductance regulator, and the Cl− secretory response to vasopressin in cultured renal cells, it is hypothesized that PPARγ agonists will inhibit cyst growth. The current studies show that a 7- or 14-week pioglitazone feeding regimen inhibits renal and hepatic bile duct cyst growth in the PCK rat, a rodent model orthologous to human PKD. These studies provide proof of concept for the mechanism of action of the PPARγ agonists and suggest that this class of drugs may be effective in controlling both renal and hepatic cyst growth and fibrosis in PKD.

  14. Antioxidant supplementation for lung disease in cystic fibrosis

    DEFF Research Database (Denmark)

    Ciofu, Oana; Lykkesfeldt, Jens

    2014-01-01

    BACKGROUND: Airway infection leads to progressive damage of the lungs in cystic fibrosis and oxidative stress has been implicated in the etiology. Supplementation of antioxidant micronutrients (vitamin E, vitamin C, ß-carotene and selenium) or glutathione may therefore potentially help maintain a...

  15. Disease-specific clinical trials networks: the example of cystic fibrosis.

    Science.gov (United States)

    De Boeck, Kris; Bulteel, Veerle; Fajac, Isabelle

    2016-06-01

    This article describes the steps of the development and the structure of a disease-specific clinical trials network for cystic fibrosis in Europe. Activities such as reviewing study protocols, feasibility assessments, training and standardizing of procedures, and outcome measurements help to bring high-quality clinical trials to the patients. Cooperation with the pharmaceutical industry, other research networks, patient organizations, and regulatory agencies is very important throughout all activities. The European Cystic Fibrosis Society-Clinical Trials Network facilitates the development of new treatments for a rare disease and could be a prototype for other diseases. • Clinical research has led to the first approved treatments targeting the basic Cystic Fibrosis defect. • For a rare disease like Cystic Fibrosis, multicenter international collaboration is needed to obtain solid evidence when testing possible new treatments. What is New: • The Clinical Trials Network established by the European Cystic Fibrosis Society has grown to a fully operational network with well-defined structures, procedures and partnerships. • Standardization of outcome parameters, protocol review, feasibility assessment and other activities help to develop high quality, efficient, relevant and feasible clinical trials, with the aim to bring new treatments to the patients.

  16. Conventional papillary thyroid carcinoma: effects of cystic changes visible on ultrasonography on disease prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ja Young; Kim, Eun Kyung; Kwak, Jin Young [Dept. of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Lee, Hye Sun [Dept. of Biostatistics, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-12-15

    To investigate the characteristics of papillary thyroid carcinoma (PTC) with cystic changes visible on ultrasonography (US). This study included 553 PTCs in 553 patients between January 2003 and August 2004. One radiologist with 10 years of experience in thyroid imaging retrospectively reviewed the preoperative US images. Two different groups were formed according to two different reference points (group 1, 25%; group 2, 50%) of the cystic component. Patients between the groups were compared according to their clinicopathologic characteristics. Disease-free survival (DFS) was estimated. Cox's multivariate proportional hazards regression model was used to identify the effect of variable factors on the recurrence risk. Fifty-six patients (10.1%) were confirmed to have tumor recurrence within the follow-up period. Thirty-five patients had regional metastasis, one had distant metastasis, eight had multiple site metastases, and 12 had biochemical recurrence. PTC patients with a ≤ 50% or PTC patients with a ≤ 25% cystic component did not have a statistically significant longer DFS than those with a >50% (hazard ratio [HR], 1.118; 95% confidence interval [CI], 0.255 to 4.910; P=0.883) or those with a >25% cystic component (HR, 0.569; 95% CI, 0.164 to 1.976; P=0.375), respectively. Moreover, independent predictors of recurrence were pathologic size, male gender, and lymph node metastasis, not a >50% or >25% cystic component. The proportion of the cystic component in PTCs did not affect DFS.

  17. Papillary thyroid microcarcinoma in Graves′ disease presenting as a cystic neck mass

    Directory of Open Access Journals (Sweden)

    Milind Patil

    2015-01-01

    Full Text Available The presentation of papillary thyroid microcarcinoma (PTMC as a solitary cystic neck mass is uncommon. Additionally, its association with Graves′ disease is very rare. We report a case of occult PTMC, who presented with a cystic neck mass in the background of Graves′ disease without any goiter. Imaging like ultrasound of neck, single photon emission computed tomography-CT (SPECT-CT, and technetium scan failed to detect any lesion in the thyroid, which was picked up only by the contrast-enhanced computed tomography (CECT of neck. The patient underwent total thyroidectomy with right modified lymph node dissection. Our case highlights the presentation of metastatic PTMC as a differential diagnosis of a cystic neck mass even in a patient with Graves′ disease without any thyroid enlargement.

  18. Investigating self-efficacy, disease knowledge and adherence to treatment in adolescents with cystic fibrosis.

    Science.gov (United States)

    Faint, Nicholas R; Staton, Janelle M; Stick, Stephen M; Foster, Juliet M; Schultz, André

    2017-05-01

    Patient adherence is integral to the effectiveness of prescribed treatment, and is associated with beneficial disease outcomes, yet in adolescents with cystic fibrosis, adherence is often sub-optimal. Multiple factors may contribute to treatment adherence, including disease knowledge and self-efficacy. In adolescents with cystic fibrosis: (i) to compare the disease knowledge of adolescents and their parents before transition to adult care; (ii) to determine the relationship between disease knowledge (adolescent, parent) and adherence; and (iii) to evaluate self-efficacy and its association with disease knowledge and adherence. Adolescents with cystic fibrosis and their parents were recruited from a tertiary children's hospital. Disease knowledge and self-efficacy was assessed using the Knowledge of Disease Management-CF and General Self-Efficacy Scales respectively. Using pharmacy records, medication possession ratio was calculated to measure treatment adherence in the preceding year. Thirty-nine adolescent (aged 12-17 (median 14) years) and parent pairs were recruited. Adherence to hypertonic saline, but not other medications, was significantly associated with disease knowledge in adolescents (r (2)  = 0.40, P = 0.029). Mean (SD) adolescent self-efficacy was 30.8 (4.0), and not associated with disease knowledge or adherence. Mean (SD) disease knowledge was less in adolescents than parents (55 (16)% and 72 (14)% respectively, P Disease knowledge is sub-optimal in adolescents with cystic fibrosis, even in the 2 years immediately before transition to adult care. Given that adherence with some treatments has been associated with disease knowledge our results suggest the need for educational interventions in adolescents with cystic fibrosis to optimise self-management and health outcomes. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  19. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis : A European consensus

    NARCIS (Netherlands)

    Heijerman, Harry; Westerman, Elsbeth; Conway, Steven; Touw, Daan; Döring, Gerd; Frijlink, Henderik

    In cystic fibrosis inhalation of drugs for the treatment of CF related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. In this European consensus document we

  20. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

    Science.gov (United States)

    Lee, Tim W R; Southern, Kevin W; Perry, Luke A; Penny-Dimri, Jahan C; Aslam, Aisha A

    2016-06-17

    Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.Date of most recent search: 05 May 2016.An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2015.Date of most recent search: 20 April 2016. Randomised controlled studies comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs. Four randomised controlled studies met the inclusion criteria for this review, involving a total of 302 participants lasting from 29 days to 13 months; 14 studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis. One study only enrolled adult males, the remaining studies included both males and females aged 12 years and over.Risk of bias in the studies was moderate. Random sequence generation and allocation concealment was only described in the more recent study; the remaining three studies were

  1. Transcellular sodium transport in cultured cystic fibrosis human nasal epithelium

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

    Cystic fibrosis (CF) airway epithelia exhibit raised transepithelial Na+ transport rates, as determined by open-circuit isotope fluxes and estimates of the amiloride-sensitive equivalent short-circuit current (Ieq). To study the contribution of apical and basolateral membrane paths to raised Na...

  2. "Intermittent claudication intermittence" as a manifestation of adventitial cystic disease communicating with the knee joint.

    Science.gov (United States)

    Buijsrogge, Marc P; van der Meij, Suzan; Korte, Jan H; Fritschy, Wilbert M

    2006-09-01

    In this report, we describe a patient with adventitial cystic disease of the popliteal artery, in which direct communication via a duct-like structure between the cystic lesion and the knee-joint synovium resulted in recurrent episodes of intermittent claudication and complete symptom-free intervals (intermittent claudication intermittence). This unusual observation could shed more light on the debated etiology of the disease. Moreover, it emphasizes the importance of complete excision of the cyst along with the presenting anatomic connection with the knee joint.

  3. Hypokalemic paralysis associated with cystic disease of the kidney: case report

    Directory of Open Access Journals (Sweden)

    Jayasinghe Saroj

    2011-04-01

    Full Text Available Abstract Background Severe hypokalemia is known to cause muscle paralysis, and renal tubular acidosis is a recognized cause. Cystic disease of the kidney is associated with severe hypokalemia. Case presentation We report a 33-year-old male patient who presented with generalized limb weakness caused by severe hypokalemia due to renal tubular acidosis, who was found to have renal medullary cysts. Conclusion The association of cystic renal disease with hypokalemia, and the possible pathophysiological basis of the development of renal cysts in patients with severe hypokalemia, are discussed.

  4. The Chitinase-Like Protein YKL-40 Modulates Cystic Fibrosis Lung Disease

    Science.gov (United States)

    Latzin, Philipp; Casaulta, Carmen; Kieninger, Elisabeth; Zhou, Zhe; Yildirim, Ali Ö.; Bohla, Alexander; Rieber, Nikolaus; Kappler, Matthias; Koller, Barbara; Eber, Ernst; Eickmeier, Olaf; Zielen, Stefan; Eickelberg, Oliver; Griese, Matthias; Mall, Marcus A.; Hartl, Dominik

    2011-01-01

    The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two disease conditions featuring neutrophilic infiltrates. Based on these studies and a previous report indicating that neutrophils secrete YKL-40, we hypothesized that YKL-40 plays a key role in cystic fibrosis (CF) lung disease, a prototypic neutrophilic disease. The aim of this study was (i) to analyze YKL-40 levels in human and murine CF lung disease and (ii) to investigate whether YKL-40 single-nucleotide polymorphisms (SNPs) modulate CF lung disease severity. YKL-40 protein levels were quantified in serum and sputum supernatants from CF patients and control individuals. Levels of the murine homologue BRP-39 were analyzed in airway fluids from CF-like βENaC-Tg mice. YKL-40SNPs were analyzed in CF patients. YKL-40 levels were increased in sputum supernatants and in serum from CF patients compared to healthy control individuals. Within CF patients, YKL-40 levels were higher in sputum than in serum. BRP-39 levels were increased in airways fluids from βENaC-Tg mice compared to wild-type littermates. In both CF patients and βENaC-Tg mice, YKL-40/BRP-39 airway levels correlated with the severity of pulmonary obstruction. Two YKL-40 SNPs (rs871799 and rs880633) were found to modulate age-adjusted lung function in CF patients. YKL-40/BRP-39 levelsare increased in human and murine CF airway fluids, correlate with pulmonary function and modulate CF lung disease severity genetically. These findings suggest YKL-40 as a potential biomarker in CF lung disease. PMID:21949714

  5. Metabolomic biomarkers predictive of early structural lung disease in cystic fibrosis.

    Science.gov (United States)

    Esther, Charles R; Turkovic, Lidija; Rosenow, Tim; Muhlebach, Marianne S; Boucher, Richard C; Ranganathan, Sarath; Stick, Stephen M

    2016-12-01

    Neutrophilic airway inflammation plays a role in early structural lung disease in cystic fibrosis, but the mechanisms underlying this pathway are incompletely understood.Metabolites associated with neutrophilic inflammation were identified by discovery metabolomics on bronchoalveolar lavage fluid supernatant from 20 preschool children (2.9±1.3 years) with cystic fibrosis. Targeted mass-spectrometric detection of relevant metabolites was then applied to 34 children (3.5±1.5 years) enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) who underwent chest computed tomography and bronchoalveolar lavage from two separate lobes during 42 visits. Relationships between metabolites and localised structural lung disease were assessed using multivariate analyses.Discovery metabolomics identified 93 metabolites associated with neutrophilic inflammation, including pathways involved in metabolism of adenyl purines, amino acids and small peptides, cellular energy and lipids. In targeted mass spectrometry, products of adenosine metabolism, protein catabolism and oxidative stress were associated with structural lung disease and predicted future bronchiectasis, and activities of enzymes associated with adenosine metabolism were elevated in the samples with early disease.Metabolomics analyses revealed metabolites and pathways altered with neutrophilic inflammation and destructive lung disease. These pathways can serve as biomarkers and potential therapeutic targets for early cystic fibrosis lung disease. Copyright ©ERS 2016.

  6. Stenting of the Cystic Duct in Benign Disease: A Definitive Treatment for the Elderly and Unwell

    Energy Technology Data Exchange (ETDEWEB)

    Hersey, N., E-mail: naomi.hersey@sth.nhs.uk [Sheffield Teaching Hospitals NHS Trust, Department of Radiology, Northern General Hospital (United Kingdom); Goode, S. D., E-mail: s.goode@sheffield.sc.uk [Sheffield Teaching Hospitals NHS Trust, Sheffield Vascular Institute (United Kingdom); Peck, R. J., E-mail: robert.peck@sth.nhs.uk; Lee, F., E-mail: fred.lee@sth.nhs.uk [Sheffield Teaching Hospitals NHS Trust, Department of Radiology, Northern General Hospital (United Kingdom)

    2015-08-15

    PurposeThere have been few case reports describing cystic duct stent insertion in the management of acute cholecystitis secondary to benign disease with no case series published to date. We present our series demonstrating the role of cystic duct stents in managing benign gallbladder disease in those patients unfit for surgery.Materials and MethodsThirty three patients unfit for surgery in our institution underwent cystic duct stent insertion for the management of acute cholecystitis in the period June 2008 to June 2013. Patients underwent a mixture of transperitoneal and transhepatic gallbladder puncture. The cystic duct was cannulated with a hydrophilic guidewire which was subsequently passed through the common bile duct and into the duodenum. An 8Fr 12-cm double-pigtail stent was placed with the distal end lying within the duodenum and the proximal end within the gallbladder.ResultsTen patients presented with gallbladder perforation, 21 patients with acute cholecystitis, 1 with acute cholangitis and 1 with necrotising pancreatitis. The technical success rate was 91 %. We experienced a 13 % complication rate with 3 % mortality rate at 30 days.ConclusionCystic duct stent insertion can be successfully used to manage acute cholecystitis, gallbladder empyema or gallbladder perforations in those unfit for surgery and should be considered alongside external gallbladder drainage as a definitive mid-term treatment option.

  7. Concentration of aluminium in breast cyst fluids collected from women affected by gross cystic breast disease.

    Science.gov (United States)

    Mannello, Ferdinando; Tonti, Gaetana A; Darbre, Philippa D

    2009-01-01

    Gross cystic breast disease (GCBD) is the most common benign breast disorder, but the molecular basis of cyst formation remains to be identified. If the use of aluminium-based antiperspirant salts is involved in the etiology of gross breast cyst formation, it might be expected that aluminium would be at elevated levels in human breast cyst fluid (BCF). Aluminium was measured by ICP-MS in 48 samples of BCF, 30 samples of human blood serum and 45 samples of human breast milk at different stages of lactation (colostrum, intermediate, mature). The median level of aluminium in apocrine type I BCF (n = 27, 150 microg l(-1)) was significantly higher than in transudative type II BCF (n = 21, 32 microg l(-1); P breast milk, with no difference between colostrum, intermediate and mature milk. Levels of aluminium were significantly higher in both types of BCF than in human serum (P breast milk, aluminium levels were only significantly higher in apocrine type I BCF (P breast cysts, then it might become possible to prevent this common breast disorder. Copyright (c) 2008 John Wiley & Sons, Ltd.

  8. The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis.

    Science.gov (United States)

    Frayman, Katherine B; Armstrong, David S; Carzino, Rosemary; Ferkol, Thomas W; Grimwood, Keith; Storch, Gregory A; Teo, Shu Mei; Wylie, Kristine M; Ranganathan, Sarath C

    2017-12-01

    In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain. To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years. Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records. Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2-78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years. In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age. 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/.

  9. Neonatal cystic fibrosis screening test

    Science.gov (United States)

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

  10. Inspiratory muscle strength relative to disease severity in adults with stable cystic fibrosis.

    Science.gov (United States)

    Dekerlegand, Robert L; Hadjiliadis, Denis; Swisher, Anne K; Parrott, J Scott; Heuer, Albert J; Myslinski, Mary Jane

    2015-09-01

    Due to heterogeneity in pulmonary disease, current literature may misrepresent inspiratory muscle involvement in cystic fibrosis (CF). This study investigated inspiratory muscle strength (IMS) relative to disease severity in adults with CF. Maximal inspiratory pressure (MIP) was assessed in 58 adults with stable CF grouped by disease severity (20 mild, 20 moderate, 18 severe) and compared to 20 controls. Relationships between MIP, lung function, dyspnea and anthropometrics were evaluated using multivariable linear models. MIP in cmH2O and %-predicted was decreased in advanced CF lung disease as compared to mild disease and healthy controls (pDisease severity accounted for 24% of the variance in IMS after controlling for confounding variables (pdisease, and is related to dyspnea. Future studies should determine if decreased IMS contributes inefficient breathing patterns, respiratory pump dysfunction, and/or exercise intolerance in advanced CF. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  11. Localized cystic disease of the kidney: A rare diagnosis of this uncommon condition in a child

    Directory of Open Access Journals (Sweden)

    Christopher A. Behr

    2016-09-01

    Full Text Available Localized cystic disease of the kidney (LCDK is a rare condition found primarily in adults, with the total number of documented cases less than 75. Its incidence in the pediatric population is even more minuscule. It is a benign condition, but can be difficult to classify with certainty on imaging, often necessitating surgical excision to adequately rule out a malignancy. We present the case of a six-year-old child with a cystic mass of the kidney who underwent a radical nephroureterectomy, for which pathology showed LCDK. We then review the literature on the subject.

  12. Genetics Home Reference: cystic fibrosis

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Cystic fibrosis Cystic fibrosis Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Cystic fibrosis is an inherited disease characterized by the buildup ...

  13. Diagnosis, follow-up and treatment of cystic fibrosis-related liver disease

    NARCIS (Netherlands)

    van de Peppel, Ivo P; Bertolini, Anna; Jonker, Johan W; Bodewes, Frank A J A; Verkade, Henkjan J

    2017-01-01

    Purpose of review To provide an insight and overview of the challenges in the diagnosis, follow-up and treatment of cystic fibrosis-related liver disease (CFLD). Recent findings The variable pathophysiology of CFLD complicates its diagnosis and treatment. A 'gold standard' for CFLD diagnosis is

  14. Simultaneous liver-pancreas transplantation for cystic fibrosis-related liver disease : A multicenter experience

    NARCIS (Netherlands)

    Bandsma, R. H. J.; Bozic, M. A.; Fridell, J. A.; Crull, M. H.; Molleston, J.; Avitzur, Y.; Mozer-Glassberg, Y.; Gonzalez-Peralta, R. P.; Hodik, M.; Fecteau, A.; de Angelis, M.; Durie, P.; Ng, V. L.

    Background: Diabetes is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). While liver transplantation is well established for CF-related liver disease (CFLD), the role of simultaneous liver pancreas transplantation is less understood. Methods: We polled 81

  15. PRAGMA-CF. A quantitative structural lung disease CT outcome in young children with cystic fibrosis

    DEFF Research Database (Denmark)

    Rosenow, Tim; Oudraad, Merel C.J.; Murray, Conor P.

    2015-01-01

    RATIONALE: Chest computed tomography (CT) is the gold standard for demonstrating cystic fibrosis (CF) airways disease. However, there are no standardised outcome measures appropriate for children under 6 years. OBJECTIVES: We developed the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF...

  16. Increase of Serum gamma-Glutamyltransferase Associated With Development of Cirrhotic Cystic Fibrosis Liver Disease

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; van der Doef, Hubert P. J.; Houwen, Roderick H. J.; Verkade, Henkjan J.

    Background:Identification of patients at risk for developing cirrhotic cystic fibrosis liver disease (CCFLD) is essential for targeting potentially preventive treatment. We studied the evolution of serum liver enzymes and thrombocyte counts as predictors of CCFLD development.Methods:For this study,

  17. Very mild disease phenotype of congenic CftrTgH(neoim)Hgu cystic fibrosis mice

    NARCIS (Netherlands)

    B. Tóth (Balázs); M. Wilke (Martina); F. Stanke (Frauke); M. Dorsch (Martina); S. Jansen (Silke); D. Wedekind (Dirk); N. Charizopoulou (Nikoletta); A.G. Bot (Alice); M. Burmester (Marion); S. Leonhard-Marek (Sabine); H.R. de Jonge (Hugo); H.J. Hedrich; G. Breves (Gerhard); B. Tümmler (Burkhard)

    2008-01-01

    textabstractBackground: A major boost to cystic fibrosis disease research was given by the generation of various mouse models using gene targeting in embryonal stem cells. Moreover, the introduction of the same mutation on different inbred strains generating congenic strains facilitated the search

  18. Nontuberculous Mycobacterial Disease Is Not a Contraindication to Lung Transplantation in Patients With Cystic Fibrosis

    DEFF Research Database (Denmark)

    Qvist, Tavs; Pressler, Tanja; Thomsen, V O

    2013-01-01

    Whether nontuberculous mycobacterial (NTM) disease is a contraindication to lung transplantation remains controversial. We conducted a nationwide study to evaluate the clinical importance of NTM infection among lung transplant patients with cystic fibrosis (CF) in Denmark and to determine if NTM...

  19. Genetic parameters for cystic ovarian disease in Dutch Black and White dairy cattle

    NARCIS (Netherlands)

    Hooijer, G.A.; Lubbers, R.B.F.; Ducro, B.J.; Arendonk, van J.A.M.; Kaal-Lansbergen, L.M.T.E.; Lende, van der T.

    2001-01-01

    Cystic ovarian disease (COD) is one of the most frequently diagnosed gynecological findings in dairy cattle. It causes temporary infertility and is likely to affect reproduction as well as production parameters in cows. The objectives of this study were to investigate the heritability of COD in a

  20. Lithiasis in cystic kidney disease and malformations of the urinary tract.

    Science.gov (United States)

    Gambaro, G; Fabris, A; Puliatta, D; Lupo, A

    2006-04-01

    The prevalence of renal stones in renal cystic and malformative conditions exceeds the prevalence of renal stones in the general population, suggesting that the above-mentioned cystic and malformative disorders favor stone formation. Urinary stasis is generally assumed to play a major part in the pathogenesis of the nephrolithiasis associated with distorted renal anatomy due to a delayed washout of crystals and risk of urinary infections. However metabolic factors are also important in the pathogenesis of stones in these conditions. Indeed, metabolic abnormalities have been observed in the majority of stone-forming patients with conditions such as horseshoe kidney and ureteropelvic junction obstruction. Five different models of stone formation can be identified, depending on stone composition, risk of infection stones, and pathogenesis of renal cystic and malformative conditions. A proper metabolic evaluation should be conducted to diagnose specific, treatable metabolic disorders, thereby reducing the frequency of recurrent stone disease in these conditions as well.

  1. Proteomics investigation of human platelets in healthy donors and cystic fibrosis patients by shotgun nUPLC-MSE and 2DE: a comparative study.

    Science.gov (United States)

    Pieroni, Luisa; Finamore, Francesco; Ronci, Maurizio; Mattoscio, Domenico; Marzano, Valeria; Mortera, Stefano Levi; Quattrucci, Serena; Federici, Giorgio; Romano, Mario; Urbani, Andrea

    2011-03-01

    Platelets are of pathophysiological relevance in haemostasis, wound repair, inflammation and cardiovascular disease. We have shown that human platelets express a biologically active Cystic Fibrosis Transmembrane Conductance Regulator, which is dysfunctional in Cystic Fibrosis (CF) patients, and regulate platelet responses related to inflammation and its resolution. In order to further elucidate platelet involvement in CF inflammation, we pursued a comparative proteomic analysis of cells from healthy donors and CF patients, in association with a non-supervised comparative analysis of the Gene Ontology. Our results, showing changes in the integrin signalling in CF, support a pro-inflammatory profile of CF platelets.

  2. The triterpenoid CDDO limits inflammation in preclinical models of cystic fibrosis lung disease

    Science.gov (United States)

    Ziady, Assem G.; Shank, Samuel L.; Eastman, Jean F.; Davis, Pamela B.

    2009-01-01

    Excessive inflammation in cystic fibrosis (CF) lung disease is a contributor to progressive pulmonary decline. Effective and well-tolerated anti-inflammatory therapy may preserve lung function, thereby improving quality and length of life. In this paper, we assess the anti-inflammatory effects of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) in preclinical models of CF airway inflammation. In our experiments, mice carrying the R117H Cftr mutation have significantly reduced airway inflammatory responses to both LPS and flagellin when treated with CDDO before inflammatory challenge. Anti-inflammatory effects observed include reduced airway neutrophilia, reduced concentrations of proinflammatory cytokines and chemokines, and reduced weight loss. Our findings with the synthetic triterpenoids in multiple cell culture models of CF human airway epithelia agree with effects previously described in other disease models (e.g., neoplastic cells). These include the ability to reduce NF-κB activation while increasing nuclear factor erythroid-related factor 2 (Nrf2) activity. As these two signaling pathways appear to be pivotal in regulating the net inflammatory response in the CF airway, these compounds are a promising potential anti-inflammatory therapy for CF lung disease. PMID:19700644

  3. Genetic Expression in Cystic Fibrosis Related Bone Disease. An Observational, Transversal, Cross-Sectional Study.

    Science.gov (United States)

    Ciuca, Ioana M; Pop, Liviu L; Rogobete, Alexandru F; Onet, Dan I; Guta-Almajan, Bogdan; Popa, Zoran; Horhat, Florin G

    2016-09-01

    Cystic fibrosis (CF) is the most frequent monogenic genetic disease with autosomal recessive transmission and characterized by important clinical polymorphism and significant lethal prospective. CF related bone disease occurs frequently in adults with CF. Childhood is the period of bone formation, and therefore, children are more susceptible to low bone density. Several factors like pancreatic insufficiency, hormone imbalance, and physical inactivity contribute to CF bone disease development. Revealing this would be important for prophylactic treatment against bone disease occurrence. The study was observational, transversal, with a cross-sectional design. The study included 68 children with cystic fibrosis, genotyped and monitored in the National CF Centre. At the annual assessment, besides clinical examination, biochemical evaluation for pancreatic insufficiency, and diabetes, they were evaluated for bone mineral density using dual energy X-ray absorptiometry (DXA). Twenty-six patients, aged over 10 years were diagnosed with CF bone disease, without significant gender gap. Bone disease was frequent in patients aged over 10 years with exocrine pancreatic insufficiency, carriers of severe mutations, and CF liver disease. CF carriers of a severe genotype which associates pancreatic insufficiency and CF liver disease, are more likely predisposed to low bone mineral density. Further studies should discover other significant influences in order to prevent the development of CF bone disease and an improved quality of life in cystic fibrosis children.

  4. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene

    Science.gov (United States)

    Sosnay, Patrick R; Siklosi, Karen R; Van Goor, Fredrick; Kaniecki, Kyle; Yu, Haihui; Sharma, Neeraj; Ramalho, Anabela S; Amaral, Margarida D; Dorfman, Ruslan; Zielenski, Julian; Masica, David L; Karchin, Rachel; Millen, Linda; Thomas, Philip J; Patrinos, George P; Corey, Mary; Lewis, Michelle H; Rommens, Johanna M; Castellani, Carlo; Penland, Christopher M; Cutting, Garry R

    2013-01-01

    Allelic heterogeneity in disease-causing genes presents a substantial challenge to the translation of genomic variation to clinical practice. Few of the almost 2,000 variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have empirical evidence that they cause cystic fibrosis. To address this gap, we collected both genotype and phenotype data for 39,696 cystic fibrosis patients in registries and clinics in North America and Europe. Among these patients, 159 CFTR variants had an allele frequency of ≥0.01%. These variants were evaluated for both clinical severity and functional consequence with 127 (80%) meeting both clinical and functional criteria consistent with disease. Assessment of disease penetrance in 2,188 fathers of cystic fibrosis patients enabled assignment of 12 of the remaining 32 variants as neutral while the other 20 variants remained indeterminate. This study illustrates that sourcing data directly from well-phenotyped subjects can address the gap in our ability to interpret clinically-relevant genomic variation. PMID:23974870

  5. Recombinant human DNase nebulisation in children with cystic fibrosis: Before bedtime or after waking up?

    NARCIS (Netherlands)

    L.J. van der Giessen (Lianne); R.A.A.M. Gosselink (Rik); W.C.J. Hop (Wim); H.A.W.M. Tiddens (Harm)

    2007-01-01

    textabstractThe present study focused on patients with cystic fibrosis (CF), who were on maintenance therapy with recombinant human deoxyribonuclease (rhDNase), with the aim of comparing efficacy and possible side effects of nebulisation of rhDNase when taken before bedtime with efficacy and side

  6. Best practices in the treatment of early cystic fibrosis lung disease.

    Science.gov (United States)

    Proesmans, Marijke

    2017-02-01

    For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.

  7. UP-TO-DATE MANAGEMENT OF LUNG DISEASE IN CHILDREN AND ADOLESCENTS WITH CYSTIC FIBROSIS

    OpenAIRE

    Marina Praprotnik; Ana Kotnik Pirš; Barbara Salobir; Majda Oštir; Matjaž Turel; Uroš Krivec

    2015-01-01

    Cystic fibrosis (CF) is a multi-organ disease,  affecting mostly lungs and gastrointestinal tract. Data from patient registries show that the survival of patients with CF has progressively improved over the past several decades, as a result of advances in antibiotic treatment, supplementation of pancreatic enzymes, better nutrition and a holistic approach to treatment in CF centres.The purpose of this review is to survey recent developments in the treatment of lung disease  in children and ad...

  8. Lung Ultrasound Has Limited Diagnostic Value in Rare Cystic Lung Diseases

    DEFF Research Database (Denmark)

    Davidsen, Jesper Rømhild; Bendstrup, Elisabeth; Henriksen, Daniel P

    2017-01-01

    Background: Lung ultrasound (LUS) used to identify interstitial syndrome (IS) and pleural thickening related to diffuse parenchymal lung disease (DPLD) has shown significant correlations with ground glass opacity (GGO) on high-resolution computed tomography (HRCT). However, the applicability of L...... value as a diagnostic tool in patients with LAM, PLCH, and BHDS as normal LUS findings did not rule out severe cystic lung disease....

  9. Risk factors relevant to cystic breast disease: a case-control study.

    OpenAIRE

    Duffy, S W; Roberts, M M; Elton, R A

    1983-01-01

    A total of 188 women aged 40-54 with cystic breast disease and 2213 asymptomatic controls were questioned in Edinburgh between 1974 and 1978 concerning marital, reproductive, and menstrual status, history of oral contraception use, history of previous breast complaints, and a family history of breast cancer. Women with a history of breast biopsy were at an increased risk of the disease and those past the menopause were at a decreased risk. These results agree with previous findings that the d...

  10. Cystic fibrosis - nutritional considerations

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002437.htm Cystic fibrosis - nutrition To use the sharing features on this page, please enable JavaScript. Cystic fibrosis (CF) is a life-threatening disease that causes ...

  11. Rehabilitation in patients with chronic respiratory disease other than chronic obstructive pulmonary disease: exercise and physical activity interventions in cystic fibrosis and non-cystic fibrosis bronchiectasis.

    Science.gov (United States)

    Burtin, Chris; Hebestreit, Helge

    2015-01-01

    A relevant proportion of children and adults with cystic fibrosis (CF) have a marked decrease in exercise tolerance, which can be partly related to impaired muscle function and decreased physical activity levels in daily life, in addition to lung disease. Preliminary findings suggest that patients with non-CF bronchiectasis face the same problems. These patients might be excellent candidates for exercise and physical activity interventions. This review elaborates on the rationale for exercise training and activity behaviour changes and summarizes the existing evidence for these rehabilitation strategies in patients with bronchiectasis, both CF and non-CF bronchiectasis. Furthermore, practical considerations and safety aspects are discussed.

  12. Pathologic and Radiologic Correlation of Adult Cystic Lung Disease: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Prajwal Boddu

    2017-01-01

    Full Text Available The presence of pulmonary parenchymal cysts on computed tomography (CT imaging presents a significant diagnostic challenge. The diverse range of possible etiologies can usually be differentiated based on the clinical setting and radiologic features. In fact, the advent of high-resolution CT has facilitated making a diagnosis solely on analysis of CT image patterns, thus averting the need for a biopsy. While it is possible to make a fairly specific diagnosis during early stages of disease evolution by its characteristic radiological presentation, distinct features may progress to temporally converge into relatively nonspecific radiologic presentations sometimes necessitating histological examination to make a diagnosis. The aim of this review study is to provide both the pathologist and the radiologist with an overview of the diseases most commonly associated with cystic lung lesions primarily in adults by illustration and description of pathologic and radiologic features of each entity. Brief descriptions and characteristic radiologic features of the various disease entities are included and illustrative examples are provided for the common majority of them. In this article, we also classify pulmonary cystic disease with an emphasis on the pathophysiology behind cyst formation in an attempt to elucidate the characteristics of similar cystic appearances seen in various disease entities.

  13. Cystic degeneration of neuro endocrine tumor of pancreas and Crohn's disease: true or coincidental association?

    Science.gov (United States)

    Hedfi, Mohamed; Abbasi, Imed; Intissar, Chibani; Salwa, Ammar; Chouchen, Adnen

    2016-01-01

    Pancreatic endocrine tumors (PETs) or islet cell tumors are rare lesions, the incidence of which is estimated to be less than 1 per 100,000 person-years in the general population. PETs can be divided into functional (exhibit a distinct clinical syndrome due to hormone hypersecretion) and non-functional tumors. The majority of PETs are non-functional. In spite of their rarity, cystic neoplasms of the pancreas are characterized by existing or potential malignancy that cannot be ignored during decisive process with regard to the choice of treatment. The purpose of this workis to find an association with Crohn's disease and cystic degeneration of a neuroendocrine tumor of the pancreas. Crohn's disease may affect extraintestinal organs, including the pancreas. In such cases, It seems certain that many patients diagnosed with Crohn disease (CD) are predisposed to a wider spectrum of cancers. We present a case of pancreatic cyst with no typical features of pseudocyst in the medical interview, with history of Crohn's disease, treated by caudal pancreatectomy. We tried to evaluate the clinical and morphological features of so-called cystic neoplasms associated with inflammatory bowel disease and to define their pathological characteristics.

  14. Pulmonary congenital cystic disease in adults. Spiral computed tomography findings with pathologic correlation and management.

    Science.gov (United States)

    Scialpi, M; Cappabianca, S; Rotondo, A; Scalera, G B; Barberini, F; Cagini, L; Donato, S; Brunese, L; Piscioli, I; Lupattelli, L

    2010-06-01

    The aim of this study was to assess the computed tomography (CT) features of intrapulmonary congenital cystic diseases in adults and to correlate the imaging features with the pathological findings, with emphasis on the oncogenic potential of the lesions. We retrospectively reviewed the CT scans in three institutions from August 1996 to December 2008, of nine patients (six men, three women; mean age 48.6 years; range 26-75 years) who had histological diagnosis of pulmonary cystic disease after surgery. Six patients had a diagnosis of intrapulmonary bronchogenic cyst (IBC), and three had a type-I cystic adenomatoid malformation (CAM). In one case, intralobar sequestration (ILS) was associated with type-I CAM. Three patients were symptomatic and six were asymptomatic. On CT scans, IBCs showed homogeneous fluid attenuation (n=2), air-fluid level (n=2), air attenuation (n=1) or soft-tissue attenuation (n=1). The surrounding lung tissue showed areas of band-like linear attenuation in three IBCs, atelectasia in two and mucocele-like areas in one. On CT, type-I CAM appeared as a unilocular cystic lesion with air-fluid level (n=1) or air content (n=1). Both cases had thin walls surrounded by normal lung parenchyma. ILS appeared as a fluid-filled cyst with afferent and efferent vessels. Of the six IBCs, one occurred in the upper right lobe, two in the middle lobe and three in the lower right lobe. Of the three type-I CAMs, one was in the upper left lobe and one in the middle lobe. The type-I CAM associated with ILS was located in the left lower lobe. The similar CT patterns preclude differentiation between IBC and type-I CAM. Surgical resection of all intrapulmonary cystic lesions detected in adults is mandatory because type-I CAM is a precursor of mucinous bronchioloalveolar carcinoma.

  15. Human Epididymis Protein 4: A Novel Serum Inflammatory Biomarker in Cystic Fibrosis.

    Science.gov (United States)

    Nagy, Béla; Nagy, Béla; Fila, Libor; Clarke, Luka A; Gönczy, Ferenc; Bede, Olga; Nagy, Dóra; Újhelyi, Rita; Szabó, Ágnes; Anghelyi, Andrea; Major, Miklós; Bene, Zsolt; Fejes, Zsolt; Antal-Szalmás, Péter; Bhattoa, Harjit Pal; Balla, György; Kappelmayer, János; Amaral, Margarida D; Macek, Milan; Balogh, István

    2016-09-01

    Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF. Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR. Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P < .0001). This observation was replicated in adults with CF (115.7 [77.8-148.7] pmol/L; P < .0001). In contrast, abnormal but lower HE4 concentrations were found in cases of severe bronchitis, asthma, pneumonia, and bronchiectasis. In patients with CF, the concentrations of HE4 were positively correlated with overall disease severity and C-reactive protein concentrations, whereas a significant inverse relationship was found between HE4 and the spirometric FEV1 value. Relative HE4 mRNA levels were significantly upregulated (P = .011) with a decreased miR-140-5p expression (P = .020) in the CF vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator

  16. Bilateral multiple cystic kidney disease and renal cortical abscess in a Boerboel

    Directory of Open Access Journals (Sweden)

    A. M. Kitshoffa

    2011-04-01

    Full Text Available Cystic renal disease is rare in dogs and although infected renal cysts have been reported in humans, no report could be found in dogs. A 58 kg, 5-year-old, castrated, male Boerboel presented with weight loss, pyrexia, lethargy and vomiting, 20 months after an incident of haematuria was reported. The initial ultrasonographic diagnosis was bilateral multiple renal cysts of unknown aetiology. The cysts had significantly increased in size over the 20-month period and some contained echogenic specks which could be related to infection, normal cellular debris or haemorrhage. In both kidneys the renal contours were distorted (the left more than the right. The abnormal shape of the left kidney was largely due to multiple cysts and a large crescent-shaped septate mass on the cranial pole of the kidney. Aspirates of the septate mass were performed (left kidney and the cytology and culture were indicative of an abscess. It is suggested that the previous incident of haematuria provided a portal of entry for bacteria into the cysts resulting in renal cortical abscess formation.

  17. Cystic echinococcosis: a disease mimicking cancer in a non-endemic country report of two cases.

    Science.gov (United States)

    Comrnejo-Juárez, P; Espinosa-Altamirano, A; Ibarra-del-Río, M; Pacheco-Bravo, I; Volkow-Fernández, P

    2013-03-01

    Echinococcosis is a parasitic disease that involves dogs as definitive host and sheep as intermediate host. Humans become infected incidentally through fecal-oral contact, particularly in the course of playful and close contact with an infected dog. Mexico is considered a region that is virtually free of cystic echinoccocosis. This manuscript describes two cases that were referred to a tertiary-care oncology hospital with a diagnosis of cancer. In one case, the presumptive diagnosis was liver cancer because abdominal ultrasonography revealed a low-density mass in the right hepatic lobe. Drainage was performed and cytologic examination of the fluid showed multiple Echinococcus cyst as well as prostoscolex. The case was resolved with percutaneous drainage and administration of albendazole for two months. In the second case, the patient was referred with a diagnosis of disseminated cervical cancer A cyst was identified in the upper right lung lobe; a diagnostic puncture was performed showing an Echinococcus cyst. This resolved solely with two months of albendazole administration.

  18. The ultrastructural localization of gross cystic disease fluid protein (GCDFP-15) in breast epithelium.

    OpenAIRE

    Mazoujian, G.; Warhol, M. J.; Haagensen, D. E.

    1984-01-01

    GCDFP-15 is a major constituent protein of 15,000-dalton monomer size present in breast gross cystic disease fluid. Immunoperoxidase staining of GCDFP-15 has shown the protein to be present in normal apocrine epithelium, metaplastic apocrine epithelium of the breast, and breast carcinomas with apocrine features. To delineate ultrastructurally the localization of GCDFP-15 in benign breast epithelium, a low-temperature embedding colloidal gold technique was used. Metaplastic apocrine epithelium...

  19. A case of renal oncocytoma associated with acquired cystic disease of the kidney

    OpenAIRE

    佐藤, 威文; 永田, 幹男; 貫井, 文彦; 黒川, 純; 岡本, 重禮; 福井, 準之助; 大岩, 孝誌

    1998-01-01

    We report a case of renal oncocytoma associated with acquired cystic disease of kidney (ACDK). A right renal mass was incidentally found on an annual ultrasonography of the kidneys in a 56-year-old female patient who had been on maintenance hemodialysis for 6 years. Computerized tomography (CT) showed a right hypervascular renal mass, suggesting a renal cell carcinoma associated with ACDK. Right radical nephrectomy was performed. The post-operative pathological diagnosis was renal oncocytoma....

  20. The proteome speciation of an immortalized cystic fibrosis cell line: New perspectives on the pathophysiology of the disease.

    Science.gov (United States)

    Puglia, Michele; Landi, Claudia; Gagliardi, Assunta; Breslin, Loretta; Armini, Alessandro; Brunetti, Jlenia; Pini, Alessandro; Bianchi, Laura; Bini, Luca

    2018-01-06

    Cystic Fibrosis (CF) is a recessively inherited disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR has a pivotal role in the onset of CF, and several proteins are involved in its homeostasis. To study CFTR interactors at protein species level, we used a functional proteomics approach combining 2D-DIGE, mass spectrometry and enrichment analysis. A human bronchial epithelial cell line with cystic fibrosis (CFBE41o-) and the control (16HBE14o-) were used for the comparison. 73 differentially abundant spots were identified and some validated by western-blot. Enrichment analysis highlighted molecular pathways in which ezrin, HSP70, endoplasmin and lamin A/C, in addition to CFTR, were considered central hubs in CFTR homeostasis. These proteins acquire different functions through post-translational modifications, emphasizing the importance of studying the CF proteome at protein species level. Moreover, serpin H1, prelamin A/C, protein-SET and cystatin-B were associated to CF, demonstrating the importance of heat shock response, cross-talk between the cytoskeleton and signal transduction, chronic inflammation and alteration of CFTR gating in the pathophysiology of the disease. These results open new perspectives for the understanding of the proteostasis network, characteristic of CF pathology, and could provide a springboard for new therapeutic strategies. Homeostasis of CFTR is a dynamic process managed by multiple proteostatic pathways. The used gel-based proteomic approach and enrichment analysis pointed out protein species variations among Human Bronchial (16HBE14o-) and Cystic Fibrosis Bronchial Epithelial cell lines (CFBE41o-) and specific molecular mechanisms involved in CF. In particular, we have highlighted HSP70 (HSP7C), HSP90 (endoplasmin), ERM proteins (ezrin), and lamin-A/C as central hubs of the functional analysis. Moreover, for the first time we consider serpin H1, lamin A/C, protein-SET and cystatin

  1. Remote results of pathogenetic therapy of cystic breast disease

    OpenAIRE

    G. Kh. Khanafiev; S. A. Berzin; S. M. Demidov

    2014-01-01

    With 2000 year of pathogenetic treatment of fibrocystic breast disease preventing cystadenocarcinoma has led to positive results. In 2000–2001 years the percentage devoted to oncological indications for surgical treatment of patients with fibrocystic disease of the breast, was less than 3 % of the total number of operated on for various diseases of the breast.

  2. Remote results of pathogenetic therapy of cystic breast disease

    Directory of Open Access Journals (Sweden)

    G. Kh. Khanafiev

    2014-01-01

    Full Text Available With 2000 year of pathogenetic treatment of fibrocystic breast disease preventing cystadenocarcinoma has led to positive results. In 2000–2001 years the percentage devoted to oncological indications for surgical treatment of patients with fibrocystic disease of the breast, was less than 3 % of the total number of operated on for various diseases of the breast.

  3. Knockdown of bicaudal C in zebrafish (Danio rerio) causes cystic kidneys: a nonmammalian model of polycystic kidney disease.

    Science.gov (United States)

    Bouvrette, Denise J; Sittaramane, Vinoth; Heidel, Jerry R; Chandrasekhar, Anand; Bryda, Elizabeth C

    2010-04-01

    Polycystic kidney disease (PKD) is one of the leading causes of end-stage renal disease in humans and is characterized by progressive cyst formation, renal enlargement, and abnormal tubular development. Currently, there is no cure for PKD. Although a number of PKD genes have been identified, their precise role in cystogenesis remains unclear. In the jcpk mouse model of PKD, mutations in the bicaudal C gene (Bicc1) are responsible for the cystic phenotype; however, the function of Bicc1 is unknown. In this study, we establish an alternative, nonmammalian zebrafish model to study the role of Bicc1 in PKD pathogenesis. Antisense morpholinos were used to evaluate loss of Bicc1 function in zebrafish. The resulting morphants were examined histologically for kidney cysts and structural abnormalities. Immunostaining and fluorescent dye injection were used to evaluate pronephric cilia and kidney morphogenesis. Knockdown of zebrafish Bicc1 expression resulted in the formation of kidney cysts; however, defects in kidney structure or pronephric cilia were not observed. Importantly, expression of mouse Bicc1 rescues the cystic phenotype of the morphants. These results demonstrate that the function of Bicc1 in the kidney is evolutionarily conserved, thus supporting the use of zebrafish as an alternative in vivo model to study the role of mammalian Bicc1 in renal cyst formation.

  4. Acquired cystic kidney disease: an under-recognized condition in children with end-stage renal disease.

    Science.gov (United States)

    Chan, Eugene Y H; Warady, Bradley A

    2018-01-01

    Acquired cystic kidney disease (ACKD) is a condition that occurs predominantly in patients with end-stage renal disease (ESRD). In contrast to hereditary cystic kidney disease, ACKD is characterized by the presence of multiple small cysts in bilaterally small kidneys. Limited pediatric data suggest a high incidence (21.6-45.8%) of ACKD in children on dialysis, comparable to that in adults, with an increased frequency associated with a longer duration of dialysis. Recent research has shed light on the pathogenesis of ACKD, such as activation of proto-oncogenes. Although most patients with ACKD are asymptomatic, the condition can be complicated by renal cell carcinoma. Routine surveillance should therefore be considered in at-risk populations.

  5. Cystic hypersecretory carcinoma of the breast with paget disease of the nipple: a diagnostic challenge.

    Science.gov (United States)

    Sahoo, Sunati; Gopal, Purva; Roland, Lane; Pile, Nancy

    2008-04-01

    A unique case of cystic hypersecretory carcinoma in a 48-year-old woman who presented with a tender, palpable abnormality of the lower outer quadrant of her left breast in 2002 is described. Mammographic and ultrasound examinations showed heterogeneous, dense breast tissue with a focal asymmetric density and an ill-defined heterogenous hypoechoic area with anechoic spaces, respectively, that corresponded to the area of palpable abnormality. Although the imaging findings did not change significantly over 4 years, the patient complained of intermittent, spontaneous serous discharge from the left nipple and persistent induration and tenderness in the same area of the left breast. An ultrasound-guided core-needle biopsy of the lesion was performed at the last visit to rule out a malignant process. A left simple mastectomy showed a large multicystic lesion occupying most of the lower quadrants by a cystic hypersecretory carcinoma and Paget disease of the nipple.

  6. Cystic fibrosis-related liver disease: a single-center experience

    Directory of Open Access Journals (Sweden)

    Paula Catarino Costa

    2011-10-01

    Full Text Available Prospective studies concerning liver disease in pediatric cystic fibrosis patients are scarce. The present study aimed to describe the prevalence and clinical expression of cystic fibrosis - related liver disease, in a cohort of 62 pediatric patients. Descriptive study, resulting from the prospective evaluation, between 1994 and 2009, of 62 pediatric patients (age <18 years with cystic fibrosis. The follow-up protocol included a clinical assessment every 2 months, liver function tests every 6 months and annual liver ultrasonography. The cumulative prevalence of liver disease was 11.2% (7/62 cases. All patients had ΔF508 mutation and pancreatic insufficiency, none had meconium ileus. The liver involvement became clinically evident at a mean age of 8 years (3-15 years, revealed by hepatomegaly or hepatosplenomegaly (3 cases and/ or abnormalities of liver function tests (3 cases changes of liver ultrasound (7 cases with evidence of portal hypertension (2 cases. Four patients were submitted to liver biopsy; biliary fibrosis was documented in one case, focal biliary cirrhosis in 2 cases and multilobular cirrhosis in another case. Within a median 11.6 years follow-up period (all patients under UDCA therapy after liver disease diagnosis, progression of liver disease was observed in 2 patients; one patient developed refractory variceal bleeding and progressive hepatic failure, requiring liver transplant. The results of the present study agree with those of previous pediatric studies, further documenting clinical expression of liver disease in CF patients, which is usually detected in the first decade of life and emphasize the contribution of ultrasound to early diagnosis of liver involvement. Moreover, although advanced liver disease is a relatively rare event, early isolated liver transplantation may have to be considered at this age group.

  7. Cystic fibrosis-related liver disease: a single-center experience

    Science.gov (United States)

    Costa, Paula Catarino; Barreto, Celeste Canha; Pereira, Luisa; Lobo, Maria Luisa; Costa, Maria Adília; Lopes, Ana Isabel Gouveia

    2011-01-01

    Prospective studies concerning liver disease in pediatric cystic fibrosis patients are scarce. The present study aimed to describe the prevalence and clinical expression of cystic fibrosis - related liver disease, in a cohort of 62 pediatric patients. Descriptive study, resulting from the prospective evaluation, between 1994 and 2009, of 62 pediatric patients (age <18 years) with cystic fibrosis. The follow-up protocol included a clinical assessment every 2 months, liver function tests every 6 months and annual liver ultrasonography. The cumulative prevalence of liver disease was 11.2% (7/62 cases). All patients had ΔF508 mutation and pancreatic insufficiency, none had meconium ileus. The liver involvement became clinically evident at a mean age of 8 years (3–15 years), revealed by hepatomegaly or hepatosplenomegaly (3 cases) and/ or abnormalities of liver function tests (3 cases) changes of liver ultrasound (7 cases) with evidence of portal hypertension (2 cases). Four patients were submitted to liver biopsy; biliary fibrosis was documented in one case, focal biliary cirrhosis in 2 cases and multilobular cirrhosis in another case. Within a median 11.6 years follow-up period (all patients under UDCA therapy after liver disease diagnosis), progression of liver disease was observed in 2 patients; one patient developed refractory variceal bleeding and progressive hepatic failure, requiring liver transplant. The results of the present study agree with those of previous pediatric studies, further documenting clinical expression of liver disease in CF patients, which is usually detected in the first decade of life and emphasize the contribution of ultrasound to early diagnosis of liver involvement. Moreover, although advanced liver disease is a relatively rare event, early isolated liver transplantation may have to be considered at this age group. PMID:22053265

  8. Diffuse Cystic Lung Disease as the Presenting Manifestation of Sjögren Syndrome.

    Science.gov (United States)

    Gupta, Nishant; Wikenheiser-Brokamp, Kathryn A; Fischer, Aryeh; McCormack, Francis X

    2016-03-01

    Interstitial lung diseases, especially lymphoproliferative disorders such as follicular bronchiolitis and lymphoid interstitial pneumonia, are commonly seen in association with Sjögren syndrome. Although the predominant computed tomographic (CT) findings in patients with lymphoid interstitial pneumonia/follicular bronchiolitis include poorly defined centrilobular nodules and ground-glass attenuation, cystic changes can be seen in approximately two-thirds of these patients. The objective of this study was to define the clinical, radiological, and histopathological features of cyst-predominant lymphoid interstitial pneumonia/follicular bronchiolitis in patients with Sjögren syndrome. We present four patients who were referred to our institution with diffuse cystic changes on chest CT imaging. All four had a presumptive diagnosis of lymphangioleiomyomatosis but were subsequently found to have Sjögren syndrome. The diagnosis was established based on the clinical symptoms of xerostomia and xerophthalmia along with serologic detection of antinuclear antibodies, rheumatoid factor, anti-Sjögren's syndrome-related antigen A (SSA)/Ro antibodies, and anti-Sjögren's syndrome-related antigen B (SSB)/La antibodies. The cystic pattern associated with Sjögren syndrome had a characteristic appearance on chest CT images. Typical features included a wide variation in cyst size, internal structure within cysts, geographic simplification of parenchymal architecture producing a "dissolving lung appearance," perivascular and often basilar-predominant distribution, and frequent association with ground-glass opacities and nodules. In a compatible clinical context, we submit that these findings can be sufficiently distinctive to obviate the need for lung biopsy, even in the absence of confirmatory serological studies or lip biopsy. Clinicians should consider occult Sjögren syndrome in the differential diagnosis of patients presenting with idiopathic diffuse cystic lung disease.

  9. Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.

    Science.gov (United States)

    Ramsey, Bonnie W; Banks-Schlegel, Susan; Accurso, Frank J; Boucher, Richard C; Cutting, Garry R; Engelhardt, John F; Guggino, William B; Karp, Christopher L; Knowles, Michael R; Kolls, Jay K; LiPuma, John J; Lynch, Susan; McCray, Paul B; Rubenstein, Ronald C; Singh, Pradeep K; Sorscher, Eric; Welsh, Michael

    2012-04-15

    Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.

  10. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

    DEFF Research Database (Denmark)

    Heijerman, Harry; Westerman, Elsbeth; Conway, Steven

    2009-01-01

    review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics......In cystic fibrosis inhalation of drugs for the treatment of CF related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. In this European consensus document we...

  11. Octreotide reduces hepatic, renal and breast cystic volume in autosomal-dominant polycystic kidney disease.

    Science.gov (United States)

    Peces, Ramón; Cuesta-López, Emilio; Peces, Carlos; Pérez-Dueñas, Virginia; Vega-Cabrera, Cristina; Selgas, Rafael

    2011-06-01

    A 43-year-old woman with autosomal-dominant polycystic kidney disease (ADPKD) received octreotide for 12 months, and this was associated with a 6.3% reduction in liver volume, an 8% reduction in total kidney volume and stabilization of renal function. There was also a reduction of cyst size in fibrocystic disease of breast. These data suggest that the cyst fluid accumulation in different organs from patients with ADPKD is a dynamic process which can be reversed by octreotide. This is the first report of a case of simultaneous reduction in hepatic, renal and breast cystic volume with preservation of renal function in a patient with ADPKD receiving octreotide.

  12. Lung transplantation for advanced cystic lung disease due to nonamyloid kappa light chain deposits.

    Science.gov (United States)

    Hirschi, Sandrine; Colombat, Magali; Kessler, Romain; Reynaud-Gaubert, Martine; Stern, Marc; Chenard, Marie Pierre; Métivier, Anne-Cécile; Jeung, Mi-Young; Mal, Hervé

    2014-09-01

    Cystic lung light chain deposition disease (LCDD) is a severe and rare form of nonamyloid kappa light chain deposits localized in the lung, potentially leading to end-stage respiratory insufficiency. To assess the outcome after lung transplantation (LT) in this setting with particular attention to disease recurrence. We conducted a retrospective multicenter study of seven patients who underwent LT for cystic lung LCDD in France between September 1992 and June 2012 in five centers. In total, five females and two males (mean age, 39.1 ± 5.3 yr) underwent one single LT or seven double LT (one retransplantation). Before LT, the patients showed a constant obstructive ventilatory pattern with low carbon monoxide diffusing capacity and resting hypoxemia. Lung computed tomography revealed widespread cysts with occasional micronodulations. No extrapulmonary disease or plasma cell neoplasm was detected. The serum-free kappa/lambda light chain ratio was increased in three cases. The median follow-up after LT was 56 months (range, 1-110 mo). Kaplan-Meier survival was 85.7, 85.7, and 64.3% at 1, 3, and 5 years, respectively. Three patients died from multiorgan failure (n = 1), chronic rejection (n = 1), and breast cancer (n = 1) at 23 days, 56 months, and 96 months, respectively. At the end of follow-up, no patients showed recurrence on imaging or histopathology. This small case series confirms that cystic lung LCDD is a severe disease limited to the lung, affecting mostly young females. LT appears to be a good therapeutic option allowing for satisfactory long-term survival. We found no evidence of recurrence of the disease after LT.

  13. Impaired insulin signaling pathway in ovarian follicles of cows with cystic ovarian disease.

    Science.gov (United States)

    Hein, G J; Panzani, C G; Rodríguez, F M; Salvetti, N R; Díaz, P U; Gareis, N C; Benítez, G A; Ortega, H H; Rey, F

    2015-05-01

    Cystic ovarian disease (COD) is an important cause of infertility in dairy cattle. Follicular cell steroidogenesis and proliferation in ovulatory follicles is stimulated by hormones such as insulin and its necessary post-receptor response. The aim of this study was to determine the expression of insulin receptor (IR), IR substrate-1 (IRS1) and phosphatidylinositol 3-kinase (PI3K), key intermediates in the insulin pathway, in control cows and cows with spontaneous COD and ACTH-induced COD. IR and IRS1 mRNA levels were greater in granulosa cells and lower in follicular cysts than in control tertiary follicles. PI3K mRNA levels were similar in all follicles evaluated, whereas the expression of IR, IRS1 and PI3K was similar in theca cells. Protein expression of IR was higher in control tertiary follicles than in the same structures in animals with COD and with cysts. IRS1 and PI3K protein expression showed the same pattern in tertiary and cystic follicles. However, the protein expression of subunit alpha p85 of PI3K was greater in theca cells from tertiary follicles than in cystic follicles. These results provide new insights into the insulin response in cows with COD. The lower gene and protein expressions of some insulin downstream effectors at an early stage of the signaling pathway could negatively influence the functionality of ovaries and contribute to follicle persistence. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. [Rare case of congenital cystic adenomatoid malformation associated with polycystic kidney disease].

    Science.gov (United States)

    Jabłoński, Janusz; Jankowski, Zbigniew; Sitkiewicz, Anna; Lewandowska, Małgorzata; Andrzejewska, Ewa

    2011-01-01

    Congenital cystic adenomatoid malformation (CCAM) is a rare pulmonary abnormality that results from aberrant fetal lung development. It about 4-26% of cases it can be associated with other congenital abnormalities. We describe a case of congenital cystic adenomatoid malformation 2 associated with polycystic kidney disease. The association of these two congenital malformations is exceptional. Only four similar cases have been reported in the literature. A 2-year-old girl was referred to the Department of Paediatric Surgery and Oncology Medical University of Lodz with pneumonia and left pneumothorax. For three weeks prior to referral the patient was treated with antibiotics. Chest x-ray revealed hyperinflation of left upper lobe with mediastinal shift to right. Computer tomographic scan of the lung revealed multiple cyst in the left upper lobe, left-site pneumothorax and mediastinal shift to the right. The patient underwent thoracotomy. Intraoperatively, multiple cysts in the left upper lobe were found and left upper lobectomy was performed. Histologic study was compatible with type 2 congenital cystic adenomatoid malformation. Ultrasound examination showed multilocular cysts in both kidneys. The dimensions of the cysts were: MWR4. 54x45x45 mm and 25x21x24 mm on the left and right sides, respectively. Significant increase in cyst size on the left side was observed. Ten months after first hospitalization resection of the cystic lower pole of the left kidney was performed. The presence of even a single renal cyst in a child with CCAM is an indication for further follow up examinations.

  15. Adventitial cystic disease of the popliteal artery treated by bypass graft utilizing the short saphenous vein: A case report.

    Science.gov (United States)

    Miyake, Katsunori; Sawamura, Naoki; Ikegaya, Yuki; Isogai, Naoko; Kawachi, Jun; Shimoyama, Rai; Fukai, Ryuta; Kashiwagi, Hiroyuki; Ogino, Hidemitsu

    2017-01-01

    Adventitial cystic disease is relatively rare vascular disease, frequently occurred in the popliteal artery. No definitive treatment has been established yet. A 53-year-old woman presenting intermittent claudication of the right leg was diagnosed as adventitial cystic disease of popliteal artery. Percutaneous balloon dilation yielded an immediate recurrence. The disease was successfully treated by bypass grafting utilizing the short saphenous vein to replace the part of the popliteal artery containing the adventitial cyst. No postoperative complication was found six months after surgery. Comparing to a great saphenous vein, a short saphenous vein as a material of bypass graft has a significant advantage, as only a single surgical field is necessary. We propose that bypass graft surgery employing a short saphenous vein is worth considering as a treatment of adventitial cystic disease at the popliteal artery. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Assessing disease disclosure in adults with cystic fibrosis: the Adult Data for Understanding Lifestyle and Transitions (ADULT survey Disclosure of disease in adults with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Modi Avani C

    2010-09-01

    Full Text Available Abstract Background As more patients with cystic fibrosis (CF reach adulthood and participate in age-appropriate activities (e.g. employment, dating, disclosure of medical status becomes more important. This study assessed rates of disclosure and its perceived impact on relationships using the Adult Data for Understanding Lifestyle and Transitions (ADULT online survey. Methods Adults with CF participated in the survey via the United States national network of CF Centers. Descriptive and inferential statistics were utilized. Results Participants (n = 865 were more likely to disclose to relatives (94% and close friends (81% than to dating partners (73%, bosses/supervisors/teachers (51% or co-workers (39%. Respondents generally reported a neutral/positive effect on relationships following disclosure. Negative effects of disclosure were infrequent, but more likely with dating partners or bosses/supervisors/teachers. Results also indicated that disclosure may be influenced by severity of lung disease and gender, with those having normal/mild lung disease less likely to disclose their diagnosis to both co-workers (p Conclusions Most adults with CF disclosed their disease to relatives and close friends. Individuals with severe CF lung disease were more likely to disclose their diagnosis to coworkers and supervisors/teachers. It may be helpful to provide support for disclosure of disease in situations such as employment and dating.

  17. Kluyvera ascorbata infection in Cystic Fibrosis airway disease

    Directory of Open Access Journals (Sweden)

    Antonietta Lambiase

    2011-09-01

    Full Text Available Bacilli belonged to genus Kluyvera are Gram negative non-fermentative microorganisms described in the Enterobacteriaceae family, generally considered as saprophytes of the digestive tract.Their role in pathogenesis of infectious disease is unclear, but recently, they are emerged as a cause of clinically significant disease in no-CFpopulation and several anatomic sites are involved as urinary, respiratory and gastrointestinal tracts. In the present note, we describe the identification of Kluyvera ascorbata isolates, obtained from sputum samples of one CF patient (male, 10 years old. The note concerns a patient suffering from chronic obstructive bronchopulmonary disease and chronic Pseudomonas aeruginosa infection. Isolates showed a good growth on MacConkey agar and BCSA, after incubation at 37°C for 24-48 h and they were sensitive to several antibiotics, as cephalosporins, carbapenems, quinolones and trimethoprim-sulfamethoxazole. Clinical observation and the spirometric parameters early before and after isolation of microrganism did not show any worsening status in our patient. The selective pressure given by intensive use of antibiotics in CF patients increases susceptibility to infections by opportunistic microrganisms. Our report underlines the importance of careful bacterial identification and antimicrobial susceptibility study in defining the potential role of new pathogen bacteria in CF lung and to address possible therapeutic strategies that may help to guide antibiotic therapy regimes in CF patients.

  18. Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes

    Science.gov (United States)

    Ellsworth, Rachel E.; Jamison, D. Curtis; Touchman, Jeffrey W.; Chissoe, Stephanie L.; Braden Maduro, Valerie V.; Bouffard, Gerard G.; Dietrich, Nicole L.; Beckstrom-Sternberg, Stephen M.; Iyer, Leslie M.; Weintraub, Lauren A.; Cotton, Marc; Courtney, Laura; Edwards, Jennifer; Maupin, Rachel; Ozersky, Philip; Rohlfing, Theresa; Wohldmann, Patricia; Miner, Tracie; Kemp, Kimberley; Kramer, Jason; Korf, Ian; Pepin, Kimberlie; Antonacci-Fulton, Lucinda; Fulton, Robert S.; Minx, Patrick; Hillier, LaDeana W.; Wilson, Richard K.; Waterston, Robert H.; Miller, Webb; Green, Eric D.

    2000-01-01

    The identification of the cystic fibrosis transmembrane conductance regulator gene (CFTR) in 1989 represents a landmark accomplishment in human genetics. Since that time, there have been numerous advances in elucidating the function of the encoded protein and the physiological basis of cystic fibrosis. However, numerous areas of cystic fibrosis biology require additional investigation, some of which would be facilitated by information about the long-range sequence context of the CFTR gene. For example, the latter might provide clues about the sequence elements responsible for the temporal and spatial regulation of CFTR expression. We thus sought to establish the sequence of the chromosomal segments encompassing the human CFTR and mouse Cftr genes, with the hope of identifying conserved regions of biologic interest by sequence comparison. Bacterial clone-based physical maps of the relevant human and mouse genomic regions were constructed, and minimally overlapping sets of clones were selected and sequenced, eventually yielding ≈1.6 Mb and ≈358 kb of contiguous human and mouse sequence, respectively. These efforts have produced the complete sequence of the ≈189-kb and ≈152-kb segments containing the human CFTR and mouse Cftr genes, respectively, as well as significant amounts of flanking DNA. Analyses of the resulting data provide insights about the organization of the CFTR/Cftr genes and potential sequence elements regulating their expression. Furthermore, the generated sequence reveals the precise architecture of genes residing near CFTR/Cftr, including one known gene (WNT2/Wnt2) and two previously unknown genes that immediately flank CFTR/Cftr. PMID:10655503

  19. Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease.

    Science.gov (United States)

    Debray, Dominique; Kelly, Deirdre; Houwen, Roderick; Strandvik, Birgitta; Colombo, Carla

    2011-06-01

    Approximately 5-10% of cystic fibrosis (CF) patients develop multilobular cirrhosis during the first decade of life. Most CF patients later develop signs of portal hypertension with complications, mainly variceal bleeding. Liver failure usually occurs later, after the paediatric age. Annual screening for liver disease is recommended to detect pre-symptomatic signs and initiate ursodeoxycholic acid therapy, which might halt disease progression. Liver disease should be considered if at least two of the following variables are present: abnormal physical examination, persistently abnormal liver function tests and pathological ultrasonography. If there is diagnostic doubt, a liver biopsy is indicated. All CF patients with liver disease need annual follow-up to evaluate the development of cirrhosis, portal hypertension or liver failure. Management should focus on nutrition, prevention of bleeding and variceal decompression. Deterioration of pulmonary function is an important consideration for liver transplantation, particularly in children with hepatic dysfunction or advanced portal hypertension. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. What Are the Signs and Symptoms of Cystic Fibrosis?

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  1. Interaction between IGF1 and IGFBPs in bovine cystic ovarian disease

    OpenAIRE

    Rodríguez, Fernanda Mariel; Salvetti, Natalia Raquel; Colombero, M.; Stangaferro, M.; Barbeito, Claudio Gustavo; Ortega, Hugo Hector; Rey, Florencia

    2016-01-01

    Cystic ovarian disease (COD) is one of the main factors responsible for reproductive disorders in cattle. Although the pathogenesis and mechanism of cyst formation are not fully understood, it has been proposed that the IGF system could play an essential role, as it is a key intraovarian regulator. The aim of the present study was to determine whether the altered levels in IGF1 detected in bovines with COD are associated with changes at mRNA level or with differential modulation by IGFBPs. Th...

  2. Missense variants in CFTR nucleotide-binding domains predict quantitative phenotypes associated with cystic fibrosis disease severity.

    Science.gov (United States)

    Masica, David L; Sosnay, Patrick R; Raraigh, Karen S; Cutting, Garry R; Karchin, Rachel

    2015-04-01

    Predicting the impact of genetic variation on human health remains an important and difficult challenge. Often, algorithmic classifiers are tasked with predicting binary traits (e.g. positive or negative for a disease) from missense variation. Though useful, this arrangement is limiting and contrived, because human diseases often comprise a spectrum of severities, rather than a discrete partitioning of patient populations. Furthermore, labeling variants as causal or benign can be error prone, which is problematic for training supervised learning algorithms (the so-called garbage in, garbage out phenomenon). We explore the potential value of training classifiers using continuous-valued quantitative measurements, rather than binary traits. Using 20 variants from cystic fibrosis transmembrane conductance regulator (CFTR) nucleotide-binding domains and six quantitative measures of cystic fibrosis (CF) severity, we trained classifiers to predict CF severity from CFTR variants. Employing cross validation, classifier prediction and measured clinical/functional values were significantly correlated for four of six quantitative traits (correlation P-values from 1.35 × 10(-4) to 4.15 × 10(-3)). Classifiers were also able to stratify variants by three clinically relevant risk categories with 85-100% accuracy, depending on which of the six quantitative traits was used for training. Finally, we characterized 11 additional CFTR variants using clinical sweat chloride testing, two functional assays, or all three diagnostics, and validated our classifier using blind prediction. Predictions were within the measured sweat chloride range for seven of eight variants, and captured the differential impact of specific variants on the two functional assays. This work demonstrates a promising and novel framework for assessing the impact of genetic variation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Modifying disease in cystic fibrosis: current and future therapies on the horizon.

    Science.gov (United States)

    Ong, Thida; Ramsey, Bonnie W

    2013-11-01

    Recent therapies directed at proximal targets within cystic fibrosis (CF) pathophysiology hold potential to modulate disease. This review highlights recent clinical trials and future therapies focused on these early steps of disease. Recent approval of a CF transmembrane conductance regulator (CFTR) protein modulator, ivacaftor (Kalydeco), has ignited a wave of investigations for other modulators directed at CFTR mutation classes. Gene replacement therapy continues to be pursued at a slower pace in early phase clinical trials. Airway surface liquid strategies such as dry-powder mannitol and alternate ion channel regulation are discussed as genotype-independent methods of early modulation. The breadth of therapies for early targets of CF holds considerable hope to modify the natural history of this disease. Ongoing focus to develop novel markers of early disease state is paramount. The progress of drug development requires concurrent attention on a spectrum of targets to achieve maximal impact.

  4. Relating the disease mutation spectrum to the evolution of the cystic fibrosis transmembrane conductance regulator (CFTR.

    Directory of Open Access Journals (Sweden)

    Lavanya Rishishwar

    Full Text Available Cystic fibrosis (CF is the most common genetic disease among Caucasians, and accordingly the cystic fibrosis transmembrane conductance regulator (CFTR protein has perhaps the best characterized disease mutation spectrum with more than 1,500 causative mutations having been identified. In this study, we took advantage of that wealth of mutational information in an effort to relate site-specific evolutionary parameters with the propensity and severity of CFTR disease-causing mutations. To do this, we devised a scoring scheme for known CFTR disease-causing mutations based on the Grantham amino acid chemical difference matrix. CFTR site-specific evolutionary constraint values were then computed for seven different evolutionary metrics across a range of increasing evolutionary depths. The CFTR mutational scores and the various site-specific evolutionary constraint values were compared in order to evaluate which evolutionary measures best reflect the disease-causing mutation spectrum. Site-specific evolutionary constraint values from the widely used comparative method PolyPhen2 show the best correlation with the CFTR mutation score spectrum, whereas more straightforward conservation based measures (ConSurf and ScoreCons show the greatest ability to predict individual CFTR disease-causing mutations. While far greater than could be expected by chance alone, the fraction of the variability in mutation scores explained by the PolyPhen2 metric (3.6%, along with the best set of paired sensitivity (58% and specificity (60% values for the prediction of disease-causing residues, were marginal. These data indicate that evolutionary constraint levels are informative but far from determinant with respect to disease-causing mutations in CFTR. Nevertheless, this work shows that, when combined with additional lines of evidence, information on site-specific evolutionary conservation can and should be used to guide site-directed mutagenesis experiments by more narrowly

  5. Involvement of PAPP-A and IGFR1 in Cystic Ovarian Disease in Cattle.

    Science.gov (United States)

    Rodríguez, F M; Colombero, M; Amweg, A N; Huber, E; Gareis, N C; Salvetti, N R; Ortega, H H; Rey, F

    2015-08-01

    Cystic ovarian disease (COD) is one of the main causes of infertility in dairy cattle. It has been shown that intra-ovarian factors, such as members of the insulin-like growth factor (IGF) system, may contribute to follicular persistence. The bioavailability of IGF to initiate its response by binding to specific receptors (IGFRs) depends on interactions with related compounds, such as pregnancy-associated plasma protein A (PAPP-A). The aim of this study was to determine IGFR1 and PAPP-A expression both in follicles at different stages of development and in cysts, to evaluate the roles in the etiopathogenesis of COD in cattle. The mRNA expression of PAPP-A was higher in granulosa cells of large tertiary follicles than in cysts, whereas the protein PAPP-A present in the follicular fluid from these follicles showed no differences. Although no PAPP-A mRNA expression was detected in smaller tertiary follicles, in their follicular fluid, this protease was detected in lesser concentration than in cysts. The mRNA expression of IGFR1 was lower in granulosa cells from cystic follicles than in those from tertiary ones. However, the protein expression of this receptor presented the highest levels in cystic structures, probably to increase the possibility of IGF response. The data obtained would indicate that animals with COD have an altered regulation of the IGF system in the ovary, which could be involved in the pathogenesis of this disease in cattle. © 2015 Blackwell Verlag GmbH.

  6. Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis.

    Science.gov (United States)

    Lands, Larry C; Stanojevic, Sanja

    2016-04-07

    flow (25-75%) mean difference 1.80 (95% confidence interval 0.15 to 3.45). The post-hoc analysis of data from two trials split by age showed a statistically significant slower rate of annual decline of percent predicted forced expiratory volume in one second and forced vital capacity in the ibuprofen group in younger children, mean difference 1.41% (95% confidence interval 0.03 to 2.80) and mean difference 1.32% (95% confidence interval 0.04 to 2.60) respectively. In one trial, long-term use of high-dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported, but the power of the trials to identify clinically important differences in the incidence of adverse effects was low.We did not have any concerns with regards to risk of bias for the trial comparing piroxicam to placebo. However, the trial did not report many data in a form that we could analyse in this review. No data were available for the review's primary outcome of lung function; available data for hospital admissions showed no difference between the groups. No analysable data were available for any other review outcome. High-dose ibuprofen can slow the progression of lung disease in people with cystic fibrosis, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with cystic fibrosis.

  7. Management dilemma; a woman with cystic fibrosis and severe lung disease presenting with colonic carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Lees Andrea N

    2008-12-01

    Full Text Available Abstract Introduction There are increasing reports of bowel cancer in cystic fibrosis, suggesting a possible causal link. Individuals with cystic fibrosis who have advanced lung disease present a high operative risk, limiting curative treatment options in early bowel malignancy. Case presentation We describe a 41-year-old Caucasian woman with cystic fibrosis and severe lung disease who had been considered for lung transplantation, who presented with rectal bleeding and was found to have a Stage I adenocarcinoma of the sigmoid colon. After considerable discussion as to the operative risks, she underwent a laparoscopic resection and remains relatively well 1 year postoperatively with no recurrence. Conclusion We discuss the complexity of the management decisions for cystic fibrosis patients with severe lung disease and early stage colonic malignancy, particularly in the context of potential need for lung transplantation. The case demonstrates that cystic fibrosis patients with very severe lung function impairment may undergo laparoscopic abdominal surgical interventions without compromising postoperative airway clearance.

  8. Lung Clearance Index and Structural Lung Disease on Computed Tomography in Early Cystic Fibrosis.

    Science.gov (United States)

    Ramsey, Kathryn A; Rosenow, Tim; Turkovic, Lidija; Skoric, Billy; Banton, Georgia; Adams, Anne-Marie; Simpson, Shannon J; Murray, Conor; Ranganathan, Sarath C; Stick, Stephen M; Hall, Graham L

    2016-01-01

    The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. It has been suggested as a surrogate for chest computed tomography to detect structural lung abnormalities in individuals with cystic fibrosis (CF); however, the associations between lung clearance index and early structural lung disease are unclear. We assessed the ability of the lung clearance index to reflect structural lung disease on the basis of chest computed tomography across the entire pediatric age range. Lung clearance index was assessed in 42 infants (ages 0-2 yr), 39 preschool children (ages 3-6 yr), and 38 school-age children (7-16 yr) with CF before chest computed tomography and in 72 healthy control subjects. Scans were evaluated for CF-related structural lung disease using the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis quantitative outcome measure. In infants with CF, lung clearance index is insensitive to structural disease (κ = -0.03 [95% confidence interval, -0.05 to 0.16]). In preschool children with CF, lung clearance index correlates with total disease extent. In school-age children, lung clearance index correlates with extent of total disease, bronchiectasis, and air trapping. In preschool and school-age children, lung clearance index has a good positive predictive value (83-86%) but a poor negative predictive value (50-55%) to detect the presence of bronchiectasis. These data suggest that lung clearance index may be a useful surveillance tool to monitor structural lung disease in preschool and school-age children with CF. However, lung clearance index cannot replace chest computed tomography to screen for bronchiectasis in this population.

  9. Cystic nodal metastasis in patients with oropharyngeal squamous cell carcinoma receiving chemoradiotherapy: Relationship with human papillomavirus status and failure patterns.

    Directory of Open Access Journals (Sweden)

    Yu-Han Huang

    Full Text Available We investigated the relationships of cystic nodal metastasis, human papillomavirus (HPV status, and treatment failure patterns in patients with oropharyngeal squamous cell carcinoma (OPSCC treated with chemoradiotherapy.We retrospectively reviewed pretreatment MRI and clinical courses of patients with OPSCC whose tumors were tested for HPV-induced p16 expression via immunohistochemistry and who completed chemoradiotherapy. Cervical cystic nodal metastasis and necrotic nodal metastasis were classified on MRI.Of 98 patients eligible for analysis, 33 were p16-positive. Cystic nodal metastasis was significantly more prevalent in p16-positive than in p16-negative patients (39.4% versus 18.5%, respectively; p = 0.025. Necrotic nodal metastasis was significantly more prevalent in p16-negative than in p16-positive patients (73.8% versus 51.5%, respectively; p = 0.027. On multivariate analysis, necrotic nodal metastasis (odds ratio [OR] = 7.310, p = 0.011 was an independent predictor of regional failure, while advanced nodal stage (OR = 4.119, p = 0.022 and cystic nodal metastases (OR = 0.087, p = 0.026 were independent positive and negative predictors of distant failure, respectively.Cervical cystic and necrotic nodal metastases are associated with HPV-induced p16-positive and p16-negative OPSCC, respectively. Patients with necrotic nodal metastasis at presentation have an increased risk of regional failure. Distant failure is directly and inversely correlated with advanced nodal stage and cystic nodal metastasis, respectively.

  10. The clinical burden of human cystic echinococcosis in Palestine, 2010-2015.

    Science.gov (United States)

    Al-Jawabreh, Amer; Ereqat, Suheir; Dumaidi, Kamal; Nasereddin, Abdelmajeed; Al-Jawabreh, Hanan; Azmi, Kifaya; Al-Laham, Nahed; Nairat, Moath; Casulli, Adriano; Maqboul, Husni; Abdeen, Ziad

    2017-07-01

    Cystic echinococcosis (CE) is classified by the WHO as a neglected disease inflicting economic losses on the health systems of many countries worldwide. The aim of this case-series study was to investigate the burden of human CE in Palestine during the period between 2010 and 2015. Records of surgically confirmed CE patients from 13 public and private hospitals in the West Bank and Gaza Strip were reviewed. Patients' cysts were collected from surgical wards and formalin-fixed paraffin-embedded (FFPE) blocks were collected from histopathology departments. Molecular identification of CE species /genotypes was conducted by targeting a repeat DNA sequence (EgG1 Hae III) within Echinococcus nuclear genome and a fragment within the mitochondrial cytochrome c oxidase subunit 1, (CO1). Confirmation of CE species/genotypes was carried out using sequencing followed by BLAST analysis and the construction of maximum likelihood consensus dendrogram. CE cases were map-spotted and statistically significant foci identified by spatial analysis. A total of 353 CE patients were identified in 108 localities from the West Bank and Gaza Strip. The average surgical incidence in the West Bank was 2.1 per 100,000. Spot-mapping and purely spatial analysis showed 13 out of 16 Palestinian districts had cases of CE, of which 9 were in the West Bank and 4 in Gaza Strip. Al-Khalil and Bethlehem were statistically significant foci of CE in Palestine with a six-year average incidence of 4.2 and 3.7 per 100,000, respectively. To the best of our knowledge, this is the first confirmation of human CE causative agent in Palestine. This study revealed that E. granulosus sensu stricto (s.s.) was the predominating species responsible for CE in humans with 11 samples identified as G1 genotype and 2 as G3 genotype. This study emphasizes the need for a stringent surveillance system and risk assessment studies in the rural areas of high incidence as a prerequisite for control measures.

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

    Science.gov (United States)

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

    2013-12-14

    Cystic fibrosis (CF) causes chronic infections in the respiratory tract and alters the digestive tract. This paper reviews the most important aspects of drug treatment and changes in the digestive tract of patients with CF. This is a review of the literature, emphasizing the discoveries made within the last 15 years by analyzing scientific papers published in journals indexed in the Scientific Electronic Library Online, Sciences Information, United States National Library of Medicine and Medical Literature Analysis and Retrieval System Online databases, both in English and Portuguese, using the key words: cystic fibrosis, medication, therapeutic, absorption, digestion. Randomized, observational, experimental, and epidemiological clinical studies were selected, among others, with statistical significance of 5%. This review evaluates the changes found in the digestive tract of CF patients including pancreatic insufficiency, constipation and liver diseases. Changes in nutritional status are also described. Clinical treatment, nutritional supplementation and drug management were classified in this review as essential to the quality of life of CF patients, and became available through public policies for monitoring and treating CF. The information gathered on CF and a multi professional approach to the disease is essential in the treatment of these patients.

  12. Cohort study of women at risk for breast cancer and gross cystic disease.

    Science.gov (United States)

    Chun, Jennifer; Joseph, Kathie-Ann; El-Tamer, Mahmoud; Rundle, Andrew; Jacobson, Judith; Schnabel, Freya

    2005-10-01

    Gross cystic disease (GCD) is a common benign breast condition. Previous studies have reported conflicting results regarding the relationship of GCD and subsequent risk of developing breast cancer. This cohort study was conducted to investigate the association of GCD and breast cancer among women at high risk for breast cancer. The Women At Risk Registry provided the study population. The variables of interest included age at enrollment, age at breast cancer diagnosis, body mass index (BMI), presence of lobular carcinoma in situ (LCIS), and Gail scores. Statistical significance was determined by calculating multivariable-adjusted rate ratios using Cox proportional hazards regression model with years of follow-up as the time scale. The study population included 1317 high-risk women, including 363 (28%) with GCD. The mean follow-up was 5.9 years for the GCD cohort, and 5.1 years for the non-GCD cohort (P breast cancer (P breast cancer; 28 (35%) out of the 79 had a prior history of GCD. Results from the Cox proportional hazards regression model showed a nonstatistically significant association of GCD and breast cancer (hazard ratio = 1.48, 95% confidence interval 0.88-2.51). The Kaplan-Meier overall survival estimate between the exposed and unexposed groups indicate that there are no differences in overall survival between the 2 groups (P = .5). These results do not support the contention that gross cystic disease is a significant risk factor for breast cancer.

  13. Altered Expression of Pro-inflammatory Cytokines in Ovarian Follicles of Cows with Cystic Ovarian Disease.

    Science.gov (United States)

    Baravalle, M E; Stassi, A F; Velázquez, M M L; Belotti, E M; Rodríguez, F M; Ortega, H H; Salvetti, N R

    2015-01-01

    A growing body of evidence suggests that ovulation shares many of the features of an inflammatory reaction and that cytokines play many diverse and important roles in reproductive biology. The aim of this study was to examine the expression of the pro-inflammatory cytokines interleukin (IL)-1α, IL-6 and tumour necrosis factor (TNF)-α in ovarian cells from cows with cystic ovarian disease (COD) as compared with that in ovarian structures from regularly cycling cows. Expression of genes encoding IL-1α, IL-6 and TNF-α was detected by real-time polymerase chain reaction in follicular cells from ovaries from healthy cows and cows with COD with no significant differences. However, immunohistochemistry showed increased expression of IL-1α, IL-6 and TNF-α in cystic follicles, suggesting that this expression may be related to the persistence of follicular cysts. The effect of COD was evident for IL-1α and TNF-α, and a follicular structure-disease interaction was observed in the expression of all the cytokines evaluated. Thus, altered expression of these proinflammatory cytokines may be related to ovulation failure and development of follicular cysts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. A CYSTIC-FIBROSIS MUTATION ASSOCIATED WITH MILD LUNG-DISEASE

    NARCIS (Netherlands)

    GAN, KH; VEEZE, HJ; VANDENOUWELAND, AMW; HALLEY, DJJ; SCHEFFER, H; VANDERHOUT, A; OVERBEEK, SE; DEJONGSTE, JC; BAKKER, W; HEIJERMAN, HGM

    1995-01-01

    Background. Cystic fibrosis is the most common lethal autosomal recessive disorder among whites. Among Dutch patients with cystic fibrosis, Delta F508 is the most common mutation and A455E the second most common mutation of the cystic fibrosis transmembrane conductance regulator gene on chromosome

  15. Evaluation of factors related to bone disease in Polish children and adolescents with cystic fibrosis.

    Science.gov (United States)

    Sands, Dorota; Mielus, Monika; Umławska, Wioleta; Lipowicz, Anna; Oralewska, Beata; Walkowiak, Jarosław

    2015-09-01

    The aim of the study was to evaluate factors related to bone formation and resorption in Polish children and adolescents with cystic fibrosis and to examine the effect of nutritional status, biochemical parameters and clinical status on bone mineral density. The study group consisted of 100 children and adolescents with cystic fibrosis with a mean age 13.4 years old. Anthropometric measurements, included body height, body mass and body mass index (BMI); bone mineral densitometry and biochemical testing were performed. Bone mineral density was measured using a dual-energy X-ray absorption densitometer. Biochemical tests included serum calcium, phosphorus, parathyroid hormone and vitamin D concentrations, as well as 24-h urine calcium and phosphorus excretion. Pulmonary function was evaluated using FEV1%, and clinical status was estimated using the Shwachman-Kulczycki score. Standardized body height, body mass and BMI were significantly lower than in the reference population. Mean serum vitamin D concentration was decreased. Pulmonary disease was generally mild, with a mean FEV1% of 81%. Multivariate linear regression revealed that the only factors that had a significant effect on bone marrow density were BMI and FEV1%. There were no significant correlations between bone mineral density and the results of any of the biochemical tests performed. Nutritional status and bone mineral density were significantly decreased in children and adolescents with cystic fibrosis. In spite of abnormalities in biochemical testing, the factors that were found to have the strongest effect on bone mineral density were standardized BMI and clinical status. Copyright © 2015. Published by Elsevier Urban & Partner Sp. z o.o.

  16. Loss of Glis2/NPHP7 causes kidney epithelial cell senescence and suppresses cyst growth in the Kif3a mouse model of cystic kidney disease.

    Science.gov (United States)

    Lu, Dongmei; Rauhauser, Alysha; Li, Binghua; Ren, Chongyu; McEnery, Kayla; Zhu, Jili; Chaki, Moumita; Vadnagara, Komal; Elhadi, Sarah; Jetten, Anton M; Igarashi, Peter; Attanasio, Massimo

    2016-06-01

    Enlargement of kidney tubules is a common feature of multiple cystic kidney diseases in humans and mice. However, while some of these pathologies are characterized by cyst expansion and organ enlargement, in others, progressive interstitial fibrosis and kidney atrophy prevail. The Kif3a knockout mouse is an established non-orthologous mouse model of cystic kidney disease. Conditional inactivation of Kif3a in kidney tubular cells results in loss of primary cilia and rapid cyst growth. Conversely, loss of function of the gene GLIS2/NPHP7 causes progressive kidney atrophy, interstitial inflammatory infiltration, and fibrosis. Kif3a null tubular cells have unrestrained proliferation and reduced stabilization of p53 resulting in a loss of cell cycle arrest in the presence of DNA damage. In contrast, loss of Glis2 is associated with activation of checkpoint kinase 1, stabilization of p53, and induction of cell senescence. Interestingly, the cystic phenotype of Kif3a knockout mice is partially rescued by genetic ablation of Glis2 and pharmacological stabilization of p53. Thus, Kif3a is required for cell cycle regulation and the DNA damage response, whereas cell senescence is significantly enhanced in Glis2 null cells. Hence, cell senescence is a central feature in nephronophthisis type 7 and Kif3a is unexpectedly required for efficient DNA damage response and cell cycle arrest. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  17. Diagnostic and therapeutic challenges of an ambiguous cystic kidney disease in a resource limited setting: a case report.

    Science.gov (United States)

    Dimala, Christian Akem; Bechem, Ndemazie Nkafu; Kadia, Benjamin Momo; Feteh, Vitalis Fambombi; Choukem, Simeon Pierre

    2017-03-01

    Unilateral renal cystic disease is a rare condition that shares morphological similarities with multicystic dysplastic kidney, the former often distinguished from the latter on some clinical and histopathological grounds. However serious diagnostic and therapeutic dilemmas set in when there is a considerable overlap in the distinguishing features between these entities. A 19-year-old African female presented with a chronic severe debilitating right lower quadrant abdominal pain refractory to analgesics. Biochemical investigations and imaging studies revealed a non-functional polycystic right kidney and no identifiable pelvicalyceal system or ureter but with preserved renal function. The marked overlap in clinical presentation between unilateral renal cystic disease and multicystic dysplastic kidney in this patient necessitated further investigation to pose an appropriate diagnosis. A right nephrectomy was performed and histopathological analysis of the resected kidney done, the results of which were more consistent with unilateral renal cystic disease. The post-operative course was favorable. Unilateral renal cystic disease with an ipsilateral non-functional kidney and an atretic pelvicalyceal system is a very rare condition that needs to be distinguished from multicystic dysplastic kidney in order to guide management and set prognosis. A suspicion of either of these diseases therefore warrants a thorough clinical evaluation and the appropriate combination of biochemical and imaging investigations.

  18. Transcriptional Activation of Mucin by Pseudomonas aeruginosa Lipopolysaccharide in the Pathogenesis of Cystic Fibrosis Lung Disease

    Science.gov (United States)

    Li, Jian-Dong; Dohrman, Austin F.; Gallup, Marianne; Miyata, Susumu; Gum, James R.; Kim, Young S.; Nadel, Jay A.; Prince, Alice; Basbaum, Carol B.

    1997-02-01

    An unresolved question in cystic fibrosis (CF) research is how mutations of the CF transmembrane conductance regulator, a CI ion channel, cause airway mucus obstruction leading to fatal lung disease. Recent evidence has linked the CF transmembrane conductance regulator mutation to the onset and persistence of Pseudomonas aeruginosa infection in the airways, and here we provide evidence directly linking P. aeruginosa infection to mucus overproduction. We show that P. aeruginosa lipopolysaccharide profoundly upregulates transcription of the mucin gene MUC 2 in epithelial cells via inducible enhancer elements and that this effect is blocked by the tyrosine kinase inhibitors genistein and tyrphostin AG 126. These findings improve our understanding of CF pathogenesis and suggest that the attenuation of mucin production by lipopolysaccharide antagonists and tyrosine kinase inhibitors could reduce morbidity and mortality in this disease.

  19. [The spectrum of cystic kidney disease in adulthood: differential diagnosis and complications].

    Science.gov (United States)

    Peces, R; Costero, O

    2003-01-01

    Simple renal cysts are the most common renal masses, accounting for roughly 65 to 70% of cases. They most often occur in patients over the age of 50 as determined from post-mortem examination or renal ultrasonography. The major concern with simple renal cysts is differentiating them from more serious disorders, such as polycystic kidney disease and solid masses such as a renal carcinoma or abscess. Renal arteriovenous malformations may present with ultrasound picture mimicking simple parapelvic cyst. Ultrasound, doppler ultrasound, computed tomography and magnetic resonance imaging are effective in documenting the underlying lesions non-invasively. Arteriography may be useful to characterise vascular lesion. We report here the spectrum of cystic kidney disease in adulthood in a group of patient with different disorders. The differential diagnosis, complications and associated process are discussed.

  20. Very mild disease phenotype of congenic CftrTgH(neoimHgu cystic fibrosis mice

    Directory of Open Access Journals (Sweden)

    Leonhard-Marek Sabine

    2008-04-01

    Full Text Available Abstract Background A major boost to cystic fibrosis disease research was given by the generation of various mouse models using gene targeting in embryonal stem cells. Moreover, the introduction of the same mutation on different inbred strains generating congenic strains facilitated the search for modifier genes. From the original CftrTgH(neoimHgu mouse model with a divergent genetic background (129/Sv, C57BL/6, HsdOla:MF1 two inbred mutant mouse strains CF/1-CftrTgH(neoimHgu and CF/3-CftrTgH(neoimHgu had been generated using strict brother × sister mating. CF/1-CftrTgH(neoimHgu and CF/3-CftrTgH(neoimHgu mice were fertile and showed normal growth and lifespan. In this work the CftrTgH(neoimHgu insertional mutation was backcrossed from CF/3-CftrTgH(neoimHgu onto the inbred backgrounds C57BL/6J and DBA/2J generating congenic animals in order to clarify the differential impact of the Cftr mutation and the genetic background on the disease phenotype of the cystic fibrosis mutant mice. Clinical and electrophysiological features of the two congenic strains were compared with those of CF/1-CftrTgH(neoimHgu and CF/3-CftrTgH(neoimHgu and wild type controls. Results Under the standardized housing conditions of the animal facility, the four mouse strains CF/1-CftrTgH(neoimHgu, CF/3-CftrTgH(neoimHgu, D2.129P2(CF/3-CftrTgH(neoimHgu and B6.129P2(CF/3-CftrTgH(neoimHgu exhibited normal life expectancy. Growth of congenic cystic fibrosis mice was comparable with that of wild type controls. All mice but D2.129P2(CF/3-CftrTgH(neoimHgu females were fertile. Short circuit current measurements revealed characteristic response profiles of the HsdOla:MF1, DBA/2J and C57BL/6J backgrounds in nose, ileum and colon. All cystic fibrosis mouse lines showed the disease-typical hyperresponsiveness to amiloride in the respiratory epithelium. The mean chloride secretory responses to carbachol or forskolin were 15–100% of those of the cognate wild type control animals

  1. Interaction between IGF1 and IGFBPs in bovine cystic ovarian disease.

    Science.gov (United States)

    Rodríguez, F M; Salvetti, N R; Colombero, M; Stangaferro, M L; Barbeito, C G; Ortega, H H; Rey, F

    2013-07-01

    Cystic ovarian disease (COD) is one of the main factors responsible for reproductive disorders in cattle. Although the pathogenesis and mechanism of cyst formation are not fully understood, it has been proposed that the IGF system could play an essential role, as it is a key intraovarian regulator. The aim of the present study was to determine whether the altered levels in IGF1 detected in bovines with COD are associated with changes at mRNA level or with differential modulation by IGFBPs. The mRNA levels of the IGF components studied were analyzed by real time PCR and in situ hybridization, and IGFBP expression and activity were assayed by immunohistochemistry and ligand blot, respectively. Results showed a decreased IGF1 mRNA level due to a lower granulosa cell gene expression in cystic follicles (Pfollicular fluid, and suggest that IGFBP3 is a key regulator of intrafollicular IGF1 in animals with COD. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. UP-TO-DATE MANAGEMENT OF LUNG DISEASE IN CHILDREN AND ADOLESCENTS WITH CYSTIC FIBROSIS

    Directory of Open Access Journals (Sweden)

    Marina Praprotnik

    2015-04-01

    Full Text Available Cystic fibrosis (CF is a multi-organ disease,  affecting mostly lungs and gastrointestinal tract. Data from patient registries show that the survival of patients with CF has progressively improved over the past several decades, as a result of advances in antibiotic treatment, supplementation of pancreatic enzymes, better nutrition and a holistic approach to treatment in CF centres.The purpose of this review is to survey recent developments in the treatment of lung disease  in children and adolescents with CF.We describe newborn screening for CF.When chronic respiratory insufficiency occurs, lung transplantation becomes a very important issue.Lung disease is the most common cause of morbidity and mortality in CF patients. Emerging new therapies are targeted at all points in the pathogenesis of lung disease, from drugs that treat infection and inflammation in the airways to gene transfer studies  and to drugs that augment airway surface liquid height. A number of antibacterial agents formulated for inhalation are at various stages of study and there are several anti-inflammatory candidate drugs in  clinical trials.  The most important development  in the recent years is  modulation of the abnormal protein that causes CF, the cystic fibrosis transmembrane regulator (CFTR, where drugs are targeted at specific defects in the transcription, processing or functioning.When chronic respiratory insufficiency occurs, lung transplantation becomes a very important issue. The role of the CF nurse, who has responsibilities in educating and teaching clinical skills to patients and families, is described.

  3. Parent knowledge of disease management in cystic fibrosis: Assessing behavioral treatment management.

    Science.gov (United States)

    Nicolais, Christina J; Bernstein, Ruth; Riekert, Kristin A; Quittner, Alexandra L

    2018-02-01

    Cystic fibrosis (CF) is a life-shortening, burdensome disease requiring complex knowledge to manage the disease. Significant gaps in knowledge have been documented for parents, which may lead to unintentionally poor adherence and insufficient transfer of treatment responsibility from parents to adolescents. There are no current, validated measures of parent knowledge for this population and there are no measures that assess the knowledge required for day-to-day behavioral management of CF. We assessed the psychometric properties of the parent version of the Knowledge of Disease Management-Cystic Fibrosis measure (KDM-CF-P) using data from iCARE (I Change Adherence and Raise Expectations), a randomized control adherence intervention trial. A total of 196 parents in the iCARE standard care/control arm completed 35 items assessing their knowledge of disease management at their 12-month study visit, prior to beginning the intervention. Items were eliminated from the measure if they met the threshold for ceiling effects, were deemed clinically irrelevant, or did not correlate well with their intended scale. Item-to-total correlations, confirmatory factor analysis, discriminant function, reliability, and convergent validity were calculated. The KDM-CF-P (19 items) demonstrated internal consistency of KR20 = 0.60 on each scale and a two-scale structure. Convergent validity for knowledge scores was found with maternal education, family income, and type of medical insurance. Parents correctly answered approximately 85% of items on the KDM-CF-P. The KDM-CF-P psychometrics support a two-scale measure with clinical utility. It is useful for assessing gaps in knowledge that can be remediated through individualized, tailored interventions. © 2017 Wiley Periodicals, Inc.

  4. Overexpression of RANKL in osteoblasts: a possible mechanism of susceptibility to bone disease in cystic fibrosis.

    Science.gov (United States)

    Delion, Martial; Braux, Julien; Jourdain, Marie-Laure; Guillaume, Christine; Bour, Camille; Gangloff, Sophie; Pimpec-Barthes, Françoise Le; Sermet-Gaudelus, Isabelle; Jacquot, Jacky; Velard, Frédéric

    2016-09-01

    Bone fragility and loss are a significant cause of morbidity in patients with cystic fibrosis (CF), and the lack of effective therapeutic options means that treatment is more often palliative rather than curative. A deeper understanding of the pathogenesis of CF-related bone disease (CFBD) is necessary to develop new therapies. Defective CF transmembrane conductance regulator (CFTR) protein and chronic inflammation in bone are important components of the CFBD development. The receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) drive the regulation of bone turnover. To investigate their roles in CFBD, we evaluated the involvement of defective CFTR in their production level in CF primary human osteoblasts with and without inflammatory stimulation, in the presence or not of pharmacological correctors of the CFTR. No major difference in cell ultrastructure was noted between cultured CF and non-CF osteoblasts, but a delayed bone matrix mineralization was observed in CF osteoblasts. Strikingly, resting CF osteoblasts exhibited strong production of RANKL protein, which was highly localized at the cell membrane and was enhanced in TNF (TNF-α) or IL-17-stimulated conditions. Under TNF stimulation, a defective response in OPG production was observed in CF osteoblasts in contrast to the elevated OPG production of non-CF osteoblasts, leading to an elevated RANKL-to-OPG protein ratio in CF osteoblasts. Pharmacological inhibition of CFTR chloride channel conductance in non-CF osteoblasts replicated both the decreased OPG production and the enhanced RANKL-to-OPG ratio. Interestingly, using CFTR correctors such as C18, we significantly reduced the production of RANKL by CF osteoblasts, in both resting and TNF-stimulated conditions. In conclusion, the overexpression of RANKL and high membranous RANKL localization in osteoblasts are related to defective CFTR, and may worsen bone resorption, leading to bone loss in patients with CF. Targeting

  5. Medullary cystic disease of the kidney: report of a case diagnosed by ultrasonography and computed tomography examinations; Doenca cistica medular do rim: relato de um caso diagnosticado por ultra-sonografia e tomografia computadorizada

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Tarcisio Nunes; Araujo Junior, Cyrillo Rodrigues de; Fraguas Filho, Sergio Roberto; Costa, Marlos Augusto Bittencourt; Teixeira, Kim-Ir-Sen Santos [Goias Univ., Goiania, GO (Brazil). Hospital de Clinicas. Dept. de Diagnostico por Imagem]. E-mail: Tracisionunes@hotmail.com.br; Ribeiro, Flavia Aparecida de Souza [Goias Univ., Goiania, GO (Brazil). Hospital de Clinicas. Servico de Diagnostico por Imagem

    2003-12-01

    The terms medullary cystic disease, juvenile nephronophthisis or medullary cystic disease complex refer to a group of similar diseases in which the basic pathological abnormality is progressive renal tubular atrophy with secondary glomerular sclerosis and medullary cystic formation. Medullary cystic disease is an important cause of renal failure in adolescent patients. Imaging methods play a primary role in the diagnosis of these diseases. Cysts are characteristically seen in the renal medulla and cortico medullary junction whereas kidneys may be of normal to small size. In this article we present the ultrasonography and computed tomography findings of a female adolescent patient with characteristic clinical picture of medullary cystic disease. (author)

  6. Adult cystic lymphangioma in the inner quadrant of the breast-Rare location for a rare disease: A case report.

    Science.gov (United States)

    Rusdianto, Eve; Murray, Mary; Davis, Jennifer; Caveny, Anne

    2016-01-01

    Adult cystic lymphangioma of the breast is extremely rare, especially in the breast's upper, inner quadrant. Review of literature is discussed, including etiology, differential diagnosis, workup, and treatment of the disease. A 20-year-old female presented with a recurrent left breast cyst. Previous aspirations showed no malignancy. Ultrasonography showed a lobulated anechoic lesion with internal debris and thin septations. The patient then underwent a lumpectomy of the left breast cyst, and pathology showed lymphangioma. Cystic lymphangiomas of the breast are benign lymphatic malformations. Consistent with the main drainage pattern of the breast, cystic lymphangiomas are typically located in the upper, outer quadrant, tail of Spence, and subareolar area. Radiologic evaluation may include ultrasound, mammogram, and MRI. FNA cytology and core biopsy assist in the diagnosis of breast lymphangioma. Although different treatment options exist, complete surgical excision remains the most effective treatment modality for adult cystic lymphangioma of the breast. Breast cystic lymphangioma is an extremely rare condition, especially in the upper, inner quadrant of the breast. The patient had multiple recurrences of the lesion after fine needle aspirations. Proper index of suspicion, prompt diagnosis, and definitive treatment is necessary to prevent recurrence and complications. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Adult cystic lymphangioma in the inner quadrant of the breast—Rare location for a rare disease: A case report

    Science.gov (United States)

    Rusdianto, Eve; Murray, Mary; Davis, Jennifer; Caveny, Anne

    2016-01-01

    Introduction Adult cystic lymphangioma of the breast is extremely rare, especially in the breast’s upper, inner quadrant. Review of literature is discussed, including etiology, differential diagnosis, workup, and treatment of the disease. Presentation of case A 20-year-old female presented with a recurrent left breast cyst. Previous aspirations showed no malignancy. Ultrasonography showed a lobulated anechoic lesion with internal debris and thin septations. The patient then underwent a lumpectomy of the left breast cyst, and pathology showed lymphangioma. Discussion Cystic lymphangiomas of the breast are benign lymphatic malformations. Consistent with the main drainage pattern of the breast, cystic lymphangiomas are typically located in the upper, outer quadrant, tail of Spence, and subareolar area. Radiologic evaluation may include ultrasound, mammogram, and MRI. FNA cytology and core biopsy assist in the diagnosis of breast lymphangioma. Although different treatment options exist, complete surgical excision remains the most effective treatment modality for adult cystic lymphangioma of the breast. Conclusion Breast cystic lymphangioma is an extremely rare condition, especially in the upper, inner quadrant of the breast. The patient had multiple recurrences of the lesion after fine needle aspirations. Proper index of suspicion, prompt diagnosis, and definitive treatment is necessary to prevent recurrence and complications. PMID:26852362

  8. Impact of lung disease on respiratory impedance in young children with cystic fibrosis.

    Science.gov (United States)

    Ramsey, Kathryn A; Ranganathan, Sarath C; Gangell, Catherine L; Turkovic, Lidija; Park, Judy; Skoric, Billy; Stick, Stephen M; Sly, Peter D; Hall, Graham L

    2015-12-01

    This study aimed to evaluate the ability of the forced oscillation technique (FOT) to detect underlying lung disease in preschool children with cystic fibrosis (CF) diagnosed following newborn screening.184 children (aged 3-6 years) with CF underwent lung function testing on 422 occasions using the FOT to assess respiratory resistance and reactance at the time of their annual bronchoalveolar lavage collection and chest computed tomography scan. We examined associations between FOT outcomes and the presence and progression of respiratory inflammation, infection and structural lung disease.Children with CF who had pronounced respiratory disease, including free neutrophil elastase activity, infection with pro-inflammatory pathogens and structural lung abnormalities had similar FOT outcomes to those children without detectable lung disease. In addition, the progression of lung disease over 1 year was not associated with worsening FOT outcomes.We conclude that the forced oscillation technique is relatively insensitive to detect underlying lung disease in preschool children with CF. However, FOT may still be of value in improving our understanding of the physiological changes associated with early CF lung disease. Copyright ©ERS 2015.

  9. Risk factors for the progression of cystic fibrosis lung disease throughout childhood.

    Science.gov (United States)

    Sanders, Don B; Li, Zhanhai; Laxova, Anita; Rock, Michael J; Levy, Hara; Collins, Jannette; Ferec, Claude; Farrell, Philip M

    2014-01-01

    Previous studies of risk factors for progression of lung disease in cystic fibrosis (CF) have suffered from limitations that preclude a comprehensive understanding of the determinants of CF lung disease throughout childhood. The epidemiologic component of the 27-year Wisconsin Randomized Clinical Trial of CF Neonatal Screening Project (WI RCT) afforded us a unique opportunity to evaluate the significance of potential intrinsic and extrinsic risk factors for lung disease in children with CF. Describe the most important intrinsic and extrinsic risk factors for progression of lung disease in children with CF. Variables hypothesized at the onset of the WI RCT study to be determinants of the progression of lung disease and potential risk factors previously identified in the WI RCT study were assessed with multivariable generalized estimating equation models for repeated measures of chest radiograph scores and pulmonary function tests in the WI RCT cohort. Combining all patients in the WI RCT, 132 subjects were observed for a mean of 16 years and contributed 1,579 chest radiographs, and 1,792 pulmonary function tests. The significant determinants of lung disease include genotype, poor growth, hospitalizations, meconium ileus, and infection with mucoid Pseudomonas aeruginosa. The previously described negative effect of female sex was not seen. Modifiable extrinsic risk factors are the major determinants of progression of lung disease in children with CF. Better interventions to prevent or treat these risk factors may lead to improvements in lung health for children with CF.

  10. DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis.

    Science.gov (United States)

    Magalhães, Milena; Rivals, Isabelle; Claustres, Mireille; Varilh, Jessica; Thomasset, Mélodie; Bergougnoux, Anne; Mely, Laurent; Leroy, Sylvie; Corvol, Harriet; Guillot, Loïc; Murris, Marlène; Beyne, Emmanuelle; Caimmi, Davide; Vachier, Isabelle; Chiron, Raphaël; De Sario, Albertina

    2017-01-01

    Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease modifier genes, and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. In this project, we hypothesized that (i) reiterative stress alters the epigenome in CF-affected tissues and (ii) DNA methylation variations at disease modifier genes modulate the lung function in CF patients. We profiled DNA methylation at CFTR, the disease-causing gene, and at 13 lung modifier genes in nasal epithelial cells and whole blood samples from 48 CF patients and 24 healthy controls. CF patients homozygous for the p.Phe508del mutation and ≥18-year-old were stratified according to the lung disease severity. DNA methylation was measured by bisulfite and next-generation sequencing. The DNA methylation profile allowed us to correctly classify 75% of the subjects, thus providing a CF-specific molecular signature. Moreover, in CF patients, DNA methylation at specific genes was highly correlated in the same tissue sample. We suggest that gene methylation in CF cells may be co-regulated by disease-specific trans-factors. Three genes were differentially methylated in CF patients compared with controls and/or in groups of pulmonary severity: HMOX1 and GSTM3 in nasal epithelial samples; HMOX1 and EDNRA in blood samples. The association between pulmonary severity and DNA methylation at EDNRA was confirmed in blood samples from an independent set of CF patients. Also, lower DNA methylation levels at GSTM3 were associated with the GSTM3*B allele, a polymorphic 3-bp deletion that has a protective effect in cystic fibrosis. DNA methylation levels are altered in nasal epithelial and blood cell samples from CF patients. Analysis of CFTR and 13 lung disease modifier genes shows DNA methylation changes of small

  11. Milk production parameters in early lactiation: potential risk factors of cystic ovarian disease in Dutch dairy cows

    NARCIS (Netherlands)

    Hooijer, G.A.; Oijen, van M.A.A.J.; Frankena, K.; Noordhuizen, J.P.T.M.

    2003-01-01

    The aim of this field study was to investigate whether the incidence of cystic ovarian disease (COD) in dairy cows was related to milk production parameters (milk yield, milk fat and protein) in early lactation with special emphasis on the negative energy balance (NEB). The diagnosis of COD was made

  12. The Pseudomonas aeruginosa Secretory Product Pyocyanin Inactivates α1 Protease Inhibitor: Implications for the Pathogenesis of Cystic Fibrosis Lung Disease

    Science.gov (United States)

    Britigan, Bradley E.; Railsback, Michelle A.; Cox, Charles D.

    1999-01-01

    α1 Protease inhibitor (α1PI) modulates serine protease activity in the lung. Reactive oxygen species inactivate α1PI, and this process has been implicated in the pathogenesis of a variety of forms of lung injury. An imbalance of protease-antiprotease activity is also detected in the airways of patients with cystic fibrosis-associated lung disease who are infected with Pseudomonas aeruginosa. P. aeruginosa secretes pyocyanin, which, through its ability to redox cycle, induces cells to generate reactive oxygen species. We tested the hypothesis that redox cycling of pyocyanin could lead to inactivation of α1PI. When α1PI was exposed to NADH and pyocyanin, a combination that results in superoxide production, α1PI lost its ability to form an inhibitory complex with both porcine pancreatic elastase (PPE) and trypsin. Similarly, addition of pyocyanin to cultures of human airway epithelial cells to which α1PI was also added resulted in a loss of the ability of α1PI to form a complex with PPE or trypsin. Neither superoxide dismutase, catalase, nor dimethylthiourea nor depletion of the media of O2 to prevent formation of reactive oxygen species blocked pyocyanin-mediated inactivation of α1PI. These data raise the possibility that a direct interaction between reduced pyocyanin and α1PI is involved in the process. Consistent with this possibility, pretreatment of α1PI with the reducing agent β-mercaptoethanol also inhibited binding of trypsin to α1PI. These data suggest that pyocyanin could contribute to lung injury in the P. aeruginosa-infected airway of cystic fibrosis patients by decreasing the ability of α1PI to control the local activity of serine proteases. PMID:10024562

  13. Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel.

    Science.gov (United States)

    Al-Hamed, Mohamed H; Kurdi, Wesam; Alsahan, Nada; Alabdullah, Zainab; Abudraz, Rania; Tulbah, Maha; Alnemer, Maha; Khan, Rubina; Al-Jurayb, Haya; Alahmed, Ahmed; Tahir, Asma I; Khalil, Dania; Edwards, Noel; Al Abdulaziz, Basma; Binhumaid, Faisal S; Majid, Salma; Faquih, Tariq; El-Kalioby, Mohamed; Abouelhoda, Mohamed; Altassan, Nada; Monies, Dorota; Meyer, Brian; Sayer, John A; Albaqumi, Mamdouh

    2016-05-01

    Inherited cystic kidney disorders are a common cause of end-stage renal disease. Over 50 ciliopathy genes, which encode proteins that influence the structure and function of the primary cilia, are implicated in cystic kidney disease. To define the phenotype and genotype of cystic kidney disease in fetuses and neonates, we correlated antenatal ultrasound examination and postnatal renal ultrasound examination with targeted exon sequencing, using a renal gene panel. A cohort of 44 families in whom antenatal renal ultrasound scanning findings in affected cases included bilateral cystic kidney disease, echogenic kidneys or enlarged kidneys was investigated. In this cohort, disease phenotypes were severe with 36 cases of stillbirth or perinatal death. Extra renal malformations, including encephalocele, polydactyly and heart malformations, consistent with ciliopathy phenotypes, were frequently detected. Renal gene panel testing identified causative mutations in 21 out of 34 families (62%), where patient and parental DNA was available. In the remaining 10 families, where only parental DNA was available, 7 inferred causative mutations were found. Together, mutations were found in 12 different genes with a total of 13 novel pathogenic variants, including an inferred novel variant in NEK8. Mutations in CC2D2A were the most common cause of an antenatal cystic kidney disease and a suspected ciliopathy in our cohort. In families with ciliopathy phenotypes, mutational analysis using a targeted renal gene panel allows a rapid molecular diagnosis and provides important information for patients, parents and their physicians. 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. Thickening and enhancement of multiple cranial nerves in conjunction with cystic white matter lesions in early infantile Krabbe disease

    Energy Technology Data Exchange (ETDEWEB)

    Beslow, Lauren A.; Boennemann, Carsten G. [Children' s Hospital of Philadelphia, Division of Neurology, Philadelphia, PA (United States); Schwartz, Erin S. [Children' s Hospital of Philadelphia, Division of Neuroradiology, Philadelphia, PA (United States)

    2008-06-15

    We present serial MR findings in a child ultimately diagnosed with the early infantile form of Krabbe disease. MR showed typical features of Krabbe disease including cerebellar and brainstem hyperintensity, periventricular and deep white matter hyperintensity, and cerebral atrophy. In addition, the combination of both enlargement and enhancement of multiple cranial nerves in conjunction with unusual cystic lesions adjacent to the frontal horns of the lateral ventricles was previously unreported and expands the spectrum of imaging findings in early Krabbe disease. (orig.)

  15. Establishment and long-term culture of human cystic fibrosis endothelial cells.

    Science.gov (United States)

    Plebani, Roberto; Tripaldi, Romina; Lanuti, Paola; Recchiuti, Antonio; Patruno, Sara; Di Silvestre, Sara; Simeone, Pasquale; Anile, Marco; Venuta, Federico; Prioletta, Marco; Mucilli, Felice; Del Porto, Paola; Marchisio, Marco; Pandolfi, Assunta; Romano, Mario

    2017-11-01

    Endothelial cell (EC) dysfunction has been reported in cystic fibrosis (CF) patients. Thus, the availability of CF EC is paramount to uncover mechanisms of endothelial dysfunction in CF. Using collagenase digestion, we isolated cells from small fragments of pulmonary artery dissected from non-CF lobes or explanted CF lungs. These cells were a heterogeneous mixture, containing variable percentages of EC. To obtain virtually pure pulmonary artery endothelial cells (PAEC), we developed an easy, inexpensive, and reliable method, based on the differential adhesion time of pulmonary artery cells collected after collagenase digestion. With this method, we obtained up to 95% pure non-CF and CF-PAEC. Moreover, we also succeed at immortalizing both PAEC and CF-PAEC, which remained viable and with unchanged phenotype and proliferation rate over the 30th passage. These cells recapitulated cystic fibrosis transmembrane conductance regulator expression and functions of the parental cells. Thus, we isolated for the first time endothelial cells from CF patients, providing a valuable tool to define the emerging role of EC in CF lung and vascular disease.

  16. [Hepatoporto-appendicostomy. Our experience in 3 cases of biliary cystic disease].

    Science.gov (United States)

    Vila, J J; Lluna, J; Sala, T; García-Sala, C; Ruiz, S

    1997-04-01

    This report details our preliminary experience with hepaticoporto-appendicostomy in three patients with biliary cystic disease. The surgical procedure was total resection of choledochal cyst and vascularized appendix interposition between biliary tree and duodenum. The children have been followed by clinical, ultrasonography and endoscopic (ECPR) during a period between 1-4 years. There was no episodes of ascending colangitis. All the patients remain free of jaundice and the biochemical abnormalities have become normal three months after interposition. Our results suggest that this procedure is more physiologic than the standard bilioenteric derivation Roux-in-Y, because allow bile to enter freely to duodenum and prevent reflux, stasis and ascending cholangitis. This procedure allows postoperative endoscopic valoration, not possible in another kind of bilioenteric derivations.

  17. The involvement of glycosaminoglycans in airway disease associated with cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2012-02-01

    Individuals with cystic fibrosis (CF) present with severe airway destruction and extensive bronchiectasis. It has been assumed that these structural airway changes have occurred secondary to infection and inflammation, but recent studies suggest that glycosaminoglycan (GAG) remodelling may be an important independent parallel process. Evidence is accumulating that not only the concentration, but also sulphation of GAGs is markedly increased in CF bronchial cells and tissues. Increased expression of GAGs and, in particular, heparan sulphate, has been linked to a sustained inflammatory response and neutrophil recruitment to the CF airways. This present review discusses the biological role of GAGs in the lung, as well as their involvement in CF respiratory disease, and their potential as therapeutic targets.

  18. Adeno-associated virus for cystic fibrosis gene therapy

    Directory of Open Access Journals (Sweden)

    S.V. Martini

    2011-11-01

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

  19. Retrospective analysis of the efficacy of different hormone treatments of cystic ovarian disease in cattle.

    Science.gov (United States)

    Nanda, A S; Ward, W R; Williams, P C; Dobson, H

    1988-02-13

    Cystic ovarian disease in cows was treated either with a single intramuscular injection of 500 micrograms cloprostenol, a prostaglandin F2 alpha analogue, in 77 cases of luteal cysts or with 500 micrograms gonadorelin or 20 micrograms buserelin, gonadotrophin releasing hormone or its analogue (GnRH), in 116 cases of follicular cysts. Recovery was defined as the absence of cysts and the formation of a corpus luteum either with or without observed oestrus within 10 days after treatment with cloprostenol and 15 days after treatment with GnRH. Recovery occurred in 65 per cent and 52.6 per cent of cases, respectively, in average times of 4.9 and 19 days. Fifteen days after treatment with GnRH, 20 cows with luteinised cysts were treated with cloprostenol and 15 recovered in a mean of 20.4 days, while 10 which still had follicular cysts, were given GnRH and one recovered 31 days after the beginning of treatment. Another 27 cows, in which cysts became luteinised, were treated with cloprostenol seven days after treatment with GnRH to give quicker (average 11.5 days) but poor (48 per cent) recovery and with a higher rate (33 per cent) of recurrence of cysts. A progesterone releasing intrauterine device was used in 25 cases of cystic ovarian disease, some of which had been previously treated. Sixty-eight per cent recovered in an average of 15 days. The proportions of cows becoming pregnant to one to three inseminations after the different methods of treatment were similar (77 to 94 per cent).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Human Environmental Disease Network

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...

  1. An overview of international literature from cystic fibrosis registries. Part 5: Update 2012-2015 on lung disease.

    Science.gov (United States)

    Salvatore, Donatello; Buzzetti, Roberto; Mastella, Gianni

    2016-11-01

    Patient registry data is a tool for defining the clinical course and risk factors in patients with less common diseases like Cystic Fibrosis. Forty-one registry-based reports on lung disease in Cystic Fibrosis were published between 2011 and 2015. The aim of this review is to describe and discuss the results of these reports, focusing on the risk factors for lung disease progression, specific microbiologic pathogens (e.g., non-tuberculous mycobacteria), disease complications, comparisons between registries of different countries, the impact of socio-economic status, and evaluation of benefits and costs of therapies. Techniques for improved clinical trial design were also studied. Pediatr Pulmonol. 2016;51:1251-1263. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Disparate Presentations of Localized Cystic Disease of Kidney: A Review with an Objective of Correct Approach for Accurate Treatment Plan.

    Science.gov (United States)

    Khanduri, Sachin; Chaudhary, Mriganki; Sabharwal, Tushar; Goyal, Aakshit; Katyal, Gaurav

    2017-04-22

    Localized cystic disease of the kidney is a rare, non-familial condition. Its imaging and clinical features are unique and need to be differentiated from autosomal dominant polycystic kidney disease and focal cystic masses such as multicystic nephroma and cystic renal cell carcinoma. It is always restricted to one kidney and is characterized by multiple cysts of varying sizes separated by residual normal renal tissue. This study reports 12 cases of localized cystic disease of the kidney based on imaging findings and clinical histories. The modalities of choice were ultrasonography followed by contrast-enhanced computed tomography. Eight out of 12 patients were men and the average age of presentation was 46 years. The screening of family members and relatives was done to rule out the differentials. Localized cystic disease of kidney was diagnosed in all the patients and it presented in two different forms. In three patients, multiple cysts involved whole of the kidney, resulting in thinned-out residual renal parenchyma. In the rest nine patients it remained localised to a particular segment of the kidney. No cysts were observed in the contralateral kidney in seven patients, and one or two simple cysts were observed in five. Clinical presentations included only flank pain in six patients, flank pain with palpable abdominal mass in four patients, two patients presented as asymptomatic cases with diagnosis as an incidental finding and one patient with hematuria. Eight patients underwent imaging and two underwent clinical follow-up for a period of two years showing stability of the disease. One patient underwent nephrectomy for suspected renal neoplasm. Localized cystic disease of the kidney is a unilateral, rare and stable disease that has two different forms of presentations. Its imaging findings should be clearly understood so as to not classify it as a separate disease and avoid unnecessary surgery. It rarely leads to hypertension or polycythemia, and until

  3. Chitinase activation in patients with fungus-associated cystic fibrosis lung disease.

    Science.gov (United States)

    Hector, Andreas; Chotirmall, Sanjay H; Lavelle, Gillian M; Mirković, Bojana; Horan, Deirdre; Eichler, Laura; Mezger, Markus; Singh, Anurag; Ralhan, Anjai; Berenbrinker, Sina; Mack, Ines; Ensenauer, Regina; Riethmüller, Joachim; Graepler-Mainka, Ute; Murray, Michelle A; Griese, Matthias; McElvaney, N Gerry; Hartl, Dominik

    2016-10-01

    Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear. The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Cystic lung disease in Sjögren's syndrome: An observational study.

    Science.gov (United States)

    Lechtman, Sarah; Debray, Marie-Pierre; Crestani, Bruno; Bancal, Catherine; Hourseau, Muriel; Dossier, Antoine; Alexandra, Jean-François; Chauveheid, Marie-Paule; Papo, Thomas; Sacre, Karim

    2017-05-01

    To analyze the prevalence, characteristics and outcome of cystic lung disease associated with Sjögren's syndrome (SS). From June 2010 to February 2015, 90 consecutive SS patients [60.1±14.8years; 88 (97.8%) female, 75 (83.3%) primary SS] had a systematic chest CT-scan. The presence of thin-walled cysts was analyzed by one experienced radiologist. Demographic data, clinical history, laboratory findings, and pulmonary function tests were extracted retrospectively from medical records. Twenty-one (23.3%) patients had cysts on CT scan performed 40.5±54.5months after SS diagnosis. Cysts number ranged from 1 to 25 were often bilateral (52.4%) and mostly located in the middle lung zone (76.2%). Cysts were isolated (n=6, 28.6%) or associated with other lesions, including bronchiectasis (n=5, 23.8%), micronodules (n=5, 23.8%), ground-glass opacity (n=4, 19%) and/or air trapping (n=3, 14.3%). Most patients with cysts (57.1%) had no respiratory symptoms. When comparing SS patients with and without cysts, patients with cysts tended to be older (65.3±15.3 versus 58.5±14.4years, P=0.06). Smoking habits were similar in both groups. Anti-SSB antibodies were more frequently detected in patients with cysts (57.1% vs. 26.1%, P=0.02). Pulmonary function tests were normal or displayed only mild small airways obstruction and reduced diffusion capacity to carbon monoxide. Four (19%) patients with cysts had a past history of associated pulmonary disease, including interstitial lung disease. During follow-up (25.1±17.7months), no patient developed specific lung disease or lymphoproliferative disorders. Cystic lung disease is frequent, benign, associated with anti-SSB/La antibodies and has no impact on outcome in SS. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  5. Validating chest MRI to detect and monitor cystic fibrosis lung disease in a pediatric cohort.

    Science.gov (United States)

    Tepper, Leonie A; Ciet, Pierluigi; Caudri, Daan; Quittner, Alexandra L; Utens, Elisabeth M W J; Tiddens, Harm A W M

    2016-01-01

    Computed Tomography (CT) is the gold standard to assess bronchiectasis and trapped air in cystic fibrosis (CF) lung disease, but has the disadvantage of radiation exposure. Magnetic Resonance Imaging (MRI) is a radiation free alternative. To validate MRI as outcome measure by: correlating MRI scores for bronchiectasis and trapped air with clinical parameters, and by comparing those MRI scores with CT scores. In patients with CF (aged 5.6-17.4 years), MRI and CT were alternated annually during routine annual check-ups between July 2007 and January 2010. Twenty-three children had an MRI performed 1 year prior to CT, 34 children had a CT 1 year prior to MRI. Bronchiectasis and trapped air were scored using the CF-MRI and CF-CT scoring system. CF-MRI scores were correlated with clinical parameters: FEV1 , Pseudomonas aeruginosa, pulmonary exacerbations and patient-reported respiratory symptoms measured on the Cystic Fibrosis Questionnaire-Revised (CFQ-R), using Spearman's correlation coefficient. MRI and CT scores were compared using intra-class correlation coefficients (ICC) and Bland-Altman plots. Fifty-seven patients who had an MRI, CT and CFQ-R during the study period were included. CF-MRI bronchiectasis correlated with FEV1 , Pseudomonas aeruginosa, pulmonary exacerbations and patient-reported respiratory symptoms. CF-MRI trapped air only correlated with FEV1 and Pseudomonas aeruginosa. ICCs between MRI and CT bronchiectasis and trapped air were 0.41 and 0.35 respectively. MRI tended to overestimate bronchiectasis compared to CT. The associations between CF-MRI scores and several important clinical parameters further contributes to the validation of MRI. MRI provides different information than CT. © 2015 Wiley Periodicals, Inc.

  6. Acquired cystic disease and renal cell carcinoma in hemodialysis patients--A case report on three patients.

    Science.gov (United States)

    Mijušković, Mirjana; Milović, Novak; Kovačević, Bozidar; Jovanović, Dragan; Stefanović, Dara; Ignjatović, Ljiljana; Terzić, Brankica; Pilčević, Jelena Tadić; Petrović, Marijana; Pilčević, Dejan; Obrencević, Katarina; Cerović, Snezana

    2015-10-01

    Renal cell carcinoma (RCC) is derived from renal tubular epithelial cells and represents approximately 3.8% of all malignancies in adults. The incidence of renal cell carcinoma has been growing steadily and ranging from 0.6 to 14.7 for every 100,000 inhabitants. Patients with end-stage renal disease and acquired cystic kidney disease are at increased risk of developing RCC while undergoing dialysis treatment or after renal transplantation. We presented 3 patients undergoing hemodialysis, with acquired cystic kidney disease accompanied by the development of RCC. In all the patients tumor was asymptomatic and discovered through ultrasound screening in 2 patients and in 1 of the patients by post-surgery pathohistological analysis of the tissue of the kidney excised using nephrectomy. All the three patients had organ-limited disease at the time of the diagnosis and they did not require additional therapy after surgical treatment. During the follow-up after nephrectomy from 6 months to 7 years, local recurrence or metastasis of RCC were not diagnosed. Acquired cystic kidney disease represents a predisposing factor for the development of renal cell carcinoma in dialysis patients and requires regular ultrasound examinations of the abdomen aimed at early diagnosis of malignancies. Prognosis for patients with end-stage renal disease and RCC is mostly good because these tumors are usually of indolent course.

  7. A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease

    Science.gov (United States)

    Bacci, Giovanni; Fiscarelli, Ersilia; Taccetti, Giovanni; Dolce, Daniela; Paganin, Patrizia; Morelli, Patrizia; Tuccio, Vanessa; De Alessandri, Alessandra; Lucidi, Vincenzina

    2017-01-01

    In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease. PMID:28758937

  8. Supporting cystic fibrosis disease management during adolescence: the role of family and friends.

    Science.gov (United States)

    Barker, D H; Driscoll, K A; Modi, A C; Light, M J; Quittner, A L

    2012-07-01

    Successful management of a complex disease, such as cystic fibrosis (CF), requires support from family and friends; however, few studies have examined social support in adolescents with CF. Twenty-four adolescents were interviewed about the support they receive from family and friends. Interviews were transcribed, coded and analysed to determine the types, frequency and perceived supportiveness of specific behaviours. Both family and friends provided treatment-related support to adolescents with CF. Family provided more tangible support and friends provided more relational support. Adolescents also reported that the manner, timing and context of support behaviours influenced their perceptions of the behaviours' supportiveness. A subset of adolescents (17%) chose not to disclose their diagnosis to their friends. The provision of support appears to be distinct from adolescent's perception of support and there may be some behaviours, such as treatment reminders, that are important to disease management but viewed as less supportive by adolescents. Facilitating increased social support holds the promise of improving disease management during adolescents, but more work is need to understand which aspects of support are related to management outcomes. © 2011 Blackwell Publishing Ltd.

  9. Computed tomography scanning techniques for the evaluation of cystic fibrosis lung disease.

    Science.gov (United States)

    Robinson, Terry E

    2007-08-01

    Multidetector computed tomography (MDCT) scanners allow diagnosis and monitoring of cystic fibrosis (CF) lung disease at substantially lower radiation doses than with prior scanners. Complete spiral chest CT scans are accomplished in less than 10 seconds and scanner advances now allow the acquisition of comprehensive volumetric datasets for three-dimensional reconstruction of the lungs and airways. There are two types of CT scanning protocols currently used to assess CF lung disease: (1) high-resolution CT (HRCT) imaging, in which thin 0.5-1.5-mm slices are obtained every 0.5, 1, or 2 cm from apex to base for inspiratory scans, and limited, spaced HRCT slices obtained for expiratory scans; and (2) complete spiral CT imaging covering the entire lung for inspiratory and expiratory scanning. These scanning protocols allow scoring of CF lung disease and provide CT datasets to quantify airway and air-trapping measurements. CF CT scoring systems typically assess bronchiectasis, bronchial wall thickening, mucus plugging, and atelectasis/consolidation from inspiratory scans, whereas air trapping is scored from expiratory imaging. Recently, CT algorithms have been developed for both HRCT and complete spiral CT imaging to quantify several airway indices, to determine the volume and density of the lung, and to assess regional and global air trapping. CT scans are currently acquired by either controlled-volume scanning techniques (controlled-ventilation infant CT scanning or spirometer-controlled CT scanning in children and adults) or by voluntary breath holds at full inflation and deflation.

  10. GATA3 expression in morphologic subtypes of breast carcinoma: a comparison with gross cystic disease fluid protein 15 and mammaglobin.

    Science.gov (United States)

    Wendroth, Scott M; Mentrikoski, Mark J; Wick, Mark R

    2015-02-01

    GATA3 is a transcription factor, which is involved in the growth and differentiation of several human tissues. Immunohistochemical staining for this marker has proven to be useful in recognizing a number of tumors, most notably those in the urinary tract and breasts. To date, no study has specifically assessed the distribution of GATA3 among different histomorphologic subtypes of breast carcinoma. The surgical pathology archive at our institution was searched, to retrieve cases of breast carcinomas of the following microscopic types-ductal, lobular, mucinous, metaplastic, medullary, apocrine, signet-ring cell, and micropapillary. Tissue microarrays were created, with four 0.6-mm punch specimens from each case. The tissue microarrays were cut at a 5-μm thickness and stained with monoclonal antibodies to GATA3 (Biocare Medical Inc, Concord, CA), mammaglobin (Dako, Carpinteria, CA), and gross cystic disease fluid protein 15 (Dako). Tumors were considered to be positive for those markers if more than 5% of the cells were labeled. Of 55 ductal adenocarcinomas, 51 (92.7%) expressed GATA3. All 4 GATA3-negative tumors were Nottingham grade III lesions that were also nonreactive for estrogen receptor protein. GATA3 was present in 28 (96.6%) of 29 lobular adenocarcinomas, 10 (90.9%) of 11 apocrine adenocarcinomas, 10 (83.3%) of 12 medullary carcinomas, 5 (55.5%) of 9 metaplastic carcinomas, and 1 of 2 signet-ring cell carcinomas. Mucinous carcinomas (23 cases) and micropapillary carcinomas (12 cases) uniformly and strongly labeled for GATA3. GATA3 equaled or surpassed the sensitivity of mammaglobin and gross cystic disease fluid protein 15 in all histologic subgroups of breast cancer in the study. Although most ductal adenocarcinomas were labeled for GATA3, it was absent in high-grade tumors that also lacked estrogen receptor protein. Favorable prognosis types of breast carcinoma (eg, mucinous carcinoma) and aggressive variants such as micropapillary carcinoma were equally

  11. Physiological markers of exercise capacity and lung disease severity in cystic fibrosis.

    Science.gov (United States)

    Smith, Laurie; Reilly, Charles C; MacBean, Victoria; Jolley, Caroline J; Elston, Caroline; Moxham, John; Rafferty, Gerrard F

    2017-05-01

    Peak aerobic capacity (VO2 peak) is an important outcome measure in cystic fibrosis (CF), but measurement is not widely available and can be influenced by patient motivation, pain and fatigue. Alternative markers of disease severity would be helpful. Neural respiratory drive, measured using parasternal intercostal muscle electromyography (EMGpara), reflects the load to capacity balance of the respiratory system and provides a composite measure of pulmonary function impairment in CF. The aim of the study was to investigate the relationship between exercise capacity, EMGpara and established measures of pulmonary function in clinically stable adult CF patients. Twenty CF patients (12 males, median (range) age: 22.3 (17.0-43.1) years) performed the 10-m incremental shuttle walk test (ISWT) maximally with contemporaneous measures of aerobic metabolism. EMGpara was recorded from second intercostal space at rest and normalized using peak electromyogram activity obtained during maximum respiratory manoeuvres and expressed as EMGpara%max (EMGpara expressed as a percentage of maximum). VO2 peak was strongly correlated with ISWT distance (r = 0.864, P disease progression. © 2016 Asian Pacific Society of Respirology.

  12. Localized Cystic Disease of the Kidney: A Rare Cause of Hypertension in a Young Adult

    Directory of Open Access Journals (Sweden)

    Aynur Solak

    2013-01-01

    Full Text Available Localized cystic disease of kidney (LCDK is a rare, non-familial, non-progressive renal disorder that is not associated with cysts or disorders in other organs. Only a few cases have been reported in the literature. While this condition is morphologically identical to the autosomal dominant form of polycystic kidney disease, it is not inherited and is not associated with significant deterioration of renal function. We present a case of a 16-year-old male patient who suffered from hypertension for over two years. On imaging we found several, variable-sized cysts in the upper half of the right kidney. The left kidney and lower segment of the right kidney were normal. Selective renal vein catheterization and sampling showed markedly elevated renin level in the right upper segmental vein (92 pg/ml, normal value: 11-33 pg/ml. The patient underwent a right upper heminephrectomy and histopathology was suggestive of LCDK. After surgery, the patient′s blood pressure returned to normal levels without any need of antihypertensive medication and he is under follow-up on outpatient basis for the past two years.

  13. A pilot study for control of hyperendemic cystic hydatid disease in China.

    Directory of Open Access Journals (Sweden)

    Wenbao Zhang

    Full Text Available BACKGROUND: Cystic hydatid disease (CHD is a global parasitic zoonosis caused by the dog tapeworm, Echinococcus granulosus. The disease is hyperendemic in western China because of poor economic development; limited community knowledge of CHD; widespread, small-scale household animal production; home killing of livestock; and the feeding of dogs with uncooked offal. METHODOLOGY/PRINCIPAL FINDINGS: A control program focusing on monthly praziquantel (PZQ treatment of all registered dogs and culling unwanted and stray dogs has been designed to control CHD in hyperendemic areas in China. A pilot field control project in two counties (Hutubi and Wensu in Xinjiang, China showed that after 4 years of treatment, the prevalence of dogs with E. granulosus was reduced from 14.7% and 18.6%, respectively, to 0%, and this caused a 90%-100% decrease of CHD in sheep born after commencement of the control program. CONCLUSIONS/SIGNIFICANCE: The strategy aimed at preventing eggs being released from dogs into the environment by treating animals before adult tapeworms are patent can decrease E. granulosus transmission and considerably reduce hyperendemic CHD. Monthly treatment of dogs with PZQ and culling unwanted and stray dogs have been shown to be an efficient, highly cost-effective and practicable measure for implementation in rural communities. As a result, the Chinese Ministry of Health has launched an extensive CHD control program in 117 counties in western China using this control strategy.

  14. Altered expression of transforming growth factor-beta isoforms in bovine cystic ovarian disease.

    Science.gov (United States)

    Matiller, V; Stangaferro, M L; Díaz, P U; Ortega, H H; Rey, F; Huber, E; Salvetti, N R

    2014-10-01

    Cystic ovarian disease (COD) is one of the main causes of infertility in dairy cattle. It has been shown that intra-ovarian factors may contribute to follicular persistence. Transforming growth factor-beta (TGFB) isoforms are important paracrine and autocrine signalling molecules that regulate ovarian follicle growth and physiology. Considering the importance of these factors in the ovarian physiology, in this study, we examined the expression of TGFB isoforms (TGFB1, TGFB2 and TGFB3) in the ovary of healthy cows and animals with spontaneous and adrenocorticotrophic hormone (ACTH)-induced COD. In the oestrous-synchronized control group, the expression of TGFB1 in granulosa and theca cells was higher in spontaneous cysts than in atretic or tertiary follicles. When we compared TGFB2 expression in granulosa cells from atretic or tertiary follicles from the oestrous-synchronized control group with that in ACTH-induced or spontaneous follicular cysts, we found a higher expression in the latter. The expression of the TGFB isoforms studied was also altered during folliculogenesis in both the spontaneous and ACTH-induced COD groups. As it has been previously shown that TGFB influences steroidogenesis, ovarian follicular proliferation and apoptosis, an alteration in its expression may contribute to the pathogenesis of this disease. © 2014 Blackwell Verlag GmbH.

  15. Role of activin, inhibin, and follistatin in the pathogenesis of bovine cystic ovarian disease.

    Science.gov (United States)

    Stangaferro, Matías L; Matiller, Valentina; Díaz, Pablo U; Ortega, Hugo H; Rey, Florencia; Rodríguez, Fernanda M; Silva, Manuel A; Salvetti, Natalia R

    2014-08-01

    Cystic ovarian disease (COD) is an important cause of infertility in dairy cattle. Although many researchers have focused their work on the endocrine changes related to this disease, evidence indicates that intraovarian components play an important role in follicular persistence. Activin, inhibin, and follistatin participate as intraovarian regulatory molecules involved in follicular cell proliferation, differentiation, steroidogenesis, oocyte maturation, and corpus luteum function. Given the importance of these factors in folliculogenesis, we examined the expression and immunolocalization of activin/inhibin βA-subunit, inhibin α-subunit, and follistatin in the ovaries of healthy estrus-synchronized cows and in those of cows with spontaneous or adrenocorticotropic hormone (ACTH)-induced COD. We also studied inhibin B (α βB) levels in serum and follicular fluid. We found an increased expression of the βA-subunit of activin A/inhibin A, the α-subunit of inhibin, and follistatin in granulosa cells of spontaneous follicular cysts by immunohistochemistry, and decreased concentrations of inhibin B (α βB) in the follicular fluid of spontaneous follicular cysts. These results, together with those previously obtained, indicate that the expression of the components of the activin-inhibin-follistatin system is altered. This could lead to multiple alterations in important functions in the ovary like the balance between pro- and anti-apoptotic factors, follicular proliferation/apoptosis, and steroidogenesis, which may contribute to the follicular persistence and endocrine changes found in cattle with COD. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease.

    Directory of Open Access Journals (Sweden)

    William T Harris

    Full Text Available TGF-β, a mediator of pulmonary fibrosis, is a genetic modifier of CF respiratory deterioration. The mechanistic relationship between TGF-β signaling and CF lung disease has not been determined.To investigate myofibroblast differentiation in CF lung tissue as a novel pathway by which TGF-β signaling may contribute to pulmonary decline, airway remodeling and tissue fibrosis.Lung samples from CF and non-CF subjects were analyzed morphometrically for total TGF-β1, TGF-β signaling (Smad2 phosphorylation, myofibroblast differentiation (α-smooth muscle actin, and collagen deposition (Masson trichrome stain.TGF-β signaling and fibrosis are markedly increased in CF (p<0.01, and the presence of myofibroblasts is four-fold higher in CF vs. normal lung tissue (p<0.005. In lung tissue with prominent TGF-β signaling, both myofibroblast differentiation and tissue fibrosis are significantly augmented (p<0.005.These studies establish for the first time that a pathogenic mechanism described previously in pulmonary fibrosis is also prominent in cystic fibrosis lung disease. The presence of TGF-β dependent signaling in areas of prominent myofibroblast proliferation and fibrosis in CF suggests that strategies under development for other pro-fibrotic lung conditions may also be evaluated for use in CF.

  17. Effects of cystic fibrosis lung disease on gas mixing indices derived from alveolar slope analysis.

    Science.gov (United States)

    Horsley, Alex R; Macleod, Kenneth A; Robson, Andrew G; Lenney, Jill; Bell, Nicholas J; Cunningham, Steve; Greening, Andrew P; Gustafsson, Per M; Innes, J Alastair

    2008-08-31

    S(cond) and S(acin) are derived from analysis of concentration-normalized phase III slopes (Sn(III)) of a multiple breath inert gas washout. Studies in healthy and COPD subjects suggest these reflect ventilation heterogeneity in conducting and acinar airway zones respectively, but similar studies in cystic fibrosis (CF) are lacking. S(cond), S(acin) and lung clearance index (LCI, a measure of overall gas mixing efficiency) were measured in 22 adults and 18 children with CF and 17 adult and 29 child controls. Plethysmography and gas transfer measurements were performed in adults, and spirometry in all subjects. S(cond) was elevated in almost all CF patients, including children with mild disease and normal LCI. However, S(cond) did not correlate with other measurements and appeared to reach a maximum; further increase in ventilation heterogeneity being restricted to S(acin). The nature and/or severity of CF lung disease may invalidate assumptions underlying the ability to separate phase III slope analysis of ventilation heterogeneity into proximal and peripheral components, and LCI may be a better indicator of gas mixing in this population.

  18. Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease.

    Science.gov (United States)

    Newman, Christopher L; Creecy, Amy; Granke, Mathilde; Nyman, Jeffry S; Tian, Nannan; Hammond, Max A; Wallace, Joseph M; Brown, Drew M; Chen, Neal; Moe, Sharon M; Allen, Matthew R

    2016-01-01

    Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild antiresorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole-bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared with normal controls, as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. Although it had little effect on cortical bone geometry, it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation, and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole-bone mechanical properties in CKD through its impact on skeletal material properties. Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  19. Acquired cystic kidney disease in dialysis and renal transplant patients: ultrasonography and CT analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Young Tae; Lee, Hae Kyung; Jung, Mi Sun; Yoon, Jong Pil; Hong, Hyun Sook; Kwon, Kui Hyang; Choi, Deuk Lin; Hwang, Seung Duk; Lee, Hi Bahl [Soonchunhyang Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-04-01

    To evaluate by US and CT the incidence and complications of acquired cystic kidney disease (ACKD) in dialysis and renal transplant patients and to compare the effectiveness of US and CT in the diagnosis of this entity. This study was prospectively performed in 70 dialysis patients and 13 renal transplant patients, and excluded any with multiple renal cysts or polycystic kidney disease, on as seen on initial films. US were obtained in all patients, and CT scans were randomly obtained in 27 who had been on dialysis for 3 years or more; all these US and CT scans were analyzed, with particular emphasis on whether or not cysts were present. In order to correlate the numbers of cysts with duration of dialysis, all patients were assigned to one of three groups, according to the number of cysts found (group 1, 0; group 2, 1-4; group 3, >4). Only group 3 was diagnosed as suffering from ACKD. In order to compare the cyst-detection capability of US with that of CT, 27 dialysis patients who had undergone US and CT were divided into four groups according to the number of cysts found (grade 1, 0; grade 2, 1-4; grade 3, 5-10; grade 4, >10). Seventy dialysis patients were divided according to the results of US, as follows : group 1, 20%; group 2, 47.1%; group 3, 32.9%. The mean duration of dialysis in group 1 (31.9 months) was statistically different from that in group 2 (50.6 months) and in group 3 (95.8 months) (p < 0.000). Thirteen renal transplant patients were divided as follows : group 1, 61.5%; group 2, 38.5%; group 3, 0%. In dialysis patients with ACKD, complications noted were renal cell carcinoma (n=1), hemorrhagic cysts (n=2), and hematomas (n=2). Among the 27 dialysis patients who underwent CT, this and US showed an equal grade of cystic change in 53.7%, while CT showed a higher grade in 46.3%. The detection rate of ACKD in these 27 patients was 46% on US and 63% on CT. A prolongation of dialysis corresponded to an increased incidence of ACKD; renal neoplasm and

  20. Adult cystic lymphangioma in the inner quadrant of the breast?Rare location for a rare disease: A case report

    OpenAIRE

    Rusdianto, Eve; Murray, Mary; Davis, Jennifer; Caveny, Anne

    2016-01-01

    Introduction: Adult cystic lymphangioma of the breast is extremely rare, especially in the breast’s upper, inner quadrant. Review of literature is discussed, including etiology, differential diagnosis, workup, and treatment of the disease. Presentation of case: A 20-year-old female presented with a recurrent left breast cyst. Previous aspirations showed no malignancy. Ultrasonography showed a lobulated anechoic lesion with internal debris and thin septations. The patient then underwent a l...

  1. CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease.

    Science.gov (United States)

    Bonadia, Luciana Cardoso; de Lima Marson, Fernando Augusto; Ribeiro, Jose Dirceu; Paschoal, Ilma Aparecida; Pereira, Monica Corso; Ribeiro, Antonio Fernando; Bertuzzo, Carmen Silvia

    2014-05-01

    There are nearly 2000 cystic fibrosis transmembrane regulator (CFTR) mutations that cause cystic fibrosis (CF). These mutations are classified into six classes; on the one hand, the first three classes cause severe disease involvement in early childhood, on the other hand, the Class IV, V and VI mutations cause minor severe disease in the same age. Nowadays, with therapeutic advances in CF management and competence of pediatricians, physicians of adults have to deal with two groups of CF patients: (i) adults diagnosed in childhood with severe mutations and (ii) adults who initiated symptoms in adulthood and with Class IV, V and VI mutations. The aim of this study was to analyze adults from a clinical center, treated as CF disease, screening the CFTR genotype and evaluating the clinical characteristics. Thirty patients followed as CF disease at the University Hospital were enrolled. After a complete molecular CFTR negative screening and sweat test levels between 40 and 59mEq/L, five patients were characterized as non-CF disease and were excluded. Molecular screening was performed by CFTR gene sequencing/MLPA or by specific mutation screening. Clinical data was obtained from medical records. The patients were divided into three groups: (1) patients with Class I, II and III mutations in two CFTR alleles; (2) genotype with at least one allele of Class IV, V or VI CFTR mutations and, (3) non-identified CFTR mutation+one patient with one allele with CFTR mutation screened (Class I). There was an association of CFTR class mutation and sodium/chloride concentration in the sweat test (sodium: p=0.040; chloride: p=0.016), onset of digestive symptoms (p=0.012), lung function parameter (SpO2 - p=0.016), Bhalla score (p=0.021), age at diagnosis (p=0.008) and CF-related diabetes (p=0.029). There was an association between Pseudomonas aeruginosa chronic colonization (as clinical marker for the lung disease status) and lung impairment (FEV1% - p=0.027; Bhalla score - p=0.021), CF

  2. Novel Computed Tomography Scoring System for Sinus Disease in Adults With Cystic Fibrosis.

    Science.gov (United States)

    Sheikh, Shahid I; Handly, Brian; Ryan-Wenger, Nancy A; Hayes, Don; Kirkby, Stephen E; McCoy, Karen S; Lind, Meredith

    2016-10-01

    There is no easy to use scoring system for computed tomography (CT) scans of the sinuses that is specific to cystic fibrosis (CF). We propose a simple and easily implemented scoring system to quantify severity of sinus disease in adults with CF. Case series with chart review. Academic tertiary-care referral center. Sixty-nine adult patients with CF and 50 age-matched controls. We validated a scoring system for CF sinus disease. The CT scans were interpreted by 3 physicians on 2 separate sittings. Parameters include maxillary opacification, nasal obstruction, lateral nasal wall displacement, uncinate process absence/demineralization, and presence/absence of mucocele. Patients with CF aged 21 to 30 years (mean = 24.7 ± 2.49). In CF cohort (n = 69), intrarater reliability for the 10 CT categories ranged from .70 to 1.00. Twenty-six (87%) were in the excellent range, and the remaining 4 (13%) were evaluated as good. In the non-CF cohort (n = 50), reliabilities ranged from .44 to 1.00. Twenty-seven (90%) were in the excellent range. For interrater reliability, in the CF cohort, 10 CT categories across the 3 raters ranged from .55 to 1.00. Excellent reliability was achieved in 15 (50%) of the observations. In the non-CF cohort, reliabilities ranged from .44 to 1.00. A novel and easy to use CT scoring system for CF sinus disease in adults was validated with inter- and intrarater reliability. This new CF sinus disease-specific scoring system can be used by clinicians, surgeons, and radiologists. © The Author(s) 2016.

  3. Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1.

    Science.gov (United States)

    Bleyer, Anthony J; Kmoch, Stanislav; Antignac, Corinne; Robins, Vicki; Kidd, Kendrah; Kelsoe, John R; Hladik, Gerald; Klemmer, Philip; Knohl, Stephen J; Scheinman, Steven J; Vo, Nam; Santi, Ann; Harris, Alese; Canaday, Omar; Weller, Nelson; Hulick, Peter J; Vogel, Kristen; Rahbari-Oskoui, Frederick F; Tuazon, Jennifer; Deltas, Constantinos; Somers, Douglas; Megarbane, Andre; Kimmel, Paul L; Sperati, C John; Orr-Urtreger, Avi; Ben-Shachar, Shay; Waugh, David A; McGinn, Stella; Bleyer, Anthony J; Hodanová, Katerina; Vylet'al, Petr; Živná, Martina; Hart, Thomas C; Hart, P Suzanne

    2014-03-01

    The genetic cause of medullary cystic kidney disease type 1 was recently identified as a cytosine insertion in the variable number of tandem repeat region of MUC1 encoding mucoprotein-1 (MUC1), a protein that is present in skin, breast, and lung tissue, the gastrointestinal tract, and the distal tubules of the kidney. The purpose of this investigation was to analyze the clinical characteristics of families and individuals with this mutation. Families with autosomal dominant interstitial kidney disease were referred for genetic analysis over a 14-year period. Families without UMOD or REN mutations prospectively underwent genotyping for the presence of the MUC1 mutation. Clinical characteristics were retrospectively evaluated in individuals with the MUC1 mutation and historically affected individuals (persons who were both related to genetically affected individuals in such a way that ensured that they could be genetically affected and had a history of CKD stage IV or kidney failure resulting in death, dialysis, or transplantation). Twenty-four families were identified with the MUC1 mutation. Of 186 family members undergoing MUC1 mutational analysis, the mutation was identified in 95 individuals, 91 individuals did not have the mutation, and111 individuals were identified as historically affected. Individuals with the MUC1 mutation suffered from chronic kidney failure with a widely variable age of onset of end stage kidney disease ranging from 16 to >80 years. Urinalyses revealed minimal protein and no blood. Ultrasounds of 35 individuals showed no medullary cysts. There were no clinical manifestations of the MUC1 mutation detected in the breasts, skin, respiratory system, or gastrointestinal tract. MUC1 mutation results in progressive chronic kidney failure with a bland urinary sediment. The age of onset of end stage kidney disease is highly variable, suggesting that gene-gene or gene-environment interactions contribute to phenotypic variability.

  4. Morphologic and functional scoring of cystic fibrosis lung disease using MRI.

    Science.gov (United States)

    Eichinger, Monika; Optazaite, Daiva-Elzbieta; Kopp-Schneider, Annette; Hintze, Christian; Biederer, Jürgen; Niemann, Anne; Mall, Marcus A; Wielpütz, Mark O; Kauczor, Hans-Ulrich; Puderbach, Michael

    2012-06-01

    Magnetic resonance imaging (MRI) gains increasing importance in the assessment of cystic fibrosis (CF) lung disease. The aim of this study was to develop a morpho-functional MR-scoring-system and to evaluate its intra- and inter-observer reproducibility and clinical practicability to monitor CF lung disease over a broad severity range from infancy to adulthood. 35 CF patients with broad age range (mean 15.3 years; range 0.5-42) were examined by morphological and functional MRI. Lobe based analysis was performed for parameters bronchiectasis/bronchial-wall-thickening, mucus plugging, abscesses/sacculations, consolidations, special findings and perfusion defects. The maximum global score was 72. Two experienced radiologists scored the images at two time points (interval 10 weeks). Upper and lower limits of agreement, concordance correlation coefficients (CCC), total deviation index and coverage probability were calculated for global, morphology, function, component and lobar scores. Global scores ranged from 6 to 47. Intra- and inter-reader agreement for global scores were good (CCC: 0.98 (R1), 0.94 (R2), 0.97 (R1/R2)) and were comparable between high and low scores. Our results indicate that the proposed morpho-functional MR-scoring-system is reproducible and applicable for semi-quantitative evaluation of a large spectrum of CF lung disease severity. This scoring-system can be applied for the routine assessment of CF lung disease and maybe as endpoint for clinical trials. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. First meeting "Cystic echinococcosis in Chile, update in alternatives for control and diagnostics in animals and humans".

    Science.gov (United States)

    Alvarez Rojas, Cristian A; Fredes, Fernando; Torres, Marisa; Acosta-Jamett, Gerardo; Alvarez, Juan Francisco; Pavletic, Carlos; Paredes, Rodolfo; Cortés, Sandra

    2016-09-13

    This report summarizes the outcomes of a meeting on cystic echinococcosis (CE) in animals and humans in Chile held in Santiago, Chile, between the 21st and 22nd of January 2016. The meeting participants included representatives of the Departamento de Zoonosis, Ministerio de Salud (Zoonotic Diseases Department, Ministry of Health), representatives of the Secretarias Regionales del Ministerio de Salud (Regional Department of Health, Ministry of Health), Instituto Nacional de Desarrollo Agropecuario (National Institute for the Development of Agriculture and Livestock, INDAP), Instituto de Salud Pública (National Institute for Public Health, ISP) and the Servicio Agrícola y Ganadero (Animal Health Department, SAG), academics from various universities, veterinarians and physicians. Current and future CE control activities were discussed. It was noted that the EG95 vaccine was being implemented for the first time in pilot control programmes, with the vaccine scheduled during 2016 in two different regions in the South of Chile. In relation to use of the vaccine, the need was highlighted for acquiring good quality data, based on CE findings at slaughterhouse, previous to initiation of vaccination so as to enable correct assessment of the efficacy of the vaccine in the following years. The current world's-best-practice concerning the use of ultrasound as a diagnostic tool for the screening population in highly endemic remote and poor areas was also discussed.

  6. Cysteamine-mediated clearance of antibiotic-resistant pathogens in human cystic fibrosis macrophages.

    Directory of Open Access Journals (Sweden)

    Chandra L Shrestha

    Full Text Available Members of the Burkholderia cepacia complex are virulent, multi-drug resistant pathogens that survive and replicate intracellularly in patients with cystic fibrosis (CF. We have discovered that B. cenocepacia cannot be cleared from CF macrophages due to defective autophagy, causing continued systemic inflammation and infection. Defective autophagy in CF is mediated through constitutive reactive oxygen species (ROS activation of transglutaminase-2 (TG2, which causes the sequestration (accumulation of essential autophagy initiating proteins. Cysteamine is a TG2 inhibitor and proteostasis regulator with the potential to restore autophagy. Therefore, we sought to examine the impact of cysteamine on CF macrophage autophagy and bacterial killing. Human peripheral blood monocyte-derived macrophages (MDMs and alveolar macrophages were isolated from CF and non-CF donors. Macrophages were infected with clinical isolates of relevant CF pathogens. Cysteamine caused direct bacterial growth killing of live B. cenocepacia, B. multivorans, P. aeruginosa and MRSA in the absence of cells. Additionally, B. cenocepacia, B. multivorans, and P. aeruginosa invasion were significantly decreased in CF MDMs treated with cysteamine. Finally, cysteamine decreased TG2, p62, and beclin-1 accumulation in CF, leading to increased Burkholderia uptake into autophagosomes, increased macrophage CFTR expression, and decreased ROS and IL-1β production. Cysteamine has direct anti-bacterial growth killing and improves human CF macrophage autophagy resulting in increased macrophage-mediated bacterial clearance, decreased inflammation, and reduced constitutive ROS production. Thus, cysteamine may be an effective adjunct to antibiotic regimens in CF.

  7. Human cysteine cathepsins are not reliable markers of infection by Pseudomonas aeruginosa in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Clément Naudin

    Full Text Available Cysteine cathepsins have emerged as new players in inflammatory lung disorders. Their activities are dramatically increased in the sputum of cystic fibrosis (CF patients, suggesting that they are involved in the pathophysiology of CF. We have characterized the cathepsins in CF expectorations and evaluated their use as markers of colonization by Pseudomonas aeruginosa. The concentrations of active cathepsins B, H, K, L and S were the same in P. aeruginosa-positive (19 Ps+ and P. aeruginosa-negative (6 Ps- samples, unlike those of human neutrophil elastase. Also the cathepsin inhibitory potential and the cathepsins/cathepsin inhibitors imbalance remained unchanged and similar (∼2-fold in the Ps+ and Ps- groups (p<0.001, which correlated with the breakdown of their circulating cystatin-like inhibitors (kininogens. Procathepsins, which may be activated autocatalytically, are a potential proteolytic reservoir. Immunoblotting and active-site labeling identified the double-chain cathepsin B, the major cathepsin in CF sputum, as the main molecular form in both Ps+ and Ps- samples, despite the possible release of the ∼31 kDa single-chain form from procathepsin B by sputum elastase. Thus, the hydrolytic activity of cysteine cathepsins was not correlated with bacterial colonization, indicating that cathepsins, unlike human neutrophil elastase, are not suitable markers of P. aeruginosa infection.

  8. Human cysteine cathepsins are not reliable markers of infection by Pseudomonas aeruginosa in cystic fibrosis.

    Science.gov (United States)

    Naudin, Clément; Joulin-Giet, Alix; Couetdic, Gérard; Plésiat, Patrick; Szymanska, Aneta; Gorna, Emilia; Gauthier, Francis; Kasprzykowski, Franciszek; Lecaille, Fabien; Lalmanach, Gilles

    2011-01-01

    Cysteine cathepsins have emerged as new players in inflammatory lung disorders. Their activities are dramatically increased in the sputum of cystic fibrosis (CF) patients, suggesting that they are involved in the pathophysiology of CF. We have characterized the cathepsins in CF expectorations and evaluated their use as markers of colonization by Pseudomonas aeruginosa. The concentrations of active cathepsins B, H, K, L and S were the same in P. aeruginosa-positive (19 Ps+) and P. aeruginosa-negative (6 Ps-) samples, unlike those of human neutrophil elastase. Also the cathepsin inhibitory potential and the cathepsins/cathepsin inhibitors imbalance remained unchanged and similar (∼2-fold) in the Ps+ and Ps- groups (p<0.001), which correlated with the breakdown of their circulating cystatin-like inhibitors (kininogens). Procathepsins, which may be activated autocatalytically, are a potential proteolytic reservoir. Immunoblotting and active-site labeling identified the double-chain cathepsin B, the major cathepsin in CF sputum, as the main molecular form in both Ps+ and Ps- samples, despite the possible release of the ∼31 kDa single-chain form from procathepsin B by sputum elastase. Thus, the hydrolytic activity of cysteine cathepsins was not correlated with bacterial colonization, indicating that cathepsins, unlike human neutrophil elastase, are not suitable markers of P. aeruginosa infection.

  9. Human prion diseases.

    Science.gov (United States)

    Thakur, Rajeev; Vincent, Yasmeen Marbaniang; Chaturvedi, Sujata

    2002-01-01

    Prion diseases is another name for a group of 'transmissible spongiform encephalopathies'. Creutzfeldt-Jakob disease, the first prion disease described in humans, occurs in sporadic, familial or iatrogenic form. Other transmissible spongiform encephalopathies in humans such as familial Creutzfeldt-]akob disease, Gerstmann-Sträussler-Scheinker disease and fatal familial Insomnia have been shown to be associated with specific prion protein gene mutations. In 1996, a new variant of Creutzfeldt-Jakob disease was reported in the United Kingdom among young patients with unusual clinical features and unique neuropathological findings. This new form could be due to transmission to humans of the agent causing bovine spongiform encephalopathy. While examination of brain tissue is the key to making a diagnosis, it is not always possible antemortem. Immunological tests such as ELISA or western blot assays along with tests for 1 4-3-3 protein in the cerebrospinal fluid remain the main tools of diagnosis. Conventional disinfection and sterilization practices are Ineffective for these agents. The unusual properties of prions pose a challenge for treatment, surveillance and control of these diseases.

  10. Percutaneous ethanol sclerotherapy for recurrent adventitial cystic disease of external iliac vein after surgical treatment: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Ann, Jun Hyung; Kim, Jeong Ho; Byun, Sung Su; Kang, Jin Mo; Kim, Hyung Sik; Choi, Hye Young [Gachon University Gil Medical Center, Incheon (Korea, Republic of)

    2015-12-15

    Adventitial cystic disease (ACD) is a rare, but well-characterized vascular disease. It is most commonly seen in the popliteal artery, but it has also been reported in the venous system. The most commonly involved segment has been the common femoral vein; the disease resulted in luminal compromise and extremity swelling. We report here on a case of percutaneous aspiration and ethanol sclerotherapy for recurrent ACD after surgery of the external iliac vein in a 70-year-old man who presented with a painless swelling of his left leg.

  11. Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Michael S. [Monroe Carell Jr. Children' s Hospital at Vanderbilt, Department of Pediatrics, Nashville, TN (United States); Chadha, Ashley D. [Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Department of Pediatrics, Nashville, TN (United States); Carroll, Clinton M.; Borinstein, Scott C. [Vanderbilt University School of Medicine, Division of Hematology and Oncology, Department of Pediatrics, Nashville, TN (United States); Young, Lisa R. [Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Department of Pediatrics, Nashville, TN (United States); Vanderbilt University School of Medicine, Division of Allergy, Pulmonary and Critical Care, Department of Medicine, Nashville, TN (United States); Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Nashville, TN (United States)

    2015-07-15

    Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. (orig.)

  12. Defective goblet cell exocytosis contributes to murine cystic fibrosis–associated intestinal disease

    Science.gov (United States)

    Liu, Jinghua; Walker, Nancy M.; Ootani, Akifumi; Strubberg, Ashlee M.; Clarke, Lane L.

    2015-01-01

    Cystic fibrosis (CF) intestinal disease is associated with the pathological manifestation mucoviscidosis, which is the secretion of tenacious, viscid mucus that plugs ducts and glands of epithelial-lined organs. Goblet cells are the principal cell type involved in exocytosis of mucin granules; however, little is known about the exocytotic process of goblet cells in the CF intestine. Using intestinal organoids from a CF mouse model, we determined that CF goblet cells have altered exocytotic dynamics, which involved intrathecal granule swelling that was abruptly followed by incomplete release of partially decondensated mucus. Some CF goblet cells exhibited an ectopic granule location and distorted cellular morphology, a phenotype that is consistent with retrograde intracellular granule movement during exocytosis. Increasing the luminal concentration of bicarbonate, which mimics CF transmembrane conductance regulator–mediated anion secretion, increased spontaneous degranulation in WT goblet cells and improved exocytotic dynamics in CF goblet cells; however, there was still an apparent incoordination between granule decondensation and exocytosis in the CF goblet cells. Compared with those within WT goblet cells, mucin granules within CF goblet cells had an alkaline pH, which may adversely affect the polyionic composition of the mucins. Together, these findings indicate that goblet cell dysfunction is an epithelial-autonomous defect in the CF intestine that likely contributes to the pathology of mucoviscidosis and the intestinal manifestations of obstruction and inflammation. PMID:25642775

  13. [Early lung disease in infants with cystic fibrosis. Diagnostic tools and possible therapeutic pathways].

    Science.gov (United States)

    Reix, P; Matecki, S; Fayon, M

    2016-02-01

    The lungs of infants with cystic fibrosis (CF) have been considered to be normal at birth. However, recent data indicates that this is unlikely to be true in most cases. Animal CF-models developed in the early 2000s have shown that constitutional airway narrowing may be present at birth, and is associated with both functional and structural abnormalities. Longitudinal birth cohort studies have shown that 25 % of CF infants followed in specialized centers, while being asymptomatic, showed decreased lung function at 3months of age. Air trapping was present in 68 % and bronchiectasis in 28 % of patients at the same age. The presence of neutrophil elastase in the bronchoalveolar lavage at 3months of age tripled the risk of bronchiectasis at the age of 3years. Currently available tools such as infant pulmonary function tests (both the jacket and multiple breath washout) as well as high-resolution volume controlled chest-computed tomography or functional magnetic resonance imaging will facilitate early intervention trials in the very near future. The role of such tools for the routine follow-up of patients, and the ability of early therapeutic interventions to alter the natural history of CF-lung disease should soon be established. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  14. Telemonitoring in chronic obstructive airway disease and adult patients with cystic fibrosis.

    Science.gov (United States)

    Jarad, Nabil A; Sund, Zoe M

    2011-01-01

    We compared the use of telemonitoring in patients with chronic obstructive pulmonary disease (COPD) and adult patients with cystic fibrosis (CF). Seventy patients (51 CF and 19 COPD) were enrolled in two studies of six months' duration. Patients used a personal data assistant (PDA) attached to a spirometer to score symptoms and to perform daily spirometry. Criteria for diagnosis of exacerbations of COPD and CF were pre-defined. When exacerbations were detected, patients were offered treatment according to a pre-designed protocol. Thirty-two (63%) CF patients and one (5%) COPD patient withdrew from the studies due to lack of adherence to daily recording. For those who remained in the study, COPD patients recorded more study days (139) than CF patients (113), P = 0.03. The median number of exacerbations detected during the study was greater in COPD than in CF patients, although this was not significant. The median number of device-detected exacerbations in the COPD group was significantly greater than in the CF group, P = 0.024. When compared to a parallel period in the previous year, the number of hospitalisations for COPD exacerbations was reduced, whereas the number of intravenous antibiotics in CF patients did not differ. Adherence to telemonitoring was much greater for COPD than CF patients and the results appear to be more favourable for COPD patients than for CF patients.

  15. Ivacaftor improves appearance of sinus disease on computerised tomography in cystic fibrosis patients with G551D mutation.

    Science.gov (United States)

    Sheikh, S I; Long, F R; McCoy, K S; Johnson, T; Ryan-Wenger, N A; Hayes, D

    2015-02-01

    Most patients with Cystic fibrosis (CF) have chronic sinus disease which may require multiple sinus surgeries and antibiotic courses. Ivacaftor can improve lung function, lower sweat chloride levels and improve weight by targeting the primary defect, a faulty gene and its protein product, cystic fibrosis transmembrane conductance regulator (CFTR) in patients with the G551D mutation. Its role in improving sinus disease has not been evaluated. The objective of this study was to evaluate efficacy of ivacaftor in improving CF related sinus disease. Observational study. Twelve patients with cystic fibrosis and a G551D-CFTR mutation. Twelve patients with a G551D-CFTR mutation were monitored for at least one year before and after starting ivacaftor. Sinus disease progression was monitored by comparing computed tomography (CT) of sinuses before and at one year on therapy. Hospital admissions, pulmonary exacerbations, weight, BMI and lung function were also compared. Median age was 17 years (range 10-44). Weight, BMI, FEV1 significantly increased and sweat chloride significantly decreased by six months on ivacaftor therapy. CT of the sinuses in all patients improved. Seven patients had severe sinus disease, improved to moderate in three and mild in remaining four. Four patients had moderate disease which improved to mild in all. One patient had normal sinus CT before and after the therapy. Patients with CF and G551D mutation, within 6 months of starting ivacaftor had significant improvements in weight, BMI and mean % FEV1. Significant lessening of underlying sinus disease measured by CT scan was noted, suggesting a disease modifying effect. © 2014 John Wiley & Sons Ltd.

  16. Impact of cystic fibrosis disease on archaea and bacteria composition of gut microbiota.

    Science.gov (United States)

    Miragoli, Francesco; Federici, Sara; Ferrari, Susanna; Minuti, Andrea; Rebecchi, Annalisa; Bruzzese, Eugenia; Buccigrossi, Vittoria; Guarino, Alfredo; Callegari, Maria Luisa

    2017-02-01

    Cystic fibrosis is often associated with intestinal inflammation due to several factors, including altered gut microbiota composition. In this study, we analyzed the fecal microbiota among patients with cystic fibrosis of 10-22 years of age, and compared the findings with age-matched healthy subjects. The participating patients included 14 homozygotes and 14 heterozygotes with the delF508 mutation, and 2 heterozygotes presenting non-delF508 mutations. We used PCR-DGGE and qPCR to analyze the presence of bacteria, archaea and sulfate-reducing bacteria. Overall, our findings confirmed disruption of the cystic fibrosis gut microbiota. Principal component analysis of the qPCR data revealed no differences between homozygotes and heterozygotes, while both groups were distinct from healthy subjects who showed higher biodiversity. Archaea were under the detection limit in all homozygotes subjects, whereas methanogens were detected in 62% of both cystic fibrosis heterozygotes and healthy subjects. Our qPCR results revealed a low frequency of sulfate-reducing bacteria in the homozygote (13%) and heterozygote (13%) patients with cystic fibrosis compared with healthy subjects (87.5%). This is a pioneer study showing that patients with cystic fibrosis exhibit significant reduction of H 2 -consuming microorganisms, which could increase hydrogen accumulation in the colon and the expulsion of this gas through non-microbial routes. © FEMS 2016.

  17. Immunoblotting with Human Native Antigen Shows Stage-Related Sensitivity in the Serodiagnosis of Hepatic Cystic Echinococcosis

    OpenAIRE

    Mariconti, Mara; Bazzocchi, Chiara; Tamarozzi, Francesca; Meroni, Valeria; Genco, Francesca; Maserati, Roberta; Brunetti, Enrico

    2014-01-01

    The diagnosis of hepatic cystic echinococcosis is based on ultrasonography and confirmed by serology. However, no biological marker of cyst viability is currently available implying years-long patient follow-up, which is not always feasible in endemic areas. We characterized the performance of an immunoblotting test based on human hydatid cyst fluid with particular regard to its ability to distinguish between cyst stages. Sera from patients with cysts in different stages showed distinctive ba...

  18. Changes in the expression of Heat Shock Proteins in ovaries from bovines with cystic ovarian disease induced by ACTH.

    Science.gov (United States)

    Velázquez, Melisa M L; Salvetti, Natalia R; Amweg, Ayelen N; Díaz, Pablo U; Matiller, Valentina; Ortega, Hugo H

    2013-12-01

    Cystic ovarian disease (COD), which is considered one of the most important causes of reproductive failure in dairy cattle, induces intraovarian changes in the expression of numerous genes. The purpose of this study was to analyze the changes in the expression of Heat Shock Proteins (HSPs) in ovaries from bovines with cystic ovarian disease induced by ACTH. Immunoreactivity for Heat Shock Proteins (HSPs) in ovaries of cows with induced COD showed differential expression patterns in growing follicles from the control group. The immunopositive area for Hsp27 and Hsp60 in granulosa cells showed significant differences between tertiary follicles from normal cycling animals and those from animals with induced COD. The cysts showed increased Hsp27 immunostaining in theca cells in relation to tertiary follicles from normal cycling cows. Hsp70 immunostaining was more intense in cystic follicles than in other follicular categories from animals with induced COD, in both granulosa and theca cells. In granulosa cells, tertiary follicles from the control group showed higher levels of Hsp90 than cysts. These results demonstrate that there are differences in HSP protein expression when COD is induced. In fact, HSP expression would be part of the functional response to the changes in hormones and neurotransmitters induced by stress, indicating that HSPs can control hormonal functions and vice versa. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Sulfatases and human disease.

    Science.gov (United States)

    Diez-Roux, Graciana; Ballabio, Andrea

    2005-01-01

    Sulfatases are a highly conserved family of proteins that cleave sulfate esters from a wide range of substrates. The importance of sulfatases in human metabolism is underscored by the presence of at least eight human monogenic diseases caused by the deficiency of individual sulfatases. Sulfatase activity requires a unique posttranslational modification, which is impaired in patients with multiple sulfatase deficiency (MSD) due to a mutation of the sulfatase modifying factor 1 (SUMF1). Here we review current knowledge and future perspectives on the evolution of the sulfatase gene family, on the role of these enzymes in human metabolism, and on new developments in the therapy of sulfatase deficiencies.

  20. Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis

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    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.

  1. 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.

  2. Progress toward generating a ferret model of cystic fibrosis by somatic cell nuclear transfer

    OpenAIRE

    Engelhardt John F; Li Ziyi

    2003-01-01

    Abstract Mammalian cloning by nuclear transfer from somatic cells has created new opportunities to generate animal models of genetic diseases in species other than mice. Although genetic mouse models play a critical role in basic and applied research for numerous diseases, often mouse models do not adequately reproduce the human disease phenotype. Cystic fibrosis (CF) is one such disease. Targeted ablation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in mice does not...

  3. DETERMINATION OF GENOTYPE CHARACTERISTICS IN WOMEN WITH ENDOMETRIOSIS AND FIBROUS-CYSTIC MASTITIS AND THEIR ROLE IN DISEASE SEVERITY

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    L. M. Malanchuk

    2015-10-01

    Full Text Available The scientific work is devoted to the urgent problem of our time - dishormonal disease of the female reproductive system, namely endometriosis and fibrosis-cystic mastitis. During the last years there has been a steady increase in the dual pathology of genital and breast diseases. According to statistics dishormonal frequency of breast diseases in the population of the female population suffering from various gynecological diseases varies between 76-98 %. It is known that the risk of this disease is closely associated with some alleles detoxification system, glutathione family - S- transferase and proonkogenom p 53, characterized by significant polymorphism. The article presents the results of research on the role of deletion variants of genes GSTT1, GSTM1 and p 53 in the development of endometriosis and fibrosis-cystic mastitis. Screening populations on carriage of alleles reveals women who are likely to develop these diseases and choose the most effective tactics of medical treatment in the event of the disease.

  4. Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer subtypes.

    Science.gov (United States)

    Darb-Esfahani, Silvia; von Minckwitz, Gunter; Denkert, Carsten; Ataseven, Beyhan; Högel, Bernhard; Mehta, Keyur; Kaltenecker, Gabriele; Rüdiger, Thomas; Pfitzner, Berit; Kittel, Kornelia; Fiedler, Bettina; Baumann, Klaus; Moll, Roland; Dietel, Manfred; Eidtmann, Holger; Thomssen, Christoph; Loibl, Sibylle

    2014-07-28

    Gross cystic disease fluid protein 15 (GCDFP-15), which is regulated by the androgen receptor (AR), is a diagnostic marker for mammary differentiation in histopathology. We determined the expression of GCDFP-15 in breast cancer subtypes, its potential prognostic and predictive value, as well as its relationship to AR expression. 602 pre-therapeutic breast cancer core biopsies from the phase III randomized neoadjuvant GeparTrio trial (NCT00544765) were investigated for GCDFP-15 expression by immunohistochemistry. Expression data were correlated with disease-free (DFS) and overall survival (OS) time as well as pathological complete response (pCR) to neoadjuvant chemotherapy. 239 tumors (39.7%) were GCDFP-15 positive. GCDFP-15 expression was positively linked to hormone receptor (HR) and HER2 positive tumor type, while most triple negative carcinomas were negative (p < 0.0001). GCDFP-15 was also strongly correlated to AR expression (p 0.001), and to the so-called molecular apocrine subtype (HR-/AR+, p < 0.0001). Higher rates of GCDFP-15 positivity were seen in tumors of lower grade (<0.0001) and negative nodal status (p = 0.008). GCDFP-15 positive tumors tended to have a more favourable prognosis than GCDFP-15 negative tumors (DFS (p = 0.052) and OS (p = 0.044)), which was not independent from other factors in multivariate analysis. GCDFP-15 expression was not linked to pCR. Histological apocrine differentiation was frequent in molecular apocrine carcinomas (60.7%), and was associated with GCDFP-15 within this group (p = 0.039). GCDFP-15 expression is higher in tumors with favorable prognostic features. GCDFP-15 expression is further a frequent feature of AR positive tumors and the molecular apocrine subtype. It might have reduced sensitivity as a diagnostic marker for mammary differentiation in triple negative tumors as compared to HR or HER2 positive tumor types.

  5. Lung function and disease severity in cystic fibrosis patients heterozygous for p.Arg117His

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    Michal Shteinberg

    2017-03-01

    Full Text Available Expression of p.Arg117His cystic fibrosis (CF transmembrane conductance regulator is influenced by a polythymidine (poly-T tract and a thymidine–guanine (TG repeat on intron 9, which vary in length and affect exon 10 skipping. We compared clinical characteristics and the rate of progression of lung disease of CF patients carrying the p.Arg117His mutation with different intron 9 varying sequences (poly-T and mutation classes in trans. Data were collected from patients in Northern Ireland, UK, including diagnostic features, sweat chloride, nutritional status, sputum microbiology, CF-related complications and lung function. Poly-T and TG repeats were determined by PCR. Forced expiratory volume in 1 s (FEV1 decline was determined from linear regression of FEV1 measurements of patients over time. We identified 62 patients with p.Arg117His, 55 with a class I/II mutation in trans and six with p.Arg117His/p.Gly551Asp. 42 patients had 5T and 13 had 7T. All patients had 12 TG repeats. Patients with p.Arg117His-5T had greater lung function decline, sweat chloride concentrations, pancreatic insufficiency and prevalence of Pseudomonas aeruginosa infection compared with patients with p.Arg117His-7T. Lung function decline and disease severity in p.Arg117His is determined by the poly-T tract length and identity of the mutation in trans. Patients with p.Arg117His-5T and a second class I/II mutation have a severity similar to p.Phe508del homozygous patients, although lung function decline is delayed to an older age. There may be linkage disequilibrium between p.Arg117His and 12 TG repeats.

  6. [Liver disease, gastrointestinal complications, nutritional management and feeding disorders in pediatric cystic fibrosis].

    Science.gov (United States)

    Debray, D; Mas, E; Munck, A; Gérardin, M; Clouzeau, H

    2016-12-01

    In cystic fibrosis (CF), approximately 5-8% of the patients develop multilobular cirrhosis during the first decade of life. Annual screening (clinical examination, liver biochemistry, ultrasonography) is recommended in order to identify early signs of liver involvement, initiate ursodeoxycholic acid therapy and detect complications (portal hypertension and liver failure). Management should focus on nutrition and prevention of variceal bleeding. The gut may also be involved in children with CF. Gastroesophageal reflux is frequent, although often neglected and should be investigated by pH monitoring and impedancemetry, if available. Acute pancreatitis occurs in patients with persistent exocrine pancreatic activity. Intussusception, appendicular mucocele, distal intestinal occlusion syndrome, small bowel bacterial overgrowth and Clostridium difficile colitis should be considered in case of abdominal pain. Preventive nutritional support should be started as soon as possible after diagnosis of CF. Attainment of normal growth is one of the main goals and can be achieved with hypercaloric and salt supplemented food. Pancreatic enzyme replacement therapy should be started as soon as exocrine pancreatic insufficiency is confirmed and ingested immediately prior to meals with intake of fat-soluble vitamins. Curative nutritional interventions are more likely to be effective in the early stages of pulmonary disease. Feeding disorders, related to the physiopathology and the psychologic aspects of the disease are frequent. Repeated corporeal aggressions, associated with inappropriate medical and parental pressure, may increase the child's refusal of food. The multidisciplinary team should guide parents in order to avoid all intrusive feeding practices and promote pleasant mealtimes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Polysomnographic differences associated with pulmonary hypertension in patients with advanced lung disease due to cystic fibrosis.

    Science.gov (United States)

    Hayes, Don; Daniels, Curt J; Kirkby, Stephen; Kopp, Benjamin T; Nicholson, Kerri L; Nance, Ashley E; Splaingard, Mark L

    2014-06-01

    Pulmonary hypertension (PH) commonly occurs in patients with cystic fibrosis (CF), but there is no current data regarding alterations of sleep in patients with PH. A single-center, retrospective review was performed in patients with advanced lung disease due to CF who completed both nocturnal polysomnography and right heart catheterization (RHC) from January 2010 to June 2013. For statistical analysis, two-tailed unpaired t tests and Pearson correlation coefficient analysis were performed after normal distribution was confirmed. A total of 18 consecutive CF patients were enrolled with RHC identifying PH in 56 % (10/18) of patients. The PH group had significantly lower mean sleep efficiency (72 ± 4 vs. 87 ± 3 %, p = 0.01), significantly higher ETCO(2) levels (54.5 ± 2.2 vs. 43.8 ± 3.0 mmHg, p = 0.01) on capnography, and significantly lower PO(2) (53.8 ± 3.1 vs. 65.5 ± 3.9 mmHg, p = 0.03) on capillary blood gas. Correlations with poor sleep efficiency included mean PAP (r = - 0.55, p = 0.01), systolic PAP (r = -0.5, p = 0.03), ETCO(2) (r = - 0.53, p = 0.02), and PO(2)) (r = 0.62, p = 0.01); ETCO(2) with systolic PAP (r = 0.47, p = 0.04) and PCO(2) (r = - 0.57, p = 0.01); and PO(2) to 6-min walk distance (r = 0.55, p = 0.02). We found significant differences in sleep efficiency and gas exchange associated with PH in CF patients with advanced lung disease.

  8. Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis

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    Löfdahl Claes-Göran

    2011-10-01

    Full Text Available Abstract Background Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF and idiopathic pulmonary fibrosis (IPF has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls. Methods Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients, IPF (21 regions; 7 patients and controls (16 regions; 8 subjects. In each compartment the densities and distribution of MCT and MCTC mast cell populations were studied as well as the mast cell expression of IL-6 and TGF-β. Results In the alveolar parenchyma in lungs from patients with CF, MCTC numbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MCTC and MCT cells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MCTC density was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-β. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MCTC correlated positively with the degree of fibrosis. The increased density of MCTC, as well as MCTC expression of TGF-β, correlated negatively with patient lung function. Conclusions The present study reveals that altered mast cell populations, with increased numbers of MCTC in diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further

  9. Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology.

    Science.gov (United States)

    Lasalvia, Maria; Castellani, Stefano; D'Antonio, Palma; Perna, Giuseppe; Carbone, Annalucia; Colia, Anna Laura; Maffione, Angela Bruna; Capozzi, Vito; Conese, Massimo

    2016-10-15

    The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. IFN-γ stimulates autophagy-mediated clearance of Burkholderia cenocepacia in human cystic fibrosis macrophages.

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    Kaivon Assani

    Full Text Available Burkholderia cenocepacia is a virulent pathogen that causes significant morbidity and mortality in patients with cystic fibrosis (CF, survives intracellularly in macrophages, and uniquely causes systemic infections in CF. Autophagy is a physiologic process that involves engulfing non-functional organelles and proteins and delivering them for lysosomal degradation, but also plays a role in eliminating intracellular pathogens, including B. cenocepacia. Autophagy is defective in CF but can be stimulated in murine CF models leading to increased clearance of B. cenocepacia, but little is known about autophagy stimulation in human CF macrophages. IFN-γ activates macrophages and increases antigen presentation while also inducing autophagy in macrophages. We therefore, hypothesized that treatment with IFN-γ would increase autophagy and macrophage activation in patients with CF. Peripheral blood monocyte derived macrophages (MDMs were obtained from CF and non-CF donors and subsequently infected with B. cenocepacia. Basal serum levels of IFN-γ were similar between CF and non-CF patients, however after B. cenocepacia infection there is deficient IFN-γ production in CF MDMs. IFN-γ treated CF MDMs demonstrate increased co-localization with the autophagy molecule p62, increased autophagosome formation, and increased trafficking to lysosomes compared to untreated CF MDMs. Electron microscopy confirmed IFN-γ promotes double membrane vacuole formation around bacteria in CF MDMs, while only single membrane vacuoles form in untreated CF cells. Bacterial burden is significantly reduced in autophagy stimulated CF MDMs, comparable to non-CF levels. IL-1β production is decreased in CF MDMs after IFN-γ treatment. Together, these results demonstrate that IFN-γ promotes autophagy-mediated clearance of B. cenocepacia in human CF macrophages.

  11. Expression of mammaglobin and gross cystic disease fluid protein-15 in breast carcinomas.

    Science.gov (United States)

    Luo, Ming-Hua; Huang, Yu-Hua; Ni, Yun-Bi; Tsang, Julia Y S; Chan, Siu-Ki; Shao, Mu-Min; Tse, Gary M

    2013-07-01

    Immunohistochemical analysis of gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin (MGB) is frequently used in routine practice for assessment of metastases or regional recurrences of breast origin. Breast cancer is highly heterogeneous. Expression of these 2 markers in various breast cancer subtypes has not been well studied. In addition, the usefulness of these two markers in combination in detecting breast origin has not been explored. In this study, a large cohort of breast cancers was evaluated for GCDFP-15 and MGB expression, both individually and combined. Their expression was correlated with cancer subtypes, other biomarkers and clinicopathologic parameters. A higher sensitivity for MGB (42.3%) than GCDFP-15 (31.6%) in detecting cancers of breast origin was observed. Combining both increased the sensitivity further, both for primary tumor (53.0%) and for nodal metastases (69.0%). GCDFP-15 was associated significantly with a breast cancer profile of good prognosis tumors, including lower grade (P < .001), pN (P = .029) and Ki-67 (P < .001) as well as negative basal markers expression (P = .043, .009, and .049 for c-Kit, CK5/6 and epidermal growth factor receptor, respectively) and, thus, may not be sensitive for detection of poor prognosis tumors. MGB has the highest expression in HER2-overexpressing cancers (56.6%), and may be a potentially useful marker for this subtype. Nonetheless, both markers showed low expression in the basal like (BLBC) subtype (11.9% and 21.4% for GCDFP-15 and MGB respectively), therefore, the detection of BLBC remains problematic. Negative results need to be interpreted with caution, and correlation with other clinical findings may be required to exclude the possibility of metastatic BLBC. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Involvement of Matrix Metalloproteinases and their Inhibitors in Bovine Cystic Ovarian Disease.

    Science.gov (United States)

    Peralta, M B; Baravalle, M E; Belotti, E M; Stassi, A F; Salvetti, N R; Ortega, H H; Rey, F; Velázquez, M M L

    The most important regulators of tissue remodelling during ovarian follicular growth, development, ovulation and atresia are gonadotropins, steroid hormones, growth factors and different proteolytic enzymes. Matrix metalloproteinases (MMPs) such as collagenase or gelatinase (i.e. MMP-1, -8, -2 and -9) and associated tissue inhibitors of metalloproteinases (TIMP-1, -2, -3 and -4) control connective tissue remodelling during follicular rupture. In this study, we hypothesized that an imbalance in the MMP-TIMP system may be an intra-ovarian component that contributes to the pathogenesis of cystic ovarian disease (COD) in cows. Taking into account that the control of MMP activity by TIMPs could determine their effects in both physiological and pathological conditions, MMP and TIMP mRNA and protein expression was examined by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), respectively, in ovaries from control cows and cows with COD. Expression of mRNA encoding MMP-2, TIMP-1 and TIMP-2 was lower in follicular cysts than in control pre-ovulatory follicles, while the results by IHC showed this imbalance only for TIMP-2 protein expression. Additional analysis by zymography to evaluate the gelatinase activity of MMP-2 and MMP-9 demonstrated higher MMP-2 activity in follicular fluid (FF) of cysts than in FF of pre-ovulatory follicles. On the other hand, MMP-9 activity was increased in follicular cysts and absent in the FF of pre-ovulatory follicles. These findings suggest that the altered mRNA expression and activities of the MMP-TIMP system may be related to the failure in ovulation and follicular development observed in COD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Management of endocrine disease: Cystic fibrosis-related diabetes: novel pathogenic insights opening new therapeutic avenues.

    Science.gov (United States)

    Barrio, Raquel

    2015-04-01

    Cystic fibrosis (CF) is a recessive genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR). CFTR is primarily present in epithelial cells of the airways, intestine and in cells with exocrine and endocrine functions. Mutations in the gene encoding the channel protein complex (CFTR) cause alterations in the ionic composition of secretions from the lung, gastrointestinal tract, liver, and also the pancreas. CF-related diabetes (CFRD), the most common complication of CF, has a major detrimental impact on pulmonary function, nutrition and survival. Glucose derangements in CF seem to start from early infancy and, even when the pathophysiology is multifactorial, insulin insufficiency is clearly a major component. Consistently, recent evidence has confirmed that CFTR is an important regulator of insulin secretion by islet β-cells. In addition, several other mechanisms were also recognized from cellular and animals models also contributing to either β-cell mass reduction or β-cell malfunction. Understanding such mechanisms is crucial for the development of the so-called 'transformational' therapies in CF, including the preservation of insulin secretion. Innovative therapeutic approaches aim to modify specific CFTR mutant proteins or positively modulate their function. CFTR modulators have recently shown in vitro capacity to enhance insulin secretion and thereby potential clinical utility in CFDR, including synergistic effects between corrector and potentiator drugs. The introduction of incretins and the optimization of exocrine pancreatic replacement complete the number of therapeutic options of CFRD besides early diagnosis and implementation of insulin therapy. This review focuses on the recently identified pathogenic mechanisms leading to CFRD relevant for the development of novel pharmacological avenues in CFRD therapy. © 2015 European Society of Endocrinology.

  14. Characterizing Lung Disease in Cystic Fibrosis with Magnetic Resonance Imaging and Airway Physiology.

    Directory of Open Access Journals (Sweden)

    Rebecca J Theilmann

    Full Text Available Translational investigations in cystic fibrosis (CF have a need for improved quantitative and longitudinal measures of disease status. To establish a non-invasive quantitative MRI technique to monitor lung health in patients with CF and correlate MR metrics with airway physiology as measured by multiple breath washout (MBW. Data were collected in 12 CF patients and 12 healthy controls. Regional (central and peripheral lung measures of fractional lung water density (FLD: air to 100% fluid were acquired both at FRC and TLC on a 1.5T MRI. The median FLD (mFLD and the FRC-to-TLC mFLD ratio were calculated for each region at both lung volumes. Spirometry and MBW data were also acquired for each subject. Ventilation inhomogeneities were quantified by the lung clearance index (LCI and by indices Scond* and Sacin* that assess inhomogeneities in the conducting (central and acinar (peripheral lung regions, respectively. MBW indices and mFLD at TLC (both regions were significantly elevated in CF (p<0.01 compared to controls. The mFLD at TLC (central: R = 0.82 and the FRC-to-TLC mFLD ratio (peripheral: R = -0.77 were strongly correlated with Scond* and LCI. CF patients had high lung water content at TLC when compared to controls. This is likely due to the presence of retained airway secretions and airway wall edema (more water and to limited expansions of air trapping areas (less air in CF subjects. FRC-to-TLC ratios of mFLD strongly correlated with central ventilation inhomogeneities. These combined measures may provide a useful marker of both retained mucus and air trapping in CF lungs.

  15. [Cystic fibrosis -- disease burden and health-related quality of life of patients and their caregivers: results of the European BURQOL-RD survey in Hungary].

    Science.gov (United States)

    Péntek, Márta; Kosztolányi, György; Melegh, Béla; Halász, Adrienn; Pogány, Gábor; Baji, Petra; Brodszky, Valentin; Vártokné Hevér, Noémi; Boncz, Imre; Gulácsi, László

    2014-10-19

    Data on disease burden of cystic fibrosis in Hungary are scarce. To assess quality of life and resource utilisations of patients with cystic fibrosis. In a cross-sectional survey (BURQOL-RD project), the EQ-5D-5L questionnaire was applied and healthcare utilisations were retrospectively surveyed. 110 patients participated in the study (age-groups, year: 0-13, N = 48; 14-17, N = 12; ≥18, N = 50), median age at the diagnosis was 1 year. EQ-5D-5L score in age-groups 18-24 and 25-34 was significantly lower than in the general population (pCystic fibrosis leads to significant deterioration of quality of life. This study is the first from the Central Eastern European region that provides basic inputs for further health economic evaluations of cystic fibrosis care.

  16. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.

    Science.gov (United States)

    Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J; Tyler, Scott R; Tisoncik-Go, Jennifer; Brawand, David; Law, G Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J; Kelly, Sara M; Chang, Jean; Thomas, Matthew J; Johnson, Jeremy; Berlin, Aaron M; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M; Tumpey, Terrence M; Siepel, Adam; Wisely, Samantha M; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F; Palermo, Robert E; Katze, Michael G

    2014-12-01

    The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

  17. CFTR Expression in Human Neutrophils and the Phagolysosomal Chlorination Defect in Cystic Fibrosis

    Science.gov (United States)

    Painter, Richard G.; Valentine, Vincent G.; Lanson, Nicholas A.; Leidal, Kevin; Zhang, Qiang; Lombard, Gisele; Thompson, Connie; Viswanathan, Anand; Nauseef, William M.; Wang, Guangdi; Wang, Guoshun

    2010-01-01

    Production of hypochlorous acid (HOCl) in neutrophils, a critical oxidant involved in bacterial killing, requires chloride anions. Because the primary defect of cystic fibrosis (CF) is the loss of chloride transport function of the CF transmembrane conductance regulator (CFTR), we hypothesized that CF neutrophils may be deficient in chlorination of bacterial components due to limited chloride supply to the phagolysosomal compartment. Multiple approaches, including RT-PCR, immunofluorescence staining, and immunoblotting, were used to demonstrate that CFTR is expressed in resting neutrophils at the mRNA and protein levels. Probing fractions of resting neutrophils isolated by Percoll gradient fractionation and free flow electrophoresis for CFTR revealed its presence exclusively in secretory vesicles. The CFTR chloride channel was also detected in phagolysosomes, a special organelle formed after phagocytosis. Interestingly, HL-60 cells, a human promyelocytic leukemia cell line, upregulated CFTR when induced to differentiate into neutrophils with DMSO, strongly suggesting its potential role in mature neutrophil function. Analyses by gas chromatography and mass spectrometry (GC/MS) revealed that neutrophils from CF patients had a defect in their ability to chlorinate bacterial proteins from Pseudomonas aeruginosa metabolically pre-labeled with 13C-L-tyrosine, unveiling defective intraphagolysosomal HOCl production. In contrast, both normal and CF neutrophils exhibited normal extracellular production of HOCl when stimulated with phorbol ester, indicating that CF neutrophils had the normal ability to produce this oxidant in the extracellular medium. This report provides the evidence to suggest that CFTR channel expression in neutrophils and its dysfunction affects neutrophil chlorination of phagocytosed bacteria. PMID:16922501

  18. Cystic Fibrosis-related Liver Disease : Research Challenges and Future Perspectives

    NARCIS (Netherlands)

    Debray, Dominique; Narkewicz, Michael R; Bodewes, Frank A J A; Colombo, Carla; Housset, Chantal; de Jonge, Hugo R; Jonker, Johan W; Kelly, Deirdre A; Ling, Simon C; Poynard, Thierry; Sogni, Philippe; Trauner, Michael; Witters, Peter; Baumann, Ulrich; Wilschanski, Michael; Verkade, Henkjan J

    2017-01-01

    Objectives: Hepatobiliary complications are a leading cause of morbidity and mortality in cystic fibrosis (CF) patients. Knowledge of the underlying pathological aspects and optimal clinical management is, however, sorely lacking. Methods: We provide a summary of the lectures given by international

  19. Overview: ABC transporters and human disease.

    Science.gov (United States)

    Gottesman, M M; Ambudkar, S V

    2001-12-01

    ABC transporters are found in all known organisms, and approximately 1,100 different transporters belonging to this family have been described in the literature. The family is defined by homology within the ATP-binding cassette (ABC) region, which extends outside of the more typical Walker motifs found in all ATP-binding proteins. Most family members also contain transmembrane domains involved in recognition of substrates, which are transported across, into, and out of cell membranes, but some members utilize ABCs as engines to regulate ion channels. There are approximately 50 known ABC transporters in the human, and there are currently 13 genetic diseases associated with defects in 14 of these transporters. The most common genetic disease conditions include cystic fibrosis, Stargardt disease, age-related macular degeneration, adrenoleukodystrophy, Tangier disease, Dubin-Johnson syndrome and progressive familial intrahepatic cholestasis. At least 8 members of this family are involved in the transport of a variety of amphipathic compounds, including anticancer drugs, and some appear to contribute to the resistance of cancer cells to chemotherapy.

  20. The Microbiota, Chemical Symbiosis, and Human Disease

    Science.gov (United States)

    Redinbo, Matthew R.

    2014-01-01

    Our understanding of mammalian-microbial mutualism has expanded by combing microbial sequencing with evolving molecular and cellular methods, and unique model systems. Here, the recent literature linking the microbiota to diseases of three of the key mammalian mucosal epithelial compartments – nasal, lung and gastrointestinal (GI) tract – is reviewed with a focus on new knowledge about the taxa, species, proteins and chemistry that promote health and impact progression toward disease. The information presented is further organized by specific diseases now associated with the microbiota:, Staphylococcus aureus infection and rhinosinusitis in the nasal-sinus mucosa; cystic fibrosis (CF), chronic obstructive pulmonary disorder (COPD), and asthma in the pulmonary tissues. For the vast and microbially dynamic GI compartment, several disorders are considered, including obesity, atherosclerosis, Crohn’s disease, ulcerative colitis, drug toxicity, and even autism. Our appreciation of the chemical symbiosis ongoing between human systems and the microbiota continues to grow, and suggest new opportunities for modulating this symbiosis using designed interventions. PMID:25305474

  1. High Spatial Resolution MRI of Cystic Adventitial Disease of the Iliofemoral Vein Communicating with the Hip Joint

    Energy Technology Data Exchange (ETDEWEB)

    Michaelides, Michael, E-mail: mihalismihailidis@gmail.com [Ygia Polyclinic Hospital, MRI/CT Department (Cyprus); Papas, Stylianos, E-mail: vascular@drpapas.com [Ygia Polyclinic Hospital, Vascular Surgery Department (Cyprus); Pantziara, Maria, E-mail: mgpantziara@gmail.com; Ioannidis, Kleanthis, E-mail: aktinodiagnostis@gmail.com [Ygia Polyclinic Hospital, MRI/CT Department (Cyprus)

    2013-05-14

    Venous cystic adventitial disease (CAD) is an extremely rare entity, and so far less than 20 cases have been described in the literature. Herein, we describe the imaging findings of CAD of iliofemoral vein in a 51-year-old woman who presented with leg swelling with special emphasis on high spatial resolution MRI, which demonstrated communication of the cyst with the hip joint. To our knowledge, this is the first description of high spatial resolution MRI findings in venous CAD supporting a new theory about the pathogenesis of venous CAD.

  2. High spatial resolution MRI of cystic adventitial disease of the iliofemoral vein communicating with the hip joint.

    Science.gov (United States)

    Michaelides, Michael; Papas, Stylianos; Pantziara, Maria; Ioannidis, Kleanthis

    2014-02-01

    Venous cystic adventitial disease (CAD) is an extremely rare entity, and so far less than 20 cases have been described in the literature. Herein, we describe the imaging findings of CAD of iliofemoral vein in a 51-year-old woman who presented with leg swelling with special emphasis on high spatial resolution MRI, which demonstrated communication of the cyst with the hip joint. To our knowledge, this is the first description of high spatial resolution MRI findings in venous CAD supporting a new theory about the pathogenesis of venous CAD.

  3. Pseudotyped AAV vector-mediated gene transfer in a human fetal trachea xenograft model: implications for in utero gene therapy for cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Sundeep G Keswani

    Full Text Available Lung disease including airway infection and inflammation currently causes the majority of morbidities and mortalities associated with cystic fibrosis (CF, making the airway epithelium and the submucosal glands (SMG novel target cells for gene therapy in CF. These target cells are relatively inaccessible to postnatal gene transfer limiting the success of gene therapy. Our previous work in a human-fetal trachea xenograft model suggests the potential benefit for treating CF in utero. In this study, we aim to validate adeno-associated virus serotype 2 (AAV2 gene transfer in a human fetal trachea xenograft model and to compare transduction efficiencies of pseudotyping AAV2 vectors in fetal xenografts and postnatal xenograft controls.Human fetal trachea or postnatal bronchus controls were xenografted onto immunocompromised SCID mice for a four-week engraftment period. After injection of AAV2/2, 2/1, 2/5, 2/7 or 2/8 with a LacZ reporter into both types of xenografts, we analyzed for transgene expression in the respiratory epithelium and SMGs. At 1 month, transduction by AAV2/2 and AAV2/8 in respiratory epithelium and SMG cells was significantly greater than that of AAV2/1, 2/5, and 2/7 in xenograft tracheas. Efficiency in SMG transduction was significantly greater in AAV2/8 than AAV2/2. At 3 months, AAV2/2 and AAV2/8 transgene expression was >99% of respiratory epithelium and SMG. At 1 month, transduction efficiency of AAV2/2 and AAV2/8 was significantly less in adult postnatal bronchial xenografts than in fetal tracheal xenografts.Based on the effectiveness of AAV vectors in SMG transduction, our findings suggest the potential utility of pseudotyped AAV vectors for treatment of cystic fibrosis. The human fetal trachea xenograft model may serve as an effective tool for further development of fetal gene therapy strategies for the in utero treatment of cystic fibrosis.

  4. Human cystic echinococcosis in Turkey: a preliminary study on DNA polymorphisms of hydatid cysts removed from confirmed patients.

    Science.gov (United States)

    Orsten, Serra; Boufana, Belgees; Ciftci, Turkmen; Akinci, Devrim; Karaagaoglu, Ergun; Ozkuyumcu, Cumhur; Casulli, Adriano; Akhan, Okan

    2018-02-23

    Cystic echinococcosis caused by the larval stages of Echinococcus granulosus sensu lato s.l is endemic in Turkey with a high public health impact particularly in rural areas. The aim of this study was to investigate the genetic variation and population structure of E. granulosus s.s using metacestode isolates removed from surgically confirmed patients originating from several regions in Turkey and to investigate the occurrence of autochthonous transmission. Using DNA extracted from a total of 46 human-derived CE isolates, we successfully analysed an 827-bp fragment within the cox1 mitochondrial gene and confirmed the causative agent of human cystic echinococcosis in patients included in this study to be Echinococcus granulosus s.s (G1 and G3 genotypes). The haplotype parsimony network consisted of 28 haplotypes arranged within three main clusters and the neutrality indices were both negative and significant indicating negative selection or population expansion. The assessment carried out in this study using GenBank nucleotide sequence data from Turkey for sheep and cattle hosts demonstrated the importance of autochthonous transmission with sheep, cattle and humans harbouring the same haplotypes. Further studies are required to investigate the biological significance, if any, of E. granulosus s.s haplotypes and the genetic variability of CE from human patients using longer nucleotide sequences and a larger sample set.

  5. Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

    Energy Technology Data Exchange (ETDEWEB)

    Lasalvia, Maria [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Castellani, Stefano [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); D’Antonio, Palma [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Perna, Giuseppe [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Carbone, Annalucia [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); Colia, Anna Laura; Maffione, Angela Bruna [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Capozzi, Vito [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Conese, Massimo, E-mail: massimo.conese@unifg.it [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy)

    2016-10-15

    The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in

  6. Potential Risk Factors Associated with Human Cystic Echinococcosis: Systematic Review and Meta-analysis

    Science.gov (United States)

    Possenti, Alessia; Manzano-Román, Raúl; Sánchez-Ovejero, Carlos; Boufana, Belgees; La Torre, Giuseppe; Siles-Lucas, Mar; Casulli, Adriano

    2016-01-01

    Background Scientific literature on cystic echinococcosis (CE) reporting data on risk factors is limited and to the best of our knowledge, no global evaluation of human CE risk factors has to date been performed. This systematic review (SR) summarizes available data on statistically relevant potential risk factors (PRFs) associated with human CE. Methodology/Principal Findings Database searches identified 1,367 papers, of which thirty-seven were eligible for inclusion. Of these, eight and twenty-nine were case-control and cross-sectional studies, respectively. Among the eligible papers, twenty-one were included in the meta-analyses. Pooled odds ratio (OR) were used as a measure of effect and separately analysed for the two study designs. PRFs derived from case-control studies that were significantly associated with higher odds of outcome were “dog free to roam” (OR 5.23; 95% CI 2.45–11.14), “feeding dogs with viscera” (OR 4.69; 95% CI 3.02–7.29), “slaughter at home” (OR 4.67; 95% CI 2.02–10.78) or at “slaughterhouses” (OR 2.7; 95% CI 1.15–6.3), “dog ownership” (OR 3.54; 95% CI 1.27–9.85), “living in rural areas” (OR 1.83; 95% CI 1.16–2.9) and “low income” (OR 1.68; 95% CI 1.02–2.76). Statistically significant PRFs from cross-sectional studies with higher odds of outcome were “age >16 years” (OR 6.08; 95% CI 4.05–9.13), “living in rural areas” (OR 2.26; 95% CI 1.41–3.61), “being female” (OR 1.38; 95% CI 1.06–1.8) and “dog ownership” (OR 1.37; 95% CI 1.01–1.86). Conclusions/Significance Living in endemic rural areas, in which free roaming dogs have access to offal and being a dog-owner, seem to be among the most significant PRFs for acquiring this parasitic infection. Results of data analysed here may contribute to our understanding of the PRFs for CE and may potentially be useful in planning community interventions aimed at controlling CE in endemic areas. PMID:27820824

  7. Steroid receptors in benign breast disease, gross cystic disease and fibroadenoma.

    Science.gov (United States)

    Nardelli, G B; Lamaina, V; Siliotti, F

    1987-01-01

    The benign breast pathology embraces a wide variety of anatomo-clinical-pathological conditions producing confusion in nomenclature. The Authors collected three different types of BBP and investigated the hormonal receptor status for each. The following concentrations of ERc were found: 1-6 fmol/mg in BBD; less than 2 fmol/mg in GCD; 12-18 fmol/mg in the cytoplasm and 29-37.5 fmol/mg in the nucleus in FA. In FA, PgR was found in concentrations of 43.5-50 fmol/mg in the cytoplasm and 0.2-10 fmol/mg in the nucleus. Even if we consider these three histo-pathological entities (BBD, GCD, FA) separately, no correlation can be seen between the presence of receptors and benign breast disease. The only observation we can make is that the fibroadenomas contain more easily identifiable receptor concentrations than BBD and GCD.

  8. Pseudomonas aeruginosa in cystic fibrosis: pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease.

    Science.gov (United States)

    Carlsson, Malin; Shukla, Swati; Petersson, Ann Cathrine; Segelmark, Mårten; Hellmark, Thomas

    2011-07-01

    The clinical consequence of chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF) varies between individuals for unknown reasons. Auto-antibodies against bactericidal/permeability increasing protein (BPI-ANCA) are associated with poor prognosis in CF. We hypothesize that there is a correlation between the presence of BPI-ANCA, the properties of the colonizing bacteria and the clinical conditions of the host. We compared isolates of P. aeruginosa from BPI-ANCA positive CF patients who have deteriorating lung disease with BPI-ANCA negative CF patients who are in stable clinical conditions. Epithelial cells (A549) and isolated polymorphonuclear granulocytes (PMNs) were stimulated with the isolates and cell death was analyzed with flow cytometry. We found that the ANCA associated strains in most cases showed pyocyanin negative phenotypes. These strains also induced less inflammatory response than the non-ANCA associated strains as shown by apoptosis and necrosis of epithelial cells and neutrophils. Our results suggest that colonization with strains of P. aeruginosa that induce a weak inflammatory response is associated with unfavorable outcome in CF. We speculate that inadequate control of pathogen proliferation through an insufficient inflammatory response results in a slowly increasing number of bacteria and accumulation of dying PMNs in the airways, contributing to progression in CF lung disease. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  9. Cystic fibrosis genetics: from molecular understanding to clinical application

    Science.gov (United States)

    Cutting, Garry R.

    2015-01-01

    The availability of the human genome sequence and tools for interrogating individual genomes provide an unprecedented opportunity to apply genetics to medicine. Mendelian conditions, which are caused by dysfunction of a single gene, offer powerful examples that illustrate how genetics can provide insights into disease. Cystic fibrosis, one of the more common lethalautosomal recessive Mendelian disorders, is presented here as an example. Recent progress in elucidating disease mechanism and causes of phenotypic variation, as well as in the development of treatments, demonstrates that genetics continues to play an important part in cystic fibrosis research 25 years after the d iscove1y of the disease-causing gene. PMID:25404111

  10. Effect of selected factors associated with the clinical course of the disease on nutritional status in children with cystic fibrosis.

    Science.gov (United States)

    Umławska, Wioleta; Krzyżanowska, Monika; Zielińska, Anna; Sands, Dorota

    2014-01-01

    Malnutrition and delayed growth are commonly seen in children with cystic fibrosis and are indicators of poor prognosis. Understanding the factors that affect growth and nutritional status may improve care, treatment and longevity. To determine how nutritional status, as estimated using anthropometric measurements, in children with cystic fibrosis is affected by 1) the type of CFTR mutation, 2) colonization by Pseudomonas aeruginosa, and 3) age at diagnosis. The relationship between nutritional status and pulmonary function was also investigated. Anthropometric data on height, weight, circumferences and skinfold thicknesses were extracted from the medical histories of 41 boys and 48 girls diagnosed with cystic fibrosis who were treated at the Institute of Mother and Child in Warsaw, Poland. Muscle and fat tissue area were calculated from these measurements. The values for children with CF were compared to the Polish national growth reference charts. Multivariate linear regression tested the effect of three factors on nutritional status: colonization with P. aeruginosa, age at diagnosis, and the type of CFTR mutation. All values for children with CF were significantly lower than in the reference population. The results show that, in the children examined, nutritional status is more adversely affected than growth. Of the factors related to the clinical picture of the disease, only the presence of respiratory tract colonization by P. aeruginosa had an effect on physical development in the children examined. Neither the type of mutation present nor age at diagnosis had any significant effect. Chronic colonization by P. aeruginosa interfered with growth and markedly worsened nutritional status, and was also associated with reductions in both total and lean body mass. Early nutritional intervention can improve nutritional state and pulmonary function in children with CF.

  11. Insulin-like growth factor I in sera, ovarian follicles and follicular fluid of cows with spontaneous or induced cystic ovarian disease.

    Science.gov (United States)

    Ortega, Hugo H; Palomar, Martin M; Acosta, Juan C; Salvetti, Natalia R; Dallard, Bibiana E; Lorente, Juan A; Barbeito, Claudio G; Gimeno, Eduardo J

    2008-06-01

    The objective of this research was to determine changes in IGF-I levels in serum and follicular fluid, and immunoreactivity of the follicle wall of cows with spontaneous (slaughter specimens) or ACTH-induced follicular cysts, and to compare results to normal cycling (control) cows after selection of the ovulatory follicle. Concentrations of IGF-I in serum did not differ between control and cystic animals (p=0.76). Fluid from the ovulatory follicle in control cows had 41% higher concentrations of IGF-I than that from cystic follicles collected at slaughter (spontaneous cysts; pfollicular cysts (povarian disease in cattle is associated with decreased concentrations of IGF-I in follicular fluid, but not in serum, and decreased production of IGF-I in the follicular wall. These data support the notion that IGF-I plays a role in the regulation of folliculogenesis, and may participate in the pathogenesis of cystic ovarian disease in cattle.

  12. Patient's perception of the meaning of life in cystic fibrosis--its evaluation with respect to the stage of the disease and treatment.

    Science.gov (United States)

    Cepuch, Grażyna; Dębska, Grażyna; Pawlik, Lidia; Mazurek, Henryk

    2012-10-19

    Cystic fibrosis (CF) is related to physical and mental barriers. The objective of this work was to evaluate and compare patients' perception of sense of life in cystic fibrosis in different stages of their disease and therapeutic methods. The study group included 45 patients divided into 3 subgroups: after lung transplantation, waiting for lung transplantation and with cystic fibrosis in stable condition. The evaluation and comparison of patient's perception of sense of life and purpose of life was performed with the Purpose in Life Test. All patients with CF felt their lives were meaningful and purposeful. However, their pursuits for designated aims depended on the progression of their disease. CF with its poor prognosis has a significant impact on patient's hierarchy of respected values and life priorities. High level of acceptance for suicidal behaviours observed in all diagnostic subgroups of patients with CF indicates a need for organized intensified psychological care.

  13. 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

  14. Human Echinococcosis: A Neglected Disease

    Directory of Open Access Journals (Sweden)

    António Menezes da Silva

    2010-01-01

    Full Text Available Echinococcosis is among the most neglected parasitic diseases. Development of new drugs and other treatment modalities receives very little attention, if any. In most developed countries, Cystic Echinococcosis (CE is an imported disease of very low incidence and prevalence and is found almost exclusively in migrants from endemic regions. In endemic regions, predominantly settings with limited resources, patient numbers are high. Whole communities do not have access to appropriate treatment. The choice of treatment modalities is limited because of poor infrastructure and shortage of equipment and drugs. In this context, CE meets the criteria for a neglected disease. Furthermore, the terminology related to the designations around the parasite, its evolution and some therapeutic procedures is not uniform and sometimes inappropriate terms and wrong designations are used based on incorrect concepts. Although all of us know the different aspects of the disease it is pertinent to remember some important points and, above all, to clarify some aspects concerning the hydatid cyst's nomenclature in order to understand better the therapeutic options in the liver locations, particularly the different surgical approaches.

  15. Detection of five rare cystic fibrosis mutations peculiar to Southern Italy: implications in screening for the disease and phenotype characterization for patients with homozygote mutations.

    Science.gov (United States)

    Castaldo, G; Fuccio, A; Cazeneuve, C; Picci, L; Salvatore, D; Raia, V; Scarpa, M; Goossens, M; Salvatore, F

    1999-07-01

    The search for the eight most frequent mutations (i.e., DeltaF508, G542X, W1282X, N1303K, 1717-1G-->A, R553X, 2183AA-->G, and I148T) by allele-specific oligonucleotide dot-blot analysis revealed 78% of 396 cystic fibrosis alleles in Southern Italy. The observation of frequent haplotypes on the unidentified cystic fibrosis alleles suggested that a few mutations could account for a large number of unidentified alleles. We screened most of the coding sequence of the cystic fibrosis transmembrane regulator gene by denaturing gradient gel electrophoresis to determine the spectrum of these mutations in 68 unrelated cystic fibrosis patients bearing one or both unidentified mutations. The screening revealed five mutations, R1158X, 711+1G-->T, 4016insT, L1065P, and G1244E, each of which had a frequency of 1.3-1.8% (7% collectively). The 7% increase in the detection rate (85% vs 78%) reduces by >50% the residual risk of being cystic fibrosis carriers for couples who had tested negative by molecular analysis. We therefore designed a second allele-specific oligonucleotide set to analyze the five mutations. Among the patients analyzed, one patient homozygous for the L1065P mutation expressed a mild pulmonary and intestinal form of the disease with pancreatic insufficiency. Two other patients, homozygous for mutations R1158X and 4016insT, both expressed a severe cystic fibrosis phenotype. Five cystic fibrosis mutations are peculiar to patients from Southern Italy. The method described for their analysis is efficient, inexpensive, and can be semi-automated by use of a robotic workstation. The results obtained in patients from Southern Italy may have an impact on laboratories in other countries, given the large migrations of populations from Southern Italy to other countries in the last two centuries.

  16. Thoracoscopic Vs open resection of congenital cystic lung disease- utilization and outcomes in 1120 children in the United States.

    Science.gov (United States)

    Polites, Stephanie F; Habermann, Elizabeth B; Zarroug, Abdalla E; Thomsen, Kristine M; Potter, Donald D

    2016-07-01

    To determine if utilization of thoracoscopic resection of congenital cystic lung disease (CLD) is increasing and if this approach is associated with improved outcomes using a large national sample. Children ≤20years old who underwent resection of a congenital cystic adenomatoid malformation, bronchopulmonary sequestration, or bronchogenic cyst were identified from the Healthcare Cost and Utilization Project Kids' Inpatient Database (2009, 2012) and Nationwide Inpatient Sample (2008, 2010-2011). Patient characteristics and outcomes were compared between thoracoscopic and open approaches using univariate and multivariable analyses stratified by magnitude of resection. Thoracoscopic resection was used in 39.4% of 1120 children who underwent resection of CLD. Utilization of the thoracoscopic approach increased from 32.2% in 2008 to 48.2% in 2012. Use of thoracoscopy was lower in lobectomy than segmental resection (32.5 vs 48.4%, p<.001). Newborns, those with comorbid congenital conditions, and those with respiratory infections also had lower rates of thoracoscopy. After stratifying by magnitude of resection and adjusting for patient complexity, complication rates and postoperative length of stay were similar between thoracoscopic and open approaches. Utilization of thoracoscopic resection for CLD in the United States is increasing with time. After adjusting for patient complexity, there is no difference in postoperative length of stay or complications between thoracoscopic and open lobectomy and sub-lobar resection. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Soy Protein Alleviates Hypertension and Fish Oil Improves Diastolic Heart Function in the Han:SPRD-Cy Rat Model of Cystic Kidney Disease.

    Science.gov (United States)

    Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold

    2016-05-01

    Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.

  18. Carrier screening for cystic fibrosis, Gaucher disease, and Tay-Sachs disease in the Ashkenazi Jewish population: the first 1000 cases at New York University Medical Center, New York, NY.

    Science.gov (United States)

    Kronn, D; Jansen, V; Ostrer, H

    1998-04-13

    By late 1993, the genes for cystic fibrosis and Gaucher disease and the mutations common among Ashkenazi Jews had been identified. In response to these advances, heterozygote screening for cystic fibrosis and Gaucher disease was added to the more than 20-year-old Tay-Sachs disease screening program at New York University Medical Center, New York, NY. To review the outcomes from the first 1000 patients screened through this program. Patients and their referring physicians were informed about the new carrier tests. At the time of screening, patients could choose their tests (hexosaminidase A by enzyme analysis for Tay-Sachs disease or mutation analysis for cystic fibrosis and Gaucher disease). All partners of Tay-Sachs and cystic fibrosis carriers were tested. Prenatal diagnosis was offered and performed for carrier couples or mixed-marriage couples in whom the Ashkenazi Jewish partner was a carrier of Gaucher disease. Outcomes were measured by: (1) choice of tests, (2) decisions regarding prenatal diagnosis, and (3) phenotypes of children born to patients who underwent screening. The majority of Ashkenazi Jewish patients chose to have testing for all 3 diseases. If they previously underwent screening for Tay-Sachs disease, then they chose to undergo testing for cystic fibrosis and Gaucher disease. All carrier couples for each of these diseases went on to have prenatal testing. All mixed-marriage couples in whom the Jewish partner was found to be a carrier for Gaucher disease chose to have prenatal diagnosis. One fetus was identified as having cystic fibrosis. Since the program was initiated, no Ashkenazi Jewish baby has been born with any of these diseases at New York University Medical Center. New tests can be readily incorporated into established heterozygote screening programs. The Ashkenazi Jewish population described herein tends to choose testing for all conditions for which heterozygote screening is available.

  19. A survey of seropositivity to antigen B, an immunodiagnostic antigen for human cystic echinococcosis, in domestic animals in Mongolia.

    Science.gov (United States)

    Chinchuluun, B; Sako, Y; Khatanbaatar, I; Bayarmaa, B; Lkhagvatseren, S; Battsetseg, G; Yanagida, T; Itoh, S; Temuulen, D; Budke, C M; Ito, A; Batsukh, Z

    2014-04-01

    Cystic echinococcosis (CE) is well known to be an important zoonotic disease and national disease due to the traditional nomadic life style in Mongolia. The present study was carried out to obtain data on the seropositivity to antigen B, in domestic livestock, goats, sheep and cattle, in each province of Mongolia. The seropositivity to antigen B varied by province and ranged from 0% to 25.0% in goats, 0% to 12.5% in sheep, and 0% to 13.3% in cattle. In total, 9.2% of goats, 3.6% of sheep and 5.9% of cattle in Mongolia showed seropositivity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Adenoid cystic breast cancer.

    Science.gov (United States)

    McClenathan, James H; de la Roza, Gustavo

    2002-06-01

    Adenoid cystic carcinoma is a rare type of breast cancer that is generally reported in individual case reports or as series from major referral centers. To characterize early diagnostic criteria for adenoid cystic carcinoma and to determine whether breast-preserving surgery with radiotherapy is as effective as mastectomy for eradicating the disease, we reviewed clinical records of a large series of patients treated for adenoid cystic carcinoma of the breast at a large health maintenance organization (HMO) that includes primary care facilities and referral centers. Using the data bank of the Northern California Cancer Registry of the Kaiser Permanente Northern California Region (KPNCR), we retrospectively reviewed medical records of patients treated for adenoid cystic carcinoma of the breast. Follow-up also was done for these patients. Adenoid cystic carcinoma of the breast was diagnosed in 22 of 27,970 patients treated for breast cancer at KPNCR from 1960 through 2000. All 22 patients were female and were available for follow-up. Mean age of patients at diagnosis was 61 years (range, 37 to 94 years). In 17 (77%) of the women, a lump in the breast led to initial suspicion of a tumor; in 4 (23%) of the 22 patients, mammography led to suspicion of a tumor. Median tumor size was 20 mm. Pain was a prominent symptom. Surgical management evolved from radical and modified radical mastectomy to simple mastectomy or lumpectomy during the study period, during which time 1 patient died of previous ordinary ductal carcinoma of the contralateral breast, and 7 died of unrelated disease. At follow-up, 12 of the 13 remaining patients were free of disease; 1 patient died of the disease; and 1 patient remained alive despite late occurrence of lymph node and pulmonary metastases. Whether breast-preserving surgery with radiotherapy is as effective as mastectomy for treating adenoid cystic carcinoma of the breast has not been determined.

  1. Morbidity pattern of hydatid disease (cystic echinococcosis) and lack of its knowledge in patients attending Mamata General Hospital, Khammam, Andhra Pradesh.

    Science.gov (United States)

    Hemachander, S Suguna; Prasad, C Rajendra; Jessica, M

    2008-01-01

    There is hearsay that prevalence of hydatid disease in Khammam and Nalgonda districts of Andhra Pradesh is high. We report here a preliminary study conducted to determine the magnitude of the problem of hydatid disease and the morbidity associated with it in patients attending MGH, KMM, A.P. (rural hospital). Eleven cases were identified during the period from November 2005 to May 2006 (seven months). Pain in abdomen, mass per abdomen, loss of appetite, pregnancy complicated by cystic echinococcosis (CE), and jaundice were the main clinical symptoms and signs. Ultrasonography, detection and removal of the cysts on the operation table, microscopic examination of the aspirated hydatid fluid were confirmatory. Ziehl-Neelsen stain of the aspirated fluid revealed acid-fast scolices. Interrogation of the patients and their family members (50) revealed that there was a total lack of knowledge of dog-tapeworm-caused infection in humans. They knew 'rabies' as the only disease man gets from dogs, and tapeworms are from pork and beef.

  2. Disease consequences of human adaptation

    Directory of Open Access Journals (Sweden)

    Justin C. Fay

    2013-12-01

    Full Text Available Adaptive evolution has provided us with a unique set of characteristics that define us as humans, including morphological, physiological and cellular changes. Yet, natural selection provides no assurances that adaptation is without human health consequences; advantageous mutations will increase in frequency so long as there is a net gain in fitness. As such, the current incidence of human disease can depend on previous adaptations. Here, I review genome-wide and gene-specific studies in which adaptive evolution has played a role in shaping human genetic disease. In addition to the disease consequences of adaptive phenotypes, such as bipedal locomotion and resistance to certain pathogens, I review evidence that adaptive mutations have influenced the frequency of linked disease alleles through genetic hitchhiking. Taken together, the links between human adaptation and disease highlight the importance of their combined influence on functional variation within the human genome and offer opportunities to discover and characterize such variation.

  3. The human Bosniak model applied to a cat with renal cystadenoma. A classification to differentiate benign and malignant cystic renal masses via computed tomography and ultrasound.

    Science.gov (United States)

    Baloi, P; Del Chicca, F; Ruetten, M; Gerber, B

    2015-01-01

    A 13-year-old domestic shorthair cat was presented with weight loss and azotemia. Abdominal ultrasound revealed a large cystic space- occupying lesion with multiple septae in the left kidney. A core needle biopsy yielded a renal cystadenoma originating from the epithelial cells. This report describes the clinical, ultrasonographic and computed tomographic features and the growth progression of a renal cystadenoma. We describe the first attempt to apply the human Bosniak classification to a cat with renal cystic neoplasia to differentiate between benign and malignant lesions. Cystadenoma should be a differential diagnosis in cases of renal cystic space-occupying lesions. Other differentials, imaging features to differentiate benign and malignant lesions and the risk of malignant transformation will be discussed.

  4. Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.

    Science.gov (United States)

    Mall, Marcus A; Graeber, Simon Y; Stahl, Mirjam; Zhou-Suckow, Zhe

    2014-07-01

    Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. The Human Disease Network

    National Research Council Canada - National Science Library

    Kwang-Il Goh; Michael E. Cusick; David Valle; Barton Childs; Marc Vidal; Albert-László Barabási

    2007-01-01

    A network of disorders and disease genes linked by known disordergene associations offers a platform to explore in a single graphtheoretic framework all known phenotype and disease gene associations...

  6. Cystic pancreatic lymphangioma

    Directory of Open Access Journals (Sweden)

    Alihan Gurkan

    2012-04-01

    Full Text Available Lymphangioma of the pancreas is a rare benign tumor of lymphatic origin. Retroperitoneal lymphangiomas account for 1% of all lymphangiomas. Herein, we report a case of cystic pancreatic lymphangioma diagnosed in 34 year-old female patient who was hospitalized for a slight pain in the epigastrium and vomiting. Radiological imaging revealed a large multiloculated cystic abdominal mass with enhancing septations involving the upper retroperitoneum. During the laparoscopic surgery, a well circumscribed polycystic tumor was completely excised preserving the pancreatic duct. The patient made a complete recovery and is disease-free 12 months postoperatively.

  7. Gastrointestinal Manifestations of Cystic Fibrosis

    Science.gov (United States)

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  8. A Rim-Enhanced Mass with Central Cystic Changes on MR Imaging: How to Distinguish Breast Cancer from Inflammatory Breast Diseases?

    Science.gov (United States)

    Wang, Lijun; Wang, Dengbin; Fei, Xiaochun; Ruan, Mei; Chai, Weimin; Xu, Lin; Li, Xiaoxiao

    2014-01-01

    Objective To evaluate the capacity of magnetic resonance imaging (MRI) to distinguish breast cancer from inflammatory breast diseases manifesting as a rim-enhanced mass with central cystic changes. Materials and Methods Forty cases of breast cancer and 52 of inflammatory breast diseases showing a rim-enhanced mass with central cystic changes were retrospectively reviewed. All cases underwent dynamic contrast-enhanced MRI and 31 of them underwent diffusion-weighted imaging (DWI). Morphological features, dynamic parameters and apparent diffusion coefficient (ADC) values were comparatively analyzed using univariate analysis and binary logistic regression analysis. Results Breast cancer had a significantly thicker wall than the inflammatory breast diseases (Pbreast diseases (P = 0.003). On DWI, 86.7% of breast cancers demonstrate a peripheral hyperintensity whereas 93.8% of inflammatory breast diseases had a central hyperintensity (Pbreast diseases, breast cancers had a lower ADC value for the wall (1.09×10−3 mm2/s vs 1.42×10−3 mm2/s, Pbreast cancer and inflammatory breast diseases could present as a rim-enhanced mass with central cystic changes on MRI. Integrated analysis of the MR findings can allow for an accurate differential diagnosis. PMID:24598845

  9. Mechanistic Approaches to Improve Correction of the Most Common Disease-Causing Mutation in Cystic Fibrosis.

    Science.gov (United States)

    Bali, Vedrana; Lazrak, Ahmed; Guroji, Purushotham; Matalon, Sadis; Bebok, Zsuzsanna

    2016-01-01

    The most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene leads to deletion of the phenylalanine at position 508 (ΔF508) in the CFTR protein and causes multiple folding and functional defects. Contrary to large-scale efforts by industry and academia, no significant therapeutic benefit has been achieved with a single "corrector". Therefore, investigations concentrate on drug combinations. Orkambi (Vertex Pharmaceuticals), the first FDA-approved drug for treatment of cystic fibrosis (CF) caused by this mutation, is a combination of a corrector (VX-809) that facilitates ΔF508 CFTR biogenesis and a potentiator (VX-770), which improves its function. Yet, clinical trials utilizing this combination showed only modest therapeutic benefit. The low efficacy Orkambi has been attributed to VX-770-mediated destabilization of VX-809-rescued ΔF508 CFTR. Here we report that the negative effects of VX-770 can be reversed by increasing the half-life of the endoplasmic reticulum (ER) form (band B) of ΔF508 CFTR with another corrector (Corr-4a.) Although Corr-4a alone has only minimal effects on ΔF508 CFTR rescue, it increases the half-life of ΔF508 CFTR band B when it is present during half-life measurements. Our data shows that stabilization of band B ΔF508 CFTR with Corr-4a and simultaneous rescue with VX-809, leads to a >2-fold increase in cAMP-activated, CFTRinh-172-inhibited currents compared to VX-809 alone, or VX-809+VX-770. The negative effects of VX-770 and the Corr-4a protection are specific to the native I507-ATT ΔF508 CFTR without affecting the inherently more stable, synonymous variant I507-ATC ΔF508 CFTR. Our studies emphasize that stabilization of ΔF508 CFTR band B in the ER might improve its functional rescue by Orkambi.

  10. A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging

    Energy Technology Data Exchange (ETDEWEB)

    Behrens, Christopher B.; Langholz, Juliane H.; Eiler, Jessika; Jenewein, Raphael; Fuchs, Konstantin; Alzen, Gerhard F.P. [University Hospital Giessen, Department of Pediatric Radiology, Giessen (Germany); Naehrlich, Lutz [University Hospital Giessen, Department of Pediatrics, Giessen (Germany); Harth, Sebastian; Krombach, Gabriele A. [University Hospital Giessen, Department of Radiology, Giessen (Germany)

    2013-03-15

    Progressive fibrotic alterations of liver tissue represent a major complication in children with cystic fibrosis. Correct assessment of cystic-fibrosis-associated liver disease (CFLD) in clinical routine is a challenging issue. Sonographic elastography based on acoustic radiation force impulse imaging (ARFI) is a new noninvasive approach for quantitatively assessing in vivo elasticity of biological tissues in many organs. To characterize ARFI elastography as a diagnostic tool to assess alteration of liver tissue elasticity related to cystic fibrosis in children. ARFI elastography and B-mode US imaging were performed in 36 children with cystic fibrosis. The children's clinical history and laboratory parameters were documented. According to the findings on conventional US, children were assigned to distinct groups indicating severity of hepatic tissue alterations. The relationship between US findings and respective elastography values was assessed. Additionally, differences between ARFI elastography values of each US group were statistically tested. Children with sonomorphologic characteristics of fibrotic tissue remodeling presented significantly increased values for tissue elasticity. Children with normal B-mode US or discrete signs of hepatic tissue alterations showed a tendency toward increased tissue stiffness indicating early tissue remodeling. Assessment of children with CFLD by means of ARFI elastography yields adequate results when compared to conventional US. For detection of early stages of liver disease with mild fibrotic reactions of hepatic tissue, ARFI elastography might offer diagnostic advantages over conventional US. Thus, liver stiffness measured by means of elastography might represent a valuable biological parameter for evaluation and follow-up of CFLD. (orig.)

  11. PRAGMA-CF. A Quantitative Structural Lung Disease Computed Tomography Outcome in Young Children with Cystic Fibrosis.

    Science.gov (United States)

    Rosenow, Tim; Oudraad, Merel C J; Murray, Conor P; Turkovic, Lidija; Kuo, Wieying; de Bruijne, Marleen; Ranganathan, Sarath C; Tiddens, Harm A W M; Stick, Stephen M

    2015-05-15

    Chest computed tomography (CT) is the gold standard for demonstrating cystic fibrosis (CF) airway disease. However, there are no standardized outcome measures appropriate for children younger than 6 years. We developed the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF), a quantitative measure of airway disease, and compared it with the commonly used CF-CT scoring method. CT scans from the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort in Western Australia were included. PRAGMA-CF was performed by annotating a grid overlaid on 10 axial slices for the presence of bronchiectasis, mucous plugging, or other airway abnormalities (inspiratory scans) and trapped air (expiratory scans). The separate proportions of total disease (%Dis), bronchiectasis (%Bx), and trapped air (%TA) were determined. Thirty scans were used for observer reliability, and 30 paired scans obtained at 1 and 3 years old were used for comparison with a validated standard and biologic plausibility. Intraobserver, intraclass correlation coefficients (95% confidence interval) for %Dis, %Bx, and %TA were 0.93 (0.86-0.97), 0.93 (0.85-0.96), and 0.96 (0.91-0.98), respectively. The change in %Dis (P = 0.004) and %Bx (P = 0.001) with PRAGMA-CF was related to neutrophil elastase presence at age 3, whereas only the change in bronchiectasis score was related to neutrophil elastase (P disease in very young children with CF.

  12. Comparison of Lung Clearance Index and Magnetic Resonance Imaging for Assessment of Lung Disease in Children with Cystic Fibrosis.

    Science.gov (United States)

    Stahl, Mirjam; Wielpütz, Mark O; Graeber, Simon Y; Joachim, Cornelia; Sommerburg, Olaf; Kauczor, Hans-Ulrich; Puderbach, Michael; Eichinger, Monika; Mall, Marcus A

    2017-02-01

    Early onset and progression of lung disease in children with cystic fibrosis (CF) indicates that sensitive noninvasive outcome measures are needed for diagnostic monitoring and early intervention clinical trials. The lung clearance index (LCI) and chest magnetic resonance imaging (MRI) were shown to detect early lung disease in CF; however, the relationship between the two measures remains unknown. To correlate the LCI with abnormalities detected by MRI and compare the sensitivity of the two techniques to detect responses to therapy for pulmonary exacerbations in children with CF. LCI determined by age-adapted multiple breath washout techniques and MRI studies were performed in 97 clinically stable children with CF across the pediatric age range (0.2-21.1 yr). Furthermore, LCI (n = 26) or MRI (n = 10) were performed at the time of pulmonary exacerbation and after antibiotic therapy. MRI was evaluated using a dedicated morphofunctional score. The LCI correlated with the global MRI score as well as MRI-defined airway wall abnormalities, mucus plugging, and abnormal lung perfusion in infants and toddlers (P disease heterogeneity, including regional mucus plugging associated with abnormal lung perfusion in early CF lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 02270476).

  13. Osteoblast CFTR inactivation reduces differentiation and osteoprotegerin expression in a mouse model of cystic fibrosis-related bone disease.

    Directory of Open Access Journals (Sweden)

    Michael S Stalvey

    Full Text Available Low bone mass and increased fracture risk are recognized complications of cystic fibrosis (CF. CF-related bone disease (CFBD is characterized by uncoupled bone turnover--impaired osteoblastic bone formation and enhanced osteoclastic bone resorption. Intestinal malabsorption, vitamin D deficiency and inflammatory cytokines contribute to CFBD. However, epidemiological investigations and animal models also support a direct causal link between inactivation of skeletal cystic fibrosis transmembrane regulator (CFTR, the gene that when mutated causes CF, and CFBD. The objective of this study was to examine the direct actions of CFTR on bone. Expression analyses revealed that CFTR mRNA and protein were expressed in murine osteoblasts, but not in osteoclasts. Functional studies were then performed to investigate the direct actions of CFTR on osteoblasts using a CFTR knockout (Cftr-/- mouse model. In the murine calvarial organ culture assay, Cftr-/- calvariae displayed significantly less bone formation and osteoblast numbers than calvariae harvested from wildtype (Cftr+/+ littermates. CFTR inactivation also reduced alkaline phosphatase expression in cultured murine calvarial osteoblasts. Although CFTR was not expressed in murine osteoclasts, significantly more osteoclasts formed in Cftr-/- compared to Cftr+/+ bone marrow cultures. Indirect regulation of osteoclastogenesis by the osteoblast through RANK/RANKL/OPG signaling was next examined. Although no difference in receptor activator of NF-κB ligand (Rankl mRNA was detected, significantly less osteoprotegerin (Opg was expressed in Cftr-/- compared to Cftr+/+ osteoblasts. Together, the Rankl:Opg ratio was significantly higher in Cftr-/- murine calvarial osteoblasts contributing to a higher osteoclastogenesis potential. The combined findings of reduced osteoblast differentiation and lower Opg expression suggested a possible defect in canonical Wnt signaling. In fact, Wnt3a and PTH-stimulated canonical Wnt

  14. [Aerosol administration of a replication defective recombinant adenovirus expressing normal human cDNA-CFTR in the respiratory tractus in patients with cystic fibrosis].

    Science.gov (United States)

    Bellon, G; Calmard, L; Thouvenot, D; Levrey, H; Jagneaux, V; Poitevin, F; Malcus, C; Accart, N; Séné, C; Layani, M P; Aymard, M; Bienvenu, J; Courtney, M; Döring, G; Gilly, B; Gilly, R; Lamy, D; Morel, Y; Paulin, C; Perraud, F; Rodillon, L; So, S; Touraine, F; Schatz, C; Pavirani, A

    1996-01-01

    At present it is conceivable to think that gene therapy represents a way to treat or even prevent the respiratory manifestations of cystic fibrosis. Consistent to such a concept, there is sufficient evidence that Ad-CFTR, a recombinant replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator cDNA, can vectorize the expression of a functional CFTR (cystic fibrosis transmembrane conductance regulator) to the nasal and airway epithelia. The clinical protocol was designed to assess the safety of single escalating doses of a replication defective adenovirus expressing the cystic fibrosis transmembrane conductance regulator gene (Ad-CFTR) when administered to the tracheobronchial portion of the airways and whether biological efficacy of CFTR delivery could be demonstrated. Six cystic fibrosis patients received nasal instillation and subsequent aerosol (Optineb, Air Liquide, Paris, France) administration of Ad-CFTR the following day. Doses (pfu) applied to the nose were 10(5) (patients SG and PB), 10(7) (patients FP and EP) and 4 x 10(8) (patients DS and FG), while aerosolised doses were 10(7) (patients SG and PB), 10(8) (patients FP and EP) and 5.4 x 10(8) (patients DS and FG), respectively. No acute toxic effects, no increase in the titer of anti-adenovirus antibodies and no spreading or shedding of Ad-CFTR were detected. In one patient Ad-CFTR DNA was found in the urine and blood two days after aerosolisation. Ad-CFTR DNA was detected in nasal and bronchial brush samples, in BAL, in saliva and tonsils 21, 8, 14 and 4 days post virus administration, respectively. Ad-CFTR mRNA (RT-PCR on bronchial cells) and CFTR protein (immunochemistry on nasal and bronchial cells) were detected up to 14 days following Ad-CFTR administration. These results show that the nebulisation of Ad-CFTR is a possible approach for treating the respiratory manifestation of cystic fibrosis.

  15. Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

    Science.gov (United States)

    Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

    2017-09-25

    von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

  16. The Streptococcus milleri group--an unrecognized cause of disease in cystic fibrosis: a case series and literature review.

    Science.gov (United States)

    Parkins, Michael D; Sibley, Christopher D; Surette, Michael G; Rabin, Harvey R

    2008-05-01

    The "Streptococcus milleri" group (SMG) is increasingly recognized for their role in pyogenic infections including empyema and solid organ abscesses. However, SMG disease has rarely been identified in cystic fibrosis (CF). Inherent difficulties in both growing the organisms and distinguishing SMG from less virulent oropharyngeal viridans streptococci may have led to a decreased recognition of this as a CF pathogen. We report on six cases of SMG-related infection over a 4-year time-frame occurring within an adult CF clinic in Canada, and a further four cases identified through a literature review. SMG manifested disease as bronchopulmonary exacerbations in 7 of 10 patients, and 4 of 10 patients had extra-pulmonary dissemination of SMG infection. Noticeably, pulmonary exacerbations were frequently associated with atypically malodorous sputum. Furthermore, patients clinically responded to anti-microbial therapies with no anti-Pseudomonal activity. There was a consistent correlation of SMG disease and co-colonization with P. aeruginosa leading to speculation of polymicrobial interactions resulting in enhanced virulence. SMG deserves considerable attention as a potential pathogen within the airways of patients with CF. Copyright 2008 Wiley-Liss, Inc.

  17. Risk stratification model to detect early pulmonary disease in infants with cystic fibrosis diagnosed by newborn screening.

    Science.gov (United States)

    Britton, Lacrecia J; Oates, Gabriela R; Oster, Robert A; Self, Staci T; Troxler, Robert B; Hoover, Wynton C; Gutierrez, Hector H; Harris, William T

    2016-11-01

    The clinical benefit of newborn screening (NBS) for cystic fibrosis (CF) has been primarily nutritional, with less overt respiratory impact. Identification of risk factors for infant CF lung disease could facilitate targeted interventions to improve pulmonary outcomes. This retrospective study evaluated socioeconomic information, clinical data, and results from routine infant pulmonary function testing (iPFT) of infants diagnosed with CF through NBS (N = 43) at a single CF center over a 4-year period (2008-2012). A five-item composite clinical score was developed and combined with socioeconomic indicators to facilitate identification of CF infants at increased risk of early-onset respiratory impairment. Paternal education was positively associated with lung function (P = 0.02). Clinical score disease. Forced expiratory volume (FEV0.5 %, mean ± SD) averaged 115 ± 19% in the low-risk group, 97 ± 17% in the intermediate-risk group, and 90 ± 8% in the high-risk group (P disease as quantified by iPFT. Our model showed significant differences in infant pulmonary function across risk groups. The developed tool offers an easily available, inexpensive, and non-invasive way to assess risk of respiratory decline in CF infants and identify those meriting targeted therapeutic attention. Pediatr Pulmonol. 2016;51:1168-1176. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Co-expression and prognostic value of gross cystic disease fluid protein 15 and mammaglobin in primary breast cancer.

    Science.gov (United States)

    Fritzsche, F R; Thomas, A; Winzer, K-J; Beyer, B; Dankof, A; Bellach, J; Dahl, E; Dietel, M; Kristiansen, G

    2007-11-01

    Gross cystic disease fluid protein (GCDFP-15) and mammaglobin are both widely used and accepted markers for epithelia of breast origin. We aimed to evaluate their relation of expression on parallel whole tissue sections in primary breast cancer by immunohistochemistry and also to correlate it with clinico-pathological parameters including patient survival. Primary breast carcinomas from 165 patients with a mean clinical follow-up of 73 months were immunostained using commercially available antibodies against GCDFP-15 and mammaglobin. An immunoreactive score (IRS) was calculated based on the cytoplasmic staining intensity and the number of cells stained. Cytoplasmic expression of GCDFP-15 and mammaglobin was observed in 73.3% and 72.1% of invasive breast carcinomas respectively. 91.8% of breast cancer cases expressed at least one of both markers. Both markers strongly correlated with each other and were significantly associated with lower tumour grading. Additionally, GCDFP-15 negativity was significantly associated with shortened disease-free survival times in univariate and multivariate analyses. We demonstrated the strong correlation of GCDFP-15 and mammaglobin with each other and showed that only very few primary breast cancers are completely negative for both markers. The significantly longer disease free survival times for patients with GCDFP-15 positive tumours clearly warrants further study.

  19. Cystic fibrosis revisited.

    Science.gov (United States)

    Larson, J E; Cohen, J C

    2000-11-01

    Cystic fibrosis is a pleiotropic disease whose primary defect is thought to be abnormal chloride conductance. Despite intensive study, the role of the protein in the airway and the mechanism for its direct participation in the disease pathology remain unclear. This paper reviews CFTR's cell regulatory functions and data supporting the role of CFTR in secretory epithelial cell development. A hypothesis for CF pathophysiology based on secretory cell differentiation is proposed. Copyright 2000 Academic Press.

  20. Cystic partially differentiated nephroblastoma.

    Science.gov (United States)

    Puvaneswary, M; Macintosh, J; Cassey, J

    2006-06-01

    Cystic partially differentiated nephroblastoma is a relatively rare tumour of the kidney usually affecting infants. Cystic Wilms' tumour and multilocular cystic nephroma should be distinguished from cystic partially differentiated nephroblastoma. Multilocular cystic nephroma is a benign tumour whereas cystic Wilms' tumour is at the malignant end of the range of classification of such tumours. Cystic partially differentiated nephroblastoma may undergo local recurrence but there is no report of metastasis.

  1. Comparative biology of cystic fibrosis animal models.

    Science.gov (United States)

    Fisher, John T; Zhang, Yulong; Engelhardt, John F

    2011-01-01

    Animal models of human diseases are critical for dissecting mechanisms of pathophysiology and developing therapies. In the context of cystic fibrosis (CF), mouse models have been the dominant species by which to study CF disease processes in vivo for the past two decades. Although much has been learned through these CF mouse models, limitations in the ability of this species to recapitulate spontaneous lung disease and several other organ abnormalities seen in CF humans have created a need for additional species on which to study CF. To this end, pig and ferret CF models have been generated by somatic cell nuclear transfer and are currently being characterized. These new larger animal models have phenotypes that appear to closely resemble human CF disease seen in newborns, and efforts to characterize their adult phenotypes are ongoing. This chapter will review current knowledge about comparative lung cell biology and cystic fibrosis transmembrane conductance regulator (CFTR) biology among mice, pigs, and ferrets that has implications for CF disease modeling in these species. We will focus on methods used to compare the biology and function of CFTR between these species and their relevance to phenotypes seen in the animal models. These cross-species comparisons and the development of both the pig and the ferret CF models may help elucidate pathophysiologic mechanisms of CF lung disease and lead to new therapeutic approaches.

  2. Soil Borne Human Diseases

    NARCIS (Netherlands)

    Jeffery, Simon; Van der Putten, Wim H.

    2011-01-01

    Soils are home to a remarkable array of biodiversity with some estimates stating that 25% of the Earth’s species find their home in the soil. Of these organisms, the vast majority are not of any threat to human health, but rather function to provide numerous ecosystem services which emerge through

  3. Evidence for a causal relationship between early exocrine pancreatic disease and cystic fibrosis-related diabetes: a Mendelian randomization study.

    Science.gov (United States)

    Soave, David; Miller, Melissa R; Keenan, Katherine; Li, Weili; Gong, Jiafen; Ip, Wan; Accurso, Frank; Sun, Lei; Rommens, Johanna M; Sontag, Marci; Durie, Peter R; Strug, Lisa J

    2014-06-01

    Circulating immunoreactive trypsinogen (IRT), a biomarker of exocrine pancreatic disease in cystic fibrosis (CF), is elevated in most CF newborns. In those with severe CF transmembrane conductance regulator (CFTR) genotypes, IRT declines rapidly in the first years of life, reflecting progressive pancreatic damage. Consistent with this progression, a less elevated newborn IRT measure would reflect more severe pancreatic disease, including compromised islet compartments, and potentially increased risk of CF-related diabetes (CFRD). We show in two independent CF populations that a lower newborn IRT estimate is associated with higher CFRD risk among individuals with severe CFTR genotypes, and we provide evidence to support a causal relationship. Increased loge(IRT) at birth was associated with decreased CFRD risk in Canadian and Colorado samples (hazard ratio 0.30 [95% CI 0.15-0.61] and 0.39 [0.18-0.81], respectively). Using Mendelian randomization with the SLC26A9 rs7512462 genotype as an instrumental variable since it is known to be associated with IRT birth levels in the CF population, we provide evidence to support a causal contribution of exocrine pancreatic status on CFRD risk. Our findings suggest CFRD risk could be predicted in early life and that maintained ductal fluid flow in the exocrine pancreas could delay the onset of CFRD. © 2014 by the American Diabetes Association.

  4. Changes in structural lung disease in cystic fibrosis children over 4 years as evaluated by high-resolution computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Carpio, Carlos; Alvarez-Sala, Rodolfo; Prados, Concepcion [University Hospital La Paz, La Paz Hospital Research Institute, Department of Respiratory Medicine, Madrid (Spain); Albi, Gustavo [Nino de Jesus Children' s Hospital, Department of Radiology, Madrid (Spain); Rayon-Aledo, Jose Carlos; Caballero, Paloma [University Hospital La Princesa, Department of Radiology, Madrid (Spain); Giron, Rosa [University Hospital La Princesa, Department of Respiratory Medicine, Madrid (Spain)

    2015-12-15

    To compare the worsening of structural lung disease on high-resolution computed tomography (HRCT) with changes in spirometry results in cystic fibrosis (CF) patients, and analyse factors associated with the worsening of structural lung disease over time. A total of 31 CF subjects (mean age 11.03 ± 3.67 years old) were prospectively evaluated by two HRCT and spirometry tests performed 4 years apart. HRCT abnormalities were scored using the Bhalla scoring system. Comparisons between changes on HRCT and spirometry were made for all patients, and also for groups categorized by age, sex, genotypic alterations and lung obstruction. The mean HRCT Bhalla scoring, forced expiratory volume in 1 s (FEV{sub 1} %pred.) and forced vital capacity (FVC %pred.) were 7.92 ± 3.59, 87.76 ± 20.52 and 96.54 ± 15.12, respectively. There was a significant deterioration in the Bhalla score (p < 0.01) and in certain categories: severity of bronchiectasis, peribronchial thickening, mucous plugging and bronchial divisions. Females had a more pronounced worsening of the Bhalla score than males (p = 0.048). No change over time was found in FEV{sub 1} and FVC. Only sex was associated with a deterioration in HRCT. HRCT Bhalla scoring changes statistically significantly over 4 years, but spirometry results do not. Worsening on HRCT is more evident in females. (orig.)

  5. Reduced mucosal associated invariant T-cells are associated with increased disease severity and Pseudomonas aeruginosa infection in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Daniel J Smith

    Full Text Available BACKGROUND: Primary defects in host immune responses have been hypothesised to contribute towards an inability of subjects with cystic fibrosis (CF to effectively clear pulmonary infections. Innate T-lymphocytes provide rapid pathogen-specific responses prior to the development of classical MHC class I and II restricted T-cell responses and are essential to the initial control of pulmonary infection. We aimed to examine the relationship between peripheral blood lymphocyte phenotype and clinical outcomes in adults with CF. METHODS: We studied 41 subjects with CF and 22, age matched, non-smoking healthy control subjects. Lymphocytes were extracted from peripheral blood samples and phenotyped by flow-cytometry. Lymphocyte phenotype was correlated with sputum microbiology and clinical parameters. RESULTS: In comparison to healthy control subjects, mucosal associated invariant T (MAIT-lymphocytes were significantly reduced in the peripheral blood of subjects with CF (1.1% versus 2.0% of T-lymphocytes, P = 0.002. MAIT cell concentration was lowest in CF subjects infected with P. aeruginosa and in subjects receiving treatment for a pulmonary exacerbation. Furthermore a reduced MAIT cell concentration correlated with severity of lung disease. CONCLUSION: Reduced numbers of MAIT cells in subjects with CF were associated with P. aeruginosa pulmonary infection, pulmonary exacerbations and more severe lung disease. These findings provide the impetus for future studies examining the utility of MAIT cells in immunotherapies and vaccine development. Longitudinal studies of MAIT cells as biomarkers of CF pulmonary infection are awaited.

  6. Cell proliferation and survival mechanisms underlying the abnormal persistence of follicular cysts in bovines with cystic ovarian disease induced by ACTH.

    Science.gov (United States)

    Salvetti, Natalia R; Stangaferro, Matías L; Palomar, Martín M; Alfaro, Natalia S; Rey, Florencia; Gimeno, Eduardo J; Ortega, Hugo H

    2010-10-01

    Cystic ovarian disease (COD) is an important cause of infertility that affects cattle. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell death in ovarian cells. Thus, the objective in the present study was to evaluate apoptosis and proliferation in induced ovarian cystic follicles in cows to investigate the follicular persistence. Stage of estrous cycle was synchronized in 10 heifers and 5 were then subjected to the induction of COD by administration of ACTH. After the ovariectomy number of in situ apoptotic cells by TUNEL assay, active caspase-3, FAS/FASLG and members of the BCL2 family were compared by immunohistochemistry and multiplex PCR and cell proliferation by evaluation of Ki-67 protein and cyclin D1 and E mRNA. Significantly (pfollicular cysts and related diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Prenatal ultrasound, genotype, and outcome in a large cohort of prenatally affected patients with autosomal-recessive polycystic kidney disease and other hereditary cystic kidney diseases.

    Science.gov (United States)

    Erger, Florian; Brüchle, Nadina Ortiz; Gembruch, Ulrich; Zerres, Klaus

    2017-04-01

    To investigate the sonographic and clinical genotype-phenotype correlations in autosomal recessive polycystic kidney disease (ARPKD) and other cystic kidney diseases (CKD) in a large cohort of prenatally detected fetuses with hereditary CKD. We retrospectively studied the clinical and diagnostic data of 398 patients referred with prenatal ultrasound findings suggestive of CKD between 1994 and 2010. Cases with confirmed hereditary CKD (n = 130) were analyzed as to their prenatal ultrasound findings, genotype, and possible predictors of clinical outcome. ARPKD was most common in our non-representative sample. Truncating PKHD1 mutations led to a significantly reduced neonatal prognosis, with two such mutations being invariably lethal. Sonographically visible kidney cysts occurred in only 3% of ARPKD cases. Renal abnormalities in Meckel syndrome (MKS) appeared earlier than in ADPKD (19.6 ± 3.7 vs. 29.8 ± 5.1 GW) or ARPKD (19.6 ± 3.7 vs. 30.2 ± 1.2 GW). Additional CNS malformations were not found in ARPKD, but were highly sensitive for MKS. Pulmonary hypoplasia, oligo/anhydramnios (OAH), and kidney enlargement were associated with a significantly worse neonatal prognosis. Genotype, sonographic signs of OAH, enlarged kidney size, and pulmonary hypoplasia can be useful predictors of neonatal survival. We propose sonographic morphological criteria for ARPKD, ADPKD, MKS, and renal cyst and diabetes syndrome (RCAD). We further propose a clinical diagnostic algorithm for differentiating cystic kidney diseases.

  8. Nutrition in Cystic Fibrosis: Macro- and Micronutrients

    NARCIS (Netherlands)

    Oudshoorn, Johanna Hermiena

    2006-01-01

    Cystic fibrosis (CF) is the most common life-threatening autosomal recessive inherited disease in Caucasians, and is characterized by progressive lung disease, pancreatic insufficiency, malnutrition, hepatobiliary disease and elevated sweat electrolyte levels. The increased survival of CF patients

  9. Viral diseases and human evolution

    Directory of Open Access Journals (Sweden)

    Leal Élcio de Souza

    2000-01-01

    Full Text Available The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc. are becoming formidable challenges, which may have a direct impact on the fate of our species.

  10. Gastroenterological endpoints in drug trials for cystic fibrosis

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; Verkade, Henkjan J.; Wilschanski, Micheal

    2016-01-01

    The phenotype of cystic fibrosis includes a wide variety of clinical and biochemical gastrointestinal presentations. These gastrointestinal characteristics of the disease have come under renewed interest as potential outcome measures and clinical endpoints for therapeutic trials in cystic fibrosis.

  11. Parents' Experiences of Receiving the Initial Positive Newborn Screening (NBS) Result for Cystic Fibrosis and Sickle Cell Disease.

    Science.gov (United States)

    Chudleigh, Jane; Buckingham, Sarah; Dignan, Jo; O'Driscoll, Sandra; Johnson, Kemi; Rees, David; Wyatt, Hilary; Metcalfe, Alison

    2016-12-01

    The clinical advantages of the newborn screening programme (NBS) in the UK are well described in the literature. However, there has been little exploration of the psychosocial impact on the family. This study followed the principles of grounded theory to explore parents' experiences of receiving the initial positive NBS result for their child with cystic fibrosis (CF) or sickle cell disease (SCD). Semi-structured, qualitative interviews were conducted with 22 parents (12 mothers and 10 fathers) whose children had been diagnosed with CF or SCD via NBS and were under the age of 1 year at the time of interview. The main themes that arose from the data were; parents previous knowledge of the condition and the NBS programme, the method of delivery and parental reactions to the result, sharing the results with others, the impact on parental relationships and support strategies. Study conclusions indicate that most parents thought initial positive NBS results should be delivered by a health professional with condition specific knowledge, preferably with both parents present. Genetic counselling needs to include a focus on the impact of NBS results on parental relationships. Careful consideration needs to be given to strategies to support parents of babies who have positive NBS results both in terms of the psychological health and to assist them in sharing the diagnosis.

  12. Utility of mammaglobin and gross cystic disease fluid protein-15 (GCDFP-15) in confirming a breast origin for recurrent tumors.

    Science.gov (United States)

    Chia, Shi Yun; Thike, Aye Aye; Cheok, Poh Yian; Tan, Puay Hoon

    2010-10-01

    There are limited data that compare the utility of immunohistochemical detection of mammaglobin with Gross Cystic Disease Fluid Protein-15 (GCDFP-15) in locally recurrent and metastatic breast cancers. Forty-three local and 72 distant recurrences of breast cancer, 8 metastatic lesions to the breast from other organs, and 30 metastases from non-breast primaries were immunohistochemically stained with mammaglobin and GCDFP-15 antibodies. Mammaglobin was expressed in 55 (47.8%) and GCDFP-15 detected in 13 (11.3%) locally and distantly recurrent breast cancers. A higher percentage of tumor cells was stained with mammaglobin at greater staining intensity than GCDFP-15, for both metastatic and locally recurrent breast cancers. The difference in staining intensity as well as mean percentage of tumor cells stained for both markers was statistically significant (p breast from other organs and metastatic lesions from non-breast primaries were uniformly negative for both mammaglobin and GCDFP-15. Our study demonstrates that immunohistochemical analysis of mammaglobin is superior to GCDFP-15 in detecting a tumor of breast origin, and can be incorporated into immunohistochemical panels evaluating tumors from unknown primary sites. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Relationship between molecular subtype of invasive breast carcinoma and expression of gross cystic disease fluid protein 15 and mammaglobin.

    Science.gov (United States)

    Lewis, Gloria H; Subhawong, Andrea Proctor; Nassar, Hind; Vang, Russell; Illei, Peter B; Park, Ben Ho; Argani, Pedram

    2011-04-01

    We investigated the expression of gross cystic disease fluid protein 15 (GCDFP) and mammaglobin (MGB) by immunohistochemical analysis in 71 invasive breast carcinomas (IBCs) subtyped into luminal (A and B), HER2, basal-like carcinoma (BLC), and unclassified triple-negative carcinoma (UTNC) by established surrogate immunohistochemical profiles. GCDFP and MGB were less likely to be expressed in BLC than in HER2 cancers (P = .000021 and P = .013, respectively) or luminal cancers (P = .00002 and P = .00008, respectively). However, the difference in GCDFP or MGB expression between HER2 and luminal cancers was not significant (P = 1.0 and P = .671, respectively). Our results suggest that luminal cancers demonstrate similar degrees of apocrine differentiation as HER2 cancers. Most BLCs and UTNCs are negative for MGB and GCDFP. Correlation with clinical findings may be needed to exclude the possibility of a metastasis to the breast when BLCs or UTNCs are encountered in a limited sample such as a core biopsy sample.

  14. Complement C3f serum levels may predict breast cancer risk in women with gross cystic disease of the breast.

    Science.gov (United States)

    Profumo, Aldo; Mangerini, Rosa; Rubagotti, Alessandra; Romano, Paolo; Damonte, Gianluca; Guglielmini, Pamela; Facchiano, Angelo; Ferri, Fabio; Ricci, Francesco; Rocco, Mattia; Boccardo, Francesco

    2013-06-24

    Gross cystic disease (GCDB) is a breast benign condition predisposing to breast cancer. Cryopreserved sera from GCDB patients, some of whom later developed a cancer (cases), were studied to identify potential risk markers. A MALDI-TOF mass spectrometry analysis found several complement C3f fragments having a significant increased abundance in cases compared to controls. After multivariate analysis, the full-length form of C3f maintained a predictive value of breast cancer risk. Higher levels of C3f in the serum of women affected by a benign condition like GCDB thus appears to be correlated to the development of breast cancer even 20 years later. Increased complement system activation has been found in the sera of women affected by GCDB who developed a breast cancer, even twenty or more years later. C3f may predict an increased breast cancer risk in the healthy population and in women affected by predisposing conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Development, validation, and implementation of a questionnaire assessing disease knowledge and understanding in adult cystic fibrosis patients.

    LENUS (Irish Health Repository)

    Siklosi, Karen R

    2012-02-01

    BACKGROUND: The number of adults living with cystic fibrosis (CF) is increasing, necessitating an assessment of knowledge in this growing population. METHODS: A questionnaire assessing CF knowledge was completed by 100 CF patients (median age: 26.0 years, range 17-49 years; median FEV: 57.0% predicted, range 20-127% predicted). Level of knowledge was correlated with clinical and sociodemographic characteristics. RESULTS: Questionnaire validation showed acceptable internal consistency (alpha=0.75) and test-retest reliability (0.94). Patients had fair overall understanding of CF (mean=72.4%, SD=13.1), with greater knowledge of lung and gastrointestinal topics (mean=81.6%, SD=11.6) than reproduction and genetics topics (mean=57.9%, SD=24.1). Females and those with post-secondary education scored significantly higher (p<0.05). CONCLUSIONS: This study validated a questionnaire that can be utilized to assess CF knowledge. Although CF patients understand most aspects of their disease, knowledge deficits are common - particularly regarding genetics and reproduction - and should be considered when developing CF education programs.

  16. Brasfield and Wisconsin scoring systems have equal value as outcome assessment tools of cystic fibrosis lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Cleveland, Robert H.; Stamoulis, Catherine; Sawicki, Gregory; Kelliher, Emma; Wood, Christopher; Zurakowski, David; Lee, Edward [Boston Children' s Hospital, Harvard Medical School, Department of Radiology, Boston, MA (United States); Zucker, Evan J. [Tufts Medical School, Boston, MA (United States)

    2014-05-15

    Several imaging-based scoring systems have been used as outcome measures in assessing the severity of cystic fibrosis (CF) lung disease. It has been shown that chest radiography performs equally to computed tomography (CT). There is the opinion that of the two most commonly used chest radiograph (CXR) systems, the Brasfield system is less sensitive and reliable than the Wisconsin system. This report assesses the reproducibility and reliability of the two systems. Thirty patients with CXRs during a 5-year period were randomly selected. One hundred eighty-two studies had data for all CXRs and pulmonary function tests (PFTs), Forced Expiratory Volume in One Second (FEV-1) and Forced Vital Capacity (FVC). PFT values closest to the date of each CXR were recorded. Four radiologists scored each image twice by both the Brasfield and Wisconsin systems. Intra- and inter-rater reliability, correlation with PFTs and direct correlation of the two systems were calculated. Intra-rater agreement: r = 0.86-0.99 Brasfield, r = 0.78-0.96 Wisconsin. Inter-rater agreement: 0.76-0.90 Brasfield, r = 0.74-0.97 Wisconsin. Brasfield vs. FEV-1: r = 0.55, vs. FVC r = 0.61. Wisconsin vs. FEV-1: r = 0.57, vs. FVC r = 0.66. Correlation of the two systems: r = 0.86 (all P < 0.001). The Brasfield and Wisconsin systems performed very similarly providing equally reproducible, robust and reliable measures. (orig.)

  17. Diagnostic Accuracy of Antigen 5-Based ELISAs for Human Cystic Echinococcosis.

    Science.gov (United States)

    Pagnozzi, Daniela; Addis, Maria Filippa; Biosa, Grazia; Roggio, Anna Maria; Tedde, Vittorio; Mariconti, Mara; Tamarozzi, Francesca; Meroni, Valeria; Masu, Gabriella; Masala, Giovanna; Brunetti, Enrico; Uzzau, Sergio

    2016-03-01

    Clinical diagnosis and follow up of cystic echinococcosis (CE) are based on imaging complemented by serology. Several immunodiagnostic tests are commercially available, but the development of new tools is still needed to overcome the lack of standardization of the target antigen, generally consisting of a crude extract of Echinococcus granulosus hydatid cyst fluid. In a previous work, we described a chromatographic method for the preparation of a highly enriched Antigen 5 fraction from hydatid cyst fluid. The high reactivity of patient sera against this preparation prompted us to evaluate further this antigen for the serodiagnosis of CE on a larger cohort of samples. A total of 327 sera from CE patients with heterogeneous conditions for cyst stage, cyst number, organ localization, drug therapy, and surgical intervention, together with 253 sera from healthy controls, were first analyzed by an ELISA based on the Ag5 preparation in two different experimental setups and, in parallel, by a commercial ELISA routinely used in clinical laboratories for CE serodiagnosis. The Ag5 ELISAs revealed different sensitivity (88.3% vs 95.3%) without significant differences in specificity (94.1% vs 92.5%), for the two setups, respectively. Moreover, possible relationships between the Ag5 ELISA absorbance results and clinical variables were investigated. Chi squared test, bivariate logistic regression and multiple regression analyses highlighted differences in the serology reactivity according to pharmacological treatment, cyst activity, and cyst number. The two Ag5 ELISAs revealed different performances depending on the setup. The good diagnostic sensitivity and the high reliability of the Ag5 preparation method make this antigen a promising candidate for the serodiagnosis of CE. Further studies will be needed to evaluate the ability of our test to provide useful information on specific CE clinical traits.

  18. Diagnostic Accuracy of Antigen 5-Based ELISAs for Human Cystic Echinococcosis.

    Directory of Open Access Journals (Sweden)

    Daniela Pagnozzi

    2016-03-01

    Full Text Available Clinical diagnosis and follow up of cystic echinococcosis (CE are based on imaging complemented by serology. Several immunodiagnostic tests are commercially available, but the development of new tools is still needed to overcome the lack of standardization of the target antigen, generally consisting of a crude extract of Echinococcus granulosus hydatid cyst fluid. In a previous work, we described a chromatographic method for the preparation of a highly enriched Antigen 5 fraction from hydatid cyst fluid. The high reactivity of patient sera against this preparation prompted us to evaluate further this antigen for the serodiagnosis of CE on a larger cohort of samples.A total of 327 sera from CE patients with heterogeneous conditions for cyst stage, cyst number, organ localization, drug therapy, and surgical intervention, together with 253 sera from healthy controls, were first analyzed by an ELISA based on the Ag5 preparation in two different experimental setups and, in parallel, by a commercial ELISA routinely used in clinical laboratories for CE serodiagnosis. The Ag5 ELISAs revealed different sensitivity (88.3% vs 95.3% without significant differences in specificity (94.1% vs 92.5%, for the two setups, respectively. Moreover, possible relationships between the Ag5 ELISA absorbance results and clinical variables were investigated. Chi squared test, bivariate logistic regression and multiple regression analyses highlighted differences in the serology reactivity according to pharmacological treatment, cyst activity, and cyst number.The two Ag5 ELISAs revealed different performances depending on the setup. The good diagnostic sensitivity and the high reliability of the Ag5 preparation method make this antigen a promising candidate for the serodiagnosis of CE. Further studies will be needed to evaluate the ability of our test to provide useful information on specific CE clinical traits.

  19. Vaccine induced Hepatitis A and B protection in children at risk for cystic fibrosis associated liver disease.

    Science.gov (United States)

    Shapiro, Adam J; Esther, Charles R; Leigh, Margaret W; Dellon, Elisabeth P

    2013-01-30

    Hepatitis A (HAV) and Hepatitis B (HBV) infections can cause serious morbidity in patients with liver disease, including cystic fibrosis associated liver disease (CFALD). HAV and HBV vaccinations are recommended in CFALD, and maintenance of detectable antibody levels is also recommended with chronic liver disease. A better understanding of factors predicting low HAV and HBV antibodies may help physicians improve protection from these viruses in CFALD patients. We examined HAV and HBV vaccine protection in children at risk for CFALD. Clinical and vaccine histories were reviewed, and HAV and HBV antibody titers measured. Those with no vaccination history or low HAV or HBV titers received primary or booster vaccinations, and responses were measured. Thirty-four of 308 children were at risk for CFALD per project criteria. Ten had previous HAV vaccination, of which 90% had positive anti-HAV antibodies. Thirty-three of 34 had previously received primary HBV vaccination (most in infancy), but only 12 (35%) had adequate anti-HBs levels (≥10mIU/mL). Children with adequate anti-HBs levels were older at first HBV vaccine (median 2.3 vs. 0.1 years, pvaccine (median 4.0 vs. 0.8 years, p=0.01). Fourteen of 19 (74%) responded to HBV boosters. Z-scores for BMI at HBV booster were significantly lower in booster non-responders (p=0.04). Children at increased risk of CFALD have inadequate HAV and HBV antibody levels, and HBV antibody protection can be enhanced through vaccine boosters. HBV antibody titers should be assessed in CFALD patients with a history of vaccination, particularly in those who received HBV vaccines in infancy or who are malnourished. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. First experience in Switzerland in Phe508del homozygous cystic fibrosis patients with end-stage pulmonary disease enrolled in a lumacaftor-ivacaftor therapy trial - preliminary results.

    Science.gov (United States)

    Murer, Christian; Huber, Lars Christian; Kurowski, Thomas; Hirt, Astrid; Robinson, Cécile A; Bürgi, Urs; Benden, Christian

    2018-02-16

    Cystic fibrosis is the most common genetic disorder in Caucasians. The combination of the cystic fibrosis transmembrane conductance regulator (CFTR) corrector lumacaftor / potentiator ivacaftor (LUM/IVA) has been shown to increase forced expiratory volume in 1 second (FEV1) moderately, but predominantly reduce acute exacerbation rate (AER) in Phe508del homozygous cystic fibrosis patients; however, patients with FEV1 therapy. If LTX candidates stabilise clinically, conditions for LTX, when it is indicated, improve. This is particularly important in countries such as Switzerland with a low organ donation rate and long waiting times for suitable donor organs. We included all patients from the Adult Cystic Fibrosis Centre at the University Hospital Zurich with Phe508del homozygous genotype and a predicted FEV1 AER, 6-minute walking distance (6-MWD), FEV1, forced vital capacity (FVC), mid-expiratory flow (MEF 25-75%), sweat chloride, body mass index (BMI) and quality of life. Respiratory-related adverse events (RAEs) were recorded. LUM/IVA treatment was initiated at a low dose and the dose increased stepwise. Twenty patients were on trial with LUM/IVA; at the cut-off date, 6-month follow-up was complete for 10 patients. RAEs were severe and occurred early. The dropout rate due to RAE or lack of clinical success was 20%. Median AER decreased from 2.5 in the 6 months pre-treatment to 1 during the observation period. FEV1 increased from 32 to 34.5% predicted, p = 0.292. The 6-MWD increased by a median 33 m (p = 0.6086). Sweat chloride decreased significantly by a median of 25 mmol/l (p = 0.0003). Median BMI increased from 19 to 19.9 kg/m2 (p = 0.1488). At the cut-off, three previously listed patients were paused on the transplant waiting list. Phe508del homozygous cystic fibrosis patients with end-stage pulmonary disease tolerated LUM/IVA, although RAEs occurred early and were severe. This positive finding was probably due to the stepwise dose increases. There was clinical

  1. [Cystic fibrosis: nutritional considerations].

    Science.gov (United States)

    Molina Arias, M; Prieto Bozano, G; Sarría Osés, J; Polanco Allué, I

    2001-06-01

    During the last few decades, improved treatment measures and nutritional support in cystic fibrosis have increased survival and quality of life in these patients. There is a clear relationship between the development of malnutrition and worsening in respiratory function and both factors have been related to poor disease outcome. Malnutrition is a very frequent complication of this disease and is found in 20% of patients, due to negative energy-proteic balance. This disequilibrium can be explained by increased energy expenditure, high nutritional requirements and decreased oral intake. Periodic monitoring of clinical, anthropometrical and functional nutritional status is mandatory. Intake must be greater than requirements and specific nutritional support should be established when required. Patients with cystic fibrosis must receive a hypercaloric and hyperproteotic diet, with a high fat content, a normal quantity of carbohydrates and with pancreatic and liposoluble vitamin supplements in case of pancreatic insufficiency.

  2. Personalized or Precision Medicine? The Example of Cystic Fibrosis

    OpenAIRE

    Marson, Fernando A. L.; Bertuzzo, Carmen S.; Ribeiro, Jos? D.

    2017-01-01

    The advent of the knowledge on human genetics, by the identification of disease-associated variants, culminated in the understanding of human variability. With the genetic knowledge, the specificity of the clinical phenotype and the drug response of each individual were understood. Using the cystic fibrosis (CF) as an example, the new terms that emerged such as personalized medicine and precision medicine can be characterized. The genetic knowledge in CF is broad and the presence of a monogen...

  3. Cystic echinococcosis in Algeria: cattle act as reservoirs of a sheep strain and may contribute to human contamination.

    Science.gov (United States)

    Bardonnet, K; Benchikh-Elfegoun, M C; Bart, J M; Harraga, S; Hannache, N; Haddad, S; Dumon, H; Vuitton, D A; Piarroux, R

    2003-08-29

    In Algeria, cystic echinococcosis (CE) is a serious economic and public health problem. The common sheep/dog cycle is usually considered as the major source of human contamination. But to date the main strain of Echinococcus granulosus involved in the human contamination and the role of other hosts are still unknown. This paper reports an original work performed in northern Algeria combining field observations and molecular analysis. In a first step, examination of 6237 carcasses in slaughterhouses showed high infection and fertility rates in cattle and dromedaries. Then, in a second step, we used a molecular biology approach to identify the E. granulosus strain(s) involved. Forty-six samples from various origins were collected. They were analysed using comparison of PCR-amplified DNA sequences with one genomic (BG 1/3) and two mitochondrial (COI and NDI) targets. Results show the presence of a "sheep" strain of E. granulosus in North Algeria circulating between cattle and ovines and infectious to humans, whereas in South Algeria, a "camel" strain and a "sheep" strain were found to circulate in camels and in sheep, respectively. This study also reports an ambiguous genotype which resembled the "sheep" strain genotype (Gl) on the basis of the partial COI gene sequence, whereas on the basis of the partial NDI gene sequence, it was similar either to the "sheep" strain (Gl) or to the "camel" strain (G6). Besides its basic interest, our study confirms the role of other hosts (mainly cattle) in leading to transmission to humans and suggests that control measures should not only target sheep.

  4. Linking Microbiota to Human Diseases

    DEFF Research Database (Denmark)

    Wu, Hao; Tremaroli, Valentina; Bäckhed, F

    2015-01-01

    The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2...... may disentangle some of the mechanistic details in the complex interactions of diet, microbiota, and host metabolism and may provide testable hypotheses for advancing our current understanding of human-microbiota interaction....... diabetes (T2D), and irritable bowel syndrome, and some animal experiments have suggested causality. However, few studies have validated causality in humans and the underlying mechanisms remain largely to be elucidated. We discuss how systems biology approaches combined with new experimental technologies...

  5. Assessing the residual CFTR gene expression in human nasal epithelium cells bearing CFTR splicing mutations causing cystic fibrosis.

    Science.gov (United States)

    Masvidal, Laia; Igreja, Susana; Ramos, Maria D; Alvarez, Antoni; de Gracia, Javier; Ramalho, Anabela; Amaral, Margarida D; Larriba, Sara; Casals, Teresa

    2014-06-01

    The major purpose of the present study was to quantify correctly spliced CFTR transcripts in human nasal epithelial cells from cystic fibrosis (CF) patients carrying the splicing mutations c.580-1G>T (712-1G>T) and c.2657+5G>A (2789+5G>A) and to assess the applicability of this model in CFTR therapeutic approaches. We performed the relative quantification of CFTR mRNA by reverse transcription quantitative PCR (RT-qPCR) of these splicing mutations in four groups (wild type, CF-F508del controls, CF patients and CF carriers) of individuals. In addition, in vitro assays using minigene constructs were performed to evaluate the effect of a new CF complex allele c.[2657+5G>A; 2562T>G]. Ex vivo qPCR data show that the primary consequence of both mutations at the RNA level is the skipping of their neighboring exon (6 and 16, respectively). The CFTR minigenes results mimicked the ex vivo data, as exon 16 skipping is the main aberrant transcript, and the correctly spliced transcript level was observed in a similar proportion when the c.2657+5G>A mutation is present. In summary, we provide evidence that ex vivo quantitative transcripts analysis using RT/qPCR is a robust technology that could be useful for measuring the efficacy of therapeutic approaches that attempt to achieve an increase in CFTR gene expression.

  6. Immunoblotting with human native antigen shows stage-related sensitivity in the serodiagnosis of hepatic cystic echinococcosis.

    Science.gov (United States)

    Mariconti, Mara; Bazzocchi, Chiara; Tamarozzi, Francesca; Meroni, Valeria; Genco, Francesca; Maserati, Roberta; Brunetti, Enrico

    2014-01-01

    The diagnosis of hepatic cystic echinococcosis is based on ultrasonography and confirmed by serology. However, no biological marker of cyst viability is currently available implying years-long patient follow-up, which is not always feasible in endemic areas. We characterized the performance of an immunoblotting test based on human hydatid cyst fluid with particular regard to its ability to distinguish between cyst stages. Sera from patients with cysts in different stages showed distinctive band pattern recognition. Most importantly, the test discriminated in 80% of cases CE3a from CE3b transitional cysts, known to have different viability profiles. Interestingly, we observed a rapid change in band pattern recognition of sera from one patient at time points when his cyst passed from active to transitional to inactive stages. Further identification of different antigens expressed by different cyst stages will support the development of diagnostic tools that could early define cyst viability, to guide clinical decision making, and shorten patient follow-up.

  7. Heat shock protein 27 and gross cystic disease fluid protein 15 play critical roles in molecular apocrine breast cancer.

    Science.gov (United States)

    Liu, Xiaozhen; Feng, Changyun; Liu, Junjun; Zhao, Lin; Liu, Jian; Zhang, Wei; Liu, Ning; Niu, Yun

    2016-06-01

    Molecular apocrine breast cancer (MABC) has a distinct hormonal profile, being estrogen receptor (ER) and progesterone receptor (PR) negative but androgen receptor (AR) positive. The clinical significance of MABC and its relative variables have not been absolutely clarified and remain to be determined. Five hundred cases of invasive breast carcinoma were randomly selected in this study, including 158 MABC cases and 342 nonMABC cases. Expression of ER, PR, epidermal growth factor receptor 2 (HER2), Ki67, AR, gross cystic disease fluid protein 15 (GCDFP15), and heat shock protein 27 (HSP27) were analyzed by immunohistochemistry. Differences of continuous variables between MABC and nonMABC subgroups were evaluated by the chi-square test. The Kaplan-Meier method was performed to evaluate disease-free survival (DFS) and overall survival (OS). The MABC subgroup had higher histological grade, bigger tumor size, more lymph node metastasis, and higher pTNM stage than the nonMABC subgroup (P < 0.05), and patients with MABC had poorer prognosis than those of the nonMABC subgroup (P < 0.05). Both GCDFP15 and HSP27 were expressed differently in the MABC and nonMABC subgroups (P < 0.05). Furthermore, in the MABC subgroup, positive HSP27 expression indicated higher risk of recurrence (P < 0.05) and positive GCDFP15 expression was also a poor marker for patient outcome (P < 0.05). MABC patients with HSP27 and GCDFP15 co-expression had worse outcome (P < 0.05). Our data suggested that MABC had a high risk of recurrence. Positive expression of both GCDFP15 and HSP27 were correlated with MABC malignancy. Targeting AR and HSP27 at the same time might offer a useful strategy to MABC.

  8. Histo-blood group gene polymorphisms as potential genetic modifiers of infection and cystic fibrosis lung disease severity.

    Directory of Open Access Journals (Sweden)

    Jennifer L Taylor-Cousar

    Full Text Available The pulmonary phenotype in cystic fibrosis (CF is variable; thus, environmental and genetic factors likely contribute to clinical heterogeneity. We hypothesized that genetically determined ABO histo-blood group antigen (ABH differences in glycosylation may lead to differences in microbial binding by airway mucus, and thus predispose to early lung infection and more severe lung disease in a subset of patients with CF.Clinical information and DNA was collected on >800 patients with the DeltaF508/DeltaF508 genotype. Patients in the most severe and mildest quartiles for lung phenotype were enrolled. Blood samples underwent lymphocyte transformation and DNA extraction using standard methods. PCR and sequencing were performed using standard techniques to identify the 9 SNPs required to determine ABO blood type, and to identify the four SNPs that account for 90-95% of Lewis status in Caucasians. Allele identification of the one nonsynonymous SNP in FUT2 that accounts for >95% of the incidence of nonsecretor phenotype in Caucasians was completed using an ABI Taqman assay. The overall prevalence of ABO types, and of FUT2 (secretor and FUT 3 (Lewis alleles was consistent with that found in the Caucasian population. There was no difference in distribution of ABH type in the severe versus mild patients, or the age of onset of Pseudomonas aeruginosa infection in the severe or mild groups. Multivariate analyses of other clinical phenotypes, including gender, asthma, and meconium ileus demonstrated no differences between groups based on ABH type.Polymorphisms in the genes encoding ABO blood type, secretor or Lewis genotypes were not shown to associate with severity of CF lung disease, or age of onset of P. aeruginosa infection, nor was there any association with other clinical phenotypes in a group of 808 patients homozygous for the DeltaF508 mutation.

  9. Human cystic echinococcosis in Morocco: Ultrasound screening in the Mid Atlas through an Italian-Moroccan partnership.

    Directory of Open Access Journals (Sweden)

    Houda Chebli

    2017-03-01

    Full Text Available Cystic echinococcosis (CE is a neglected parasitic zoonosis with considerable socioeconomic impact on affected pastoral communities. CE is endemic throughout the Mediterranean, including Morocco, where the Mid Atlas is the most prevalent area for both human and animal infection. The highest hospital annual incidence of human CE is recorded in the provinces of Ifrane and El Hajeb. However, hospital-based statistics likely underestimate the real prevalence of infection, as a proportion of cases never reach medical attention or official records.In 2012, a project on clinical management of CE in Morocco was launched with the aims of estimating the prevalence of human abdominal CE in selected rural communes of the above mentioned provinces using ultrasound (US screening and training local physicians to implement US-based focused assessment and rational clinical management of CE according to the WHO-IWGE Expert Consensus. A total of 5367 people received abdominal US during four campaigns in April-May 2014. During the campaigns, 24 local general practitioners received >24 hours of hands-on training and 143 health education sessions were organized for local communities. We found an overall CE prevalence of 1.9%, with significantly higher values in the rural communes of Ifrane than El Hajeb (2.6% vs 1.3%; p<0.001. CE cysts were predominantly in inactive stage, especially in older age groups. However, active cysts were present also in adults, indicating acquisition of infection at all ages. Province of residence was the only risk factor consistently associated with CE infection.Our results show a high prevalence and on-going, likely environmental transmission of CE in the investigated provinces of Morocco, supporting the implementation of control activities in the area by national health authorities and encouraging the acceptance and divulgation of diagnosis and treatment algorithms based on imaging for CE at both national and local level.

  10. Development of real-time PCR assay for simultaneous detection and genotyping of cystic echinococcosis in humans and livestock

    Directory of Open Access Journals (Sweden)

    Mohamed Elamin Ahmed

    2017-11-01

    Full Text Available Objective: To develop and evaluate a single-tube one-step real-time quantitative PCR (qPCR assay for simultaneous diagnosis and genotyping of cystic echinococcosis (CE in humans and livestock in the Sudan, and to compare it with conventional PCR assay. Methods: Hydatid cysts were obtained from slaughtered animals and from humans after surgical interventions. DNA from the hydatid cysts and associated germ layers was extracted using a commercially available kit. The mitochondrial NADH dehydrogenase subunit 1 (NAD1 was used as a target for PCR amplifications. qPCR and conventional nested PCR assays were compared in this study. Results: The qPCR assay amplified the NAD 1 gene of hydatid cysts on melting temperature generated at 80 °C. Ten-folds serial dilutions of DNA with known dilution of 1 × 106 to 1 × 101 (1 ng–1 fg resulted in detection of as little as 1 fg of DNA with an R2 value equivalent to 0.997. Similar sensitivities were encountered from both qPCR and the conventional nested PCR. The two assays did not amplify DNAs from Fasciola gigantica, Taenia saginata, Schistosoma bovis and DNA-free samples (negative controls. The PCR amplified products were purified for subsequent sequencing. The sequence data were analysed to insure the specificity of the amplified PCR products and to identify the genotype(s of hydatid cysts. All cysts were identified as E. canadensis genotype 6 (G6. Conclusions: The developed qPCR should be used as a rapid and reliable assay for diagnosis and genotyping of CE. The assay is highly recommended for the epidemiological surveillance in humans and livestock in endemic countries.

  11. GATA3 is a sensitive marker for primary genital extramammary paget disease: an immunohistochemical study of 72 cases with comparison to gross cystic disease fluid protein 15.

    Science.gov (United States)

    Zhao, Ming; Zhou, Lixin; Sun, Li; Song, Yan; Guo, Yunquan; Zhang, Xun; Zhao, Feng; Wang, Peng; Yue, Junqiu; Niu, Dongfeng; Li, Zhongwu; Huang, Xiaozheng; Kang, Qiang; Jia, Lin; Lai, Jinping; Cao, Dengfeng

    2017-07-10

    GATA-binding protein 3 (GATA3) has been identified as a sensitive marker for breast carcinoma but its sensitivity in primary genital extramammary Paget diseases (EMPDs) has not been well studied. Here we investigated immunohistochemical expression of GATA3 in 72 primary genital EMPDs (35 from female, 37 from male; 45 with intraepithelial disease only, 26 with both intraepithelial disease and invasive adenocarcinoma including 14 also metastasis, 1 with metastatic adenocarcinoma only for study). We also compared GATA3 to gross cystic disease fluid protein 15 (GCDFP15) for their sensitivity. Positive GATA3 staining was seen in all 71 (100%) intraepithelial diseases, 25/26 (96%; female 10/10, male 15/16) invasive adenocarcinomas and 14/15 (93%; female 3/3, male 11/12) metastatic adenocarcinomas, respectively. Positive GCDFP15 staining was seen in 46/71 (65%; female 28/34 or 82%, male 18/37 or 49%) intraepithelial diseases, 20/26 (77%; female 9/10, male 11/16) invasive adenocarcinomas, and 12/15 (80%; female 2/3, male 10/12) metastatic adenocarcinomas, respectively (GATA3 versus GCDFP15: p disease and invasive adenocarcinoma, p = 0.28 for metastatic adenocarcinoma). In positive-stained cases, GATA3 stained more tumor cells than GCDFP15 (79% versus 25% for intraepithelial disease, 71% vs 34% for invasive adenocarcinoma, 73% vs 50% for metastatic adenocarcinoma, p < 0.01 for all 3 components). Our findings indicate that GATA3 is a very sensitive marker for primary genital EMPDs and is more sensitive than GCDFP15.

  12. Bortezomib Followed by the Addition of Doxorubicin at Disease Progression in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma (Cancer) of the Head and Neck

    Science.gov (United States)

    2013-01-23

    Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Salivary Gland Adenoid Cystic Carcinoma; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer

  13. Early Lung Disease in Infants and Preschool Children with Cystic Fibrosis. What Have We Learned and What Should We Do about It?

    Science.gov (United States)

    Ranganathan, Sarath C; Hall, Graham L; Sly, Peter D; Stick, Stephen M; Douglas, Tonia A

    2017-06-15

    The past decade has seen significant advances in understanding of the pathogenesis and progression of lung disease in cystic fibrosis (CF). Pulmonary inflammation, infection, and structural lung damage manifest very early in life and are prevalent among preschool children and infants, often in the absence of symptoms or signs. Early childhood represents a pivotal period amenable to intervention strategies that could delay or prevent the onset of lung damage and alter the longer-term clinical trajectory for individuals with CF. This review summarizes what we have learned about early lung disease in children with CF and discusses the implications for future clinical practice and research.

  14. Rodent models for human diseases.

    Science.gov (United States)

    Vandamme, Thierry F

    2015-07-15

    One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. Except in the case of highly controlled and regulated clinical trials, geneticists and scientists do not use humans for their experimental investigations because of the obvious risk to life. Instead, they use various animal, fungal, bacterial, and plant species as model organisms for their studies. Amongst these model organisms, rodent models are the most used due to the easiness for the experiments and the possibility to modify genetically these model animals. Nevertheless, due to the fact that animal models typically do not contract the same genetic diseases as people, so scientists must alter their genomes to induce human disease states and to know what kind of mutation causes the disease. In this brief review, we will discuss the interests of rodent models that have been developed to simulate human pathologies, focusing in models that employ xenografts and genetic modification. Within the framework of genetically engineered mouse (GEM) models, we will review some of the current genetic strategies for modeling diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Stabilization of a nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator yields insight into disease-causing mutations.

    Science.gov (United States)

    Vernon, Robert M; Chong, P Andrew; Lin, Hong; Yang, Zhengrong; Zhou, Qingxian; Aleksandrov, Andrei A; Dawson, Jennifer E; Riordan, John R; Brouillette, Christie G; Thibodeau, Patrick H; Forman-Kay, Julie D

    2017-08-25

    Characterization of the second nucleotide-binding domain (NBD2) of the cystic fibrosis transmembrane conductance regulator (CFTR) has lagged behind research into the NBD1 domain, in part because NBD1 contains the F508del mutation, which is the dominant cause of cystic fibrosis. Research on NBD2 has also been hampered by the overall instability of the domain and the difficulty of producing reagents. Nonetheless, multiple disease-causing mutations reside in NBD2, and the domain is critical for CFTR function, because channel gating involves NBD1/NBD2 dimerization, and NBD2 contains the catalytically active ATPase site in CFTR. Recognizing the paucity of structural and biophysical data on NBD2, here we have defined a bioinformatics-based method for manually identifying stabilizing substitutions in NBD2, and we used an iterative process of screening single substitutions against thermal melting points to both produce minimally mutated stable constructs and individually characterize mutations. We present a range of stable constructs with minimal mutations to help inform further research on NBD2. We have used this stabilized background to study the effects of NBD2 mutations identified in cystic fibrosis (CF) patients, demonstrating that mutants such as N1303K and G1349D are characterized by lower stability, as shown previously for some NBD1 mutations, suggesting a potential role for NBD2 instability in the pathology of CF. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Water lily sign and serpent sign in pulmonary hydatid cystic disease

    Directory of Open Access Journals (Sweden)

    Ashish Ranjan

    2017-01-01

    Full Text Available The teaching image depicts sections of CT chest showing water lily sign and serpent sign. In the diagnosis of pulmonary hydatid disease, these signs are pathognomonic, these must be corroborated clinically, and early interventions should be done to avoid rupture of cysts leading to complications.

  17. Co-spray-dried mannitol-ciprofloxacin dry powder inhaler formulation for cystic fibrosis and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Adi, Handoko; Young, Paul M; Chan, Hak-Kim; Agus, Helen; Traini, Daniela

    2010-06-14

    The aim of this study was to assess the potential of delivering a combination therapy, containing mannitol (a sugar alcohol with osmotic characteristics), and ciprofloxacin hydrochloride (an antibacterial fluoroquinolone), as a dry powder inhaler (DPI) formulation for inhalation. Single and combination powders were produced by spray drying ciprofloxacin and mannitol, from aqueous solution, at different ratios and under controlled conditions, as to obtain similar particle size distributions. Each formulation was characterised using laser diffraction, scanning electron microscopy, differential scanning calorimetry, dynamic vapour sorption, X-ray powder diffraction, and colloidal force microscopy. The in vitro aerosol performance of each formulation was studied using an Aerolizer DPI device and a multi-stage liquid impinger (analysed using high performance liquid chromatography). In addition, a disk diffusion test was performed to assess the in vitro antimicrobial activity of each formulation and starting materials. All formulations had similar particle size distributions, however, the morphology, thermal properties and moisture sorption was dependent on the relative percentages of each component. In general, the combination formulation containing 50% (w/w) mannitol appeared to have the best aerosol performance, good stability and lowest particle cohesion (as measured by colloid probe microscopy). Furthermore, of the formulations tested, mannitol did not appear to alter the effectiveness of the ciprofloxacin antimicrobial activity to Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pyogenes. The combination of co-spray-dried mannitol and ciprofloxacin from a DPI is an attractive approach to promote mucous clearance in the respiratory tract while simultaneously treating local chronic infection, such as chronic obstructive pulmonary disease and cystic fibrosis. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  18. Congenital Cystic Adenomatoid Malformation of Lung-Rare Case Report

    Directory of Open Access Journals (Sweden)

    N. S. Kamakeri

    2016-10-01

    Full Text Available Congenital cystic adenomatoid malformation of lung associated with Cystic dysplasia of kidney, cystic disease of liver with mixed gonadal dysgenesis is rare and is not reported in literature so far. Hence an attempt is made to present this rarest entity.

  19. Living with Cystic Fibrosis: A Guide for the Young Adult.

    Science.gov (United States)

    Cystic Fibrosis Foundation, Atlanta, GA.

    Intended for the young adult with cystic fibrosis, the booklet provides information on dealing with problems and on advances in treatment and detection related to the disease. Addressed are the following topics: description of cystic fibrosis; inheritance of cystic fibrosis; early diagnosis; friends, careers, and other matters; treatment;…

  20. Cystic pulmonary chondroid hamartoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Eun Young; Lee, Kyung Soo; Han, Jeong Ho; Kim, Yoon Kyung [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2008-06-15

    Hamartomata is the most common benign type of tumor, occurring in the lung. However, a cystic pulmonary hamartoma is extremely rare, and is difficult to diagnose due to its nonspecific nature. We report a case of cystic pulmonary hamartoma in which a popcorn-like calcification is clearly identified, thus enabling a confident diagnosis of the disease.

  1. IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis

    NARCIS (Netherlands)

    Iannitti, R.G.; Napolioni, V.; Oikonomou, V.; Luca, A. De; Galosi, C.; Pariano, M.; Massi-Benedetti, C.; Borghi, M.; Puccetti, M.; Lucidi, V.; Colombo, C.; Fiscarelli, E.; Lass-Florl, C.; Majo, F.; Cariani, L.; Russo, M.; Porcaro, L.; Ricciotti, G.; Ellemunter, H.; Ratclif, L.; Benedictis, F.M. De; Talesa, V.N.; Dinarello, C.A.; Veerdonk, F.L. van de; Romani, L.

    2016-01-01

    Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory

  2. Herpesviruses in human periodontal disease.

    Science.gov (United States)

    Contreras, A; Slots, J

    2000-02-01

    Recent studies have identified various herpesviruses in human periodontal disease. Epstein-Barr virus type 1 (EBV-1) infects periodontal B-lymphocytes and human cytomegalovirus (HCMV) infects periodontal monocytes/ macrophages and T-lymphocytes. EBV-1, HCMV and other herpesviruses are present more frequently in periodontitis lesions and acute necrotizing ulcerative gingivitis-lesions than in gingivitis or periodontally healthy sites. Reactivation of HCMV in periodontitis lesions tends to be associated with progressing periodontal disease. Herpesvirus-associated periodontitis lesions harbor elevated levels of periodontopathic bacteria, including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteriodes forsythus, Prevotella intermedia, Prevotella nigrescens and Treponema denticola. It may be that active periodontal herpesvirus infection impairs periodontal defenses, thereby permitting subgingival overgrowth of periodontopathic bacteria. Alteration between latent and active herpesvirus infection in the periodontium might lead to transient local immunosuppression and explain in part the episodic progressive nature of human periodontitis. Tissue tropism of herpesvirus infections might help explain the localized pattern of tissue destruction in periodontitis. Absence of herpesvirus infection or viral reactivation might explain why some individuals carry periodontopathic bacteria while still maintaining periodontal health. Further studies are warranted to delineate whether the proposed herpesvirus-periodontopathic bacteria model might account for some of the pathogenic features of human periodontal disease.

  3. Proteins aggregation and human diseases

    Science.gov (United States)

    Hu, Chin-Kun

    2015-04-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  4. The association between combined non-cystic fibrosis bronchiectasis and lung cancer in patients with chronic obstructive lung disease

    Directory of Open Access Journals (Sweden)

    Kim YW

    2015-05-01

    Full Text Available Yeon Wook Kim,1 Kwang-Nam Jin,2 Eun Young Heo,3 Sung Soo Park,3 Hee Soon Chung,3 Deog Kyeom Kim31Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Department of Radiology, Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of KoreaBackground: Whereas the epidemiological association between lung cancer and chronic obstructive pulmonary disease (COPD, a chronic inflammatory respiratory disease, is well known, limited studies have examined the association between lung cancer and non-cystic fibrosis bronchiectasis, a representative chronic airway inflammatory disease. This study evaluated the association between bronchiectasis and lung cancer in patients with COPD.Methods: A matched case–control study was conducted in a referral hospital in South Korea. Among COPD patients with moderate to very severe airflow limitation (forced expiratory volume in one second/forced vital capacity <0.7 and forced expiratory volume in one second ≤70% [% predicted] who underwent chest computed tomography (CT between January 1, 2010 and May 30, 2013, patients with lung cancer and controls matched for age, sex, and smoking history were selected. The risk of lung cancer was assessed according to the presence of underlying bronchiectasis confirmed by chest CT.Results: The study enrolled 99 cases and 198 controls. Combined bronchiectasis on chest CT was inversely associated with the risk of lung cancer compared with controls (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.12–0.52, P<0.001. Significant associations were found in

  5. Human hydatid disease in Peru is basically restricted to Echinococcus granulosus genotype G1.

    Science.gov (United States)

    Santivañez, Saul J; Gutierrez, Ariana M; Rosenzvit, Mara C; Muzulin, Patricia M; Rodriguez, Mary L; Vasquez, Julio C; Rodriguez, Silvia; Gonzalez, Armando E; Gilman, Robert H; Garcia, Hector H

    2008-07-01

    A molecular PCR study using DNA from 21 hydatid cysts was performed to determine which strain type is responsible for human infection in Peru. The mitochondrial cytochrome c oxidase subunit 1 (CO1) gene was amplified in 20 out of 21 samples, revealing that all but 1 sample (19/20, 95%) belonged to the common sheep strain (G1). The remaining samples belonged to the camel strain (G6). The G1 genotype was most frequently found in human cases of cystic hydatid disease (CHD) in Peru. Local control measures should focus primarily on decreasing dog and sheep infection rather than intermediate reservoirs.

  6. Severity and outcome of cystic lung disease in women with tuberous sclerosis complex.

    Science.gov (United States)

    Taveira-DaSilva, Angelo M; Jones, Amanda M; Julien-Williams, Patricia; Yao, Jianhua; Stylianou, Mario; Moss, Joel

    2015-01-01

    What are the clinical features, severity, and rate of progression of lung disease in women with tuberous sclerosis and lymphangioleiomyomatosis (LAM) and how do they differ from patients with sporadic LAM? Data from 94 tuberous sclerosis/LAM and 460 sporadic LAM women were compared. 40 tuberous sclerosis/LAM and 40 sporadic LAM patients were age- and lung function-matched, and changes in volume occupied by cysts (cyst score) and pulmonary function occurring over 6.5 years were evaluated. Tuberous sclerosis/LAM patients had better lung function than sporadic LAM patients, but no difference was observed from sporadic LAM patients in yearly rates of change in forced expiratory volume in 1 s (-1.9±2.7 versus -1.9±1.9% predicted; p=0.302), diffusing capacity of the lung for CO (-2.1±2.8 versus -1.9±2.7% predicted; p=0.282) or cyst scores (+1.0±1.3 versus +1.4±1.7%, p=0.213). However, the proportion of patients with abnormal lung function and higher rates of FEV1 decline was greater in sporadic LAM. Some young tuberous sclerosis/LAM patients (mean age 25.7±3 years) progressed rapidly from minimal to severe lung disease. Tuberous sclerosis/LAM patients may experience abrupt declines in lung function. Consequently, women with tuberous sclerosis found to have lung cysts should undergo periodic functional and radiological testing to follow disease progression and determine need for therapy. Copyright ©ERS 2015.

  7. Prevalence and characteristics of chronic kidney disease among Danish adults with cystic fibrosis

    DEFF Research Database (Denmark)

    Berg, Kristina H; Ryom, Lene; Faurholt-Jepsen, Daniel

    2018-01-01

    BACKGROUND: With improved prognosis of CF, comorbidities including chronic kidney disease (CKD) are becoming increasingly important. Identification of those at highest CKD risk is hence a priority. METHODS: In this cross-sectional study, adults with CF attending the Copenhagen CF Centre...... median duration of chronic pulmonary infection (28.3 (20.0-35.8) vs. 20.0 (9.9-34.7) years; p=0.008) and with longer intravenous aminoglycosides use (606 (IQR, 455-917) vs. 273 (IQR, 91-826) days, p=0.005). CONCLUSIONS: The CKD prevalence is high and related to age, diabetes, chronic infection...

  8. Cystic Lung Disease in Down Syndrome: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Mathew George

    2016-01-01

    Full Text Available Subpleural lung cysts (SPC are seen in children with Down syndrome (DS. The incidence and the long term course of these lesions are not known. It is important for pediatricians and pediatric radiologists to be aware of these lung lesions since the DS patients’ longevity has increased and they have greater frequency to encounter the clinicians. Autopsy and the radiology series have shown that these lesions are often found in association with congenital heart disease, particularly the endocardial cushion defect and prematurity.

  9. Methodology and Applications of Disease Biomarker Identification in Human Serum

    Directory of Open Access Journals (Sweden)

    Ziad J. Sahab

    2007-01-01

    Full Text Available Biomarkers are biomolecules that serve as indicators of biological and pathological processes, or physiological and pharmacological responses to a drug treatment. Because of the high abundance of albumin and heterogeneity of plasma lipoproteins and glycoproteins, biomarkers are difficult to identify in human serum. Due to the clinical significance the identification of disease biomarkers in serum holds great promise for personalized medicine, especially for disease diagnosis and prognosis. This review summarizes some common and emerging proteomics techniques utilized in the separation of serum samples and identification of disease signatures. The practical application of each protein separation or identification technique is analyzed using specific examples. Biomarkers of cancers of prostate, breast, ovary, and lung in human serum have been reviewed, as well as those of heart disease, arthritis, asthma, and cystic fibrosis. Despite the advancement of technology few biomarkers have been approved by the Food and Drug Administration for disease diagnosis and prognosis due to the complexity of structure and function of protein biomarkers and lack of high sensitivity, specificity, and reproducibility for those putative biomarkers. The combination of different types of technologies and statistical analysis may provide more effective methods to identify and validate new disease biomarkers in blood.Abbreviations: 2-DE, two-dimensional gel electrophoresis; 2DLC-MS, two-dimensional liquid chromatography mass spectrometry; CA 15.3, cancer antigen 15.3; CA 19–9, cancer antigen 19–9, a tumor-associated antigen; CA125, cancer antigen 125, a mucin-like protein; CEA, carcinoembryonic antigen; CF, Cystic Fibrosis; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; ESI-MS/MS, electrospray ionization tandem mass spectrometry; FDA, Food and Drug Administration; IPG, immobilized pH gradient; MALDI-TOF-MS, matrix-assisted laser desorption

  10. A Study of the Safety and Tolerability of Inhaled SNSP113 in Healthy Subjects and Subjects With Stable Cystic Fibrosis

    Science.gov (United States)

    2017-10-12

    Lung Diseases; Pulmonary Disease; Cystic Fibrosis; Cystic Fibrosis Lung; Cystic Fibrosis Pulmonary Exacerbation; Cystic Fibrosis With Exacerbation; Respiratory Tract Disease; Pulmonary Inflammation; Multi-antibiotic Resistance; Antibiotic Resistant Infection; Lung Infection; Lung Infection Pseudomonal; Lung; Infection, Atypical Mycobacterium; Burkholderia Infections; Burkholderia Cepacia Infection; Lung Inflammation

  11. Adult cystic lymphangioma in the inner quadrant of the breast—Rare location for a rare disease: A case report

    Directory of Open Access Journals (Sweden)

    Eve Rusdianto

    2016-01-01

    Conclusion: Breast cystic lymphangioma is an extremely rare condition, especially in the upper, inner quadrant of the breast. The patient had multiple recurrences of the lesion after fine needle aspirations. Proper index of suspicion, prompt diagnosis, and definitive treatment is necessary to prevent recurrence and complications.

  12. Human papillomavirus-related carcinoma with adenoid cystic-like features of the sinonasal tract: clinical and morphological characterization of six new cases.

    Science.gov (United States)

    Andreasen, Simon; Bishop, Justin A; Hansen, Thomas van Overeem; Westra, William H; Bilde, Anders; von Buchwald, Christian; Kiss, Katalin

    2017-05-01

    Human papillomavirus (HPV) is known as causative for squamous cell carcinoma (SCC) of the oropharynx, but is also found not infrequently in carcinomas of the sinonasal tract. Recently, a subset of these carcinomas was recognized to harbour HPV33 and have a significant morphological overlap with adenoid cystic carcinoma (ACC), a rare and aggressive carcinoma originating in the minor salivary glands. Termed 'HPV-related carcinoma with ACC-like features', only nine cases have been reported. To clarify the occurrence of these tumours we screened a large material for the presence of HPV-related ACC-like carcinoma. The identified tumours were characterized immunohistochemically and with fluorescence in-situ hybridization, and clinicopathological information for all cases is presented. Forty-seven candidate cases were screened for presence of HPV. Six cases were identified and genotyped as HPV types 33, 35, and 56. All six cases had areas of dysplastic mucosal lining and showed remarkable heterogeneous morphologies. MYB, MYBL1, and NFIB genes were intact and, interestingly, staining for MYB protein was largely negative in contrast to what was found in ACC. One patient experienced a local recurrence 11 years after initial treatment and the remaining five patients were alive without evidence of disease. We report six new cases of HPV-related ACC-like carcinoma and found that, although in a small material, the prognosis for these patients seems more favourable than for ACC. For the distinction between ACC and HPV-related ACC-like carcinoma, p16, MYB immunohistochemistry or investigation of MYB, MYBL1 and NFIB gene status are valuable. © 2016 John Wiley & Sons Ltd.

  13. [Alzheimer's disease and human memory].

    Science.gov (United States)

    Eustache, F; Giffard, B; Rauchs, G; Chételat, G; Piolino, P; Desgranges, B

    2006-10-01

    Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to a detailed analysis into the framework of cognitive neuropsychology which aimed at describing the deficits of very specific processes. Beyond their clinical interest, these studies contributed to the modelisation of human memory thanks to the characterization of different memory systems and their relationships. The first part of this paper gives an overview of the memory deficits in Alzheimer's disease and insists on particular cognitive phenomena. Hence, several examples are developed in the domains of semantic memory (such as hyperpriming and hypopriming effects) and autobiographical memory. Recent results highlight the existence of severe autobiographical amnesia observed in all neurodegenerative diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's disease (showing that remote memories are better preserved than recent ones), reverse gradient in semantic dementia and no clear gradient in the frontal variant of frontotemporal dementia. The second part of this article presents advances in cognitive neuroscience searching to disclose the cerebral substrates of these cognitive deficits in Alzheimer's disease. The studies using functional imaging techniques are the most informative regarding this problematic. While showing the dysfunctions of an extended network, they emphasize the selectivity of cerebral damages that are at the root of very specific cognitive dysfunctions, coming close in that way to the conceptions of cognitive neuropsychology. These neuroimaging studies unravel the existence of compensatory mechanisms, which until recently were clearly missing in the literature on neurodegenerative diseases. These different researches lead to a wide conception of human memory, not just limited to simple instrumental processes (encoding, storage, retrieval), but necessarily covering models of identity and continuity of the subject, which interact in a dynamic way

  14. Transfer RNA and human disease

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    Jamie A Abbott

    2014-06-01

    Full Text Available Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA genes are hotspots for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase, mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing. Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

  15. SERCA pumps and human diseases.

    Science.gov (United States)

    Hovnanian, A

    2007-01-01

    Sarco(endo)plasmic reticulum (SER) Ca2+ ATPases represent a highly conserved family of Ca2+ pumps which actively transport Ca2+ from the cytosol to the SER against a large concentration gradient. In humans, 3 genes (ATP2A1-3) generate multiple isoforms (SERCAla,b, SERCA2a-c, SECA3a-f) by developmental or tissue-specific alternative splicing. These pumps differ by their regulatory and kinetic properties, allowing for optimized function in the tissue where they are expressed. They play a central role in calcium signalling through regenerating SER Ca2+ stores, maintaining appropriate Ca2+ levels in this organelle and shaping cytosolic and nuclear Ca2+ variations which govern cell response. Defects in ATP2A1 encoding SERCA1 cause recessive Brody myopathy, mutations in ATP2A2 coding for SERCA2 underlie a dominant skin disease, Darier disease and its clinical variants. SERCA2a expression is reduced in heart failure in human and in mice models. Gene-targeting studies in mouse confirmed the expected function of these isoforms in some cases, but also resulted in unexpected phenotypes: SERCA1 null mutants die from respiratory failure, SERCA2 heterozygous mutant mice develop skin cancer with age and SERCA3 null mice display no diabetes. These unique phenotypes have provided invaluable information on the role of these pumps in specific tissues and species, and have improved our understanding of Ca2+ regulated processes in muscles, the heart and the skin in human and in mice. Although the understanding of the pathogenesis of these diseases is still incomplete, these recent advances hold the promise of improved knowledge on the disease processes and the identification of new targets for therapeutic interventions.

  16. Kidney Injury Molecule-1 Is Specifically Expressed in Cystically-Transformed Proximal Tubules of the PKD/Mhm (cy/+ Rat Model of Polycystic Kidney Disease

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    Stefan Gauer

    2016-05-01

    Full Text Available Expression of kidney injury molecule-1 (Kim-1 is rapidly upregulated following tubular injury, constituting a biomarker for acute kidney damage. We examined the renal localization of Kim-1 expression in PKD/Mhm (polycystic kidney disease, Mannheim (cy/+ rats (cy: mutated allel, +: wild type allel, an established model for autosomal dominant polycystic kidney disease, with chronic, mainly proximal tubulointerstitial alterations. For immunohistochemistry or Western blot analysis, kidneys of male adult heterozygously-affected (cy/+ and unaffected (+/+ littermates were perfusion-fixed or directly removed. Kim-1 expression was determined using peroxidase- or fluorescence-linked immunohistochemistry (alone or in combination with markers for tubule segments or differentiation. Compared to (+/+, only in (cy/+ kidneys, a chronic expression of Kim-1 could be detected by Western blot analysis, which was histologically confined to an apical cellular localization in areas of cystically-transformed proximal tubules with varying size and morphology, but not in distal tubular segments. Kim-1 was expressed by cystic epithelia exhibiting varying extents of dedifferentiation, as shown by double labeling with aquaporin-1, vimentin or osteopontin, yielding partial cellular coexpression. In this model, in contrast to other known molecules indicating renal injury and/or repair mechanisms, the chronic renal expression of Kim-1 is strictly confined to proximal cysts. Its exact role in interfering with tubulo-interstitial alterations in polycystic kidney disease warrants future investigations.

  17. Human Microbiota and Ophthalmic Disease.

    Science.gov (United States)

    Lu, Louise J; Liu, Ji

    2016-09-01

    The human ocular surface, consisting of the cornea and conjunctiva, is colonized by an expansive, diverse microbial community. Molecular-based methods, such as 16S rRNA sequencing, has allowed for more comprehensive and precise identification of the species composition of the ocular surface microbiota compared to traditional culture-based methods. Evidence suggests that the normal microbiota plays a protective immunological role in preventing the proliferation of pathogenic species and thus, alterations in the homeostatic microbiome may be linked to ophthalmic pathologies. Further investigation of the ocular surface microbiome, as well as the microbiome of other areas of the body such as the oral mucosa and gut, and their role in the pathophysiology of diseases is a significant, emerging field of research, and may someday enable the development of novel probiotic approaches for the treatment and prevention of ophthalmic diseases.

  18. Human Cytomegalovirus and Autoimmune Disease

    Science.gov (United States)

    2014-01-01

    Human cytomegalovirus (HCMV) represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE), systemic sclerosis (SSc), diabetes mellitus type 1, and rheumatoid arthritis (RA) is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention. PMID:24967373

  19. Human Cytomegalovirus and Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Anne Halenius

    2014-01-01

    Full Text Available Human cytomegalovirus (HCMV represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE, systemic sclerosis (SSc, diabetes mellitus type 1, and rheumatoid arthritis (RA is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.

  20. UP-TO-DATE MANAGEMENT OF LIVER DISEASE AND COMPLICATIONS IN CYSTIC FIBROSIS AND TRANSITION OF ADOLESCENTS FROM PEDIATRIC TO ADULT CARE

    Directory of Open Access Journals (Sweden)

    Marina Praprotnik

    2015-05-01

    Full Text Available Cystic fibrosis (CF is the most common autosomal recessive lethal hereditary disorder among whites. Survival of patients with CF has progressively improved over the last four decades.As life expectancy has been greatly extended, complications like osteopenia and CF-related diabetes mellitus (CFRDM occur. In our article, a new management of these two complications is described.Gastrointestinal tract, exocrine pancreas and liver are also affected in CF.Maintaining good nutrition while treating pancreatic insufficiency, treating gastroesophageal reflux disease and treating liver disease are very important issues in the treatment gastrointestinal tract disease in CF.As the CF patient population median survival increases,  a growing number of adolescents require care in the adult health care system which must be capable of responding appropriately to their needs.We present a model of transition from paediatric to adult medical care in our CF center.

  1. Bordetella bronchiseptica in a paediatric cystic fibrosis patient: possible transmission from a household cat

    Science.gov (United States)

    Bordetella bronchiseptica was isolated from the sputum of a cystic fibrosis patient recently exposed to a kitten with an acute respiratory disease. Genetic characterization of the isolate and comparison with other isolates of human or feline origin strongly implicate the kitten as the source of infe...

  2. Absence of link between abortion and seropositivity of cystic hydatid disease in ewes and female goats in Turkey

    Directory of Open Access Journals (Sweden)

    Sami Simsek

    2012-09-01

    Full Text Available This study was conducted to test whether there is a statistically significant association between seropositivity to cystic echinococcosis and abortion in ewes and female goats from the Turkish provinces of Elazig (east Anatolia, Sanliurfa (south-east Anatolia and Kayseri (Inner Anatolia using the enzyme-linked immunosorbent assay (ELISA. A total of 20 of 133 sera (15.1% from ewes and 5 of 101 sera (4.9% from goats with a history of abortion gave seropositive results that were not significantly different (p>0.05 from these, 9.9% (10/101 were reported for ewes and 1.6% (2/122 for female goats without a history of abortion. Serological prevalence rates among those animals with a history of abortion were not significantly different from the control group. No positive association was established between seropositivity for cystic echinococcosis and abortion in ewes and female goats.

  3. Cystic Neoplasms of the Pancreas

    Science.gov (United States)

    Tran Cao, Hop S.; Kellogg, Benjamin; Lowy, Andrew M.; Bouvet, Michael

    2015-01-01

    Whereas pancreatic duct adenocarcinoma (PDA) is a well-studied (but still poorly understood) disease with a dismal prognosis, cystic neoplasms of the pancreas form a more recently recognized group of pancreatic tumors. They are diverse and variable in their pathologic characteristics, clinical course, and outcomes,1–3 although all portend a better overall prognosis than PDA. In recent years, with the improved sensitivity and increasing use of cross-sectional imaging in clinical practice, these lesions are more commonly identified,4 with many being discovered incidentally. Indeed, large radiological series using computed tomography (CT) or magnetic resonance imaging (MRI) have reported detection rates of pancreatic cystic lesions between 1.2% and almost 20%,5,6 approaching the 24.3% prevalence rate in an autopsy series by Kimura and colleagues.7 Although most of these lesions are pseudocysts, a significant portion consist of cystic neoplasms, which are estimated to represent 10% to 15% of all primary pancreatic cystic lesions.8 Given the growing clinical relevance of these tumors, a keen understanding of their natural history and pathophysiology is needed. This article reviews pancreatic cystic neoplasms, with a focus on the challenges encountered in their diagnosis and treatment. PMID:20159515

  4. Epidemiology and history of human parasitic diseases in Romania.

    Science.gov (United States)

    Neghina, Raul; Neghina, Adriana M; Marincu, Iosif; Iacobiciu, Ioan

    2011-06-01

    Intestinal parasitic diseases such as enterobiasis, giardiasis, and ascariasis are detected most frequently in Romania, but their importance is definitely surpassed by trichinellosis, cystic echinococcosis, and toxoplasmosis. Malaria was common until its eradication in 1963, and only imported cases are reported nowadays. The aim of this review was to bring together essential data on the epidemiology and history of human parasitoses in Romania. Information on 43 parasitic diseases was collected from numerous sources, most of them unavailable abroad or inaccessible to the international scientific community. Over time, Romanian people of all ages have paid a significant tribute to the pathogenic influences exerted by the parasites. Sanitary and socio-economical consequences of the parasites diseases have great negative impact on the quality of life of affected individuals and the overall well-being of the population. Implementation of efficient public health measures and informative campaigns for the masses as well as changing the inadequate habits that are deeply rooted in the population are mandatory for cutting successfully this Gordian knot.

  5. Medullary cystic kidney disease

    Science.gov (United States)

    ... by: Charles Silberberg, DO, private practice specializing in nephrology, affiliated with New York Medical College, Division of Nephrology, Valhalla, NY. Review provided by VeriMed Healthcare Network. ...

  6. Liver Transplantation for Cirrhosis in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    T Lamireau

    2006-01-01

    Full Text Available BACKGROUND: Liver disease is the third most common cause of death in children with cystic fibrosis (CF. Liver transplantation is an effective treatment in children with hepatic failure.

  7. CRISPR-mediated genome editing and human diseases

    Directory of Open Access Journals (Sweden)

    Liquan Cai

    2016-12-01

    Full Text Available CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene function. More recently, this technology has been increasingly applied to the study or treatment of human diseases, including Barth syndrome effects on the heart, Duchenne muscular dystrophy, hemophilia, β-Thalassemia, and cystic fibrosis. CRISPR/Cas9 (CRISPR-associated protein 9 genome editing has been used to correct disease-causing DNA mutations ranging from a single base pair to large deletions in model systems ranging from cells in vitro to animals in vivo. In addition to genetic diseases, CRISPR/Cas9 gene editing has also been applied in immunology-focused applications such as the targeting of C-C chemokine receptor type 5, the programmed death 1 gene, or the creation of chimeric antigen receptors in T cells for purposes such as the treatment of the acquired immune deficiency syndrome (AIDS or promoting anti-tumor immunotherapy. Furthermore, this technology has been applied to the genetic manipulation of domesticated animals with the goal of producing biologic medical materials, including molecules, cells or organs, on a large scale. Finally, CRISPR/Cas9 has been teamed with induced pluripotent stem (iPS cells to perform multiple tissue engineering tasks including the creation of disease models or the preparation of donor-specific tissues for transplantation. This review will explore the ways in which the use of CRISPR/Cas9 is opening new doors to the treatment of human diseases.

  8. 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

  9. Genetic and Informatic Analyses Implicate Kif12 as a Candidate Gene within the Mpkd2 Locus That Modulates Renal Cystic Disease Severity in the Cys1cpk Mouse.

    Directory of Open Access Journals (Sweden)

    Michal Mrug

    Full Text Available We have previously mapped the interval on Chromosome 4 for a major polycystic kidney disease modifier (Mpkd of the B6(Cg-Cys1cpk/J mouse model of recessive polycystic kidney disease (PKD. Informatic analyses predicted that this interval contains at least three individual renal cystic disease severity-modulating loci (Mpkd1-3. In the current study, we provide further validation of these predicted effects using a congenic mouse line carrying the entire CAST/EiJ (CAST-derived Mpkd1-3 interval on the C57BL/6J background. We have also generated a derivative congenic line with a refined CAST-derived Mpkd1-2 interval and demonstrated its dominantly-acting disease-modulating effects (e.g., 4.2-fold increase in total cyst area; p<0.001. The relative strength of these effects allowed the use of recombinants from these crosses to fine map the Mpkd2 effects to a <14 Mbp interval that contains 92 RefSeq sequences. One of them corresponds to the previously described positional Mpkd2 candidate gene, Kif12. Among the positional Mpkd2 candidates, only expression of Kif12 correlates strongly with the expression pattern of Cys1 across multiple anatomical nephron structures and developmental time points. Also, we demonstrate that Kif12 encodes a primary cilium-associated protein. Together, these data provide genetic and informatic validation of the predicted renal cystic disease-modulating effects of Mpkd1-3 loci and implicate Kif12 as the candidate locus for Mpkd2.

  10. DeltaF508 heterozygosity in cystic fibrosis and susceptibility to asthma

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, A; Lange, P

    1998-01-01

    Cystic fibrosis is a recessive disorder mainly characterised by lung disease. We tested the hypothesis that individuals heterozygous for the common cystic fibrosis deltaF508 mutation are at risk of obstructive pulmonary disease.......Cystic fibrosis is a recessive disorder mainly characterised by lung disease. We tested the hypothesis that individuals heterozygous for the common cystic fibrosis deltaF508 mutation are at risk of obstructive pulmonary disease....

  11. Cystic Fibrosis and Pregnancy

    Science.gov (United States)

    ... Global Map Premature Birth Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... complications > Cystic fibrosis and pregnancy Cystic fibrosis and pregnancy E-mail to a friend Please fill in ...

  12. Blockade of nicotinic and muscarinic receptors facilitates spontaneous migration of human peripheral granulocytes: failure in cystic fibrosis.

    Science.gov (United States)

    Wessler, Ignaz; Neumann, Stefanie; Razen, Michael; Zepp, Fred; Kirkpatrick, Charles James

    2012-11-27

    Circulating leucocytes express muscarinic (m) and nicotinic (n) receptors and synthesize acetylcholine (ACh) regulating various cell functions. Leucocytes from patients with cystic fibrosis contain less ACh; therefore it was tested whether the regulation of cellular functions like migration differed from healthy volunteers. Peripheral blood (10-20 ml) was used, leucocytes were isolated by Ficoll® gradient and the commercial MIGRATEST® combined with flow cytometric analysis was applied (pore size 3 μm). In the absence of test substances 4900±1800 (n=10) leucocytes migrated within a time period of 2 h. In the presence of tubocurarine (TC, 30 μM) the cell number increased to 7500±2700 [n=10] corresponding to an increase of 162±20% (mean of individual experiments; pGranulocytes isolated from patients with cystic fibrosis did not respond (2h migration) to 30 μM TC (control: 5180±1400 cells [n=10]; TC: 5800±1400 [n=10]). Also in the presence of atropine (1 μM) and TC (30 μM) a significant effect was not detected (5800±1300 [n=10]). Auto-paracrine acetylcholine limits the migration of unstimulated peripheral granulocytes. This effect is impaired in cystic fibrosis most likely because of a reduced endogenous cholinergic tone. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Initial interrogation, confirmation and fine mapping of modifying genes: STAT3, IL1B and IFNGR1 determine cystic fibrosis disease manifestation.

    Science.gov (United States)

    Labenski, Heike; Hedtfeld, Silke; Becker, Tim; Tümmler, Burkhard; Stanke, Frauke

    2011-12-01

    We have used a stepwise approach consisting of initial interrogation, confirmation and fine mapping to analyze STAT3, IL1B and IFNGR1 as modifiers of cystic fibrosis disease building upon the data and sample collection of the European Cystic Fibrosis Twin and Sibling Study. We have observed direct correlation between the length of the intronic microsatellite STAT3Sat to STAT3 expression levels among F508del-CFTR homozygous patients (P=0.0075), and an association of longer STAT3Sat-alleles with the presence of CFTR-mediated residual chloride secretion (P=0.0031), measured as the manifestation of the CF basic defect in intestinal tissue. Both, family-based analysis by TDT and case-reference comparison identified consistently the same intragenic IL1B haplotype as a risk variant (P(raw)=0.055 for TDT, P(raw)<0.3 for case-reference comparison). Using haplotype-guided hierarchical fine mapping, we have identified two single nucleotide exchanges for which concordant and discordant sibling pairs differ at a 7 kb-spanning core haplotype in IFNGR1 (P(raw)=0.0113). Taken together, our findings imply that immunorelevant pathways and ion secretion, dominated by CFTR in intestinal and respiratory epithelium, merge at the level of the epithelial cell to integrate the signaling of cytokines due to innate and acquired immune defense.

  14. A case of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Maria Alice Monti

    2009-09-01

    Full Text Available As the expected survival improves for patients with cystic fibrosis (CF, there is a growing population of adults with this disease. We describe a case of a 33-year-old woman with CF presenting with recurrent pancreatitis, malnutrition, borderline sweat test and respiratory diseases. The case report underlines the importance of diagnosis and management of CF in adults, and the important role played by the Family Physician in developing an adult care program.

  15. An association study on contrasting cystic fibrosis endophenotypes recognizes KRT8 but not KRT18 as a modifier of cystic fibrosis disease severity and CFTR mediated residual chloride secretion

    Directory of Open Access Journals (Sweden)

    Becker Tim

    2011-05-01

    Full Text Available Abstract Background F508del-CFTR, the most frequent disease-causing mutation among Caucasian cystic fibrosis (CF patients, has been characterised as a mutant defective in protein folding, processing and trafficking. We have investigated the two neighbouring cytokeratin genes KRT8 and KRT18 in a candidate gene approach to ask whether variants in KRT8 and/or KRT18 modify the impaired ion conductance known as the CF basic defect, and whether they are associated with correct trafficking of mutant CFTR and disease severity of CF. Methods We have selected contrasting F508del-CFTR homozygous patient subpopulations stratified for disease severity, comparing 13 concordant mildly affected sib pairs vs. 12 concordant severely affected sib pairs, or manifestation of the CF basic defect in intestinal epithelium, comparing 22 individuals who exhibit CFTR-mediated residual chloride secretion vs. 14 individuals who do not express any chloride secretion, for an association. The KRT8/KRT18 locus was initially interrogated with one informative microsatellite marker. Subsequently, a low density SNP map with four SNPs in KRT8 and two SNPs in KRT18, each selected for high polymorphism content, was used to localize the association signal. Results KRT8, but not KRT18, showed an association with CF disease severity (Pbest = 0.00131; Pcorr = 0.0185 and CFTR mediated residual chloride secretion (Pbest = 0.0004; Pcorr = 0.0069. Two major four-marker-haplotypes spanning 13 kb including the entire KRT8 gene accounted for 90% of chromosomes, demonstrating strong linkage disequilibrium at that locus. Absence of chloride secretion was associated with the recessive haplotype 1122 at rs1907671, rs4300473, rs2035878 and rs2035875. The contrasting haplotype 2211 was dominant for the presence of CFTR mediated residual chloride secretion. In consistency, the KRT8 haplotype 2211 was associated with mild CF disease while 1122 was observed as risk haplotype. Analysis of microsatellite

  16. An association study on contrasting cystic fibrosis endophenotypes recognizes KRT8 but not KRT18 as a modifier of cystic fibrosis disease severity and CFTR mediated residual chloride secretion.

    Science.gov (United States)

    Stanke, Frauke; Hedtfeld, Silke; Becker, Tim; Tümmler, Burkhard

    2011-05-06

    F508del-CFTR, the most frequent disease-causing mutation among Caucasian cystic fibrosis (CF) patients, has been characterised as a mutant defective in protein folding, processing and trafficking. We have investigated the two neighbouring cytokeratin genes KRT8 and KRT18 in a candidate gene approach to ask whether variants in KRT8 and/or KRT18 modify the impaired ion conductance known as the CF basic defect, and whether they are associated with correct trafficking of mutant CFTR and disease severity of CF. We have selected contrasting F508del-CFTR homozygous patient subpopulations stratified for disease severity, comparing 13 concordant mildly affected sib pairs vs. 12 concordant severely affected sib pairs, or manifestation of the CF basic defect in intestinal epithelium, comparing 22 individuals who exhibit CFTR-mediated residual chloride secretion vs. 14 individuals who do not express any chloride secretion, for an association. The KRT8/KRT18 locus was initially interrogated with one informative microsatellite marker. Subsequently, a low density SNP map with four SNPs in KRT8 and two SNPs in KRT18, each selected for high polymorphism content, was used to localize the association signal. KRT8, but not KRT18, showed an association with CF disease severity (Pbest=0.00131; Pcorr=0.0185) and CFTR mediated residual chloride secretion (Pbest=0.0004; Pcorr=0.0069). Two major four-marker-haplotypes spanning 13 kb including the entire KRT8 gene accounted for 90% of chromosomes, demonstrating strong linkage disequilibrium at that locus. Absence of chloride secretion was associated with the recessive haplotype 1122 at rs1907671, rs4300473, rs2035878 and rs2035875. The contrasting haplotype 2211 was dominant for the presence of CFTR mediated residual chloride secretion. In consistency, the KRT8 haplotype 2211 was associated with mild CF disease while 1122 was observed as risk haplotype. Analysis of microsatellite allele distributions on the SNP background suggests that the

  17. Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling.

    Science.gov (United States)

    Hohwieler, Meike; Illing, Anett; Hermann, Patrick C; Mayer, Tobias; Stockmann, Marianne; Perkhofer, Lukas; Eiseler, Tim; Antony, Justin S; Müller, Martin; Renz, Susanne; Kuo, Chao-Chung; Lin, Qiong; Sendler, Matthias; Breunig, Markus; Kleiderman, Susanne M; Lechel, André; Zenker, Martin; Leichsenring, Michael; Rosendahl, Jonas; Zenke, Martin; Sainz, Bruno; Mayerle, Julia; Costa, Ivan G; Seufferlein, Thomas; Kormann, Michael; Wagner, Martin; Liebau, Stefan; Kleger, Alexander

    2017-03-01

    The generation of acinar and ductal cells from human pluripotent stem cells (PSCs) is a poorly studied process, although various diseases arise from this compartment. We designed a straightforward approach to direct human PSCs towards pancreatic organoids resembling acinar and ductal progeny. Extensive phenotyping of the organoids not only shows the appropriate marker profile but also ultrastructural, global gene expression and functional hallmarks of the human pancreas in the dish. Upon orthotopic transplantation into immunodeficient mice, these organoids form normal pancreatic ducts and acinar tissue resembling fetal human pancreas without evidence of tumour formation or transformation. Finally, we implemented this unique phenotyping tool as a model to study the pancreatic facets of cystic fibrosis (CF). For the first time, we provide evidence that in vitro , but also in our xenograft transplantation assay, pancreatic commitment occurs generally unhindered in CF. Importantly, cystic fibrosis transmembrane conductance regulator (CFTR) activation in mutated pancreatic organoids not only mirrors the CF phenotype in functional assays but also at a global expression level. We also conducted a scalable proof-of-concept screen in CF pancreatic organoids using a set of CFTR correctors and activators, and established an mRNA-mediated gene therapy approach in CF organoids. Taken together, our platform provides novel opportunities to model pancreatic disease and development, screen for disease-rescuing agents and to test therapeutic procedures. 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/.

  18. Voice disorder in cystic fibrosis patients.

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    Bruna Mendes Lourenço

    Full Text Available 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

  19. [Cystic fibrosis in adults].

    Science.gov (United States)

    Damas, C; Saleiro, S; Gomes, I; Marques, J Agostinho

    2007-01-01

    The authors reviewed adult cystic fibrosis patients followed in the Pulmonology Unit from 1994-2004 (n=8), five female and three male, aged 20-34 years old (median= 27 years). Patients were diagnosed at 18 months - 31 years old by sweat testing (positive in six patients) and genotyping (four patients homozygous for Delta F508 mutation). Respiratory involvement was characterised by sinusitis and bronchiectasis. Pulmonary involvement was accompanied by functional abnormalities and gas exchange impairment in the majority of the patients. Bronchial tree was colonised permanently in five patients: Pseudomonas aeruginosa in four and Staphilococcus aureus in four (three patients affected by both agents simultaneously). The main causes of exacerbation were respiratory infections and haemoptysis. Non-respiratory involvement was variable. Four patients had digestive involvement (one with hepatic cirrhosis), one had renal failure and only one had a sperm count to document infertility. Four patients had osteopaenia. Treatment included chest physiotherapy, bronchodilators, dornase alfa, mucolytics, digestive enzymes, vitamins, antibiotics and oxygen therapy. At review, one had left follow-up, one had died, one was awaiting lung transplant and the others evidenced no difference in clinical characteristics. In this group of patients the severity of the pulmonary disease was not related to a late diagnosis. It can be explained by the diversity of cystic fibrosis presentation in adults.

  20. Inhibitory effects of silibinin on proliferation and lung metastasis of human high metastasis cell line of salivary gland adenoid cystic carcinoma via autophagy induction

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    Jiang C

    2016-10-01

    Full Text Available Canhua Jiang,1 Shufang Jin,1 Zhisheng Jiang,1 Jie Wang2 1Department of Oral and Maxillofacial Surgery, Xiangya Hospital, 2Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China Objective: To investigate the possible mechanisms and effects of silibinin (SIL on the proliferation and lung metastasis of human lung high metastasis cell line of salivary gland adenoid cystic carcinoma (ACC-M.Methods: A methyl thiazolyl tetrazolium assay was performed to detect the inhibitory effects of SIL on the proliferation of ACC-M cells in vitro. Fluorescence microscopy and transmission electron microscopy were used to observe the autophagic process. Western blot was performed to detect the expression of microtube-related protein 1 light-chain 3 (LC3. An experimental adenoid cystic carcinoma (ACC lung metastasis model was established in nude mice to detect the impacts of SIL on lung weight and lung cancer nodules. Immunohistochemistry was used to detect the expressions of LC3 in human ACC samples and normal salivary gland tissue samples.Results: SIL inhibited the proliferation of ACC-M cells in a dose- and time-dependent manner, and inductively increased the autophagic bodies in ACC-M cells. Furthermore, SIL could increase the expression of LC3 in ACC-M cells and promote the conversion of LC3-I into LC3-II in a dose- and time-dependent manner. In the ACC lung metastasis model, the lung weight and left and right lung nodules in the SIL-treated group were significantly less than those in the control group (P<0.05. The expressions of LC3-I and LC3-II as well as the positive expression rate of LC3 (80% significantly increased, but the positive expression of LC3 in human ACC (42.22% reduced significantly.Conclusion: SIL could inhibit the proliferation and lung metastasis of ACC-M cells by possibly inducing tumor cells autophagy. Keywords: silibinin, adenoid cystic carcinoma, ACC-M cells, autophagy

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-04-15

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

  2. A CASE SERIES OF CYSTIC LESIONS OF CONJUNCTIVA

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    Srinivas Rao

    2015-05-01

    Full Text Available INTRODUCTION: Cysticercosis is the most common parasitic disease of the nervous system. The disease occurs when humans become the intermediate host in the life cycle of Taenia solium by ingesting its eggs from contaminated food. The most common sites of involvement of cysticerci are soft tissue , eye and central nervous system. Unusual location of the cysts may result in uncommon manifestations. Ocular cysticercosis can involve both the intraocular and extra ocular muscle. Extra ocular muscle cysticercosis is rare. PRESENTATION OF CAS ES : In the department of ophthalmology , G.S.L medical college , Rajahmundry we are reporting 6 cases of cystic lesions of eye

  3. Cyanide levels found in infected cystic fibrosis sputum inhibit airway ciliary function.

    Science.gov (United States)

    Nair, Chandrika; Shoemark, Amelia; Chan, Mario; Ollosson, Sarah; Dixon, Mellissa; Hogg, Claire; Alton, Eric W F W; Davies, Jane C; Williams, Huw D

    2014-11-01

    We have previously reported cyanide at concentrations of up to 150 μM in the sputum of cystic fibrosis patients infected with Pseudomonas aeruginosa and a negative correlation with lung function. Our aim was to investigate possible mechanisms for this association, focusing on the effect of pathophysiologically relevant cyanide levels on human respiratory cell function. Ciliary beat frequency measurements were performed on nasal brushings and nasal air-liquid interface (ALI) cultures obtained from healthy volunteers and cystic fibrosis patients. Potassium cyanide decreased ciliary beat frequency in healthy nasal brushings (n = 6) after 60 min (150 μM: 47% fall, pcyanide as a key component inhibiting the ciliary beat frequency. If cyanide production similarly impairs mucocilliary clearance in vivo, it could explain the link with increased disease severity observed in cystic fibrosis patients with detectable cyanide in their airway. ©ERS 2014.

  4. Fasciculations in human hereditary disease.

    Science.gov (United States)

    Finsterer, Josef; Aliyev, Rahim

    2015-06-01

    Fasciculations are a manifestation of peripheral nerve hyperexcitability in addition to myokymia, neuromyotonia, cramps, or tetany. Fasciculations occur in hereditary and non-hereditary diseases. Among the hereditary diseases, fasciculations are most frequently reported in familial amyotrophic lateral sclerosis (FALS), and spinal muscular atrophy (SMA). Among the non-hereditary diseases, fasciculations occur most frequently in peripheral nerve hyperexcitability syndromes (Isaac's syndrome, voltage-gated potassium channelopathy, cramp fasciculation syndrome, Morvan syndrome). If the cause of fasciculations remains unknown, they are called benign. Systematically reviewing the literature about fasciculations in hereditary disease shows that fasciculations can be a phenotypic feature in bulbospinal muscular atrophy (BSMA), GM2-gangliosidosis, triple-A syndrome, or hereditary neuropathy. Additionally, fasciculations have been reported in familial amyloidosis, spinocerebellar ataxias, Huntington's disease, Rett syndrome, central nervous system disease due to L1-cell adhesion molecule (L1CAM) mutations, Fabry's disease, or Gerstmann-Sträussler disease. Rarely, fasciculations may be a phenotypic feature in patients with mitochondrial disorders or other myopathies. Fasciculations are part of the phenotype in much more genetic disorders than commonly assumed. Fasciculations not only occur in motor neuron disease, but also in hereditary neuropathy, spinocerebellar ataxia, GM2-gangliosidosis, Huntington's disease, Rett syndrome, Fabry's disease, Gerstmann-Sträussler disease, mitochondrial disorders, or muscular dystrophies.

  5. Uncovering disease-disease relationships through the incomplete human interactome

    Science.gov (United States)

    Menche, Jörg; Sharma, Amitabh; Kitsak, Maksim; Ghiassian, Susan; Vidal, Marc; Loscalzo, Joseph; Barabási, Albert-László

    2015-01-01

    According to the disease module hypothesis the cellular components associated with a disease segregate in the same neighborhood of the human interactome, the map of biologically relevant molecular interactions. Yet, given the incompleteness of the interactome and the limited knowledge of disease-associated genes, it is not obvious if the available data has sufficient coverage to map out modules associated with each disease. Here we derive mathematical conditions for the identifiability of disease modules and show that the network-based location of each disease module determines its pathobiological relationship to other diseases. For example, diseases with overlapping network modules show significant co-expression patterns, symptom similarity, and comorbidity, while diseases residing in separated network neighborhoods are clinically distinct. These tools represent an interactome-based platform to predict molecular commonalities between clinically related diseases, even if they do not share disease genes. PMID:25700523

  6. Intracellular Secretory Leukoprotease Inhibitor Modulates Inositol 1,4,5-Triphosphate Generation and Exerts an Anti-Inflammatory Effect on Neutrophils of Individuals with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease

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    Emer P. Reeves

    2013-01-01

    Full Text Available Secretory leukoprotease inhibitor (SLPI is an anti-inflammatory protein present in respiratory secretions. Whilst epithelial cell SLPI is extensively studied, neutrophil associated SLPI is poorly characterised. Neutrophil function including chemotaxis and degranulation of proteolytic enzymes involves changes in cytosolic calcium (Ca2+ levels which is mediated by production of inositol 1,4,5-triphosphate (IP3 in response to G-protein-coupled receptor (GPCR stimuli. The aim of this study was to investigate the intracellular function of SLPI and the mechanism-based modulation of neutrophil function by this antiprotease. Neutrophils were isolated from healthy controls (n=10, individuals with cystic fibrosis (CF (n=5 or chronic obstructive pulmonary disease (COPD (n=5. Recombinant human SLPI significantly inhibited fMet-Leu-Phe (fMLP and interleukin(IL-8 induced neutrophil chemotaxis (P<0.05 and decreased degranulation of matrix metalloprotease-9 (MMP-9, hCAP-18, and myeloperoxidase (MPO (P<0.05. The mechanism of inhibition involved modulation of cytosolic IP3 production and downstream Ca2+ flux. The described attenuation of Ca2+ flux was overcome by inclusion of exogenous IP3 in electropermeabilized cells. Inhibition of IP3 generation and Ca2+ flux by SLPI may represent a novel anti-inflammatory mechanism, thus strengthening the attractiveness of SLPI as a potential therapeutic molecule in inflammatory airway disease associated with excessive neutrophil influx including CF, non-CF bronchiectasis, and COPD.

  7. Impact of the [delta]F508 Mutation in First Nucleotide-binding Domain of Human Cystic Fibrosis Transmembrane Conductance Regulator on Domain Folding and Structure

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Hal A.; Zhao, Xun; Wang, Chi; Sauder, J. Michael; Rooney, Isabelle; Noland, Brian W.; Lorimer, Don; Kearins, Margaret C.; Conners, Kris; Condon, Brad; Maloney, Peter C.; Guggino, William B.; Hunt, John F.; Emtage, Spencer (SG); (Columbia); (JHU)

    2010-07-19

    Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR), commonly the deletion of residue Phe-508 (DeltaF508) in the first nucleotide-binding domain (NBD1), which results in a severe reduction in the population of functional channels at the epithelial cell surface. Previous studies employing incomplete NBD1 domains have attributed this to aberrant folding of DeltaF508 NBD1. We report structural and biophysical studies on complete human NBD1 domains, which fail to demonstrate significant changes of in vitro stability or folding kinetics in the presence or absence of the DeltaF508 mutation. Crystal structures show minimal changes in protein conformation but substantial changes in local surface topography at the site of the mutation, which is located in the region of NBD1 believed to interact with the first membrane spanning domain of CFTR. These results raise the possibility that the primary effect of DeltaF508 is a disruption of proper interdomain interactions at this site in CFTR rather than interference with the folding of NBD1. Interestingly, increases in the stability of NBD1 constructs are observed upon introduction of second-site mutations that suppress the trafficking defect caused by the DeltaF508 mutation, suggesting that these suppressors might function indirectly by improving the folding efficiency of NBD1 in the context of the full-length protein. The human NBD1 structures also solidify the understanding of CFTR regulation by showing that its two protein segments that can be phosphorylated both adopt multiple conformations that modulate access to the ATPase active site and functional interdomain interfaces.

  8. Preliminary comparison of normalized T1 and non-contrast perfusion MRI assessments of regional lung disease in cystic fibrosis patients.

    Science.gov (United States)

    Donnola, Shannon B; Dasenbrook, Elliott C; Weaver, David; Lu, Lan; Gupta, Karishma; Prabhakaran, Anjali; Yu, Xin; Chmiel, James F; McBennett, Kimberly; Konstan, Michael W; Drumm, Mitchell L; Flask, Chris A

    2017-03-01

    Previous studies have shown that Magnetic Resonance Imaging (MRI) techniques can be used to non-invasively assess lung disease in CF patients. In this study, we compare the sensitivity of normalized T1 (nT1) and non-contrast perfusion MRI techniques to detect regional lung disease in CF patients. MRI data were obtained for eight adult CF patients without overt pulmonary exacerbation (FEV1=45-127%) and six healthy volunteers on a Siemens Espree 1.5T MRI scanner. Sagittal nT1 and perfusion data were acquired for each subject's left and right lungs. A region-of-interest analysis was used to calculate mean nT1 and perfusion values in the individual lobes of the left and right lungs for each subject. In comparison to healthy controls, CF subjects showed a significant decrease in nT1 values in the upper lobe of the left lung as well as in the upper and anterior lobes of the right lung (pmethods were able to detect regional lung disease, the additional nT1 reductions in the CF patients suggests that nT1 may be more sensitive to regional CF lung disease. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  9. Does biodiversity protect humans against infectious disease?

    Science.gov (United States)

    Wood, Chelsea L; Lafferty, Kevin D; DeLeo, Giulio; Young, Hillary S; Hudson, Peter J; Kuris, Armand M

    2014-04-01

    Control of human infectious disease has been promoted as a valuable ecosystem service arising from the conservation of biodiversity. There are two commonly discussed mechanisms by which biodiversity loss could increase rates of infectious disease in a landscape. First, loss of competitors or predators could facilitate an increase in the abundance of competent reservoir hosts. Second, biodiversity loss could disproportionately affect non-competent, or less competent reservoir hosts, which would otherwise interfere with pathogen transmission to human populations by, for example, wasting the bites of infected vectors. A negative association between biodiversity and disease risk, sometimes called the "dilution effect hypothesis," has been supported for a few disease agents, suggests an exciting win-win outcome for the environment and society, and has become a pervasive topic in the disease ecology literature. Case studies have been assembled to argue that the dilution effect is general across disease agents. Less touted are examples in which elevated biodiversity does not affect or increases infectious disease risk for pathogens of public health concern. In order to assess the likely generality of the dilution effect, we review the association between biodiversity and public health across a broad variety of human disease agents. Overall, we hypothesize that conditions for the dilution effect are unlikely to be met for most important diseases of humans. Biodiversity probably has little net effect on most human infectious diseases but, when it does have an effect, observation and basic logic suggest that biodiversity will be more likely to increase than to decrease infectious disease risk.

  10. Severe Cystic Periventricular Leukomalacia in a Premature Infant with Capnocytophaga Sepsis

    Directory of Open Access Journals (Sweden)

    W. Thomas Bass

    2014-11-01

    Full Text Available Capnocytophaga is an opportunistic gram-negative anaerobic bacillus found in the oropharyngeal cavity of mammals and is associated with periodontal disease in humans. Sepsis, osteomyelitis, lung abscess, endocarditis, and meningitis have been reported in humans following animal bites. Perinatal infection with Capnocytophaga is infrequent and is generally considered to have a low risk of morbidity to the mother and fetus. We report a case of neonatal Capnocytophaga sepsis associated with the development of severe cystic periventricular leukomalacia

  11. Clinical impact of chronic obstructive pulmonary disease on non-cystic fibrosis bronchiectasis. A study on 1,790 patients from the Spanish Bronchiectasis Historical Registry.

    Directory of Open Access Journals (Sweden)

    David De la Rosa

    Full Text Available Few studies have evaluated the coexistence of bronchiectasis (BE and chronic obstructive pulmonary disease (COPD in series of patients diagnosed primarily with BE. The aim of this study was to analyse the characteristics of patients with BE associated with COPD included in the Spanish Bronchiectasis Historical Registry and compare them to the remaining patients with non-cystic fibrosis BE.We conducted a multicentre observational study of historical cohorts, analysing the characteristics of 1,790 patients who had been included in the registry between 2002 and 2011. Of these, 158 (8.8% were registered as BE related to COPD and were compared to the remaining patients with BE of other aetiologies.Patients with COPD were mostly male, older, had a poorer respiratory function and more frequent exacerbations. There were no differences in the proportion of patients with chronic bronchial colonisation or in the isolated microorganisms. A significantly larger proportion of patients with COPD received treatment with bronchodilators, inhaled steroids and intravenous antibiotics, but there was no difference in the use of long term oral or inhaled antibiotherapy. During a follow-up period of 3.36 years, the overall proportion of deaths was 13.8%. When compared to the remaining aetiologies, patients with BE associated with COPD presented the highest mortality rate. The multivariate analysis showed that the diagnosis of COPD in a patient with BE as a primary diagnosis increased the risk of death by 1.77.Patients with BE related to COPD have the same microbiological characteristics as patients with BE due to other aetiologies. They receive treatment with long term oral and inhaled antibiotics aimed at controlling chronic bronchial colonisation, even though the current COPD treatment guidelines do not envisage this type of therapy. These patients' mortality is notably higher than that of remaining patients with non-cystic fibrosis BE.

  12. Clinical impact of chronic obstructive pulmonary disease on non-cystic fibrosis bronchiectasis. A study on 1,790 patients from the Spanish Bronchiectasis Historical Registry.

    Science.gov (United States)

    De la Rosa, David; Martínez-Garcia, Miguel-Angel; Giron, Rosa Maria; Vendrell, Montserrat; Olveira, Casilda; Borderias, Luis; Maiz, Luis; Torres, Antoni; Martinez-Moragon, Eva; Rajas, Olga; Casas, Francisco; Cordovilla, Rosa; de Gracia, Javier

    2017-01-01

    Few studies have evaluated the coexistence of bronchiectasis (BE) and chronic obstructive pulmonary disease (COPD) in series of patients diagnosed primarily with BE. The aim of this study was to analyse the characteristics of patients with BE associated with COPD included in the Spanish Bronchiectasis Historical Registry and compare them to the remaining patients with non-cystic fibrosis BE. We conducted a multicentre observational study of historical cohorts, analysing the characteristics of 1,790 patients who had been included in the registry between 2002 and 2011. Of these, 158 (8.8%) were registered as BE related to COPD and were compared to the remaining patients with BE of other aetiologies. Patients with COPD were mostly male, older, had a poorer respiratory function and more frequent exacerbations. There were no differences in the proportion of patients with chronic bronchial colonisation or in the isolated microorganisms. A significantly larger proportion of patients with COPD received treatment with bronchodilators, inhaled steroids and intravenous antibiotics, but there was no difference in the use of long term oral or inhaled antibiotherapy. During a follow-up period of 3.36 years, the overall proportion of deaths was 13.8%. When compared to the remaining aetiologies, patients with BE associated with COPD presented the highest mortality rate. The multivariate analysis showed that the diagnosis of COPD in a patient with BE as a primary diagnosis increased the risk of death by 1.77. Patients with BE related to COPD have the same microbiological characteristics as patients with BE due to other aetiologies. They receive treatment with long term oral and inhaled antibiotics aimed at controlling chronic bronchial colonisation, even though the current COPD treatment guidelines do not envisage this type of therapy. These patients' mortality is notably higher than that of remaining patients with non-cystic fibrosis BE.

  13. Animal and model systems for studying cystic fibrosis.

    Science.gov (United States)

    Rosen, Bradley H; Chanson, Marc; Gawenis, Lara R; Liu, Jinghua; Sofoluwe, Aderonke; Zoso, Alice; Engelhardt, John F

    2017-09-19

    The cystic fibrosis (CF) field is the beneficiary of five species of animal models that lack functional cystic fibrosis transmembrane conductance regulator (CFTR) channel. These models are rapidly informing mechanisms of disease pathogenesis and CFTR function regardless of how faithfully a given organ reproduces the human CF phenotype. New approaches of genetic engineering with RNA-guided nucleases are rapidly expanding both the potential types of models available and the approaches to correct the CFTR defect. The application of new CRISPR/Cas9 genome editing techniques are similarly increasing capabilities for in vitro modeling of CFTR functions in cell lines and primary cells using air-liquid interface cultures and organoids. Gene editing of CFTR mutations in somatic stem cells and induced pluripotent stem cells is also transforming gene therapy approaches for CF. This short review evaluates several areas that are key to building animal and cell systems capable of modeling CF disease and testing potential treatments. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  14. Chemoprophylactic and therapeutic efficacy of thymol in murine cystic echinococcosis.

    Science.gov (United States)

    Maggiore, M; Pensel, P E; Denegri, G; Elissondo, M C

    2015-10-01

    Cystic echinococcosis is a zoonotic disease caused by the larval stage of the cestode Echinococcus granulosus. The drugs commonly used against cystic echinococcosis are benzimidazoles. Unfortunately, 20%-40% of cases do not respond favorably to such chemotherapy. Consequently, the search of new therapeutic alternatives such as the use of traditional medicinal plants has been increased. The aim of the current experimental work was to investigate the chemoprophylactic and clinical efficacy of thymol on mice infected with E. granulosus metacestodes. Thymol (40 mg/kg) was administered under two different therapeutic schemes: dosing every 24h over 20 days and treatment every 12h for 10 days. Thymol demonstrated efficacy against experimental murine cystic echinococcosis. The chemoprophylactic and therapeutic effects of thymol were comparable to that of albendazole. Due to the lack of toxicity observed in mice at the tested doses; we consider that thymol is a potential alternative to be applied for the treatment of human hydatid disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Frequency and Duration of Rhinovirus Infections in Children with Cystic Fibrosis and Healthy Controls : A Longitudinal Cohort Study

    NARCIS (Netherlands)

    Dijkema, Jasper S; van Ewijk, Bart E; Wilbrink, Berry; Wolfs, Tom FW; Kimpen, Jan L L; van der Ent, Cornelis K

    BACKGROUND: Respiratory viral infections are an important cause of morbidity in patients with chronic respiratory diseases, such as cystic fibrosis (CF). We hypothesized that patients with CF are more susceptible to human rhinovirus (HRV) infections than healthy controls. METHODS: In a 6-months

  16. Drosophila as a Model for Human Diseases-Focus on Innate Immunity in Barrier Epithelia.

    Science.gov (United States)

    Bergman, P; Seyedoleslami Esfahani, S; Engström, Y

    2017-01-01

    Epithelial immunity protects the host from harmful microbial invaders but also controls the beneficial microbiota on epithelial surfaces. When this delicate balance between pathogen and symbiont is disturbed, clinical disease often occurs, such as in inflammatory bowel disease, cystic fibrosis, or atopic dermatitis, which all can be in part linked to impairment of barrier epithelia. Many innate immune receptors, signaling pathways, and effector molecules are evolutionarily conserved between human and Drosophila. This review describes the current knowledge on Drosophila as a model for human diseases, with a special focus on innate immune-related disorders of the gut, lung, and skin. The discovery of antimicrobial peptides, the crucial role of Toll and Toll-like receptors, and the evolutionary conservation of signaling to the immune systems of both human and Drosophila are described in a historical perspective. Similarities and differences between human and Drosophila are discussed; current knowledge on receptors, signaling pathways, and effectors are reviewed, including antimicrobial peptides, reactive oxygen species, as well as autophagy. We also give examples of human diseases for which Drosophila appears to be a useful model. In addition, the limitations of the Drosophila model are mentioned. Finally, we propose areas for future research, which include using the Drosophila model for drug screening, as a validation tool for novel genetic mutations in humans and for exploratory research of microbiota-host interactions, with relevance for infection, wound healing, and cancer. © 2017 Elsevier Inc. All rights reserved.

  17. Lactate in cystic fibrosis sputum

    DEFF Research Database (Denmark)

    Bensel, Tobias; Stotz, Martin; Borneff-Lipp, Marianne

    2011-01-01

    Antibiotic therapy is thought to improve lung function in patients with cystic fibrosis (CF) by decreasing neutrophil-derived inflammation. We investigated the origin and clinical significance of lactate in the chronically inflamed CF lung. Methods Lactate was measured in sputa of 18 exacerbated...... and 25 stable CF patients via spectrophotometry and gaschromatography. Lung function was assessed via spirometry. Seven patients with chronic obstructive pulmonary disease (COPD) and three patients with acute lung inflammation served as control groups. Neutrophil and bacterial lactate production...

  18. Trichosporon mycotoxinivorans, a Novel Respiratory Pathogen in Patients with Cystic Fibrosis▿

    Science.gov (United States)

    Hickey, Patrick W.; Sutton, Deanna A.; Fothergill, Annette W.; Rinaldi, Michael G.; Wickes, Brian L.; Schmidt, Howard J.; Walsh, Thomas J.

    2009-01-01

    This report describes the molecular epidemiology, in vitro susceptibility, colonial and microscopic morphologies, and biochemical features of Trichosporon mycotoxinivorans, a newly recognized pathogen that appears to have a propensity for patients with cystic fibrosis. The index patient died with histologically documented Trichosporon pneumonia complicating cystic fibrosis. This is also the first report of disease caused by a Trichosporon species in a nontransplant patient with cystic fibrosis. As T. mycotoxinivorans has not previously been recognized as a respiratory pathogen, the significance of its recovery from sputum samples was not initially appreciated. Genetic analysis of archived clinical samples found three additional cases of T. mycotoxinivorans infection which had previously been identified as other members of the genus. An additional isolate of T. mycotoxinivorans was identified from a clinical sample on initial testing. Three of these four cases were also patients with cystic fibrosis. All isolates had MICs at 48 h of amphotericin B of ≥1 μg/ml and of echinocandins of ≥16 μg/ml, but they displayed various susceptibilities to the triazoles. In summary, Trichosporon mycotoxinivorans is a newly recognized human pathogen that is associated with cystic fibrosis. PMID:19656976

  19. Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis.

    Science.gov (United States)

    Eickmeier, Olaf; Fussbroich, Daniela; Mueller, Klaus; Serve, Friederike; Smaczny, Christina; Zielen, Stefan; Schubert, Ralf

    2017-01-01

    Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF. In this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach. DHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p< 0.05). SPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was present in sputum and plasma of CF patients

  20. Protein Misfolding and Human Disease

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter Gerd; Vang, Søren

    2006-01-01

    phenylketonuria, Parkinson's disease, α-1-antitrypsin deficiency, familial neurohypophyseal diabetes insipidus, and short-chain acyl-CoA dehydrogenase deficiency. Despite the differences, an emerging paradigm suggests that the cellular effects of protein misfolding provide a common framework that may contribute...... to the elucidation of the cell pathology and guide intervention and treatment strategies of many genetic and age-dependent diseases.......Protein misfolding is a common event in living cells. In young and healthy cells, the misfolded protein load is disposed of by protein quality control (PQC) systems. In aging cells and in cells from certain individuals with genetic diseases, the load may overwhelm the PQC capacity, resulting...

  1. Control programme for cystic echinococcosis in Uruguay

    Directory of Open Access Journals (Sweden)

    Pilar Irabedra

    2016-06-01

    Full Text Available Cystic echinococcosis is a highly endemic parasitic zoonosis that is present in the Southern Cone countries of America. For several decades, various prevention and control programmes have been implemented in different countries and regions, with varying results. In Uruguay, a new control programme was implemented in 2006 that employed new strategies for canine diagnosis and treatment, dog population control, diagnosis in humans, epidemiological surveillance, and health education, including community participation. The control programme in Uruguay addresses the control and surveillance of the disease from a holistic perspective based on Primary Health Care, which has strengthened the community’s participation in developing and coordinating activities in an interdisciplinary manner. Similarly, the control programme that is currently implemented is based on a risk-focused approach. The surveillance and control measures were focused on small villages and extremely poor urban areas. In this study, the strategies used and the results obtained from 2008-2013 are analysed and discussed.

  2. Profile of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Mona M. El-Falaki

    2014-09-01

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

  3. [Historical compilation of cystic fibrosis].

    Science.gov (United States)

    Navarro, Salvador

    2016-01-01

    Cystic fibrosis is the most common life-shortening recessively inherited disorder in the Caucasian population. The genetic mutation that most frequently provokes cystic fibrosis (ΔF508) appeared at least 53,000years ago. For many centuries, the disease was thought to be related to witchcraft and the "evil eye" and it was only in 1938 that Dorothy H. Andersen characterized this disorder and suspected its genetic origin. The present article reviews the pathological discoveries and diagnostic and therapeutic advances made in the last 75 years. The review ends with some considerations for the future. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  4. Posttraumatic Cranial Cystic Fibrous Dysplasia

    Directory of Open Access Journals (Sweden)

    Arata Tomiyama

    2011-01-01

    Full Text Available A 14-year-old was girl admitted to our hospital with a subcutaneous mass of the occipital head. The mass had grown for 6 years, after she had sustained a head injury at the age of 6, and was located directly under a previous wound. Skull X-ray Photograph (xp, computed tomography (CT, and magnetic resonance imaging (MRI showed a bony defect and cystic changes in the skull corresponding to a subcutaneous mass. Bone scintigraphy revealed partial accumulation. The patient underwent total removal of the skull mass, and the diagnosis from the pathological findings of the cyst wall was fibrous dysplasia (FD. The radiographic findings for cystic cranial FD can be various. Progressive skull disease has been reported to be associated with head trauma, but the relationship between cranial FD and head trauma has not been previously reported. Previous studies have suggested that c-fos gene expression is a key mechanism in injury-induced FD.

  5. Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression.

    Science.gov (United States)

    Shmarina, Galina; Pukhalsky, Alexander; Avakian, Lucine; Semykin, Sergey; Pukhalskaya, Daria; Alioshkin, Vladimir

    2017-01-01

    Anti-inflammatory therapy is a logical approach to slowing the inevitable lung function deterioration in cystic fibrosis (CF) patients. This study's aim was to evaluate inflammatory markers and disease progression in paediatric CF patients chronically treated with azithromycin or low-dose prednisolone. The study included 204 patients with CF and 100 healthy controls; 102 CF patients were treated with basic therapy only (without anti-inflammatory treatment; WAT), and 102 individuals received basic therapy along with azithromycin (n = 59) or low-dose prednisolone (n = 43). The median duration of therapy was 24 months (range 12-82) with azithromycin and 31 months (range 12-180) with prednisolone. A cross-sectional analysis of plasma and sputum biomarkers was performed. Compared with the healthy controls, the WAT group showed elevated IFN-γ, IL-10 (total), and TGFβ1 concentrations, and decreased TNFα (total) and adrenocorticotropic hormone (ACTH) levels (all p disease and a significantly increased incidence of glucose metabolism disturbances. Steady-state anti-inflammatory treatments may have a sustained immunomodulatory action at systemic and local levels in CF patients. Further investigations are needed to assess the effects of supportive azithromycin therapy on the hypothalamic-pituitary-adrenal axis and the incidence of non-pulmonary CF complications. © 2017 S. Karger AG, Basel.

  6. GATA-binding protein 3, gross cystic disease fluid protein-15 and mammaglobin have distinct prognostic implications in different invasive breast carcinoma subgroups.

    Science.gov (United States)

    Ni, Yun Bi; Tsang, Julia Y S; Chan, Siu Ki; Tse, Gary M

    2015-07-01

    To evaluate the prognostic significance of GATA-binding protein 3 (GATA-3), gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin (MGB) in invasive breast carcinomas (IBCs). GATA-3, GCDFP-15 and MGB were expressed in 37.9% (370/976), 26.0% (254/978) and 35.3% (348/986) of this cohort of 1017 IBCs, respectively. GCDFP-15 was an independent favourable prognostic factor in all cases [disease-free survival (DFS), hazard ratio (HR) 0.587, P = 0.049; overall survival (OS), HR 0.512, P = 0.049], as well as in oestrogen receptor (ER)-negative (DFS, HR 0.353, P = 0.012; OS, HR 0.310, P = 0.017) and HER2-positive (DFS, HR 0.279, P = 0.036; OS, HR 0.235, P = 0.050) cases; it also refined the prognostication of molecular apocrine cancers. GATA-3 and MGB did not show any prognostic significance. The commonly used breast carcinoma biomarkers vary in their prognostic implications. GCDFP-15 independently indicated a favourable prognosis, especially in ER-negative, HER2-positive and molecular apocrine cancers. GATA-3 and MGB were not associated with outcome. © 2014 John Wiley & Sons Ltd.

  7. Genetic Deletion and Pharmacological Inhibition of PI3Kγ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease

    Directory of Open Access Journals (Sweden)

    Maria Galluzzo

    2015-01-01

    Full Text Available Purpose. Neutrophil-dominated airway inflammation is a key feature of progressive lung damage in cystic fibrosis (CF. Thus, reducing airway inflammation is a major goal to prevent lung damage in CF. However, current anti-inflammatory drugs have shown several limits. PI3Kγ plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3Kγ on airway inflammation and structural lung damage in a mouse model of CF lung disease. Methods. βENaC overexpressing mice (βENaC-Tg were backcrossed with PI3Kγ-deficient (PI3KγKO mice. Tissue damage was assessed by histology and morphometry and inflammatory cell number was evaluated in bronchoalveolar lavage fluid (BALF. Furthermore, we assessed the effect of a specific PI3Kγ inhibitor (AS-605240 on inflammatory cell number in BALF. Results. Genetic deletion of PI3Kγ decreased neutrophil numbers in BALF of PI3KγKO/βENaC-Tg mice, and this was associated with reduced emphysematous changes. Treatment with the PI3Kγ inhibitor AS-605240 decreased the number of neutrophils in BALF of βENaC-Tg mice, reproducing the effect observed with genetic deletion of the enzyme. Conclusions. These results demonstrate the biological efficacy of both genetic deletion and pharmacological inhibition of PI3Kγ in reducing chronic neutrophilic inflammation in CF-like lung disease in vivo.

  8. Exploitation of a Very Small Peptide Nucleic Acid as a New Inhibitor of miR-509-3p Involved in the Regulation of Cystic Fibrosis Disease-Gene Expression

    Directory of Open Access Journals (Sweden)

    Felice Amato

    2014-01-01

    Full Text Available Computational techniques, and in particular molecular dynamics (MD simulations, have been successfully used as a complementary technique to predict and analyse the structural behaviour of nucleic acids, including peptide nucleic acid- (PNA- RNA hybrids. This study shows that a 7-base long PNA complementary to the seed region of miR-509-3p, one of the miRNAs involved in the posttranscriptional regulation of the CFTR disease-gene of Cystic Fibrosis, and bearing suitable functionalization at its N- and C-ends aimed at improving its resistance to nucleases and cellular uptake, is able to revert the expression of the luciferase gene containing the 3′UTR of the gene in A549 human lung cancer cells, in agreement with the MD results that pointed at the formation of a stable RNA/PNA heteroduplex notwithstanding the short sequence of the latter. The here reported results widen the interest towards the use of small PNAs as effective anti-miRNA agents.

  9. Diagnosis of cystic fibrosis

    NARCIS (Netherlands)

    H.J. Veeze

    1995-01-01

    textabstractApplying the sweat-test as the first choice of test when a diagnosis of cystic fibrosis is suspected is still common practice and advisable. Since the cloning of the CFTR gene more than 400 different cystic fibrosis (CF) mutations have already been identified. The use of CF mutation

  10. Cystic hemispheric medulloepithelioma

    African Journals Online (AJOL)

    2015-12-09

    Dec 9, 2015 ... Computerised tomography (CT) of the brain (Figure 1) revealed a predominantly cystic mass in the right posterior ... Magnetic resonance imaging (MRI) of the brain (Figure 2) confirmed the predominantly cystic nature of the .... contain structures that resemble the primitive neural tube and approximately half ...

  11. Melanized Fungi in Human Disease

    Science.gov (United States)

    Revankar, Sanjay G.; Sutton, Deanna A.

    2010-01-01

    Summary: Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes. Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges. Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years. The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi. Melanin is a likely virulence factor for these fungi. Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants. Therapy varies depending upon the clinical syndrome. Local infection may be cured with excision alone, while systemic disease is often refractory to therapy. Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections. PMID:20930077

  12. Novel diagnostic and therapeutic opportunities for Cystic Fibrosis

    NARCIS (Netherlands)

    Vijftigschild, L.A.W.

    2016-01-01

    Cystic fibrosis (CF) is the most common life-shortening rare disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which was identified in 1989. The CFTR gene encodes a 3’,5’-cyclic adenosine monophosphate (cAMP)-activated transmembrane anion channel and

  13. A novel lipidomic strategy reveals plasma phospholipid signatures associated with respiratory disease severity in cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Ida Chiara Guerrera

    Full Text Available The aim of this study was to search for lipid signatures in blood plasma from cystic fibrosis (CF patients using a novel MALDI-TOF-ClinProTools strategy, initially developed for protein analysis, and thin layer chromatography coupled to MALDI-TOF (TLC-MALDI. Samples from 33 CF patients and 18 healthy children were subjected to organic extraction and column chromatography separation of lipid classes. Extracts were analyzed by MALDI-TOF, ion signatures were compared by the ClinProTools software and by parallel statistical analyses. Relevant peaks were identified by LC-MSn. The ensemble of analyses provided 11 and 4 peaks differentially displayed in CF vs healthy and in mild vs severe patients respectively. Ten ions were significantly decreased in all patients, corresponding to 4 lysophosphatidylcholine (18:0, 18:2, 20:3, and 20:5 and 6 phosphatidylcholine (36:5, O-38:0, 38:4, 38:5, 38:6, and P-40:1 species. One sphingolipid, SM(d18:0, was significantly increased in all patients. Four PC forms (36:3, 36:5, 38:5, and 38:6 were consistently downregulated in severe vs mild patients. These observations were confirmed by TLC-MALDI. These results suggest that plasma phospholipid signatures may be able to discriminate mild and severe forms of CF, and show for the first time MALDI-TOF-ClinProTools as a suitable methodology for the search of lipid markers in CF.

  14. Prognosis in Cystic Fibrosis: Trends and Predictors

    NARCIS (Netherlands)

    Slieker, M.G.

    2008-01-01

    Cystic fibrosis (CF) is a multisystem disease affecting the digestive system, sweat glands, and the reproductive tract, but progressive lung disease continues to be the major cause of morbidity and mortality. Patients develop chronic infection of the respiratory tract with a characteristic array of

  15. Cystic echinococcosis: prevalence and economic sig- nificance in ...

    African Journals Online (AJOL)

    Ethiopia owns a huge livestock population in Africa, which is estimated to be ... In humans diagno- sis are by serological and molecular techniques, imaging, and clinical. But in live animals (especially in intermediate hosts), the cystic ... effect and risk factors of the cystic echinococcosis in small ruminants and de-.

  16. Physiochemical basis of human degenerative disease

    Directory of Open Access Journals (Sweden)

    Zeliger Harold I.

    2015-03-01

    Full Text Available The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

  17. Potential Human Models of Infammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Stephen B Hanauer

    1995-01-01

    Full Text Available Similar to animal models of inflammatory bowel disease (IBD, there is no single human model representative of ulcerative colitis or Crohn's disease. An optimal human model awaits etiopathogenetic definitions and further reclassification or depiction of clinicopathological scenarios. Current human models can be classified into models depicting risk of disease; preclinical disease; acute inflammation; and miscellaneous IBD. Family studies are the best means of pursuing patients at risk. Evolving genetic and serological markers may further identify subgroups to assess with permeability probes, leukocyte scans or endoscopy for preclinical disease. Provocation with nonsteroidal anti-inflammatory drugs (NSAIDs may be useful in selected patients because NSAID mucosal damage may induce or mimic IBD. Alternative natural history or interventional studies in patients with human leukocyte antigen (HLA-B27 spondylarthropathy may be useful. The disease margin and pouchitis are models within the disease state of ulcerative colitis as are the aphthous ulcer, anastomotic margin and diverted fecal stream for Crohn's disease. Newly defined colitides, such as microscopic and collagenous colitis and diversion colitis, also provide potential comparative models to evaluate mucosal immune, inflammatory, reparative, secretory and absorptive regulation.

  18. Evolutionary Response to Human Infectious Diseases

    Science.gov (United States)

    Armelagos, George J.; Dewey, John R.

    1970-01-01

    Gives an overview of human history, relating cultural changes with resulting changes in population density and in ecological balance to patterns of infectious diseases in man. Discusses mechanisms of evolution of resistance. Suggests that in populations where infectious diseases can be controlled, attention should shift to degenerative diseases…

  19. An Empirical Biomarker-Based Calculator for Cystic Index in a Model of Autosomal Recessive Polycystic Kidney Disease-The Nieto-Narayan Formula.

    Directory of Open Access Journals (Sweden)

    Jake A Nieto

    Full Text Available Autosomal recessive polycystic kidney disease (ARPKD is associated with progressive enlargement of the kidneys fuelled by the formation and expansion of fluid-filled cysts. The disease is congenital and children that do not succumb to it during the neonatal period will, by age 10 years, more often than not, require nephrectomy+renal replacement therapy for management of both pain and renal insufficiency. Since increasing cystic index (CI; percent of kidney occupied by cysts drives both renal expansion and organ dysfunction, management of these patients, including decisions such as elective nephrectomy and prioritization on the transplant waitlist, could clearly benefit from serial determination of CI. So also, clinical trials in ARPKD evaluating the efficacy of novel drug candidates could benefit from serial determination of CI. Although ultrasound is currently the imaging modality of choice for diagnosis of ARPKD, its utilization for assessing disease progression is highly limited. Magnetic resonance imaging or computed tomography, although more reliable for determination of CI, are expensive, time-consuming and somewhat impractical in the pediatric population. Using a well-established mammalian model of ARPKD, we undertook a big data-like analysis of minimally- or non-invasive blood and urine biomarkers of renal injury/dysfunction to derive a family of equations for estimating CI. We then applied a signal averaging protocol to distill these equations to a single empirical formula for calculation of CI. Such a formula will eventually find use in identifying and monitoring patients at high risk for progressing to end-stage renal disease and aid in the conduct of clinical trials.

  20. Cystic echinococcosis: Future perspectives of molecular epidemiology

    Science.gov (United States)

    Human cystic echinococcosis (CE) has been conceived to be caused predominantly by Echinococcus granulosus sensu stricto (the dog-sheep strain). Recent molecular approaches on CE, however, have revealed that human cases are also commonly caused by another species, Echinococcus canadensis. All indices...

  1. Melatonin and human mitochondrial diseases

    Directory of Open Access Journals (Sweden)

    Reza Sharafati-Chaleshtori

    2017-01-01

    Full Text Available Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function.

  2. Phlebotomine Vectors of Human Disease.

    Science.gov (United States)

    1983-12-30

    sexes of L. (Trichophoromyia) napoensis, n.sp., L. (Trichophoromyia) wilkersoni, n.sp. and L. tortura , n. sp. (species group vexator) are described...which L. hartmanni has been found. 20. Lutzomyia tortura Young and Rogers, new species, Fig. 67-76. cr holotype (measurements in mm). Wing length 1.73...data. Paratypes, 34 d’ , 32 o, flight and light traps and human bait, 18-25.V.1976 (D. Young and T. Rogers). Discussion. Lutzomyia tortura n. sp

  3. The presence of centrioles and centrosomes in ovarian mature cystic teratoma cells suggests human parthenotes developed in vitro can differentiate into mature cells without a sperm centriole

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Bo Yon, E-mail: boyonlee@gmail.com [Department of Obstetrics and Gynecology, Kyung Hee University Hospital, Kyung Hee University, School of Medicine, Seoul (Korea, Republic of); Shim, Sang Woo; Kim, Young Sun; Kim, Seung Bo [Department of Obstetrics and Gynecology, Kyung Hee University Hospital, Kyung Hee University, School of Medicine, Seoul (Korea, Republic of)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer The sperm centriole is the progenitor of centrosomes in all somatic cells. Black-Right-Pointing-Pointer Centrioles and centrosomes exist in parthenogenetic ovarian teratoma cells. Black-Right-Pointing-Pointer Without a sperm centriole, parthenogenetic oocytes produce centrioles and centrosomes. Black-Right-Pointing-Pointer Parthenogenetic human oocytes can develop and differentiate into mature cells. -- Abstract: In most animals, somatic cell centrosomes are inherited from the centriole of the fertilizing spermatozoa. The oocyte centriole degenerates during oogenesis, and completely disappears in metaphase II. Therefore, the embryos generated by in vitro parthenogenesis are supposed to develop without any centrioles. Exceptional acentriolar and/or acentrosomal developments are possible in mice and in some experimental cells; however, in most animals, the full developmental potential of parthenogenetic cells in vitro and the fate of their centrioles/centrosomes are not clearly understood. To predict the future of in vitro human parthenogenesis, we explored the centrioles/centrosomes in ovarian mature cystic teratoma cells by immunofluorescent staining and transmission electron microscopy. We confirmed the presence of centrioles and centrosomes in these well-known parthenogenetic ovarian tumor cells. Our findings clearly demonstrate that, even without a sperm centriole, parthenotes that develop from activated oocytes can produce their own centrioles/centrosomes, and can even develop into the well-differentiated mature tissue.

  4. Unique expression of 35 KDa protein in serum and cystic fluid of women with malignant ovarian cysts substantiates its role in disease progression

    OpenAIRE

    Gulfam Ahmad; Muhammad Arslan

    2015-01-01

    Objective: The present study was undertaken as a part of a continuing search for proteomic based approaches for the diagnosis of ovarian cancers. Methods: The study comprised four groups of women with: i): malignant ovarian cysts, ii) benign ovarian cysts, iii): breast cancer (positive controls) and, iv) healthy females (negative controls). Serum and cystic fluids were processed for gel electrophoresis (SDS-PAGE). Serum and cystic follicular fluid estradiol and testosterone concentrations ...

  5. Comparison of the Diagnostic Accuracy of Three Rapid Tests for the Serodiagnosis of Hepatic Cystic Echinococcosis in Humans.

    Science.gov (United States)

    Tamarozzi, Francesca; Covini, Ilaria; Mariconti, Mara; Narra, Roberta; Tinelli, Carmine; De Silvestri, Annalisa; Manzoni, Federica; Casulli, Adriano; Ito, Akira; Neumayr, Andreas; Brunetti, Enrico

    2016-02-01

    The diagnosis of cystic echinococcosis (CE) is based primarily on imaging, in particular with ultrasound for abdominal CE, complemented by serology when imaging results are unclear. In rural endemic areas, where expertise in ultrasound may be scant and conventional serology techniques are unavailable due to lack of laboratory equipment, Rapid Diagnostic Tests (RDTs) are appealing. We evaluated the diagnostic accuracy of 3 commercial RDTs for the diagnosis of hepatic CE. Sera from 59 patients with single hepatic CE cysts in well-defined ultrasound stages (gold standard) and 25 patients with non-parasitic cysts were analyzed by RDTs VIRapid HYDATIDOSIS (Vircell, Spain), Echinococcus DIGFA (Unibiotest, China), ADAMU-CE (ICST, Japan), and by RIDASCREEN Echinococcus IgG ELISA (R-Biopharm, Germany). Sensitivity, specificity and ROC curves were compared with McNemar and t-test. For VIRapid and DIGFA, correlation between semiquantitative results and ELISA OD values were evaluated by Spearman's coefficient. Reproducibility was assessed on 16 randomly selected sera with Cohen's Kappa coefficient. Sensitivity and Specificity of VIRapid (74%, 96%) and ADAMU-CE (57%, 100%) did not differ from ELISA (69%, 96%) while DIGFA (72%, 72%) did (p = 0.045). ADAMU-CE was significantly less sensitive in the diagnosis of active cysts (p = 0.019) while DIGFA was significantly less specific (p = 0.014) compared to ELISA. All tests were poorly sensitive in diagnosing inactive cysts (33.3% ELISA and ADAMU-CE, 42.8% DIGFA, 47.6% VIRapid). The reproducibility of all RDTs was good-very good. Band intensity of VIRapid and DIGFA correlated with ELISA OD values (r = 0.76 and r = 0.79 respectively, p<0.001). RDTs may be useful in resource-poor settings to complement ultrasound diagnosis of CE in uncertain cases. VIRapid test appears to perform best among the examined kits, but all tests are poorly sensitive in the presence of inactive cysts, which may pose problems with accurate diagnosis.

  6. BTBD7 silencing inhibited epithelial- mesenchymal transition (EMT) via regulating Slug expression in human salivary adenoid cystic carcinoma.

    Science.gov (United States)

    Yang, Liu; Wang, Tiejun; Zhang, Jun; Wang, Xuxia

    2017-12-06

    Epithelial-mesenchymal transition (EMT) is a complicated process that has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs. BTB/POZ domain-containing protein 7 (BTBD7) is reported to regulate transcriptional factors and involved in the process of invasion and metastasis of some malignant tumors. Additionally, our preliminary studies have confirmed that BTBD7 expression was significantly correlated with Slug expression and poor prognosis of primary salivary adenoid cystic carcinoma (SACC). On this basis, this study further investigated function of BTBD7 in the invasion and metastasis of SACC in vitro, which may be a possible target of gene therapy in the future. The expression of BTBD7 and Slug were both examined in SACC-LM and SACC-83 cell lines by immunofluorescence staining. High invasive SACC-LM cells were transfected with BTBD7 siRNA and the expression levels of BTBD7 and Slug were detected in both gene and protein levels by qRT-PCR and western blot analysis. Assays were performed to survey cell migration, invasion and proliferation capabilities with BTBD7 silencing. BTBD7 and Slug proteins were detected in SACC-LM and SACC-83 cell lines. BTBD7 silencing down-regulated the expression of Slug and MMP9 meanwhile up-regulated the expression of E-cadherin in SACC-LM cells, the migration and invasion abilities of cells were obviously suppressed but with no influence on cell proliferation. BTBD7 silencing inhibited EMT through regulation of Slug expression in SACC-LM cells and might act as a potential molecular target for gene therapy of SACC.

  7. Attenuation of Phosphorylation-dependent Activation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by Disease-causing Mutations at the Transmission Interface.

    Science.gov (United States)

    Chin, Stephanie; Yang, Donghe; Miles, Andrew J; Eckford, Paul D W; Molinski, Steven; Wallace, B A; Bear, Christine E

    2017-02-03

    Cystic fibrosis transmembrane conductance regulator (CFTR) is a multidomain membrane protein that functions as a phosphorylation-regulated anion channel. The interface between its two cytosolic nucleotide binding domains and coupling helices conferred by intracellular loops extending from the channel pore domains has been referred to as a transmission interface and is thought to be critical for the regulated channel activity of CFTR. Phosphorylation of the regulatory domain of CFTR by protein kinase A (PKA) is required for its channel activity. However, it was unclear if phosphorylation modifies the transmission interface. Here, we studied purified full-length CFTR protein using spectroscopic techniques to determine the consequences of PKA-mediated phosphorylation. Synchrotron radiation circular dichroism spectroscopy confirmed that purified full-length wild-type CFTR is folded and structurally responsive to phosphorylation. Intrinsic tryptophan fluorescence studies of CFTR showed that phosphorylation reduced iodide-mediated quenching, consistent with an effect of phosphorylation in burying tryptophans at the transmission interface. Importantly, the rate of phosphorylation-dependent channel activation was compromised by the introduction of disease-causing mutations in either of the two coupling helices predicted to interact with nucleotide binding domain 1 at the interface. Together, these results suggest that phosphorylation modifies the interface between the catalytic and pore domains of CFTR and that this modification facilitates CFTR channel activation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Gross cystic disease fluid protein-15 and mammaglobin A expression determined by immunohistochemistry is of limited utility in triple-negative breast cancer.

    Science.gov (United States)

    Huo, Lei; Zhang, Jinxia; Gilcrease, Michael Z; Gong, Yun; Wu, Yun; Zhang, Hong; Resetkova, Erika; Hunt, Kelly K; Deavers, Michael T

    2013-01-01

      In addition to oestrogen and progesterone receptors, gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are the most common markers used to identify breast origin by immunohistochemistry. GCDFP-15 expression has been reported in approximately 60% of breast carcinomas and MAM expression in approximately 80%. Data on their expression in triple-negative breast cancer (TNBC) are very limited. The aim of this study was to examine the expression of these markers in TNBC to determine their utility in pathological diagnosis.   We studied the immunohistochemical (IHC) expression of GCDFP-15 and MAM in 63 primary and 118 metastatic TNBCs. GCDFP-15 staining was present in 14% of primary and 21% of metastatic TNBCs. MAM staining was present in 25% of primary and 41% of metastatic TNBCs. The frequency of expression of GCDFP-15 and/or MAM was 30% in primary and 43% in metastatic TNBCs, and many positive tumours had only focal staining.   Staining for GCDFP-15 and/or MAM in triple-negative carcinomas helps to confirm breast origin, but most tumours in this subgroup of breast carcinomas lack expression of either marker. © 2012 Blackwell Publishing Limited.

  9. GATA-binding protein 3 enhances the utility of gross cystic disease fluid protein-15 and mammaglobin A in triple-negative breast cancer by immunohistochemistry.

    Science.gov (United States)

    Huo, Lei; Gong, Yun; Guo, Ming; Gilcrease, Michael Z; Wu, Yun; Zhang, Hong; Zhang, Jinxia; Resetkova, Erika; Hunt, Kelly K; Deavers, Michael T

    2015-08-01

    We have demonstrated previously that gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are of limited utility in triple-negative breast cancer (TNBC). GATA-binding protein 3 (GATA-3) is an emerging breast-associated immunohistochemical (IHC) marker with limited data in TNBC. Here, we examined GATA-3 expression in TNBC in comparison with GCDFP-15 and MAM. We studied GATA-3, GCDFP-15 and MAM IHC expression in 62 primary and 68 metastatic TNBCs. In primary TNBCs, GATA-3 staining was observed in 25 cases (40%), including 16 cases that were negative for GCDFP-15 and MAM. In metastatic TNBCs, GATA-3 staining was observed in 30 cases (44%), including 16 cases that were negative for GCDFP-15 and MAM. The expression frequency of any of the markers was 56% in primary and 62% in metastatic TNBCs. However, when focal staining was excluded, the expression frequency of any marker dropped to 31% and 44%, respectively. GATA-3 is expressed at a higher frequency by IHC in TNBC compared to GCDFP-15 and MAM, although the tissue specificity of the latter markers may be superior. When evaluating a triple-negative tumour, including GATA-3 in a panel of markers may increase the diagnostic accuracy for tissue origin in the appropriate clinical setting. © 2015 John Wiley & Sons Ltd.

  10. Comparative study of monoclonal antibody B72.3 and gross cystic disease fluid protein-15 as markers of apocrine carcinoma of the breast.

    Science.gov (United States)

    Honma, Naoko; Takubo, Kaiyo; Arai, Tomio; Younes, Mamoun; Kasumi, Fujio; Akiyama, Futoshi; Sakamoto, Goi

    2006-10-01

    Gross cystic disease fluid protein-15 (GCDFP-15) is a commonly used apocrine marker; however, its expression was recently found to decrease in infiltrating, larger, or metastasizing apocrine carcinomas of the breast. In the breast, monoclonal antibody (MAb) B72.3 has been reported to be useful as an apocrine marker although it is used for that purpose much less frequently than GCDFP-15. In the search for a more consistent apocrine marker, immunoreactivity for MAb B72.3 was examined in apocrine carcinomas at different stages and compared with GCDFP-15. 47 of 51 apocrine carcinomas (92%) and 9 of 62 ordinary carcinomas (15%) were MAb B72.3 positive, while 39 of 51 apocrine carcinomas (76%) and 13 of 62 ordinary carcinomas (21%) were GCDFP-15 positive. Thus, both sensitivity and specificity were higher for MAb B72.3. Furthermore, unlike GCDFP-15, MAb B72.3 exhibited positivity irrespective of infiltrating status, tumor size, or metastatic status. There was no correlation between MAb B72.3-immunoreactivity and GCDFP-15-expression. The combined usage of MAb B72.3 with GCDFP-15 was useful to confirm the diagnosis of apocrine carcinoma, especially for advanced tumors, with only two cases being negative for both MAb B72.3 and GCDFP-15. Whether these two cases should be differentiated from ordinary apocrine carcinomas remains to be investigated.

  11. Influence of insulin-like growth factor-binding proteins-2 and -3 in the pathogenesis of cystic ovarian disease in cattle.

    Science.gov (United States)

    Rodríguez, Fernanda M; Salvetti, Natalia R; Panzani, Carolina G; Barbeito, Claudio G; Ortega, Hugo H; Rey, Florencia

    2011-10-01

    Ovarian cysts are one of the major causes of infertility in dairy cows. The development is associated with an endocrine imbalance in the hypothalamo-hypophyseal-gonadal axis in which endocrine factors participate in follicular growth and differentiation and in the secretion of ovarian hormones. Insulin-like growth factor family are essential local regulators of ovarian follicle development and functionality and actions are mediated by binding protein activity. The aim of the present study was to analyze the expression of IGFBP-2 and IGFBP-3 in developing follicles of normal estrous cycling animals and with spontaneous and induced cystic ovarian disease (COD) to determine IGF bioavailability. The mRNA of IGFBP-2 and IGFBP-3 in follicular walls was quantified by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Protein expression was analyzed by immunohistochemistry. The results demonstrated reduced amounts of mRNA of both IGFBPs in the granulosa cells of ovarian follicles of animals with COD (P<0.05). The present study suggests that the IGF system or imbalances between IGFs and IGFBPs may be involved in COD of cattle. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Ovarian localization of 11β-hydroxysteroid dehydrogenase (11βHSD): effects of ACTH stimulation and its relationship with bovine cystic ovarian disease.

    Science.gov (United States)

    Amweg, A N; Salvetti, N R; Stangaferro, M L; Paredes, A H; Lara, H H; Rodríguez, F M; Ortega, H H

    2013-10-01

    Cystic ovarian disease (COD) is an important cause of infertility in cattle, and ACTH has been involved in regulatory mechanisms related to ovarian function associated with ovulation, steroidogenesis, and luteal function. Here, we examined the localization of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 11βHSD2 proteins in the ovary of healthy cows and animals with spontaneous and ACTH-induced COD and the in vitro response of the follicular wall exposed to ACTH. After stimulation by ACTH, we documented changes in 11βHSD expression and cortisol secretion by the follicular wall of large antral and follicular cysts. Follicular cysts showed a higher constitutive expression of both enzymes, whereas ACTH induced an increase in 11βHSD1 in tertiary follicles and follicular cysts and a decrease in 11βHSD2 in follicular cysts. Moderate expression of 11βHSD1 was observed by immunohistochemistry in granulosa of control animals, with an increase (P follicular cysts, differences from controls were observed only in the expression of 11βHSD1 in the granulosa, being higher (P follicular cysts may be exposed to high local concentrations of active glucocorticoids and indicate a local role for cortisol in COD pathogenesis and in regulatory mechanisms of ovarian function. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. 'Down the rabbit hole': enhancing the transition process for youth with cystic fibrosis and congenital heart disease by re-imagining the future and time.

    Science.gov (United States)

    Moola, F J; Norman, M E

    2011-11-01

    Although the transition from paediatric to adult clinical care is an important one, the process is far from seamless. Little is known about the transition experiences of youth with cystic fibrosis (CF) and congenital heart disease (CHD). Informed by the new social studies of childhood, this qualitative study adopted a thematic analytical approach in order to explore how 50 youth and 28 parents affected by CF and CHD at a large children's hospital in Canada negotiate constructions of 'normal developmental time'--in both anticipating and dealing with the transition from adolescence to adulthood. Illness appeared to render the future as an uncertain terrain for youth living with CF and CHD. Concerns related to deteriorating health and occupational restrictions in the future were paramount for these youth. For young women with CF and CHD, the loss of 'normal' gendered roles--such as motherhood--was also a distressing future concern. For youth living with CF and their parents in particular, time was thought to be stolen and the future was abbreviated. Despite these seemingly anxiety-inducing experiences, youth and their parents demonstrated considerable creativity as they devised strategies to deal with the future and stolen time. In addition to challenging ideological assumptions about developmental time which may alienate youth with chronic illnesses, the results from this study suggest that attending to youth's temporal anxieties and future concerns may ultimately enhance the transition process for youth with CF and CHD. © 2011 Blackwell Publishing Ltd.

  14. Rapid onset of iatrogenic adrenal insufficiency in a patient with cystic fibrosis-related liver disease treated with inhaled corticosteroids and a moderate CYP3A4 inhibitor.

    Science.gov (United States)

    Hoover, Wynton C; Britton, LaCrecia J; Gardner, Jay; Jackson, Tracy; Gutierrez, Hector

    2011-07-01

    To report the rapid onset of adrenal insufficiency and subsequent development of Cushing syndrome precipitated by a CYP3A4-mediated drug-drug interaction that may have been enhanced by the presence of cystic fibrosis (CF)-related liver disease. A 9-year-old girl with CF and cirrhosis experienced a decline in lung function that led to a diagnosis of asthma. After initiation of asthma therapy with inhaled fluticasone 110 μg/actuation, the patient experienced improvement in lung function to baseline. Seven weeks after the initiation of inhaled fluticasone, she developed vaginal candidiasis and was prescribed fluconazole 100 mg/day, a CYP3A4 inhibitor. Three days after starting fluconazole, she developed polyuria and polydipsia and was found to have severe hyperglycemia, which led to the diagnosis of Cushing syndrome. Fluticasone was discontinued, and the patient's adrenal function normalized. Patients with CF are commonly prescribed complex medication regimens that may affect drug metabolism. CYP3A4 inhibitors may significantly decrease metabolic clearance in patients using chronic inhaled corticosteroids. Iatrogenic Cushing syndrome has been reported in patients with CF treated concomitantly, and for extended duration, with inhaled corticosteroids and CYP3A4 inhibitors. This case highlights rapid onset of adrenal insufficiency in a patient with CF-related liver disease treated briefly with a moderate CYP3A4 inhibitor. Use of the Horn drug interaction probability scale indicates that the interaction between fluticasone and fluconazole was probable. CYP3A4-mediated drug interactions represent a significant risk in patients treated with long-term inhaled corticosteroids. The presence of clinically significant CF-related liver disease may enhance this risk.

  15. A large retroperitoneal cystic venous malformation mimicking bilateral ovarian cystic tumors.

    Science.gov (United States)

    Nakatsuka, Shin-Ichi; Shigeta, Naoya; Ojima, Yojiro; Kimura, Hayato; Nagano, Teruaki; Ito, Kimihiko

    2012-10-01

    Retroperitoneal cysts are a rare disease. Most retroperitoneal cysts of vascular origin have been reported as hemangiomas. However, according to the recent classification of vascular anomalies accepted by the International Society for Study of Vascular Anomalies (ISSVA), these previously reported retroperitoneal hemangiomas should rather have been classified as vascular malformations. A 65-year-old woman visited our hospital complaining of a sense of unexplained abdominal fullness. Magnetic resonance imaging suggested a uterine leiomyoma and bilateral ovarian cystic tumors. However, abdominal surgery revealed normal bilateral ovaries, but huge cystic masses in the retroperitoneum. Postoperative histological diagnosis of the retroperitoneal cysts demonstrated that they were venous malformations. This is a rare case in which large cystic retroperitoneal venous malformations were preoperatively diagnosed as ovarian cystic tumors. Retroperitoneal hemangiomas should be renamed as vascular malformations following the ISSVA classification.

  16. Zoonotic diseases and human health: the human influenza example.

    Science.gov (United States)

    Schoub, Barry D

    2012-06-20

    Over the past few decades a large number of new and emerging infectious diseases have been recognised in humans, partly because of improved diagnostic technologies and increased awareness and also, partly because of dynamic ecological changes between human hosts and their exposure to animals and the environment (Coker et al. 2011). Some 177 new pathogenic organisms have been recognised to be 'emerging', that is, have newly arisen or been newly introduced into human populations; almost three quarters of these, 130 (73%), have come from zoonotic origins (Cascio et al. 2011; Cutler, Fooks & Van Der Poel 2010; Taylor, Latham & Woolhouse 2001; Woolhouse & Gowtage-Sequeria 2005). One of the most prevalent and important human infectious disease is influenza, a disease responsible globally for a quarter million deaths annually. In the USA alone the toll from influenza is estimated at 36 000 deaths and 226 000 hospitalisations, and it ranks as the most important cause of vaccine preventable mortality in that country (CDC 2010). The epidemiological behaviour of human influenza clearly defines it as an emerging infectious disease and the recent understanding of its zoonotic origins has contributed much to the understanding of its behaviour in humans (Fauci 2006).

  17. Orbital cystic neurinoma.

    Science.gov (United States)

    Tokugawa, J; Nakao, Y; Mori, K; Maeda, M

    2003-07-01

    A 64-year-old woman presented with a 6-month history of exophthalmus of her right eye. She had no neurological deficit except for the exophthalmus and numbness in the right side of her forehead (frontal nerve territory). Neuro-imaging demonstrated a cystic mass in the right orbit. The tumour was totally removed by microsurgical transcranial surgery. The histological diagnosis was neurinoma. The origin of the tumour was considered to be the frontal nerve. Only two other cases of orbital cystic neurinoma have been reported. This rare clinical entity should be included in the differential diagnosis of a cystic mass in the orbit.

  18. The complement system in human cardiometabolic disease.

    Science.gov (United States)

    Hertle, E; Stehouwer, C D A; van Greevenbroek, M M J

    2014-10-01

    The complement system has been implicated in obesity, fatty liver, diabetes and cardiovascular disease (CVD). Complement factors are produced in adipose tissue and appear to be involved in adipose tissue metabolism and local inflammation. Thereby complement links adipose tissue inflammation to systemic metabolic derangements, such as low-grade inflammation, insulin resistance and dyslipidaemia. Furthermore, complement has been implicated in pathophysiological mechanisms of diet- and alcohol induced liver damage, hyperglycaemia, endothelial dysfunction, atherosclerosis and fibrinolysis. In this review, we summarize current evidence on the role of the complement system in several processes of human cardiometabolic disease. C3 is the central component in complement activation, and has most widely been studied in humans. C3 concentrations are associated with insulin resistance, liver dysfunction, risk of the metabolic syndrome, type 2 diabetes and CVD. C3 can be activated by the classical, the lectin and the alternative pathway of complement activation; and downstream activation of C3 activates the terminal pathway. Complement may also be activated via extrinsic proteases of the coagulation, fibrinolysis and the kinin systems. Studies on the different complement activation pathways in human cardiometabolic disease are limited, but available evidence suggests that they may have distinct roles in processes underlying cardiometabolic disease. The lectin pathway appeared beneficial in some studies on type 2 diabetes and CVD, while factors of the classical and the alternative pathway were related to unfavourable cardiometabolic traits. The terminal complement pathway was also implicated in insulin resistance and liver disease, and appears to have a prominent role in acute and advanced CVD. The available human data suggest a complex and potentially causal role for the complement system in human cardiometabolic disease. Further, preferably longitudinal studies are needed to

  19. Restoration of Chloride Efflux by Azithromycin in Airway Epithelial Cells of Cystic Fibrosis Patients▿

    Science.gov (United States)

    Saint-Criq, Vinciane; Rebeyrol, Carine; Ruffin, Manon; Roque, Telma; Guillot, Loïc; Jacquot, Jacky; Clement, Annick; Tabary, Olivier

    2011-01-01

    Azithromycin (AZM) has shown promising anti-inflammatory properties in chronic obstructive pulmonary diseases, and clinical studies have presented an improvement in the respiratory condition of cystic fibrosis (CF) patients. The aim of this study was to investigate, in human airway cells, the mechanism by which AZM has beneficial effects in CF. We demonstrated that AZM did not have any anti-inflammatory effect on CF airway cells but restored Cl− efflux. PMID:21220528

  20. Prevalence and Risk Factors for Human Cystic Echinococcosis in the Cusco Region of the Peruvian Highlands Diagnosed Using Focused Abdominal Ultrasound.

    Science.gov (United States)

    Tamarozzi, Francesca; Hou, Amy; Morales, Maria Luisa; Giordani, Maria Teresa; Vilca, Freddy; Mozo, Karen; Bascope, Ruben; White, A Clinton; Brunetti, Enrico; Chen, Lin; Cabada, Miguel M

    2017-06-01

    AbstractLatin America is among the highly endemic regions for cystic echinococcosis (CE). In Peru, an estimated 1,139 disability-adjusted life years are lost annually from surgical treatment of CE. This is comparable with the combined total for Argentina, Brazil, Uruguay, and Chile. The prevalence of human infection has been investigated in the central Peruvian Andes, but there are no community-based screening data from other regions of Peru. We carried out a population survey in January 2015 using abdominal ultrasound to estimate the prevalence of abdominal CE in the Canas and Canchis provinces, in the Cusco region of Peru. Among 1,351 subjects screened, 41 (3%) had CE. There was significant variation between communities with similar socioeconomic features in a small geographical area. A history of CE was reported by 4.1% of the screened subjects, among whom 30.3% still had CE on ultrasound. Among patients reporting previous CE treatment, 14.9% had CE in active stages. Limited education, community of residence, and knowing people with CE in the community were associated with CE. These results demonstrate a significant burden of CE in the region and suggest the need for further investigations, control activities, and optimization of clinical management for CE in this area.

  1. Neem in human and plant disease therapy.

    Science.gov (United States)

    Singh, Udai Pratap; Singh, Dhananjaya Pratap

    2002-01-01

    As a therapeutic agent, neem is one of the most popular trees in traditional medicinal systems and is increasingly becoming important in herbal alternative therapy. The tree itself is considered a "village pharmacy" because of the well-established fact that every part of the tree has an application in curing human diseases. The tree has been a constant source of novel and structurally unique phytochemicals that can constitute the basis for the development of novel pharmaco-therapeutic agents against various human diseases. Being a prototype for the development of safer drugs and ecofriendly, pro-human health agrochemical agents against a vast variety of plant diseases, the tree always remains in the center of safe herbal drug and pesticide development in the service of mankind.

  2. Comparison of the Diagnostic Accuracy of Three Rapid Tests for the Serodiagnosis of Hepatic Cystic Echinococcosis in Humans.

    Directory of Open Access Journals (Sweden)

    Francesca Tamarozzi

    2016-02-01

    Full Text Available The diagnosis of cystic echinococcosis (CE is based primarily on imaging, in particular with ultrasound for abdominal CE, complemented by serology when imaging results are unclear. In rural endemic areas, where expertise in ultrasound may be scant and conventional serology techniques are unavailable due to lack of laboratory equipment, Rapid Diagnostic Tests (RDTs are appealing.We evaluated the diagnostic accuracy of 3 commercial RDTs for the diagnosis of hepatic CE. Sera from 59 patients with single hepatic CE cysts in well-defined ultrasound stages (gold standard and 25 patients with non-parasitic cysts were analyzed by RDTs VIRapid HYDATIDOSIS (Vircell, Spain, Echinococcus DIGFA (Unibiotest, China, ADAMU-CE (ICST, Japan, and by RIDASCREEN Echinococcus IgG ELISA (R-Biopharm, Germany. Sensitivity, specificity and ROC curves were compared with McNemar and t-test. For VIRapid and DIGFA, correlation between semiquantitative results and ELISA OD values were evaluated by Spearman's coefficient. Reproducibility was assessed on 16 randomly selected sera with Cohen's Kappa coefficient. Sensitivity and Specificity of VIRapid (74%, 96% and ADAMU-CE (57%, 100% did not differ from ELISA (69%, 96% while DIGFA (72%, 72% did (p = 0.045. ADAMU-CE was significantly less sensitive in the diagnosis of active cysts (p = 0.019 while DIGFA was significantly less specific (p = 0.014 compared to ELISA. All tests were poorly sensitive in diagnosing inactive cysts (33.3% ELISA and ADAMU-CE, 42.8% DIGFA, 47.6% VIRapid. The reproducibility of all RDTs was good-very good. Band intensity of VIRapid and DIGFA correlated with ELISA OD values (r = 0.76 and r = 0.79 respectively, p<0.001.RDTs may be useful in resource-poor settings to complement ultrasound diagnosis of CE in uncertain cases. VIRapid test appears to perform best among the examined kits, but all tests are poorly sensitive in the presence of inactive cysts, which may pose problems with accurate diagnosis.

  3. New insights into the pathogenesis of cystic fibrosis sinusitis

    Science.gov (United States)

    Chang, Eugene H.

    2013-01-01

    People with cystic fibrosis (CF) sinus disease have developmental sinus abnormalities with airway bacterial infection, inflammation, impaired mucociliary clearance and thick obstructive mucus. The pathophysiology of airway disease in CF is not completely understood, and current treatments in CF sinus disease ameliorate symptoms but do not provide a cure. This manuscript reviews the history of CF, its manifestations in sinus disease, and the potential impact and relationship of CF on the upper and lower airway. We discuss recent discoveries in the pathophysiology of CF using the CF porcine animal model and exciting treatments that address the primary gene defect that may translate into improved outcomes in CF and non-CF sinusitis in humans. PMID:24282147

  4. Taxonomy and Biology of Phlebotomine Vectors of Human Disease.

    Science.gov (United States)

    DIPTERA, *DISEASE VECTORS, *TAXONOMY, *VECTOR ANALYSIS , ANTIBODIES, BIOLOGY , BRAIN, CHROMOSOMES, COLOMBIA, COLONIES( BIOLOGY ), DISEASES, FEMALES... HUMANS , INFECTIOUS DISEASES, LABORATORIES, LEISHMANIA, LEISHMANIASIS, NEUTRALIZATION, PATIENTS, SEROLOGY, STRAINS( BIOLOGY ).

  5. Expression of S100A8 correlates with inflammatory lung disease in congenic mice deficient of the cystic fibrosis transmembrane conductance regulator

    Directory of Open Access Journals (Sweden)

    Keet Mary

    2006-03-01

    Full Text Available Abstract Background Lung disease in cystic fibrosis (CF patients is dominated by chronic inflammation with an early and inappropriate influx of neutrophils causing airway destruction. Congenic C57BL/6 CF mice develop lung inflammatory disease similar to that of patients. In contrast, lungs of congenic BALB/c CF mice remain unaffected. The basis of the neutrophil influx to the airways of CF patients and C57BL/6 mice, and its precipitating factor(s (spontaneous or infection induced remains unclear. Methods The lungs of 20-day old congenic C57BL/6 (before any overt signs of inflammation and BALB/c CF mouse lines maintained in sterile environments were investigated for distinctions in the neutrophil chemokines S100A8 and S100A9 by quantitative RT-PCR and RNA in situ hybridization, that were then correlated to neutrophil numbers. Results The lungs of C57BL/6 CF mice had spontaneous and significant elevation of both neutrophil chemokines S100A8 and S100A9 and a corresponding increase in neutrophils, in the absence of detectable pathogens. In contrast, BALB/c CF mouse lungs maintained under identical conditions, had similar elevations of S100A9 expression and resident neutrophil numbers, but diverged in having normal levels of S100A8. Conclusion The results indicate early and spontaneous lung inflammation in CF mice, whose progression corresponds to increased expression of both S100A8 and S100A9, but not S100A9 alone. Moreover, since both C57BL/6 and BALB/c CF lungs were maintained under identical conditions and had similar elevations in S100A9 and neutrophils, the higher S100A8 expression in the former (or suppression in latter is a result of secondary genetic influences rather than environment or differential infection.

  6. Latent physiological factors of complex human diseases revealed by independent component analysis of clinarrays

    Directory of Open Access Journals (Sweden)

    Chen David P

    2010-10-01

    Full Text Available Abstract Background Diagnosis and treatment of patients in the clinical setting is often driven by known symptomatic factors that distinguish one particular condition from another. Treatment based on noticeable symptoms, however, is limited to the types of clinical biomarkers collected, and is prone to overlooking dysfunctions in physiological factors not easily evident to medical practitioners. We used a vector-based representation of patient clinical biomarkers, or clinarrays, to search for latent physiological factors that underlie human diseases directly from clinical laboratory data. Knowledge of these factors could be used to improve assessment of disease severity and help to refine strategies for diagnosis and monitoring disease progression. Results Applying Independent Component Analysis on clinarrays built from patient laboratory measurements revealed both known and novel concomitant physiological factors for asthma, types 1 and 2 diabetes, cystic fibrosis, and Duchenne muscular dystrophy. Serum sodium was found to be the most significant factor for both type 1 and type 2 diabetes, and was also significant in asthma. TSH3, a measure of thyroid function, and blood urea nitrogen, indicative of kidney function, were factors unique to type 1 diabetes respective to type 2 diabetes. Platelet count was significant across all the diseases analyzed. Conclusions The results demonstrate that large-scale analyses of clinical biomarkers using unsupervised methods can offer novel insights into the pathophysiological basis of human disease, and suggest novel clinical utility of established laboratory measurements.

  7. Learning about Cystic Fibrosis

    Science.gov (United States)

    Skip to main content Learning About Cystic Fibrosis Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News Features Funding Divisions Funding ...

  8. About Cystic Fibrosis

    Science.gov (United States)

    ... AWARENESS Tomorrow’s Leaders About Us News Blog Chapters Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home What Is CF About Cystic Fibrosis Share Facebook Twitter Email More options Print Share Facebook Twitter ...

  9. Genetic architecture of human fibrotic diseases: disease risk and disease progression

    Directory of Open Access Journals (Sweden)

    Agnès eGardet

    2013-12-01

    Full Text Available Genetic studies of human diseases have identified multiple genetic risk loci for various fibrotic diseases. This has provided insights into the myriad of biological pathways potentially involved in disease pathogenesis. These discoveries suggest that alterations in immune responses, barrier function, metabolism and telomerase activity may be implicated in the genetic risks for fibrotic diseases. In addition to genetic disease-risks, the identification of genetic disease-modifiers associated with disease complications, severity or prognosis provides crucial insights into the biological processes implicated in disease progression. Understanding the biological processes driving disease progression may be critical to delineate more effective strategies for therapeutic interventions. This review provides an overview of current knowledge and gaps regarding genetic disease-risks and genetic disease-modifiers in human fibrotic diseases.

  10. Modeling human disease using organotypic cultures.

    Science.gov (United States)

    Schweiger, Pawel J; Jensen, Kim B

    2016-12-01

    Reliable disease models are needed in order to improve quality of healthcare. This includes gaining better understanding of disease mechanisms, developing new therapeutic interventions and personalizing treatment. Up-to-date, the majority of our knowledge about disease states comes from in vivo animal models and in vitro cell culture systems. However, it has been exceedingly difficult to model disease at the tissue level. Since recently, the gap between cell line studies and in vivo modeling has been narrowing thanks to progress in biomaterials and stem cell research. Development of reliable 3D culture systems has enabled a rapid expansion of sophisticated in vitro models. Here we focus on some of the latest advances and future perspectives in 3D organoids for human disease modeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Modeling human disease using organotypic cultures

    DEFF Research Database (Denmark)

    Schweiger, Pawel J; Jensen, Kim B

    2016-01-01

    Reliable disease models are needed in order to improve quality of healthcare. This includes gaining better understanding of disease mechanisms, developing new therapeutic interventions and personalizing treatment. Up-to-date, the majority of our knowledge about disease states comes from in vivo a...... culture systems has enabled a rapid expansion of sophisticated in vitro models. Here we focus on some of the latest advances and future perspectives in 3D organoids for human disease modeling....... animal models and in vitro cell culture systems. However, it has been exceedingly difficult to model disease at the tissue level. Since recently, the gap between cell line studies and in vivo modeling has been narrowing thanks to progress in biomaterials and stem cell research. Development of reliable 3D...

  12. Measurements of CFTR-mediated Cl- secretion in human rectal biopsies constitute a robust biomarker for Cystic Fibrosis diagnosis and prognosis.

    Directory of Open Access Journals (Sweden)

    Marisa Sousa

    Full Text Available BACKGROUND: Cystic Fibrosis (CF is caused by ∼1,900 mutations in the CF transmembrane conductance regulator (CFTR gene encoding for a cAMP-regulated chloride (Cl(- channel expressed in several epithelia. Clinical features are dominated by respiratory symptoms, but there is variable organ involvement thus causing diagnostic dilemmas, especially for non-classic cases. METHODOLOGY/PRINCIPAL FINDINGS: To further establish measurement of CFTR function as a sensitive and robust biomarker for diagnosis and prognosis of CF, we herein assessed cholinergic and cAMP-CFTR-mediated Cl(- secretion in 524 freshly excised rectal biopsies from 118 individuals, including patients with confirmed CF clinical diagnosis (n=51, individuals with clinical CF suspicion (n=49 and age-matched non-CF controls (n=18. Conclusive measurements were obtained for 96% of cases. Patients with "Classic CF", presenting earlier onset of symptoms, pancreatic insufficiency, severe lung disease and low Shwachman-Kulczycki scores were found to lack CFTR-mediated Cl(- secretion (<5%. Individuals with milder CF disease presented residual CFTR-mediated Cl(- secretion (10-57% and non-CF controls show CFTR-mediated Cl(- secretion ≥ 30-35% and data evidenced good correlations with various clinical parameters. Finally, comparison of these values with those in "CF suspicion" individuals allowed to confirm CF in 16/49 individuals (33% and exclude it in 28/49 (57%. Statistical discriminant analyses showed that colonic measurements of CFTR-mediated Cl(- secretion are the best discriminator among Classic/Non-Classic CF and non-CF groups. CONCLUSIONS/SIGNIFICANCE: Determination of CFTR-mediated Cl(- secretion in rectal biopsies is demonstrated here to be a sensitive, reproducible and robust predictive biomarker for the diagnosis and prognosis of CF. The method also has very high potential for (pre-clinical trials of CFTR-modulator therapies.

  13. The cystic fibrosis of exocrine pancreas

    DEFF Research Database (Denmark)

    Wilschanski, Michael; Novak, Ivana

    2013-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) protein is highly expressed in the pancreatic duct epithelia and permits anions and water to enter the ductal lumen. This results in an increased volume of alkaline fluid allowing the highly concentrated proteins secreted by the acinar...... cells to remain in a soluble state. This work will expound on the pathophysiology and pathology caused by the malfunctioning CFTR protein with special reference to ion transport and acid-base abnormalities both in humans and animal models. We will also discuss the relationship between cystic fibrosis...

  14. Animal models for human genetic diseases

    African Journals Online (AJOL)

    Sharif Sons

    disturbances (including anxiety and depression). (Rosenthal and Brown, 2007). Mouse models for a rare genetic disorder of the blood platelets, May-Hegglin anomaly (MHA) showed same symptoms as occur in humans (American Institute of. Physics, 2011). Also in genetic prion disease, histopathological examination of ...

  15. Primatology. Human diseases threaten great apes.

    Science.gov (United States)

    Ferber, D

    2000-08-25

    Researchers are uncovering disturbing evidence that scientists and tourists are infecting wild primates with human pathogens. In response, ape specialists, including the American Society of Primatologists, are now calling for stricter health standards for researchers and tourists. They are also urging researchers to learn how to diagnose disease in their study animals.

  16. [Cystic dystrophy on aberrant pancreas. Contribution of ultrasound-endoscopy].

    Science.gov (United States)

    Andrieu, J; Palazzo, L; Chikli, F; Doll, J; Chome, J

    1989-06-01

    Cystic dystrophy of aberrant pancreatic tissue without chronic pancreatitis is a rare disease described by Potet and Duclert in 1970. Clinical diagnosis is possible by endoscopy and intraluminalsonography; we report the first case diagnosed by intraluminalsonography.

  17. Emerging arboviral human diseases in Southern Europe.

    Science.gov (United States)

    Papa, Anna

    2017-08-01

    Southern Europe is characterized by unique landscape and climate which attract tourists, but also arthropod vectors, some of them carrying pathogens. Among several arboviral diseases that emerged in the region during the last decade, West Nile fever accounted for high number of human cases and fatalities, while Crimean-Congo hemorrhagic fever expanded its geographic distribution, and is considered as a real threat for Europe. Viruses evolve rapidly and acquire mutations making themselves stronger and naive populations more vulnerable. In an effort to tackle efficiently the emerging arboviral diseases, preparedness and strategic surveillance are needed for the early detection of the pathogen and containment and mitigation of probable outbreaks. In this review, the main human arboviral diseases that emerged in Southern Europe are described. © 2017 Wiley Periodicals, Inc.

  18. Towards a human rotavirus disease model.

    Science.gov (United States)

    Hagbom, Marie; Sharma, Sumit; Lundgren, Ove; Svensson, Lennart

    2012-08-01

    While the clinical importance of human rotavirus (RV) disease is well recognized and potent vaccines have been developed, our understanding of how human RV causes diarrhoea, vomiting and death remains unresolved. The fact that oral rehydration corrects electrolyte and water loss, indicates that enterocytes in the small intestine have a functional sodium-glucose co-transporter. Moreover, RV infection delays gastric emptying and loperamide appears to attenuate RV diarrhoea, thereby suggesting activation of the enteric nervous system. Serotonin (5-HT) receptor antagonists attenuate vomiting in young children with gastroenteritis while zinc and enkephalinase inhibitors attenuate RV-induced diarrhoea. In this review we discuss clinical symptoms, pathology, histology and treatment practices for human RV infections and compile the data into a simplified disease model. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Analysis of expression patterns of breast cancer-specific markers (mammaglobin and gross cystic disease fluid protein 15) in lung and pleural tumors.

    Science.gov (United States)

    Takeda, Yuji; Tsuta, Koji; Shibuki, Yasuo; Hoshino, Tatsuhiro; Tochigi, Naobumi; Maeshima, Akiko Miyagi; Asamura, Hisao; Sasajima, Yuko; Ito, Tsuyoshi; Matsuno, Yoshihiro

    2008-02-01

    The lung is the most common site of metastasis during the natural history of malignant tumors. Breast carcinoma has a propensity for distant metastasis, and the lung and pleura are among the most common metastatic sites. Although it is often difficult to make a clear-cut differential diagnosis between the two, distinguishing primary lung carcinoma from breast carcinoma metastatic to the lung is important because the treatment modalities are different. To elucidate the utility of mammaglobin and gross cystic disease fluid protein 15 (GCDFP-15), which are known to be breast-specific antigens, in distinguishing various primary lung and pleural tumors from breast carcinoma metastasizing to the lung. A total of 20 cases of breast carcinoma metastatic to the lung and 263 tumors of nonbreast origin located in the lung and pleura were analyzed. Of the 20 cases of breast carcinoma metastatic to the lung, 10 (50.0%) were immunoreactive for mammaglobin and 9 (45.0%) for GCDFP-15, the frequency of positivity being slightly higher for the former than for the latter. The area immunopositive for mammaglobin showed more diffuse staining than the area immunopositive for GCDFP-15. Furthermore, the specificity of mammaglobin for breast carcinoma metastatic to the lung was superior (98.9%) to that of GCDFP-15 (91.8%). The sensitivity of mammaglobin is equal or superior to that of GCDFP-15 for investigation of breast carcinoma. Immunopositivity for mammaglobin is more diffuse than that for GCDFP-15. In terms of practical diagnosis, mammaglobin immunohistochemistry can serve as a differential marker of breast carcinoma and should be added to the immunohistochemical panel.

  20. Pathogenic factors of Pseudomonas cepacia isolates from patients with cystic fibrosis.

    Science.gov (United States)

    Gessner, A R; Mortensen, J E

    1990-10-01

    One hundred and nineteen isolates of Pseudomonas cepacia, 98 of which were from cystic fibrosis (CF) patients and 21 from environmental and other human sources, were examined for biochemical and exo-enzymatic properties that may contribute to the pathogenicity of this bacterium. The following characteristics were demonstrated significantly more frequently in isolates from CF patients than in control isolates: production of catalase, ornithine decarboxylase, valine aminopeptidase, C14 lipase, alginase and trypsin; reduction of nitrate to nitrite; hydrolysis of urea and xanthine; complete haemolysis on bovine red blood cells; cold-sensitive haemolysis on human red blood cells; greening of horse and rabbit red blood cells. The role of these factors in the pulmonary disease associated with cystic fibrosis is not clear. However, several factors which have been reported previously as being associated with pathogenic processes with other bacteria have now been described in P. cepacia. Additional factors not previously reported as "pathogenicity factors" are also described.

  1. Hereditary Renal Cystic Disorders: Imaging of the Kidneys and Beyond.

    Science.gov (United States)

    Dillman, Jonathan R; Trout, Andrew T; Smith, Ethan A; Towbin, Alexander J

    2017-01-01

    The purpose of this article is to review the hereditary renal cystic diseases that can manifest in children and adults, with specific attention to pathogenesis and imaging features. Various common and uncommon hereditary renal cystic diseases are reviewed in terms of their underlying etiology, including the involved genetic mutations and the affected proteins and cellular structures. Focus is placed on the morphologic findings in each condition and the features that distinguish one disorder from another. The two most common categories of hereditary renal cystic disease are (a) the ciliopathic disorders, which are related to mutations affecting the primary cilia (called "ciliopathies"), and (b) the phakomatoses. Autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease, and the "medullary cystic disease complex" are all ciliopathies but have different phenotypes. Tuberous sclerosis complex and the associated "contiguous gene syndrome," as well as von Hippel-Lindau syndrome, are phakomatoses that can manifest with cystic renal lesions but have uniquely different extrarenal manifestations. Finally, DICER1 mutations can manifest with renal cystic lesions (typically, cystic nephromas) in patients predisposed to other malignancies in the chest, ovaries, and thyroid. Although some overlap exists in the appearance of the renal cysts associated with each of these diseases, there are clear morphologic differences (eg, cyst size, location, and complexity) that are emphasized in this review. To improve patient outcomes, it is important for the radiologist to recognize the various hereditary renal cystic diseases so that a correct diagnosis is assigned and so that the patient is adequately evaluated and followed up. ©RSNA, 2017.

  2. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona

    2010-01-01

    BACKGROUND: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release and ce...

  3. Ultrasound Imaging of Cystic Nephroma

    Directory of Open Access Journals (Sweden)

    Federico Greco

    2017-07-01

    Full Text Available Cystic nephroma is a rare, benign multicystic lesion of the kidney. This tumor occurs both in children and in adults. In children, it is highly prevalent in males; in adults, it is more frequent in women. The term “cystic nephroma” represents two apparently different entities: pediatric cystic nephroma, a benign form thought to originate from metanephric tissue, and adult cystic nephroma, considered as a lesion of mixed epithelial stromal tumor. The clinical presentation may be a palpable mass or nonspecific symptoms such as abdominal pain, hematuria, and urinary tract infections. In this review, we summarize the ultrasound imaging features of cystic nephroma and describe the characteristics of the most common renal cystic